Men's health

With united, sustained action, general practice organisations and practitioners can help stop our men dying or “diseasing” too early What is it with men’s health? Ten years ago, men’s health nights in pubs were all the go. Now we don’t even have those. There’s the occasional event or TV item, but always a one-off. Women’s health researchers, practitioners and advocates get lots of resources and publicity, and good on ’em. But men are still dying too early from stuff that can be prevented. (Anonymous man, Daylesford, Victoria, 2006) As National Convenor of GPs4Men, the Australian General Practitioners’ Network for Men’s Health, I hear occasional comments like this from patients I see in my full-time rural general practice. Recently, I have run into colleagues who, noting the absence of men’s “health bites” in the media, ask if I’m still involved. My answer is “yes, but differently”. “Spare” time previously spent on activities with GPs4Men, particularly liaison with members, has been leached away by work on the Royal Australian College of General Practitioners’ (RACGP) position statement on men’s health (to match the 1997 position statement on women’s health), now endorsed and available on online,1 and the ongoing RACGP men’s health curriculum review. GPs4Men was founded in 2003 in response to the lack of policy and funding for men’s health on a national level. Australia still has no national men’s health policy, despite the existence of a women’s health policy since 1989. It would be naïve to suggest that simply developing a policy would be sufficient to deal with all the challenges of men’s health — policy without adequately funded programs = “piffle”. Yet, for those of us involved in men’s health, there remains an overwhelming desire to see a formal acknowledgement by the federal government (whether a policy, position statement or other document) of the broad and unique issues of men’s health, and a preparedness to fund a national program to address these issues. I wonder whether the government’s problem might be that the problem seems “too big”. A multiplicity of interest groups — including sociologists, “masculinists”, “men’s shed” workers, community nurses, endocrinologists, GPs, urologists, social workers and educators — all hold valid points of view. But has this very diversity led to an apparent government standstill due to “overload”? Whatever the reason, GPs simply must do something about Australian men’s health. The recent RACGP health inequalities study clearly demonstrated the appallingly high mortality rates for men compared with women across the socioeconomic spectrum.2 Notably, it showed that: the mortality rate for 25–64-year-old men in the most socially advantaged group of the population was higher than that for 25–64-year-old women in the most socially disadvantaged group; and men in the most socially disadvantaged group had a mortality rate nearly double that of the most socially disadvantaged women. Further, there can be no argument that groups of men — Indigenous men, war and service veterans,3 and men affected by poverty — are at high risk of health problems and have specific medical needs. At present, the federal government’s response seems to be to restrict funding largely to men’s sexual health programs — based, presumably, on the unassailable assertion that testes and prostates are unequivocally male. The problem with this approach is that it ignores key issues; not only the stark statistics, but also the differences between how men and women view their bodies (especially in dysfunction), and in how they use the health care system. The major recipient of federal funding in men’s health ($4 million over 4 years) — the male reproductive health centre, Andrology Australia — runs excellent community and medical education programs. However, it is beyond this organisation’s terms of reference to tackle the crucial issue of men’s underuse of the health care system. It would again be simplistic to suggest that simply finding ways of bringing men into more effective contact with GPs would solve the problems of men dying or “diseasing” too early. Many other issues also demand attention, from men’s involvement in pregnancy and postnatal depression, to masculinity issues in schools and the workforce, to addictions, to social isolation and relationship problems. Nevertheless, bridging the chasm between GPs and their potential male patients is crucial, as GPs are the key providers of primary health care. Marketing health to men needs to be viewed as a crucial and do-able component of any worthwhile campaign to improve men’s health. Such marketing is too important to just be left in the hands of a group of enthusiastic health professionals. Men’s health needs the sort of marketing expertise used by those who are intent on persuading teenagers to smoke. It should be sustained, professional, well funded and be driven by clear goals. Men’s health is also desperate for high-profile sustained support. The Prime Minister’s newly appointed obesity ambassadors, Harry Kewell and Kieren Perkins, should have their portfolios enlarged to encompass the broader issues of men and their health. We need the support of influential figures like the Prime Minister and the Minister for Health to achieve this. Their early morning walks and bike riding, respectively, serve as excellent examples for Australia’s men. The membership of GPs4Men (of about 70 individual GPs and almost a third of the 118 Australian Divisions of General Practice [ADGP]) believes that it is the responsibility of the GP Reference Group organisations — the RACGP, the ADGP, the Australian Medical Association (AMA) and the Rural Doctors Association of Australia (RDAA) — to make a joint submission to our federal government for a federally funded men’s health program that puts into action a men’s health policy. It is up to those who fund health care to find ways of taking Australia’s overworked GPs to where men are more comfortable using their services, especially the workplace. It is up to those who deliver health care to identify the best way forward. Not only united but also sustained effort will be required from general practice organisations. The AMA produced a position statement on men’s health in 2004,4 but has since seemed to move on to other priorities. The RACGP has had a Women’s Health Taskforce since 1997; surely it is time for the college to have an active Men’s Health Taskforce. The ADGP is moving slowly towards greater activity in men’s health, with a session dedicated to men’s health at its upcoming national forum on the Gold Coast in November this year. Many GPs and Divisions would respond to local needs for men’s health programs, but cannot because of lack of funding. The RDAA has also expressed its broad support for men’s health; understandably so in the light of the dire state of rural men’s health. In the absence of any structural or funded initiatives, there is still much being done and that can be done in general practice. All GPs (and possibly all medical practitioners) should consider how they can increase the uptake of their services by the “unreachable” group — 30–60-year-old men. I believe that general practice has some way to go before we can feel satisfied with how we market health to our male population. “Man-friendly” appointment systems and consulting times with after-work times and more on-the-day appointments, waiting rooms, and reception staff are key parts of a “whole-of-practice” approach, as are outreach services to workplaces and other venues. Similarly, a “whole-of-consultation” approach involves offering options to the men we do see which take into account the fact that many men prefer a more physically-based approach to lifestyle prescription, and may require specific direction about follow-up. Community resources which meet men’s exercise needs are often lacking. For many men, a trusting relationship with a personal physician or practice is built over a series of consultations. Australia’s men, our women’s and men’s groups and our GPs believe that men’s health is much more than sexual health — this is not the case in much of the developed world. We therefore have a great opportunity to lead the world, or at least to share the lead in the important area of men’s health.

Gregory O Malcher DObstRCOG, DCH, FRACGP

I know what men want. Men want to be really, really close to someone who will leave them alone — Anonymous The ideal man — Philip Patston, comedian, consultant, columnist and (among other things) recovering social worker and human rights activist. He is gay, disabled, vegetarian and English. Six years ago, Philip created Diversityworks, now a multi-faceted enterprise that includes a business group offering expertise in managing diversity and change, and a trust that runs projects to improve diversity and professional participation in the arts <http://www.diversityworks.co.nz>. Philip lives in Auckland and travels regularly in New Zealand. His work has taken him to Australia, the United States, Canada, the United Kingdom and Belgium. In 2004, in making a radio documentary on romance which played in 10 countries around the world, I spoke to several people who experience disability. For the blokes, the theme of being disabled and male in society came up repeatedly, including issues of responsibility, dependence, dominance, and public perception. Compared with the traditional role of the strong male provider, men who experience disability are often perceived as vulnerable, needy and dependent. Over the years, I have come to understand that in many ways, like gay men, disabled men can choose to feel either shackled or liberated by the perception that they are less “manly” than their non-disabled counterparts. As a gay man who experiences disability as a result of cerebral palsy, I have a unique experience of being male. I am bound by neither heterosexual nor non-disabled role stereotypes. I feel no compulsion or expectation to be “a real man”. And yet, at the same time, I cherish my distinctive maleness, which I experience to be a healthy balance of masculine and feminine. In some ways, as I argue here, I am the ideal man. Men, function and disabilityThe four themes that emerged from my conversations with men with disabilities — responsibility, dependence, dominance, and public perception — correspond to a set of traditional male role attitude items that I stumbled across in an article about masculinity and its impact on adolescent male heterosexual relationships.1 Here are some laments of the real man: It is essential for a guy to get respect from others. A man always deserves the respect of his wife and children. I admire a guy who is totally sure of himself. A guy will lose respect if he talks about his problems. A young man should be physically tough, even if he’s not big. It bothers me when a guy acts like a girl. I don’t think a husband should have to do housework. Men are always ready for sex. I subscribe to a definition of disability based on a model that acknowledges that attitudes and barriers in society disable people more than their impairment, and this may lead to a loss of function. But what is function? Function has a vast array of meaning, ranging from the very pragmatic and physical to the somewhat esoteric or spiritual. Function is implied in all of the following: Task — work or assignment, often important or difficult. Job — paid trade or profession, something needing to be done or dealt with. Utility — the quality or state of being useful. Occupation — an activity on which time is spent; may be paid or unpaid. Role — the usual or expected function of someone, the part played in a given social context. Meaning — what something means, what someone intends to express. Purpose — the reason something or someone exists. I believe that, in our culture, men are mostly valued for the more pragmatic, physical realms of function (task, job, utility, occupation), whereas women are more valued for the esoteric, spiritual elements (role, meaning, purpose). This is, of course, a generalisation, but one that corresponds to the traditional male role attitude items listed above. When I compare what disabled and non-disabled men are valued for, aspects of function stand out as the great divide. For example, I am seldom asked the obligatory question, “What do you do?” People assume I don’t do much of any import, because I have a physical impairment. I’ve also noticed that men are far less comfortable than women with issues of impairment and disability. It’s women, far more often than men, who offer assistance, unless it’s something overtly physical like putting my wheelchair in my car. And it’s women who are far more prevalent as workers in the disability sector. However, when you examine the impact of the loss of function for men, women and people who experience disability, one thing is very clear: men have a lot more to lose. Loss of function particularly pushes blokes’ buttons. Why? It seems to me that, in a primal sort of way, male identity is situated in the realm of physical function. Male creativity is concerned with external manipulation — making things, building things, doing things — so impairment and disablement fundamentally threaten male identity. I have argued that the essential difference between the sexes is that men create “without” and women create “within”. Consider these differences between men and women: men’s sexual organs are outside the body; women’s inside. Men cannot conceive and create children, as women can — inside them. Men gather information primarily through their sense organs located primarily on the outside of their bodies whereas women gather much information through their intuition, their feelings, inside their body. And finally, without getting too much into the sex stereotype debate, look at household roles — women’s domain is generally inside and men’s, outside. My conversations with the men in the documentary made me realise that when men are threatened with loss of function, they experience huge levels of fear. I consider fear to be the absence of love (and, conversely, love the absence of fear). When people act out of fear, their actions are characterised by drive (fear of not succeeding), low creativity and judgement. Conversely, when people act out of love, they are passionate, highly creative and accepting. The idea of losing function leaves men uncreative, intolerant and driven by the fear of losing control, independence, positive public perception and responsibility. The ideal man?So how does all this make me, a gay man who experiences disability, an ideal man? Firstly, I think I have successfully surrendered control. There are aspects of my life — the result of stigma, disablement, homophobia and the like — that I cannot control. I no longer expect to control everything. More than anything, I have developed the ability to trust that everything is perfect. Secondly, I accept that, to live the busy, autonomous lifestyle that I have chosen and created, dependence on personal assistants and funding to employ them is necessary. Thirdly, I ignore public perception. Simply put, though it is still hard sometimes (especially when he’s cute), I have learnt to reject rejection. Finally, I take responsibility. I am not a victim of circumstance. I’ve moved away from my personal “fight for rights” towards a quest for creativity and identity, and a spiritual understanding of the purpose disadvantaged people have (and choose) to help humanity evolve. Sure, disabled gay men have rights and we are not yet well afforded them — this is indeed the last bastion of human rights, and breaking it down will require recognition by society that the mix of disablement and homophobia that blokes like me experience is a complex social construct, not a catastrophic personal tragedy. But while humanity catches up, I’ve chosen to move on and create an identity based on who I am rather than who I am not. Part of my creative process has been to understand and believe I am here to raise human consciousness about diversity. At the same time, I am empowered by the notion that even though it’s bloody hard at times, my soul made a choice to live this life. Which leads me to believe that that soul must be a masochist, but such is the sacrifice one makes to be the ideal man!

Philip Patston

Men seek help and use health services less frequently than women do. Men’s help-seeking practices and health service use are complex issues involving biological, psychological and sociological considerations. Most discussion on men’s help-seeking positions them as reluctant consumers or “behaving badly” with respect to their health. Few studies have explored whether health service providers are equipped to deal with men’s health issues appropriately. The current health system appears not to be tailored to meet the health needs of men. Better collaboration is required across disciplines, to further investigate men’s health using both qualitative and quantitative research methods.

James A Smith · Annette Braunack-Mayer PhD · Gary Wittert MB BS, FRACP

The must-have health guide. 2nd ed. Margaret Stearn. Oxford: Heath Press, 2005 (vi + 378 pp). ISBN: 1 903734 75 4. Anyone with young children or familiar with children’s literature will know there has been an explosion in the number of books about bottoms. Titles such as The day my bum went psycho and The bugalugs bum thief (the latter by Tim Winton no less) are on high rotation in most school libraries. UK physician Dr Margaret Stearn’s The must-have health guide perhaps represents an expansion of this publishing phenomenon into the area of consumer health. As the title page advises, the book focuses not on respectable medical conditions such as diabetes, but on “life’s embarrassing problems”. Its concerns are the floppy, the spotty, the leaky, the smelly and the discharging. Hiccups, blushing, bad breath, snoring, shaky hands, and shyness are the only topics covered that don’t directly relate to breasts, bottoms, genitals, blemishes of skin and appendages, or urination. Surprisingly, even after 35 years of women’s magazines covering every aspect of sexual anatomy, function and disease, genital conditions still constitute the bulk of embarrassing health problems, at least according to Stearn. Alphabetically organised by problem, from acne to wind, the information (including treatment), is fairly detailed, readily comprehensible, and eminently practical. Unlike most self-help guides The must-have health guide is evidence-based, providing frequent references. Each problem entry concludes with a list of contacts. While most of these are UK based, they all have web addresses. The tone of the book is English in a rather brisk, no-nonsense but not unfriendly way. It’s a little like having a very knowledgable aunt in a thick tweed skirt and sensible shoes, a slight twinkle in her eye, ever ready with practical advice. For instance, in the “small breasts” section Stearn provides extensive information about breast implants, but reminds us that small breasts are “just as functional as large ones, get less droopy, are a kilo less to carry around and are good for sports”. The book is also studded with more whimsical pieces of information. Did you know, for example, that a study of male Mensa members showed they had thicker body hair than average, and the most intelligent had hairy backs? For those embarrassed by crab lice, faecal incontinence or urinating during sex — and let’s face it, most of us still are — this is an extremely helpful guide. Simon C CowapGeneral Practitioner Newtown, NSW

Simon C Cowap

Androgen deficiency is a clinical diagnosis confirmed by hormone assays. Among younger men, androgen deficiency is usually due to underlying hypothalamopituitary or testicular disorders. Androgen replacement therapy should be started after proof of androgen deficiency and should continue lifelong with monitoring. Men presenting with erectile dysfunction should be evaluated for androgen deficiency, but it is an uncommon cause; if overt androgen deficiency is confirmed, an underlying disorder needs further specialist investigation. In the absence of characteristic underlying testicular or pituitary disorders, new diagnosis of androgen deficiency in older men is difficult because of the non-specific symptoms and the decline in blood testosterone levels seen in healthy ageing and chronic medical disorders. There remains no convincing evidence that androgen therapy is either effective treatment or safe for older men unless they have frank androgen deficiency.

David J Handelsman FRACP, PhD · Jeffrey D Zajac PhD, FRACP

The male pill. A biography of a technology in the making. Durham: Duke University Press, 2003 (xi + 306pp). ISBN 0 8223 3195 0. Why haven’t we got a contraceptive pill for men? Nelly Oudshoorn, Professor of Gender and Technology at the University of Twente in the Netherlands, attempts to provide some of the answers in this timely historical account. In 1972, the World Health Organization (WHO) Male Task Force concluded that a long-acting gestagen to suppress pituitary gonadotropin secretion, and hence testicular activity, supplemented by androgen replacement therapy, was the way to develop a male contraceptive. But which gestagen, and which androgen, in what dose, and by what route of administration? These questions still remain, 32 years later, although the latest Australian study,1 has shown that three-monthly injections of 300 mg depot medroxyprogesterone acetate and four-monthly implants of 800 mg testosterone give excellent contraceptive protection for one year. A male contraceptive implant might find a small niche market in the developed world, but in the developing world, where most of the world’s population lives, the logistics and cost of repeated implants or injections would probably make it a non-starter. Another worry is that anabolic steroids (aka androgens) are now internationally banned as performance-enhancing drugs, and hence any athlete taking a hormonal contraceptive would simply not be allowed to compete. The lack of interest shown by the pharmaceutical industry (wisdom in hindsight?) has been a major blow, as has the low profile of andrology as a medical specialty. Nelly Oudshoorn concludes that we have failed to develop a male pill simply because “technological innovation in male contraception thus facilitates a situation in which hegemonic masculinities are destabilized and nonhegemonic masculine identities are articulated and gain momentum”. The truth is somewhat simpler. A male pill is still not in sight, and the pharmaceutical industry will have to invest hundreds of millions of dollars to bring a three-monthly injectable hormone cocktail onto the market. Is it worth the investment? Roger V ShortProfessor of Obstetrics and Gynaecology Royal Women’s HospitalMelbourne, VIC 1. Turner L, Conway AJ, Jimenez M, et al. Contraceptive efficacy of a depot progestin and androgen combination in men. J Clin Endocrinol Metab 2003; 88: 4659-4667.

Roger V Short

Erectile dysfunction and related disorders. William Alexander, Culley Carson. London: Mosby, 2003 (vi + 152 pp). ISBN 0 7234 3327 5. Understanding of erectile dysfunction has progressively increased over the years due to the development of new treatments. Much of the information available today to medical practitioners is provided by the pharmaceutical industry, particularly when a new product appears on the market. This book provides up-to-date and independent information to any medical practitioner who has an interest in assessing and treating erectile dysfunction. The book’s authors are experienced practitioners in this field and the book itself comes in the neat, pocket-size format usually reserved for emergency handbooks, although it is more likely that it would sit on a desk as a reference. The first chapters, covering anatomy, diagnosis and treatment, would suffice for most doctors’ needs. There are straightforward tables, figures and illustrations supporting the written information. The section on treatment is up-to-date and includes all the current products in the UK market, although not all are available in Australia. I particularly liked the emphasis on the psychological component of erectile dysfunction, a common secondary issue that is often overlooked. Other, more detailed issues, such as ejaculatory disorders and andrology, are well covered and relevant to those with an interest in sexual medicine. The list of resources and web sites is European based. I refer Australian readers to our local resource, Impotence Australia (www.impotenceaustralia.com.au. Phone 1800 800 614). With the increasing recognition of sexual dysfunction as a medical condition, I recommend Erectile dysfunction and related disorders as an excellent publication. Michael P LowyGeneral Practitioner Sydney Centre for Men’s Health Bondi Junction, NSW

Michael P Lowy

Sex remains an important contributor to quality of life in many patients with chronic illness and their partners. The effects of chronic illness on sexuality are multifactorial and can impact on all phases of sexual response. Sexual dysfunction and dissatisfaction in chronically ill patients are underdetected and undertreated because of barriers to doctor–patient discussion about sex and lack of medical training in human sexuality. For doctors to become more motivated to broach the topic of sex, they need to recognise that people may be sexually interested even though they are old, ill or disabled. The PLISSIT model provides a graded counselling approach that allows doctors to deal with sexual issues at their own level of expertise and comfort.

Rosemary A McInnes MB BS, FACSHP

First, let's decide what we really mean by phimosis Circumcision remains a topic of significant debate in Australia, even though there has been a marked reduction in the rate of circumcision in this country, which has reflected that of England, where 95% of boys were circumcised in the 1930s, declining to 6.5% in the early 1980s.1 In this issue of the Journal (page 155), Spilsbury and colleagues report that many boys are circumcised for phimosis before the age of five years, despite phimosis being rare in boys of this age.2 They reviewed all circumcisions in Western Australian hospitals between 1981 and 1999, recording that the rate of medically indicated circumcisions increased during that period, and that, if the 1999 rate remains stable, it would be seven times the expected incidence of phimosis in the group of boys aged less than 15 years. These findings imply a high rate of unnecessary surgery, similar to the findings from studies conducted in England.1,3 Spilsbury and colleagues define phimosis as "narrowing of the preputial orifice leading to non-retractability of the prepuce". Such a definition would result in many boys under the age of five years being diagnosed with a condition for which surgery is considered to be justified. Their use of the term phimosis seems to mean pathological phimosis. To clarify, the prepuce is regarded as normal in boys if non-retractable because of preputial adhesions, or if the skin is physiologically non-retractable because of narrowing (ie, physiological phimosis). Figure 1 shows a normal foreskin that is non-retractable. The terms phimosis and non-retractable are not sufficiently clear in isolation, and need to be qualified. Rickwood and colleagues have recently given a succinct definition, stating that the ". . . normality, with an unscarred and pliant preputial orifice, is clearly distinguishable from pathological phimosis [shown in Figure 2], a condition unambiguously characterised by secondary cicatrisation of the orifice . . .".1 The addition of the word "pathological" or "physiological" is necessary to differentiate the different prognoses for phimosis, and, if the foreskin is not retractable because of adhesions to the glans, that information needs to have been included in the definition and documentation. Thus, rewriting the extract from the article by Spilsbury and colleagues, "many boys are circumcised for (pathological or physiological) phimosis before the age of five years, despite (pathological) phimosis being rare in this group". Why does the rate of circumcision for phimosis exceed the expected rate of phimosis?Clearly, the word "phimosis" in isolation does not have sufficient power to separate disease from a normal condition. Further, if parents feel there will not be support from the general practitioner, they may complain of symptoms in their child for the purpose of avoiding the debate about the appropriateness of circumcision for cosmetic reasons. Alternatively, the GP may support the parents' desire to have their boy circumcised, but expect resistance from the surgeon, and thus tend to present the child as having a pathological diagnosis. Such manipulation is not surprising when dealing with such an emotive topic. Nor is it necessarily improper given the differing cultural and medical views on the value of circumcision. A further explanation for the high circumcision rate for (pathological) phimosis might be a reluctance to record non-medical circumcision as such, using the appropriate International classification of diseases codes.4,5 What is the optimal treatment for phimosis?A wide body of evidence shows that most boys can be treated successfully with steroid cream, and that circumcision is required only infrequently.6-9 Unfortunately, almost all of these studies lack the distinction between pathological phimosis, as defined by Rickwood et al,1 and other foreskins that are non-retractable either as a result of preputial adhesions or because they are physiologically non-retractable. However, clinical experience suggests that most cases of pathological phimosis can be successfully treated with steroid cream, provided the steroid cream is applied to the partly retracted prepuce three times daily. After 4–6 weeks the prepuce should be retracted at the time of bathing and after voiding.10 It also appears that even balanitis xerotica obliterans can be successfully treated without circumcision,11 particularly if steroid treatment is supplemented with the minor operation of preputioplasty, in which the distal end of the prepuce is widened.12 Unfortunately, because the use of the term phimosis does not recognise the variations of the normal foreskin, the roles of observation, steroid cream and circumcision have not yet been compared in a study that has used a rigorous definition of pathological phimosis. There remains debate about the care of the normal prepuce in infant males. Parents are usually advised not to touch it, whereas the normal hygiene approach to body parts is one of not hurting, but keeping clean. The latter policy may help prevent skin irritation at the end of the prepuce, which may be part of the cause of pathological phimosis and balanitis (although this needs to be supported by appropriate studies). Evidence-based discussion about circumcision with parents will only be able to occur once we have undertaken prospective studies of the care of the prepuce and the use of steroids for treating phimosis. Parents will then be confident that their uncircumcised boy will not develop disease attributable to the nature of the foreskin. However, we should first focus on integrating a standard definition of phimosis into the study protocols. In the meantime, we should respect the view of parents who regard circumcision as good treatment for their child, given certain provisos. One is that they have been made aware of other options. The other is that they are making an appropriately informed decision about the management of their boy's prepuce because they are aware that "phimosis" does not equate to "pathology", and "pathology" does not always need surgery. Finally, Van Howe et al warn that physicians who perform "involuntary" circumcision are required to provide full disclosure. However, they also warn that, "with current legal precedent, this may not be enough" to protect the doctor from legal action,13 further emphasising the need to develop sound definitions on which to base our treatment of the prepuce. 1: A normal foreskin that is non-retractable, with pouting of the most distal portion when gentle retraction is attempted. 2: This foreskin shows the dome configuration of a boy with "true" phimosis. The fibrosis and pinhole meatus are also seen.

Paddy A Dewan PhD, MD, FRACS

Objective: To investigate the incidence rate of circumcision for phimosis and other medically indicated reasons in Western Australian boys from 1 January 1981 to 31 December 1999.Design and setting: A population-based incidence study using hospital discharge data of all circumcisions performed in all WA hospitals during the study period.Main outcome measures: Changes in the incidence rate of circumcision for medically indicated reasons.Results: The rate of medically indicated circumcisions increased in boys aged less than 15 years during the study period. Phimosis was the most common medical indication for circumcision in all age groups. The rate of circumcision associated with phimosis was eight times that associated with balanoposthitis and 21 times that of balanitis xerotica obliterans. Boys aged less than five years had the highest rate of circumcision to treat phimosis, at 4.6 per 1000 person-years, representing about 300 circumcisions per year. Boys aged less than five years living in country areas were 1.5 times more likely to be circumcised for phimosis than boys living in metropolitan Perth.Conclusion: The rate of circumcision to treat phimosis in boys aged less than 15 years is seven times the expected incidence rate for phimosis. Many boys are circumcised before reaching five years of age, despite phimosis being rare in this age group.

Katrina Spilsbury BSc, PhD · James B Semmens MSc, PhD · C D'Arcy J Holman MB BS, MPH, PhD · Z Stan Wisniewski MB BS, FRACS

Although many 19th-century misconceptions about the foreskin have been dispelled since it was shown that infantile phimosis was not an abnormality, the ideas that ritual or religious circumcision arose as a hygiene measure, and that circumcision makes no difference to sexual response, have persisted. The first idea should be dismissed as a myth and the second has been seriously questioned by modern research. Owsei Temkin, renowned medical historian, has written: ". . . we are all apt to accept a historical myth where we cannot rely on historical knowledge. Where history is lacking, mythology takes its place, and those who disdain history are among the foremost victims of mythology."1 This is most certainly true when we consider male circumcision. Although much progress has been made since 1949 in dispelling 19th-century myths about the male foreskin (for example, that infantile phimosis was a pathological abnormality; that circumcised men were immune to syphilis; that the foreskin was a "cesspool"; and that circumcised boys did not masturbate), others have proved more persistent. Among these are the idea that ritual circumcision, as practised by certain tribal peoples, arose as a hygiene measure; and the assertion that the removal of the foreskin makes no difference to sexual function. There is no evidence that customary circumcision originated as a hygiene measure. Many primitive cultures carried out a variety of mutilating procedures on different parts of the body, including the genitals of both boys and girls, but the reasons for these practices are obscure and contested. These cultures also practised cannibalism, human sacrifice, infanticide, widow-burial, foot-binding and other traditions not endorsed today. Conflicting theories have been advanced to account for the rise of ritual operations on the male and female genitals, among which are the following: 2 a propitiatory sacrifice or sign of submission to a deity (probably a milder form of a ritual which began as human sacrifice); an offering to the god or goddess of fertility to ensure children; a mark of tribal identification; a rite of passage from childhood to adult responsibility; an attempt to emphasise feminine or masculine characteristics in girls and boys by removing the parts of the genitals (clitoris and foreskin) believed to resemble the genitals of the opposite sex; and a means of humiliating and marking defeated enemies and slaves. The only point of agreement among proponents of the various theories is that promoting good health had nothing to do with it. In the days before aseptic surgery, any cutting of flesh was the least hygienic thing anybody could do, carrying a high risk of bleeding, infection and death. None of the ancient cultures which traditionally practised circumcision have claimed that the ritual was introduced as a hygiene measure: African tribes, Arabs, Jews, Muslims and Aboriginals explain it differently, but divine command, tribal identification, social role, respect for ancestors and promotion of chastity figure prominently.3 It was only in the late 19th century, when mass circumcision was being introduced for "health" reasons, that doctors sought legitimacy for the new procedure by claiming continuity with the distant past and reinterpreting its origins in terms of their own hygiene agenda.4,5 Although the policy statement recently issued by the Royal Australian College of Physicians reaffirms earlier statements that there is no medical indication for routine circumcision, it does suggest that tribal circumcision arose as a hygiene measure in desert environments, and it is disappointingly silent on the significance and role of the foreskin itself as a normal and prominent part of the male genitals.6 Despite the assertion of most contemporary advocates of circumcision that circumcision makes no difference to sexual response, there is a vast medical literature on the significance of the foreskin. In the Graeco-Roman world doctors considered the foreskin so important that they devised treatments to lengthen those which did not provide generous coverage of the glans.7 During the Renaissance and 18th century the centrality of the foreskin to male sexual function and the pleasure of both partners was recognised by anatomists Berengario da Carpi, Gabriello Fallopio and William Harvey, in popular sex manuals like Aristotle's master-piece,2,8 and by physicians like John Hunter, who also appreciated the importance of the foreskin in providing the slack tissue needed to accommodate an erection.9 In the 19th century the role of the foreskin in erotic sensation was well understood by physicians who wanted to cut it off precisely because they considered it the major factor leading boys to masturbation. The Victorian physician and venereologist William Acton (1814–1875) damned it as "a source of serious mischief",10 and most of his contemporaries concurred.11 Both opponents and supporters of circumcision agreed that the significant role the foreskin played in sexual response was the main reason why it should be either left in place or removed. William Hammond, a Professor of Mind in New York in the late 19th century, commented that "circumcision, when performed in early life, generally lessens the voluptuous sensations of sexual intercourse",12 and both he and Acton considered the foreskin necessary for optimal sexual function, especially in old age. Jonathan Hutchinson, English surgeon and pathologist (1828–1913), and many others, thought this was the main reason why it should be excised.13,14 In the 1970s, a United States physician who had himself circumcised was so pleased with the result that he wrote an article urging everybody else to have it done, but even he acknowledged the loss of sexual sensation: "The change in sensation during intercourse a few weeks later was surprising. The sharp pleasurable sensation was noticeably lessened, as it is when topical anaesthetics are used to delay ejaculation. . . The overpowering erotic sensation has been dulled, and with it some of the immediate pleasurable sensation. Initial excitement has decreased. . . [When fully erect the penis presents] a smooth shaft with a piston-in-cylinder-like action during coition. Friction and therefore sensation are diminished."15 It is difficult to put numbers on so subjective an experience as sexual satisfaction, but contemporary Canadian researchers who have identified the complex innervation of the penis, the ridged bands and the frenular delta16,17 have provided physiological confirmation of the 18th-century folklore that a man's foreskin was "the best of your property".18

Robert J L Darby PhD

Background: In 1889, Brown-Séquard, aged 72, reported dramatic rejuvenating effects after self-administering testicular extracts of dogs and guinea-pigs. His report resulted in widespread use of testicular extracts throughout Europe and North America for several decades. More recently, the male ageing process has been attributed to partial androgen deficiency, or "andropause", and testosterone treatment is claimed to improve well-being in middle-aged and elderly men.Design: We prepared extracts from five dog testes using Brown-Séquard's methods and assayed testosterone concentrations.Results: Testosterone concentrations were four orders of magnitude less than that required for a biological effect.Conclusions: Our study illustrates the marked placebo response that can be evoked by androgen treatment. It cautions against the empirical use of testosterone treatment for older men, unless a diagnosis of hypogonadism has been substantiated.

Andrea J Cussons MB BS · John P Walsh FRACP, PhD · Chotoo I Bhagat MD, FRCPA · Stephen J Fletcher MSc, Dip CB

To the Editor: We conducted a joinpoint analysis of death certificate data on prostate cancer from the Australian Bureau of Statistics. Between 1979 and 1994, mortality rates increased by 2.1% per year (95% CI, 1.6% to 2.5%). However, between 1994 and 1999, mortality decreased by 4.2% per year (95% CI, – 5.8% to – 2.4%). The total decrease in mortality rates for the five years to 1999 (the most recent year for which data were available) was 22.6% (95% CI, – 32.9% to – 12.7%). Joinpoint analysis is a statistical method that measures changing trends over time. It chooses the best-fitting points (called joinpoints) at which the rate of increase or decrease changes significantly.1 We did not look at the data and then choose 1994 as the start of the decreasing trend in prostate cancer mortality. The significant decrease since 1994 (and the consistent increase between 1979 and 1994) were identified by the joinpoint analysis. Whether early diagnosis and treatment of prostate cancer subsequent to screening with prostate-specific antigen (PSA) tests can save lives is still an open question that is best answered by randomised-controlled, long term trials. Nevertheless, it is important that we try to understand the recent decrease in population-based mortality. The mortality decline started in 1995, about five years after PSA testing became widely available in Australia. The use of PSA testing increased dramatically, reaching a peak in most States in 1994 and 1995.2 In 1996, the Australian Health Technology Advisory Committee reviewed the evidence and recommended against screening.3 Since then, the number of PSA tests has decreased.2 Recent mortality declines have also been observed in the United States and the United Kingdom following increases in the use of PSA testing. The mortality decline in the US has been greater than that in the UK, coinciding with more PSA testing in the US than the UK.4 At least three questions arise from these observations: Is it plausible that the decrease could be due to some factor other than PSA testing, such as better treatment? How do we explain these results to men who want to make an informed choice about whether to be tested? Is this type of evidence strong enough to warrant a change in the current recommendations on PSA testing?

Michael Coory MB BS, PhD · Peter Baade BSc, PhD

Comment: Using joinpoint analysis, Coory and Bade have identified a significant trend towards lower mortality rates from prostate cancer since 1994, and relate this chronologically to the increased use of prostate-specific antigen (PSA) testing in Australia. The authors raise three reasonable questions regarding this finding: Is it plausible that the decrease could be due to some factor other than PSA testing, such as better treatment? Ecological data such as those presented by Coory and Baade are subject to the pitfalls of ecological fallacy and confounding.1 Ecological fallacy exists when there is an apparent association (eg, more men in the population screened, fewer men in the population dying), but there is no association at an individual level. Confounding would occur when there are other factors that account for the outcome, or distort the relationship between PSA testing and mortality. Treatment is one such factor, but changes in diet and other factors could also play a role (eg, lycopene from tomato-based foods2). How do we explain these results to men who want to make an informed choice about whether to be tested? If these data were presented to men, then it would have to be explained that the data do not provide evidence of the benefits of screening and that many other factors could explain the relationship. Further, men need to be informed of the risks of false negative and false positive results associated with screening, and the risks of complications associated with treatment. It is important to assist men to make a balanced decision. Interestingly, studies in which men have been involved in such informed decisions show that information can reduce the probability that men will choose to be screened.3,4 Is this type of evidence strong enough to warrant a change in the current recommendations on PSA testing? Ecological associations generate hypotheses that are worthy of further investigation. Randomised controlled trial evidence at best, or case–control studies at least, would be required to provide evidence of the benefit of screening using PSA. Some such studies are currently in progress, including the prostate, lung, colorectal and ovarian cancer screening trial of the National Cancer Institute,5 and the European Screening Study for prostate cancer.6 Those in favour of PSA testing argue that it is the only means of diagnosing prostate cancer at an early and potentially curable stage.7 Against this is the argument that many prostate cancers are not clinically significant, as they are slow growing and will not spread, and there is a danger of diagnosis and treatment adding substantially to men's psychological and physical morbidity without benefits in terms of survival or quality of life.8 In the absence of evidence from randomised controlled trials or case–control studies, screening for prostate cancer using PSA testing remains controversial.9

Julie B Byles

In a rejoinder to Benjamin Franklin's observation that nothing is certain in life bar death and taxes, people's fondest wishes seem to be to live forever and pay no tax. The timely and provocative study of Weston et al in this issue of the Journal (page 208),1 reporting high acceptability of a hormonal male contraceptive among new fathers, prompts a reflection on wishful thinking, as such a new contraceptive remains unavailable. In some respects, contraception is closer to a consumer lifestyle choice than a conventional medical treatment, as illustrated by the impact of media-inspired contraceptive "scares" that have led to panic-driven abandonment of contraception and subsequent unwanted pregnancies.2 Creating a need for novel products is the raison d'être of advertising, and in the world of public relations presentation is the whole game. Responses to unfamiliar products or services are sensitive to how they are described, and almost any outcome may arise depending on how the access, convenience, safety and efficacy of hypothetical or existing contraceptive methods are described. At face value, however, the observations of Weston et al are consistent with recent findings from other cultures3,4 and earlier World Health Organization (WHO) studies,5,6 all of which similarly rely on forcing choices between hypothetical options. Even if the responses accurately reflect attitude, there is a vast gulf between human attitude and behaviour. This is the starting point for much of behavioural medicine, as illustrated by the failure of even low expectations of interventions that rely upon behavioural change (eg, interventions to deal with anger, smoking, drug addiction, obesity). Nevertheless, the strikingly positive attitudes reported by Weston et al herald major progress and the imminent availability of practical hormonal male contraceptives. Arguably, the epitome of successful applied science in the 20th century was the development of reliable and reversible contraception. The universal availability of numerous highly effective female contraceptives fostered unprecedented social change extending well beyond medicine and science. At the start of the 21st century, it is a sad reflection that the previous century passed without the addition of a single new contraceptive method that men could use to share more equitably the burden of reliable family planning.7 Historically, all deliberate family planning methods (apart from abortion) were shared responsibilities requiring active male involvement. The phenomenal success of female-oriented contraceptive development in recent decades has shifted the burden of responsibility for family planning disproportionately onto women. Worldwide, however, male involvement in family planning remains remarkably high, considering the inadequate means available.8 The central dilemma for men in stable relationships seeking to share more responsibility for family planning is that the reversible methods are not reliable and the reliable method (vasectomy) is not reversible. What is needed is a reversible male method as reliable as modern female methods. The biologically unique processes of sperm development offer ever-increasing numbers of new ways for clever biotechnology to interrupt male fertility temporarily, notably by modification of sperm and male reproductive tract ion channels. However, these require full development as new drugs, whereas hormonal methods are close to practical realisation. Although hormonal contraceptive methods were always equally feasible for men and women, during the decades when female contraceptive development flourished the development of analogous male methods languished, as it depended solely upon the limited resources available to academic researchers without pharmaceutical company product development. A decade ago, proof-of-concept for a hormonal male contraceptive was achieved jointly by the US Contraceptive Research and Development Agency and WHO's Male Task Force, which conducted the first efficacy studies for any chemical male contraceptive.9,10 These studies showed high reliability of a reversible prototype hormonal regimen, a crucial empirical finding about which the biggest surprise is that this finding lagged three decades behind the wide availability of analogous female hormonal methods. Continued impressive progress towards a practical product has been achieved. There is consensus that a combination progestin-plus-androgen approach is optimal, with several combinations approaching the ideal of universal azoospermia.7 Finally, some large pharmaceutical companies have recently upgraded their involvement from being spectators to participating in some active development of the well-advanced research produced by the academic community within the public sector. New hormonal male contraceptives are needed for couples in stable relationships rather than for those with changing partners, among whom condom use prevents sexually transmitted disease as well as pregnancy. The survey of Weston et al highlights a likely niche for the use of a hormonal male contraceptive — the postpartum period. This period is ideal, because it focuses on a stable couple with a predictable timing of contraceptive need and a situation in which reliable female contraceptives are not well suited, particularly during lactation. Other niche purposes for a hormonal male contraceptive include delaying vasectomy, offering an alternative to conventional female methods when they are not well tolerated, and replacing less reliable male methods. The finding that a hormonal male contraceptive is acceptable to an appropriate Australian target population is consistent with Australasian men having the highest rate of vasectomy in the world.11,12 These observations highlight the substantial need and market for a hormonal male contraceptive. Hopefully, this decade will see the long-overdue development of an eminently feasible and widely desirable product. The desultory response from multinational pharmaceutical companies, even after completion of much early-phase clinical research by the public sector, suggests implementation may be driven by populous countries such as China, Indonesia and India, whose family planning priorities value such developments more highly. In Western countries, development may require a more enterprising start-up company to capitalise on this opportunity, which eludes the imagination, or lurks beneath the commercial horizon, of the pharmaceutical industry behemoths.

David J Handelsman MB BS, PhD, FRACP

Aim: To survey the attitudes of a population of Australian men to potential use of male hormonal contraception (MHC). Design: Survey of male partners of women who had recently given birth. Men were approached while visiting their female partners on the ward. Participants: 118 out of 148 Australian-born English-speaking men who were approached. Setting: Postnatal ward of Monash Medical Centre (a public teaching hospital in Melbourne), between October 2000 and April 2001. Main outcome measure: Attitudes towards potential use of MHC, rated on a five-point scale. Results: 89/118 men surveyed (75.4%; 95% CI, 67.7%–83.2%) indicated that they would consider trying MHC if it were available. The three most popular choices for method of administration of MHC were (in descending order) an oral pill, a three-monthly injection, or a two-yearly injection. A statistically significant association was found between acceptability of vasectomy and acceptability of MHC (70.5% of men who indicated they would try MHC [MHC "triers"] found vasectomy acceptable versus 44.5% of MHC "non-triers"; P = 0.011). Triers reported a higher rate of approval of MHC by their female partners than non-triers (79.8% v 13.8%, respectively; P < 0.0001). Conclusions: MHC appears to be acceptable to a majority of Australian men when surveyed in a postpartum context. Attitudes of men towards existing male contraception, as well as the attitudes of their partners, appear to exert a strong influence on acceptability of MHC.

Gareth C Weston MB BS · Michelle L Schlipalius MB BS · Meabh Ni Bhuinneain MRCOG, MRCPI · Beverley J Vollenhoven PhD, FRANZCOG

The practice of urology continues to be affected by the compulsory wearing of seatbelts, resulting in less trauma, and antismoking initiatives. Bladder cancer is an occupationally related tumour, but cigarette smoke is by far the most significant environmental carcinogen, so a recent report suggesting that smoking rates may be declining1 is heartening. Prostate cancer. The trend to earlier diagnosis of prostate cancer continues. Detection of an elevated serum prostate specific antigen (PSA) level is usually followed by biopsies guided by transrectal ultrasound (TRUS). PSA analysis has been expanded to give more information; rate of change of total PSA (PSA velocity) and the percentage of free PSA (unbound) are most often used (lower percentages of free enzyme being associated with a higher likelihood of malignancy, especially for total PSA levels 4–10 g/L). TRUS-guided sextant prostatic biopsies are not new, but, particularly with larger prostates, repeat biopsies after negative findings have increased detection rates up to 30%.2 Consequently, eight or more biopsy samples are now often obtained. As well as pre-TRUS–PSA, Gleason score and number of tumour-containing cores (with percentage involvement) serve to predict the likelihood of cancer being localised. Thus, the PSA–transrectal ultrasound approach appears to have reached maturity and a change in direction, such as molecular characterisation of ejaculate, is now required to advance early diagnosis and natural history prediction. The focus on PSA by patients has contributed to androgen suppression starting earlier, despite unwanted side effects with all forms of hormonal treatment and a lack of convincing evidence that earlier intervention improves survival. Intermittent androgen blockade does not adequately compensate for early commencement of androgen suppression, as, certainly in the short-term, many unwanted effects, including testosterone suppression, are not always reversible. The popularity of maximal androgen blockade has waned since the publication of unsupportive meta-analysis data.3 Notwithstanding its major advantage of avoiding contrast media, spiral computed tomography (CT) serves as an adjunct to, rather than a replacement for, intravenous urography, which remains the first-line investigation for most ureteric colic patients. Non-contrast CT does not provide functional information, but may detect other abnormalities. Female urinary incontinence. This is one of the conditions managed by both urologists and gynaecologists. The mainstay of treatment for patients with overactive bladders (frequency and urgency with or without urgency incontinence in the absence of attributable local, pathological or metabolic factors4) is anticholinergic drugs, with doses limited by dry mouth and constipation especially. Recently evaluated uroselective agents have shown a considerable reduction in unwanted effects without loss of efficacy. The tension-free vaginal tape (TVT) procedure was recently introduced for stress incontinence. Its low rate of short-term complications has been attributed to its wide-mesh monofilament polypropylene composition, reputed to retain flexibility and admit macrophages, fibroblasts, blood vessels and collagen into its pores to permit elimination of infiltrating bacteria. Whether such attributes translate into lower complication rates and continued success in the longer term (more than two years) remains to be seen. Concerns about an uncritical adoption of the TVT procedure, paralleling initial enthusiasm for needle suspension operations in the 1980s, are justifiable. TVT operations are often performed as day procedures — a not insignificant attraction given the current shortage of hospital beds. Lower urinary tract symptoms (LUTS). LUTS, even when categorised as storage or emptying, are poor indicators of underlying LUT dysfunction. A third of men with LUTS do not have bladder outflow obstruction (BOO), accurate diagnosis of which is problematical. Consequently, there is a tendency to treat LUTS with medications and to identify BOO only when considering more invasive therapies. This approach relates particularly to the commonly used saw palmetto berry (Serenoa repens) extract, which affords LUTS relief for many men. Treatment by α1-blockade (doxazosin, prazosin, terazosin) is well established for benign prostatic hyperplasia (BPH) causing BOO. BPH is predominantly a stromal condition and these drugs target prostatic and bladder-neck smooth muscle. Improvements in symptom scores and flow rates often persist long-term. Seventy per cent of prostatic adrenoreceptors are of the α1A receptor subtype. Tamsulosin, a selective α1A antagonist, has a safety profile superior to non-selective α1 antagonists, with comparable effects on LUTS. However, dizziness and abnormal ejaculation may still occur. Male sexual dysfunction. The adverse impact of sexual dysfunction on quality of life has only recently been acknowledged. Papaverine and prostaglandin E1 intracavernosal injections were a significant advance. However, a dramatic change came with the serendipitous discovery of sildenafil, which prolongs nitric oxide-induced cavernosal muscle relaxation. While sildenafil therapy represents a revolution in impotence treatment, it does not address underlying pathogeneses.5 Infertility. One of the most remarkable milestones of the 1990s was intracytoplasmic sperm injection (ICSI). Despite the possibility that sperm with suboptimal genetic characteristics may be selected for this process, ICSI has become established as a valuable option in infertility management. Conclusion. Urology is continuing to evolve at a rapid rate. Consequently, urologists are tending to subspecialise rather than practise in the broad range of conditions which constitute this fascinating yet practical specialty.

Robert A Gardiner MB BS, MD, FRCS, FRACS

EBM in Action Does drinking carrot juice affect cancer of the prostate? MJA 2001; 174: 197 Clinical question - Search question - Search - Summary of findings - Outcome - References - - More articles on Men's health Clinical question "Does drinking carrot juice have any effect on prostate cancer?" A general practitioner asked this question after her patient, a 77-year-old man who had been diagnosed with invasive prostate cancer, commenced drinking four glasses of carrot juice a day. Information about the exact staging of the cancer was not available. Search question The search question was refined to "What effect does the consumption of beta-carotene have on prostate cancer? Are there any adverse effects, and if so, at what quantity of consumption do they occur?". Ideally, a randomised controlled trial of men recently diagnosed with prostate cancer, comparing a high intake of beta-carotene with no beta-carotene intake, would be the appropriate clinical study design to answer this question. The outcomes assessed would be the appearance of metastases, patient morbidity and mortality, and any adverse effects of the beta-carotene. Search The search terms "beta-carotene", "prostate" and "cancer" were combined to identify appropriate trials. We searched databases including Cochrane Library and SUMSearch (<http://sumsearch.uthscsa.edu/searchform4.htm>), which searches for systematic reviews and original research, and links to PubMed Clinical Queries. Our search yielded five relevant studies. Summary of findings The best evidence identified was a large randomised controlled trial of 29 133 healthy men who were cigarette smokers.1 The men receiving beta-carotene (20 mg) daily had an increased incidence of prostate cancer compared with those receiving placebo (138 v 112 men with prostate cancer). Further analysis of the results showed prostate cancer incidence to be 23% higher (95% CI, -4% to 59%) and mortality 15% higher (95% CI, -30% to 89%) in men who received beta-carotene compared with those who did not, but this trend was not significant.2 A prospective cohort study found no evidence of either protection or harm associated with dietary beta-carotene.3 Two case-control studies, one involving beta-carotene supplements and the other dietary beta-carotene, found a protective effect of high levels of beta-carotene intake.4,5 One of these studies reported a significant protective effect of high levels of dietary beta-carotene (relative risk of prostate cancer [RR], 0.60; 95% CI, 0.37 to 0.99), particularly in men younger than 68 years (RR, 0.30; 95% CI, 0.13 to 0.66).5We were unable to find any studies evaluating the influence of beta-carotene in patients with established prostate cancer. Outcome Although two observational studies suggested that high levels of beta-carotene intake reduced the risk of prostate cancer, the best evidence found that beta-carotene increased the incidence of prostate cancer. The GP discussed this information with her patient, who nevertheless elected to continue to drink lots of carrot juice! Christopher B Del Mar Professor Paul P Glasziou Associate Professor Anneliese B Spinks Research Officer Sharon L Sanders Research Officer Centre for General Practice Medical School, University of Queensland, Herston, QLD c.delmarATcgp.uq.edu.au References Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995; 62 (6 Suppl): 1427S-1430S. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998; 90: 440-446. Daviglus ML, Dyer AR, Persky V, et al. Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study. Epidemiology 1996; 7: 472-477. Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 1999; 59: 1225-1230. Mettlin C, Selenskas S, Natarajan N, Huben R. Beta-carotene and animal fats and their relationship to prostate cancer risks. A case-control study. Cancer 1989; 64: 605-612.

Paul P Glasziou · Anneliese B Spinks · Sharon L Sanders

Abstract - Mechanism - Injection therapy - Transurethral alprostadil - Selective inhibitors - Guidelines - Conclusion - References - Authors' details Abstract Erectile dysfunction (ED) is a common condition and can usually be managed pharmacologically, with drugs delivered by intracavernosal injection (ICI), transurethrally or orally. The cardiovascular status of the patient and his overall fitness for renewed sexual activity must be assessed before treatment for ED is initiated. The efficacy of sildenafil is related to the extent and severity of ED, and is significantly reduced in patients with severe vasculogenic ED, ED associated with diabetes and after radical prostatectomy. Alprostadil (prostaglandin E1) is the drug of first choice in patients treated with ICI; it is effective in 72.6% of men with ED and is associated with a low risk of priapism and cavernosal fibrosis. Transurethral alprostadil is significantly less effective than alprostadil ICI, producing improved erections in 30%-40%, but rigid erections in only 10%, of men with ED. There is Level II evidence that: alprostadil ICI is an effective treatment for ED papaverine ICI is associated with a high risk of cavernosal fibrosis and priapism papaverine ICI should be restricted to informed patients refractory to treatment with alprostadil ICI transurethral alprostadil is less effective than alprostadil ICI sildenafil is an effective treatment for ED. Erectile dysfunction (ED) is the inability to achieve and maintain an erection of sufficient rigidity for satisfactory sexual intercourse.1 Community-based epidemiological studies suggest that sexual dysfunction, particularly ED, is a common disorder in men, and is associated with reduced quality of life.2,3 While it was previously thought that most impotence in men was psychogenic, we now know that there is a physical basis for most men's impotence. One of the most significant advances in our understanding has been the recognition that blood flow into the corpora cavernosa is regulated by smooth muscle tone, and that this mechanism can be pharmacologically altered. Mechanism of erection An erection is initiated when psychoneuroendocrine stimuli activate efferent autonomic nerves to relax penile vascular and corpus cavernosal trabecular smooth muscle. The mechanism of erection is described in Box 1. The penis loses its rigidity when the activation of sympathetic constrictor nerves after ejaculation increases the tone of the smooth muscles and the helicine arteries and trabeculae, resulting in decreased arterial inflow and increased venous outlow. The mechanisms that maintain flaccidity are unknown. Priapism is an uncommon, but potentially serious, adverse effect associated with some of the therapies described below -- its management is outlined in Box 2. Intracavernosal injection therapy Self-administered intracavernosal injection (ICI) therapy, using vasodilator drugs which relax the arterial and trabecular smooth muscle, is an effective treatment for ED4 (E2). (See Box 3 for an explanation of level-of-evidence codes.5) Papaverine Papaverine is a potent, non-specific smooth muscle relaxant which increases smooth muscle intracellular adenosine 3',5'-monophosphate (cAMP) by its action as a non-selective cAMP phosphodiesterase inhibitor, causing vasodilatation of penile vascular and sinusoidal smooth muscle.6 Papaverine has a relatively short plasma half-life (1-2 hours) and is extensively metabolised in the liver. After intracavernosal injection, the peak serum concentration is several times lower than after extracavernosal injection, suggesting that the corpus cavernosum is a separate pharmacokinetic compartment from which elimination of papaverine is much slower than from the systemic circulation.7A meta-analysis of the largest published studies on the use of papaverine reports that it is effective in 53% of men with ED, as measured by the ability to produce an erection of sufficient rigidity for sexual intercourse8 (E1). However, the efficacy of ICI papaverine is limited by local adverse effects, principally priapism (in 7%)8 and intracavernosal fibrosis, presenting as penile deformity or curvature (reported in one study in 50% and 95%, respectively, of long term users).9 Fibrosis is related to poor injection technique, frequent injections and long term use. Because of these adverse effects, papaverine should be restricted to informed patients in whom other medications are ineffective. Papaverine hepatotoxicity is rarely a clinical problem and may manifest either as an increase in liver transaminase concentrations, which is relatively common (> 1%), or as a drug-induced hepatitis, which is rare (< 0.1%).10 Adrenergic blockers It is well recognised that drugs which block α-adrenoceptors (such as prazosin) can produce erection, and even priapism. Thus, intracavernosal injection of α-adrenergic-blocking drugs seems a logical way of producing penile erection. Phentolamine, a competitive α-adrenoceptor antagonist with affinity for α1- and α2-adrenoceptors, produces tumescence, but rarely an erection, when injected intracavernosally. However, when phentolamine is combined with papaverine, 68% of users respond with a rigid erection8 (E1). Alprostadil Alprostadil (prostaglandin E1, or PGE1) is an eicosanoid derived from arachidonic acid (see Box 4 for a profile of alprostadil). The mechanism of its vasodilating action is not completely understood. Alprostadil increases levels of intracellular cAMP by modulation of adenyl cyclase, leading to a decrease in the free calcium concentration and subsequently to smooth muscle relaxation.11 It may also modulate the presynaptic release of noradrenaline. Alprostadil has a short duration of action and a plasma half-life of less than one minute because of rapid pulmonary clearance of up to 80% after the first pass through the lung. When injected intracavernosally, approximately 30% of the drug is metabolised within the corpora cavernosa, which may explain why significantly fewer episodes of priapism occur with alprostadil than with papaverine. Multiple studies have shown that alprostadil has superior efficacy and reduced risk of priapism and intracavernosal fibrosis compared with papaverine (alone or combined with phentolamine). A meta-analysis found that alprostadil resulted in an erection of sufficient rigidity for sexual intercourse in 72.6% of men with ED8 (E1). The principal side effect of intracavernosal injection of alprostadil is pain at the site of injection, which occurs in up to 30% of patients. Priapism is a rare complication. Although early experience suggested that fibrosis was uncommon with alprostadil ICI, recent long term studies show an incidence of fibrosis and scar formation of 9%-23.3% in mid-term and long-term users, so patients should be warned of the possibility of penile fibrosis before starting treatment12,13 (E4). Studies in human fibroblasts have shown that alprostadil suppresses collagen synthesis induced by transforming growth factor (TGF-β1). An imbalance between PGE1 and TGF-β1 in the corpora cavernosa, as a result of anoxia or endothelial damage due to ischaemia, hypercholesterolaemia or hyperglycaemia, may cause increased extracellular matrix deposition, inhibition of smooth muscle growth, and eventually fibrosis.14 Inhibition of collagen synthesis by alprostadil may, in part, explain the low incidence of cavernosal fibrosis with this drug. Polyagent intracavernosal injection therapy Intracavernosal injection therapy with alprostadil in combination with other agents such as papaverine, phentolamine and atropine may be effective in patients in whom maximum-dose alprostadil monotherapy is ineffective.15,16 A comparative study reported a 91.6% response rate to a combination of alprostadil, papaverine and phentolamine15 (E32). Polyagent ICI appears effective as "salvage therapy" in patients with severe arteriogenic ED and mild to moderately severe cavernosal venous leakage in whom alprostadil alone is ineffective.16 However, a significant number of patients remain refractory to ICI therapy. Treatment guidelines proposed by the 1998 New South Wales Health Complaints Commission Inquiry into Impotence Treatment emphasise the importance of adhering to good manufacturing practices to ensure sterility of polyagent medication.17 Transurethral alprostadil Alprostadil can also be administered as a microsuppository into the distal urethra. A translucent hollow-stem applicator is used to insert the microsuppository after urination, the residual urine acting as both a lubricant and a diluent for the microsuppository. The drug is absorbed directly into the urethral endothelium and is transferred into the corpora cavernosa primarily by venous channels that communicate between the corpus spongiosum and the corpora cavernosa. These channels appear to increase in number, but particularly in size, with age. Alprostadil is rapidly absorbed from the urethra (only 20% remains after 10 minutes) and produces vasodilatation in the penile vasculature; plasma levels are either low or undetectable. Transurethral alprostadil has a brief serum half-life of between 30 seconds and 10 minutes because of rapid pulmonary clearance after the first pass through the lung. No effect on spermatozoa motility, viability or membrane integrity has been shown, and the mean increase in the PGE1 content of the ejaculate (123 mg) is less than the normal day-to-day variability for prostaglandins. In extensive double-blind placebo-controlled clinical trials sponsored by manufacturers, 65.9% of men achieved an erection adequate for intercourse after administration of transurethral alprostadil in a doctor's office,8 and 64.9% of these men reported intercourse at least once with home treatment, with significant improvements in quality of life, particularly in the domains of self-esteem and sexual and non-sexual aspects of their relationships with their partners17 (E2). The efficacy of alprostadil was found to be similar regardless of age or the cause of ED, including vascular disease, diabetes, surgery, and trauma. The use of an adjustable penile constriction band with transurethral alprostadil may augment the drug effect. However, several postmarketing studies failed to produce similar results to those of the trials sponsored by manufacturers. One reported that only 27% of patients achieved erections sufficient for intercourse during in-office testing, and that, because of this limited efficacy, adverse effects and cost, more than 80% of patients did not continue to use transurethral alprostadil at home18 (E4). Another study comparing transurethral and intracavernosal alprostadil reported total erectile response rates of 43% and 70%, respectively, complete rigid erections in only 10% versus 48%, and rates of penile pain or burning in 31.4% versus 10.6%19 (E4). The most frequently reported adverse effects associated with transurethral alprostadil are penile pain (32%), urethral bleeding or spotting (5%) and dizziness (3%).17 As syncope was reported in 0.4% of patients,17 the initial dose titration should be performed in the doctor's office. Discomfort after administration was commonly reported as mild and transient, but 7% of patients discontinued treatment because of adverse effects. Priapism and cavernosal fibrosis were found in less than 0.1% of patients using the transurethral preparation and less than 1% of those using the intracavernosal injection. Vaginal burning or itching was reported by 5.8% of partners. Unless a condom is used, transurethral alprostadil should not be used if the female partner is pregnant. Selective phosphodiesterase inhibitors Sildenafil Sildenafil citrate, a potent, competitive phosphodiesterase type 5 (PDE-5) isoenzyme inhibitor (see Box 4 for a profile of this drug), is the first oral medication to show significant and reliable efficacy in most patients with ED20 (E2). After the nitric oxide/cGMP pathway is activated by sexual arousal, inhibition of PDE-5 isoenzyme (see Box 1) by sildenafil results in increased cavernosal concentrations of cGMP and an augmented penile erection in men with ED. In early studies, sildenafil was effective in restoring erectile function and improving intercourse success rates in a wide range of patients, including those with hypertension, diabetes, spinal cord injury, other concomitant medical conditions, and in patients taking a wide variety of concomitant medications. Its efficacy was related to the cause, extent and severity of ED, and was significantly reduced in patients with severe vasculogenic ED, ED associated with diabetes, and after radical prostatectomy ED20,21 (E2, E32). More recent studies report a response rate to sildenafil of 65%, significant improvement in quality of life and a 35% incidence of adverse effects22 (E33). Failure to respond to sildenafil suggests severe vasculogenic ED resulting from advanced penile artery atherosclerosis or severe cavernosal venous leakage, or a combination of both. The action of sildenafil on the nitric oxide/cGMP pathway seems complementary to the action of other vasoactive agents, and combined therapy may be effective in patients who do not respond to a single therapy. A recent study reported that 34% of patients in whom maximum-dose ICI is ineffective responded to sildenafil, and a further 31% responded to a combination of the two, giving an overall "salvage" rate of 65%23 (E33). Sildenafil produces an erection within 25-60 minutes and remains active even at four to five hours after being taken. Sildenafil should be administered with caution in patients with retinitis pigmentosa, as some patients with this inherited condition have genetic disorders of retinal phosphodiesterase and there is no published safety information. Sildenafil is extensively metabolised, predominantly by CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes, and is converted to an active metabolite (M1), with an in-vitro potency for PDE-5 of approximately 50% of the parent drug, which accounts for about 20% of sildenafil's pharmacologic effects. Both sildenafil and the metabolite have terminal half-lives of about four hours. The adverse effects of sildenafil, reported in clinical trials, were transient, mild to moderate in nature, and dose-dependent. The most common adverse effects were headache (15.8%), flushing (10.5%), dyspepsia (6.5%) and nasal congestion (4.2%). Discontinuation of treatment was comparable for patients receiving sildenafil (2.6%) and placebo (2.3%). Priapism was not reported in these studies or in any of the clinical trials of sildenafil. As there is a degree of cardiac risk associated with sexual activity, doctors must assess the cardiovascular status of their patients before initiating any treatment for ED, including sildenafil. Sildenafil has been shown to potentiate the hypotensive effects of nitrates and may be associated with large and sudden drops in systemic blood pressure. It is therefore contraindicated in patients who use prescribed nitric oxide-donating drugs or nitrates in any form for ischaemic heart disease, or recreational nitrites (eg, amyl nitrite), regardless of frequency. Caution should also be exercised in patients with asymptomatic coronary artery disease stabilised with medical treatment, coronary revascularisation, congestive heart failure combined with borderline low blood pressure, or a multidrug regimen for high blood pressure.24 These patients remain at a slightly increased risk of developing angina pectoris or acute myocardial infarction, which may necessitate treatment with short-acting nitrates, including intravenous sodium nitroprusside, by ambulance or hospital emergency staff. Guidelines for the evaluation and treatment of erectile dysfunction Treatment for ED depends on both its cause and severity, but other factors, such as efficacy, adverse effects, acceptability to patient and partner, psychological effects, reversibility and cost, are also important. A guide to managing ED is shown in Box 5. Although the primary cause of most ED is organic, there are invariably compounding psychological factors, such as "performance anxiety"; psychosexual counselling may be an important option for both the patient and his partner. Patients and their partners should be informed of all available treatment options. Doctors remain responsible for conducting a thorough medical history, physical examination and appropriate investigations to establish the extent, severity and causes of ED. In patients regarded as fit for renewed sexual activity, first-line treatment with an oral phosphodiesterase inhibitor such as sildenafil is appropriate if there are no contraindications. Patients in whom sildenafil is ineffective, who can not tolerate its adverse effects or who have contraindications are best treated with alprostadil, either as ICI or the transurethral preparation. Men who fail to respond to maximum-dose alprostadil can be managed with ICI containing alprostadil combined with other agents such as papaverine and phentolamine. Men in whom drug treatment is ineffective may elect to undergo implantation of an intrapenile prosthesis, but many choose to limit their sexual activity to non-penetrative sex. Conclusion As the population ages, quality-of-life expectations will increase. Many men now recognise that ED need not be a consequence of advancing age, nor a result of chronic illness or radical prostate cancer surgery. Most patients with ED can be successfully treated with medications. Several new oral treatments for ED are currently undergoing clinical evaluation and may increase the therapeutic options considerably. Information for patients is given in Box 6. Disclosure: Chris G McMahon is a member of the speaker panels for Pharmacia Upjohn, Pfizer and Abbott/Vivus, the manufacturers of Caverject, Viagra and MUSE. He was also a member of the Caverject and MUSE medical advisory boards, a medical consultant to Pfizer, and a clinical investigator for Pharmacia Upjohn, Pfizer, Bayer, Eli Lilly, Icos Corporation, Abbott, Senetek PLC, Pentech and American Medical Systems. References NIH Consensus Conference. Impotence, NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-90. Pinnock CB, Stapleton AM, Marshall VR. Erectile dysfunction in the community: a prevalence study. Med J Aust 1999; 171: 353-357. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281: 537-544. Linet OI, Ogrinc FG. Efficacy and safety of intra-cavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group. N Engl J Med. 1996; 334: 873-877. National Health and Medical Research Council. A guide to the development, implementation and evaluation of clinical practice guidelines. Canberra: NHMRC, AusInfo, 1999. Poch G, Kukovetz WR. Papaverine-induced inhibition of phosphodiesterase activity in various mammalian tissues. Life Sci 1971; 10: 133-144. Hakenberg O, Wetterauer U, Koppermann U, Liffimann R. Systemic pharmacokinetics of papaverine and phentolamine: Comparison of intravenous and intracorporal application. Int J Impotence Res 1990; 2 (Suppl 2): 247-248. Porst H. The rationale for prostaglandin E1 in erectile failure: a survey of world-wide experience. J Urol 1996; 155: 802-815. De Rose AF, Oppezzi GF, Scotto S. [Local complications of papaverine-induced erection: follow-up at 7 years] [Article in Italian]. Arch Ital Urol Androl 1993; 65: 289-293. Brown LS, Christopher AH, Koehler M, et al. Hepatotoxicity related to intracorporal pharmacotherapy with papaverine. Urology 1998; 52: 844-847. Paoletti R. Biochemistry and pharmacology of prostaglandin E1: introductory remarks. In: Sinzinger H, Rogatti W, editors. Prostaglandin E1 in atherosclerosis. New York: Springer-Verlag, 1986: 3-7. Chen RN, Lakin MM, Montague DK, Ausmundson S. Penile scarring with intracorporal injection therapy using prostaglandin E1: a risk factor analysis. J Urol 1996; 155: 138-140. Chew KK, Stuckey BG, Earle CM, et al. Penile fibrosis in intracavernosal prostaglandin E1 injection therapy for erectile dysfunction. Int J Impotence Res 1997; 9: 225-229; discussion, 229-230. Moreland RB, Traish A, McMillin MA, et al. PGE1 suppresses the induction of collagen synthesis by transforming growth factor-beta 1 in human corpus cavernosum smooth muscle. J Urol 1995; 153: 826-834. Padma-Nathan H. The efficacy and synergy of polypharmacotherapy in primary and salvage therapy of vasculogenic erectile failure. Int J Impotence Res 1990; 2: 257-258. McMahon CG. Comparison of the response to the intracavernosal injection of a combination of papaverine and phentolamine, prostaglandin E1 alone and a combination of all three in the management of impotence. Int J Impotence Res 1991; 3: 133-142. Padma-Nathan H, Hellstrom WJ, Kaiser FE, et al. Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group. N Engl J Med 1997; 336: 1-7. Fulgham PF, Cochran JS, Denman JL, et al. Disappointing initial results with transurethral alprostadil for erectile dysfunction in a urology practice setting. J Urol 1998; 160: 2041-2046. Porst H. Transurethral alprostadil with MUSE (medicated urethral system for erection) vs intracorporal alprostadil -- a comparative study in 103 patients with erectile dysfunction. Int J Impotence Res 1997; 9: 187-192. Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med 1998; 338: 1397-1404. Dinsmore WW, Hodges M, Hargreaves C, et al. Sildenafil citrate (Viagra) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects. Urology 1999; 53: 800-805. Jarow JP, Burnett AL, Geringer AM. Clinical efficacy of sildenafil citrate based on etiology and response to prior treatment. J Urol 1999; 162: 722-725. McMahon CG, Samali R, Johnston HM. Treatment of Intracorporal Injection Non-Responders with Sildenafil Alone or in Combination with Polyagent Intracorporal Injections. J Urol 1999; 162: 1992-1997. Cheitlin MD, Hutter AM Jr, Brindis RG, et al. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol 1999; 33: 273-282. Authors' details North Shore Private Hospital, Sydney, NSW. Chris G McMahon, MB BS, FACSHP, Sexual Health Physician. Reprints will not be available from the author. Correspondence: Dr C G McMahon, Suite 11, Level 3, North Shore Private Hospital, 1 Westbourne Street, St Leonards, NSW 2065. cmcmahonATmail.usyd.edu.au 1: Mechanism of erection Non-adrenergic, non-cholinergic nerves and vascular endothelium release nitric oxide in response to sexual arousal, which activates cytoplasmic guanylate cyclase, converting GTP into cGMP. The increased levels of cGMP alter transmembrane calcium ion flux, resulting in cavernosal smooth muscle relaxation, dilatation of cavernosal and helicine arteries and engorgement of lacunar spaces. The expanding lacunar spaces compress the subtunical venous plexus against the tunica albuginea, decreasing cavernosal venous outflow, increasing intracavernosal pressure, with resulting penile rigidity. Cyclic nucleotides, such as cGMP, are hydrolysed by cyclic nucleotide phosphodiesterases. GTP=guanosine triphosphate; GMP=guanosine monophosphate; cGMP=cyclic guanosine monophosphate. Back to text 2: Management of prolonged erection (priapism) Always use alprostadil monotherapy as first-line ICI treatment. Use lowest possible effective dose. Inform patient of the risk of prolonged erection and the procedure to be followed if the penis is still rigid, as follows: 2 hours after administration - 120mg pseudoephedrine 4 hours after administration - repeat 120mg pseudoephedrine and walk briskly for 10-15 minutes 6 hours after administration - regard as medical emergency and contact the treating doctor or a hospital emergency department immediately. Patients may require aspiration of corpora and irrigation with dilute vasoconstrictors or, in refractory priapism, surgical drainage. Back to text 3: Level-of-evidence codes Evidence for the statements made in this article is graded according to the NHMRC system5 for assessing the level of evidence. E1 Level I: Evidence obtained from a systematic review of all relevant randomised controlled trials. E2 Level II: Evidence obtained from at least one properly designed randomised controlled trial. E31 Level III-1: Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method). E32 Level III-2: Evidence obtained from comparative studies with concurrent controls and allocation not randomised (cohort studies), case-control studies, or interrupted time series with a control group. E33 Level III-3: Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group. E4 Level IV: Evidence obtained from case-series, either post-test, or pre-test and post-test. Back to text 4: Drugs: profiles of alprostadil and sildenafil Alprostadil Action and onset Alprostadil (prostaglandin E1) induces an erection by relaxation of trabecular smooth muscle and dilatation of cavernosal arteries. Alprostadil may be administered by intra-cavernosal injection (Caverject, Pharmacia Upjohn) or by a transurethral suppository (MUSE, Abbott/Vivus Corp.). An erectile response occurs within 5-15 minutes of intracavernosal injection (ICI) and within 7-25 minutes of transurethral administration. Arousal is usually required to produce a maximal response. Detumescence usually commences within 10-20 minutes of ejaculation or cessation of sexual arousal, but complete flaccidity may not occur for a further 1-2 hours. Dosage Both Caverject and MUSE are administered 10-20 minutes before planned sexual activity. Dosage is individualised by initial supervised dosage titration, with the aim of establising the lowest possible effective dose (see below). Caverject injection is available in three different concentrations in 1mL ampoules (5µg, 10µg and 20µg), with a kit containing a syringe, needle, alcohol swab and written instructions. Patients should be instructed in sterile injection technique, used needle disposal and the management of prolonged erections (&lt 2h; Box 2) by trained medical personnel. The maximum frequency of use is no more than three times a week, with at least 24 hours between doses. For ED of vasculogenic, psychogenic or mixed aetiology, start with 5µg and titrate in 5µg increments to a maximum of 40µg until an erectile response sufficient for sexual intercourse occurs or there are intolerable adverse effects. For ED of wholly neurogenic aetiology (spinal cord injury), start with 1.25µg and titrate in 1.25µg increments until an erectile response sufficient for sexual intercourse occurs or there are intolerable adverse effects. Transurethral alprostadil (MUSE) is available in dosages of 125µg, 250µg, 500µg, and 1000µg. It is administered after urination, the patient remaining standing for approximately 10 minutes. The two lower dosages are recommended for initial dosing, with stepwise dose titration to a maximum of 1000µg, until either an erectile response sufficient for sexual intercourse or intolerable adverse effects occur. Because of the potential for symptomatic hypotension and syncope, the initial dose titration should be conducted under medical supervision. The maximum frequency of use is no more than two doses per 24-hour period. Adverse effects Alprostadil ICI: Mild penile pain (15%-20%), priapism (0.25%) and cavernosal fibrosis with long term use (5%-10%). Cavernosal fibrosis may result in the formation of nodules, penile curvature or deformity, or impaired erectile function. Adverse effects of intraurethral alprostadil include penile pain (25%-35%), urethral bleeding or spotting (5%), priapism (0.1%) and symptomatic hypotension (3%) and syncope (0.4%). Drug interactions Unlikely because only low or undetectable amounts of alprostadil (< 2pg/mL) are found in the peripheral venous circulation. Slidenafil Action and onset Sildenafil citrate is a potent, competitive phosphodiesterase type 5 (PDE-5) isoenzyme inhibitor. When sexual arousal activates the nitric oxide/cGMP pathway via non-adrenergic, non-cholinergic nerves, inhibition of PDE-5 results in increased cavernosal levels of cGMP, relaxation of penile vascular and trabecular smooth muscle, increased cavernosal blood flow and augmented penile tumescence or erection. An erectile response to sexual arousal may occur 0.5-5 hours after dosing. Ingestion on an empty stomach may result in a response after 30 minutes, whereas ingestion after a high-fat meal may delay onset for up to 3 hours. Detumescence occurs immediately after ejaculation or cessation of sexual arousal. The erectile refractory period is often reduced, allowing subsequent arousal to produce a second erection in some men. Dosage Sildenafil is available in 25mg, 50mg and 100mg tablets. The recommended starting dose is 50mg, taken one hour before planned sexual activity, with subsequent dose titration (to a maximum of 100mg) until the desired erectile response is achieved. Use is limited to once-daily administration. Patients aged over 65 years, those with significant renal impairment (creatinine clearance rate, < 30mL/min) or hepatic impairment, or those taking potent cytochrome P450 3A4 inhibitors, should start with a dose of 25mg. Adverse effects Adverse effects are dose-related and are usually of mild to moderate severity. The most common are headache, facial and upper-trunk flushing, dyspepsia and nasal congestion. Transient alteration in colour vision may occur at a dose of 100mg. No cases of priapism were reported in initial studies. Drug interactions The concomitant use of potent cytochrome P450 3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, protease inhibitors), as well as the nonspecific CYP inhibitor cimetidine, is associated with increased plasma levels of sildenafil. Concomitant administration of CYP3A4 inducers, such as rifampicin, will decrease plasma levels of sildenafil. Sildenafil potentiates the hypotensive effects of nitrates and should not be taken by patients who use nitric oxide donors or nitrates in any form. Patients' fitness for renewed sexual activity should be assessed before initiating treatment Back to text 5: Evaluation and treatment of erectile dysfuntion Back to text 6: Important messages for patients Erectile dysfunction is common and is usually due to physical disease. The speed and extent of the male and female sexual response reduces as men and women age - patient treatment expectations should be appropriate for age. Erectile dysfunction is associated with cigarette smoking, hypertension, peripheral vascular disease, diabetes mellitus and depression, and can be an indicator of other underlying, unrecognised physical disease. There is always a contributing psychological component, and psychosexual therapy may result in restoration of potency, even when there is a contributing physical cause - not all men require treatment with medication. Some men can be successfully treated with a combination of sexual education, changes in lifestyle and medication. Many couples have fulfilling sexual relationships without penetrative sexual intercourse - not all men need to have potency restored. Men with long term erectile dysfunction and chronic medical illness (eg, coronary artery disease, chronic obstructive pulmonary disease), must have their fitness for renewed sexual activity assessed before initiation of treatment. Men with angina who take prescribed nitrates should not take sildenafil. Back to text

Chris G McMahon

Long-acting testosterone/progestin combinations show great promise as contraceptives Any suggestion that men cannot be trusted with contraceptive responsibility ignores the widespread use of existing methods which involve their cooperation -- condoms, periodic abstinence and interrupted intercourse are used by millions of couples worldwide.1 For those wanting an alternative to these methods, only female contraceptive methods, permanent sterilisation or "natural" methods have been available. A wider choice of effective methods would be highly desirable, and male hormonal contraception (MHC) is likely to offer a reliable alternative in the near future. Male hormonal contraception The physiological principles of MHC have long been recognised, but the past 20 years have seen important research in this area, notably that sponsored by the World Health Organization (WHO). Real evidence for MHC effectiveness has been provided from trials involving 600 couples in 10 countries, including Australia.2,3All MHC strategies involve the administration of testosterone, which profoundly reduces serum gonadotropin (follicle-stimulating hormone [FSH] and luteinising hormone [LH]) levels.4 A reduced serum LH level markedly reduces intratesticular testosterone levels, which, in combination with a reduced serum FSH level, reversibly interrupts sperm production. (Following cessation of testosterone treatment, sperm counts return to pretreatment levels in 4-6 months.) In the WHO trials, two-thirds of men were rendered azoospermic (ie, having sperm counts of zero), while 91% of the men achieved sperm counts below 1 x 106/mL (normal value, > 20 x 106/mL).3 The pharmaceutical industry has not been active in the MHC area in the past, perhaps because of a belief that the potential market was small, or because of concerns about product litigation. Very recently, the industry has cautiously entered the area. Fortuitously for MHC development, current pharmaceutical interest in new types of androgen replacement therapies will assist this process. Marketing male hormonal contraceptives Key factors to consider in planning a marketing strategy for male hormonal contraceptives are contraceptive effectiveness, acceptability and safety. Contraceptive effectiveness. No contraceptive is 100% effective. For the female contraceptive pill the failure rate is approximately 3 conceptions per 100 person-years in the first year of use, a figure which represents a reasonable target comparator for MHC. The WHO study showed that azoospermia confers high contraceptive cover (0.8 conceptions/100 person-years; 95% CI, 0.02-4.5).2 While azoospermia continues to be the goal, the WHO data suggest that the suppression of sperm counts to very low levels (eg, less than 1 x 106/mL) may provide contraceptive cover comparable to that of the female contraceptive pill, and would almost certainly be superior to other widely used methods such as condoms.3 No pretreatment marker predicts whether an individual will attain azoospermia using MHC. Apart from interracial variation (eg, 98% of Chinese men become azoospermic2,3), there appear to be no differences in serum gonadotropin or testosterone levels, or in testosterone pharmacokinetics, between those who become azoospermic and those who do not.5 Some data suggest that men in whom sperm production is not fully suppressed have a higher level of 5a-reductase enzyme activity, which converts testosterone to the potent androgen metabolite dihydrotestosterone and thus maintains spermatogenesis.6 Understanding the variability of response to MHC is important in formulating regimens which produce the highest rates of azoospermia. Acceptability. Men's willingness to use MHC will depend upon its effectiveness, convenience of use and side effect profile. Methods which are painful, costly, or inconvenient, or which require extensive monitoring or interfere with sexual function or general health, will be declined or soon discarded. Current MHC treatments encounter problems in this area, particularly the need for frequent testosterone injections (every 1-2 weeks) or testosterone implants (every 4-6 months). Supraphysiological doses of testosterone given by intramuscular injection in the WHO studies led to androgenic side effects (acne, mood change) in 21% of men,2,3 but more physiological testosterone levels achieved with implants can reduce these problems.7 Safety. The effects of male hormonal contraceptives on prostate and cardiovascular health are of prime concern in assessing the safety of MHC. So far, prostate problems have not been encountered in MHC trials of up to 18 months' duration. Furthermore, there is no evidence for the induction or acceleration of benign or malignant prostate disease with androgen replacement therapy in hypogonadal men. A fall of around 15% in HDL-cholesterol levels was observed in MHC trials using injectable testosterone;8,9 however, these changes were not seen with the more physiological profile of testosterone delivery via implants.7 Such physiological androgen delivery should reduce androgenic side effects (eg, polycythaemia) associated with intramuscular testosterone replacement, while maintaining libido and sexual function. MHC using combined preparations Testosterone treatment alone will not reliably suppress sperm production to the point of azoospermia. The addition of a gonadotropin-releasing hormone antagonist to testosterone treatment effectively suppresses sperm production,4 but practical difficulties and expense make this a non-viable option. The combination of testosterone and a progestin promotes rapid and profound suppression of serum gonadotropins and sperm counts, and the search for the ideal testosterone-plus-progestin regimen is now the main focus of MHC research. Recent studies have used levonorgestrel,8 desogestrel and medroxyprogesterone acetate.7 One study using cyproterone acetate, an antiandrogenic progestin, produced azoospermia very rapidly and consistently.10 It was proposed that the efficacy of cyproterone acetate was due to its inhibition of testosterone action within the testis (which has a unique need for high testosterone levels) while not interfering with androgen action elsewhere in the body. The question of whether the progestin component of combined male hormonal contraceptives may have specific effects (eg, mood change) in some men requires further study. Delivery methods Delivery methods providing stable physiological levels of testosterone are critical to male hormonal contraceptive development. Delivery could be either oral or by infrequent injection or implants (the latter perhaps being preferable, to assist with compliance). In this area, there is renewed interest from the pharmaceutical industry to work collaboratively with clinical scientists. Testosterone undecanoate or buciclate are esters which are slowly absorbed from intramuscular injection sites and provide testosterone delivery for 2-3 months. Methylnortestosterone is a more potent androgen than testosterone (reducing the mass of steroid to be delivered),11 and, furthermore, its 5a-reduced metabolite is inactive and thus avoids stimulation of the prostate. Finally, our improved knowledge of steroid ligand/receptor interaction may permit the synthesis of a single agent which activates both androgen and progestin receptors in the male, thereby providing gonadotropin suppression within the testis while maintaining androgen activity elsewhere in the body. Conclusions The combination of testosterone and progestin, delivered in the form of a single long-acting injection, shows great promise for providing equally effective (or better) contraception than current widely used male contraception methods. Large and long-term MHC trials are needed to establish the optimal formulations, to provide essential safety and efficacy data, and to spur the interest of industry, which is essential in bringing these products to the market. Robert I McLachlan Associate Professor and Principal Research Fellow Prince Henry's Institute of Medical Research Monash Medical Centre, Clayton, VIC Handelsman DJ. Contraception in the male. In: DeGroot LJ, editor. Endocrinology. 3rd edition. Philadelphia: WB Saunders, 1995: 2449-2458. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 1990; 336: 955-959. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril 1996; 65: 821-829. Amory JK, Bremner WJ. The use of testosterone as a male contraceptive. Baillieres Clin Endocrinol Metab 1998; 12: 471-484. Handelsman DJ, Farley TMM, Peregoudov A, et al. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Factors in non-uniform induction of azoospermia by testosterone enanthate in normal men. Fertil Steril 1995; 63: 125-133. Anderson RA, Wallace AM, Wu FCW. Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5a-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone. J Clin Endocrinol Metab 1996; 81: 902-908. Handelsman DJ, Conway AJ, Howe CJ, et al. Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot. J Clin Endocrinol Metab 1996; 81: 4113-4121. Wu FCW, Farley TMM, Peregoudov A, et al. Effects of testosterone enanthate in normal men: experience from a multicentre contraceptive efficacy study. Fertil Steril 1996; 65: 626-636. Bebb RA, Anawalt BD, Christensen RB, et al. A promising male contraceptive approach: combined administration of testosterone and levonorgestrel. J Clin Endocrinol Metab 1996; 81: 757-762. Meriggiola MC, Bremner WJ, Paulsen CA, et al. Cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. J Clin Endocrinol Metab 1996, 81: 3018-3023. Noe G, Suvisaari J, Martin C, et al. Gonadotropin and testosterone suppression by 7α-methyl-19-nortestosterone acetate administered by subdermal implant to healthy men. Hum Reprod 1999, 14: 2200-2206.

Robert I McLachlan

Position Statement Use, misuse and abuse of androgens The Endocrine Society of Australia consensus guidelines for androgen prescribing Ann J Conway, David J Handelsman, Douglas W Lording, Bronwyn Stuckey, Jeffrey D Zajac on behalf of the Endocrine Society of Australia MJA 2000; 172: 220-224 Abstract - Use of androgens - Misuse of androgens - Abuse of androgens - Key references - Authors' details - - More articles on Endocrinology Abstract Androgen replacement therapy (ART) is usually life-long, and should only be started after androgen deficiency has been proven by hormone assays. The therapeutic goal is to maintain physiological testosterone levels. Testosterone rather than synthetic androgens should be used. Oral 17α-alkylated androgens are hepatotoxic and should not be used for ART. There is no indication for androgen therapy in male infertility. Although androgen deficiency is an uncommon cause of erectile dysfunction, all men presenting with erectile dysfunction should be evaluated for androgen deficiency. If androgen deficiency is confirmed, investigation for the underlying pathological cause is required. Contraindications to androgen therapy are prostate and breast cancer. Precautions include using lower starting doses for older men and induction of puberty. Intramuscular injections should be avoided in men with bleeding disorders. Androgen-sensitive epilepsy, migraine, sleep apnoea, polycythaemia or fluid overload need to be considered. Competitive athletes should be warned about the risks of disqualification. ART should be initiated with intramuscular injections of testosterone esters, 250 mg every two weeks. Maintenance requires tailoring treatment modality to the patient's convenience. Modalities currently available include testosterone injections, implants, or capsules. Choice depends on convenience, cost, availability and familiarity. There is no convincing evidence that, in the absence of proven androgen deficiency, androgen therapy is effective and safe for older men per se, in men with chronic non-gonadal disease, or for treatment of non-specific symptoms. Until further evidence is available, such treatment cannot be recommended. Androgens are hormones that are based on the structure of testosterone, the major male sex hormone, and are capable of developing and maintaining masculine sexual characteristics (including the genital tract, secondary sexual characteristics, and fertility) and the anabolic status of somatic tissues. All androgens have similar biological effects because they all act through the single androgen receptor. Their effects in different tissues are diversified by metabolism of testosterone to its active metabolites by the enzymes 5α reductase (which converts testosterone to 5α-dihydrotestosterone, an androgen with enhanced potency acting on the androgen receptor) and aromatase (which converts testosterone to oestradiol, which acts on the oestrogen receptor). Use of androgens The main medical use of androgens (Box 1) is as androgen replacement therapy (ART) for established androgen deficiency.1-3 Classical androgen deficiency occurs in about 1 in 200 men, due to testicular disorders that directly reduce testosterone output, or hypothalamic-pituitary disorders that reduce pituitary luteinising hormone (LH) secretion, which is the main drive to testosterone production by the interstitial (Leydig) cells of the testes. Although classical androgen deficiency is relatively easy to recognise, diagnosis of less severe androgen deficiency can be more difficult. Owing to its subtle and variable clinical features, the diagnosis may easily be missed, denying patients simple and effective medical treatment with often striking subjective benefits. Potential extensions of classical indications to partial androgen deficiency remain to be fully evaluated for clinical safety and efficacy. These indications include age, androgen deficiency secondary to a chronic medical condition or its treatment, hormonal male contraception, and postmenopausal symptoms.4-6 Until more definitive objective evidence is available regarding the safety and efficacy of prescribing androgens for these indications, they remain suitable for carefully monitored, controlled clinical research trials, but not for routine medical treatment. Pharmacological applications of androgens (Box 1) usually represent second-line therapy where more specific treatments are not yet available or have failed. Androgen treatment can evoke a strong placebo response. In men without genuine androgen deficiency, this placebo effect invariably wanes with time, leading to confusion and dissatisfaction with treatment. In addition, once androgen therapy has commenced, the biochemical changes can cloud further interpretation of results for months. Therefore, androgen replacement therapy should be commenced only after androgen deficiency is clearly established.2,3 Diagnosis of androgen deficiency1-3 Diagnosis of androgen deficiency involves the recognition of appropriate clinical features, with confirmation by biochemical testing. Important clinical features required to evaluate testicular function include reproductive history (including pubertal development), fertility status, changes in sexual function and body hair growth, known testicular pathology, drug use, and occupation. Physical examination should record androgenisation (secondary sexual characteristics, especially body hair distribution, musculature and gynaecomastia) and testis volumes (by orchidometry). Serum LH, follicle-stimulating hormone and testosterone levels should be measured, on at least two separate days and preferably in the morning, to minimise the effects of random and laboratory fluctuations and diurnal rhythms. Direct measurements of free testosterone, if available, may help establish the diagnosis of androgen deficiency, but require extensive validation. Indirect measurements of free testosterone, such as the free androgen index (testosterone/sex hormone binding globulin [SHBG] ratio), correspond poorly with direct measurements and lack empirical validation as a diagnostic test. Additional tests that may be required to identify underlying disorders include karyotyping, pituitary radiology and measurement of prolactin levels, serum ferritin levels, iron saturation and, increasingly, genetic diagnosis. Androgen deficiency is unlikely in men with mean testis volume > 20 mL without atrophy, with a plasma testosterone level consistently above 20 nmol/L, or presenting with erectile dysfunction and a plasma testosterone level consistently above 8 nmol/L (Box 2). Where the diagnosis is not clear, referral to a clinical endocrinologist with experience in this area is recommended.1 Androgen replacement therapy1-3 ART is indicated to rectify androgen deficiency of any cause sufficient to cause clinical consequences. After puberty, there is no age limit to ART. Androgen-deficiency effects may manifest as changes in one or more androgen-sensitive functions; for example, psychosexual function, or loss of anabolic effects on bone, muscle, blood-forming marrow and other androgen-responsive tissues. Apart from decreased spermatogenesis, ART can rectify all clinical features of androgen deficiency, which usually respond within 1-2 months of starting therapy, although the full effect may take longer. Dosage: Standard ART is either testosterone enanthate (Primoteston in castor oil; Schering) or mixed testosterone esters (Sustanon in arachis oil; Organon) as 250 mg in 1 mL oil at 14-day intervals. Deep intramuscular injections are usually given into the upper and outer quadrant of the buttock, although some patients prefer the deltoid or lateral thigh muscle sites. Few men can manage self-injection with the viscous oil vehicle. For all ART, testosterone and its esters should be used in preference to synthetic androgens, because of their established safety and efficacy, as well as ease of dose-titration and assay monitoring. Lower starting doses may occasionally be needed, especially in previously untreated elderly men and during first induction of puberty. Less frequent dosing intervals (eg, every three weeks) are occasionally necessary for those unable or unwilling to have standard dosage, but are accompanied by more extreme peaks and troughs in blood testosterone levels, which may exaggerate symptom fluctuations. An inadequate clinical response raises doubt about androgen deficiency as the cause of recalcitrant symptoms. Rarely, an inadequate clinical response may require increased dosage. If suboptimal symptomatic benefit is supported by biochemical evidence of inadequate maintenance of androgen levels (low trough testosterone levels with or without persistently supranormal LH levels in primary hypogonadism), the same dose may be injected at 10-day intervals. Persistently inadequate responses indicate that unresponsive symptoms are not due to androgen deficiency; further escalation in dose or frequency is not warranted. Men with mild or partial androgen resistance due to androgen-receptor mutations may benefit from high-dose androgen therapy. As the underlying disorders are almost always permanent, life-long ART after the age of puberty is usually necessary. Long term therapeutic compliance depends on an acceptable regimen. Crossover studies indicate that patients strongly prefer the stable testosterone levels and smoother clinical effects provided by implants or transdermal formulations, compared with the wide fluctuations in testosterone levels and symptoms during intramuscular testosterone ester injections. Thus, although ART should commence with injections, alternative modalities (Box 3) may improve compliance. Factors to consider include cost, convenience, availability, familiarity with alternatives, and tolerance for frequent injections. Monitoring: Monitoring of ART is mainly to ensure effective androgen replacement by a regimen tailored to the patient's needs, aiming to maintain adequate therapeutic compliance by continuation of treatment. Serial clinical observation of clinical well-being and major symptoms of androgen deficiency, together with limited numbers of hormonal assays, is usually adequate. Restoration of sexual function has a low threshold for androgen action, so adequate libido and potency is a necessary, but not sufficient, indication of clinically adequate androgen replacement. Blood hormone assays have limited utility in optimising an ART regimen at the start of treatment and in evaluating androgen replacement. Trough blood testosterone levels (ie, before the next scheduled dose) within the eugonadal reference range can be a valuable guide to the adequacy of parenteral androgen replacement, but random blood testosterone levels are not useful for monitoring with either oral or injectable testosterone. In men with hypergonadotropic hypogonadism, suppression of blood LH levels into the eugonadal reference range indicates adequate ART, whereas persistent non-suppression of LH after 3-6 months of regular treatment indicates inadequate dosage or compliance. In hypogonadotropic hypogonadism, blood gonadotropin levels are uninterpretable. Serial evaluation of bone density (especially vertebral trabecular bone) by dual-photon absorptiometry at 1-2-year intervals may be useful in evaluating the adequacy of long-term androgen effects on bone. Other biochemical indices of androgen action, such as haemoglobin, SHBG, and high density lipoprotein cholesterol levels, reflect only supraphysiological effects and are too insensitive for routine monitoring of ART. Androgen deficiency is protective against prostate disease, and ART may restore the risks to those equivalent to, but no more than, eugonadal men of similar age. Screening of men receiving ART for cardiovascular and prostate disease need be no more intensive than for men of similar age not on ART. Precautions and side effects14-17 Adverse effects of androgen treatment are uncommon. Virilisation may occur with androgen therapy in women or children; androgen therapy in these settings requires expert management. Truncal acne and hair growth, weight gain, gynaecomastia and male-pattern hair loss may be observed, and should be managed symptomatically. Certain side effects are characteristic of specific therapeutic modalities (eg, discomfort from intramuscular injections, extrusion of subdermal implants, gastrointestinal disturbance from oral testosterone undecanoate). Polycythaemia may occur disproportionately often in older men treated with testosterone ester injections. In addition, certain testosterone formulations have distinctive effects due to their pharmacokinetic features (eg, reduced levels of SHBG, high density lipoprotein cholesterol and other hepatic proteins due to supraphysiological hepatic testosterone exposure). This may be due to injectable testosterone esters (via high peak blood testosterone concentrations) or oral testosterone undecanoate (via high first-pass portal testosterone concentrations), whereas more steady formulations (transdermal, implants) exhibit fewer or no such effects. Oral synthetic androgens that have a 17α-alkyl substituent (oxandrolone, fluoxymesterone, danazol) are inherently hepatotoxic, causing cholestatic hepatitis, peliosis hepatis and hepatic tumours. Other classes of synthetic androgen, such as 19-nortestosterone derivatives (nandrolone, MENT) and the 1-methyl androgens (mesterolone, methenolone), are not hepatotoxic. Absolute contraindications to androgen therapy are prostate or breast cancer in men. Androgen therapy should be started in men over the age of 40 only after exclusion of undiagnosed prostate disease. Precautions are required for: older men starting androgen treatment, where it may precipitate urinary obstruction or unfamiliar increases in libido; pubertal boys, in whom excessive dosage may accelerate epiphyseal closure, leading to shortened final stature; parenteral androgen therapy in men with bleeding disorders; competitive athletes, who may be disqualified; androgen-sensitive epilepsy, migraine, sleep apnoea or polycythaemia; and cardiac or renal failure or severe hypertension susceptible to fluid overload from sodium and fluid retention. Misuse of androgens Medical misuse of androgens involves prescription with no acceptable medical indication. Some common examples of misguided prescribing of androgens in the absence of established androgen deficiency include: Male infertility: There is no indication for androgen therapy in male infertility. The only likely consequence is an adverse effect of suppressing spermatogenesis. Male sexual dysfunction or impotence: Androgen deficiency (with or without hyperprolactinaemia) is an uncommon (< 5%) cause of men presenting with erectile dysfunction. In such men, excluding androgen deficiency as a readily treatable underlying cause is essential. In the unusual event of severe androgen deficiency presenting with erectile dysfunction, the underlying cause needs to be identified, and plans for life-long ART need to be established. "Male menopause" or "andropause": There is still no evidence that the modest decreases in circulating blood testosterone levels which commence during mid-life have any clinical importance. The risks and benefits of androgen supplementation for partially androgen-deficient older men require further evaluation by placebo-controlled studies. Androgen treatment may be inappropriate, wasteful, and involve placebo effects. Terms such as "male menopause" and "andropause" are misleading; they have little place in meaningful medical or scientific discourse. Elderly men (> 65 years):18 There is no basis for androgen therapy based on age per se. Further controlled clinical trials are needed to evaluate the potential role of androgen supplementation in ageing. While some preliminary placebo-controlled studies suggest short-term benefits for muscle, bone and quality of life, findings are not yet consistent and the identification of appropriate treatment objectives and target subgroups, as well as overall analyses of risks, benefits and costs, are lacking. Specifically, it remains to be determined whether androgen supplementation has significant and sustained clinical benefits in older men with low-normal plasma total testosterone and normal LH levels. At present, there is no basis for androgen treatment outside properly designed clinical trials. Treatment of non-specific symptoms: There is no basis for androgen therapy based on symptoms in the absence of established androgen deficiency. In addition to the unproven safety and efficacy, the placebo effect of androgen injections may be confusing to both doctor and patient. When placebo effects wane, further confusion and dissatisfaction with treatment may be expected. Abuse of androgens Illicit use of androgens19-24 ("anabolic steroids") depends largely on obtaining androgens without legal prescription to be used in the absence of any medical indication. Illicit androgen use became epidemic over the past four decades, since androgens were reportedly first used in elite competitive power sports. A recent placebo-controlled study has shown that high-dose androgen administration does improve muscle size and strength in healthy eugonadal men. Whether these changes enhance athletic performance, whether they are sustained, and whether they apply to older men remains to be clarified. Medical prescription appears to support only a small proportion of illicit androgen use, but such activity has been formally ruled as a breach of professional standards by medical boards in most States and by the Royal Australasian College of Physicians. Highly motivated young men can be very sophisticated in manipulating and pressuring general practitioners while attempting to obtain prescriptions for androgens. The doctor is often led to believe that other practitioners are prescribing androgens for young men, and that he or she is being uncaring or negligent by not acceding to the patient's wishes. We recommend that general practitioners resist these pressures. Fortunately, most people appear ultimately to lose interest in this form of drug abuse. Background and evidence basis of recommendations The Endocrine Society of Australia (ESA) Consensus Guidelines for Androgen Prescribing were written on behalf of the Endocrine Society of Australia. The ad hoc Writing Committee commissioned by the ESA's Council was Dr A J Conway, Professor D J Handelsman (Chair), Associate Professor D W Lording, Dr B Stuckey, and Associate Professor J D Zajac. The draft guidelines were extensively circulated for comment to active members of the ESA with clinical expertise or interests in male reproductive endocrinology. Comments were incorporated into the final document, which was ratified by the ESA's Council. Androgen therapy, in regular clinical use for over 60 years, is one of the oldest hormonal regimens in modern therapeutics. As a long established standard and effective form of hormone replacement for many decades, placebo-controlled studies are unavailable and now unacceptable. Consequently, the NHMRC Quality of Evidence Ratings for these recommendations are those appropriate to an expert committee reviewing all available evidence from controlled experimental and observational studies as well as clinical experience. Key references Diagnosis and management of androgen deficiency Behre HM, Yeung CH, Nieschlag E. Diagnosis of male infertility and hypogonadism. In: Nieschlag E, Behre HM (eds): Andrology: Male Reproductive Health and Dysfunction. Berlin:Springer, 1997: 87-111. Plymate SR. Male Hypogonadism. In: Becker KL (ed): Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia: J B Lippincott Company, 1995: 1056-1082. Nieschlag E, Wang C, Handelsman DJ, et al (eds) (1992). Guidelines for the use of androgens in men. Geneva, Special Programme of Research, Development and Research Training in Human Reproduction of the World Health Organisation. Male contraception Cummings DE, Bremner WJ. Prospects for new hormonal male contraceptives. In: Bremner WJ (ed): Clinical Andrology. Philadelphia: W B Saunders Company, 1994: 893-922. Handelsman DJ. Contraception in the male. In: DeGroot LJ (ed): Endocrinology. 3rd ed. Philadelphia: W B Saunders, 1994: 2449-2458. Androgen therapy in systemic disease Liu PY, Handelsman DJ. Androgen therapy in non-gonadal disease. In: Nieschlag E, Behre HM (eds):Testosterone: Action, Deficiency and Substitution. 2nd ed. E Nieschlag, Behre HM (eds), Berlin, Springer-Verlag, 1998. Comparative pharmacology of androgen formulations Bals-Pratsch M, Langer K, Place VA, Nieschlag E. Substitution therapy of hypogonadal men with transdermal testosterone over one year. Acta Endocrinologica 1988; 118: 7-13. Behre HM, Oberpenning F, Nieschlag E. Comparative pharmacokinetics of androgen preparations: application of computer analysis and simulation. In: Nieschlag E, Behre HM (eds): Testosterone: Action, Deficiency and Substitution. Berlin: Springer-Verlag, 1990: 115-135. Cantrill JA, Dewis P, Large DM et al. Which testosterone replacement therapy? Clin Endocrinol (Oxf) 1984; 24: 97-107. Conway AJ, Boylan LM, Howe C, Ross G, Handelsman DJ. A randomised clinical trial of testosterone replacement therapy in hypogonadal men. Int J Androl 1988; 11: 247-264. Handelsman DJ, Conway AJ, Boylan LM. Pharmacokinetics and pharmacodynamics of testosterone pellets in man. J Clin Endocrinol Metab 1990; 71: 216-222. Meikle AW, Mazer NA, Moellmer JF, et al. Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992; 74: 623-628. Snyder PJ, Lawrence DA. Treatment of male hypogonadism with testosterone enanthate. J Clin Endocrinol Metab 1980; 51: 1335-1339. Safety of androgens Alexandersen P, Haarbo J, Christiansen C. The relationship of natural androgens to coronary heart disease in males: a review. Atherosclerosis 1996; 125: 1-13. Barrett-Connor E. Testosterone, HDL-cholesterol and cardiovascular disease. In: Bhasin S, Gabelnick HL, Spieler JM et al (eds): Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. New York: Wiley-Liss, 1996: 215-223. Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf) 1994; 40: 341-349. Gooren LJ, Polderman KH. Safety aspects of androgen therapy. In: Nieschlag E, Behre HM (eds): Testosterone: Action, Deficiency and Substitution. Berlin: Springer-Verlag, 1990: 182-203. Androgen and the ageing male Tenover JL. Androgen therapy in aging men. In: Bhasin S, Gabelnick HL, Spieler JM, et al (eds): Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. New York: Wiley-Liss, 1996: 309-318. Androgen abuse Bhasin S, Storer TW, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996; 335: 1-7. Handelsman DJ, Gupta L. Prevalence and risk factors for anabolic-androgenic steroid abuse in Australian secondary school students. Int J Androl 1997; 20: 159-164. Lin GC, Erinoff L (eds). (1990). Anabolic Steroid Abuse. National Institute on Drug Abuse Research Monograph Series. Rockville, US Department of Health and Human Services. Wilson JD. Androgen abuse by athletes. Endocr Rev 1988; 9: 181-199. Yesalis CE, Kennedy NJ, Kopstein AN, Bahrke MS. Anabolic-androgenic steroid use in the United States. JAMA 1993; 270: 1217-1221. Young NR, Baker HWG, Liu G, Seeman E. Body composition and muscle strength in healthy men receiving testosterone enanthate for contraception. J Clin Endocrinol Metab 1993; 77: 1028-1032. Authors' details Endocrine Society of Australia, Sydney, NSW. Ann J Conway, MB BS, FRACP; David J Handelsman, MB BS, PhD, FRACP; Douglas W Lording, MB BS, FRACP; Bronwyn Stuckey, MB BS, FRACP; Jeffrey D Zajac, PhD, FRACP. Reprints will not be available from the authors. Correspondence: Associate Professor J D Zajac, Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050. j.zajacATmedicine.unimelb.edu.au Make a comment 1: Use, misuse and abuse of androgens Use Physiological (androgen deficiency) 1-3 Classical androgen deficiency ("hypogonadism") Age-related partial androgen deficiency Micropenis (neonatal) Delayed puberty Aged men* Androgen deficiency secondary to chronic disease* Induced androgen deficiency Hormonal male contraception* Pharmacological (non-androgen deficiency)4-6 Osteoporosis Anaemia due to marrow or renal failure Advanced breast cancer Excessively tall stature in boys Misuse Inappropriate indications In absence of proven androgen deficiency: Male infertility Sexual dysfunction/impotence "Male menopause", "andropause" Older men (>65 years) Non-specific symptoms Abuse19-24 Absence of medical indication Sporting Competitive power sports (athletics, weightlifting, football, swimming, rowing, boxing) RecreationalBodybuilding Cosmetic"Body beautiful" subculture OccupationalSecurity, police, armed forces, professional sports * These indications remain to be fully evaluated for safety and efficacy in controlled clinical trials. Back to text 2: Biochemical evaluation of the diagnosis of androgen deficiency in men with clinical features consistent with hypogonadism* Testosterone level†Luteinising hormone level†Diagnosis<8 nMHigh‡Androgen deficiency (hypergonadotropic hypogonadism§)<8 nMNot highAndrogen deficiency (hypogonadotropic hypogonadism§)8-15 nMHigh‡Androgen deficiency (Leydig cell failure)8-15 nMNot highAndrogen deficiency not confirmed: unproven therapeutic benefit of androgen replacement therapy>20 nMAnyExcludes androgen deficiency>30 nM**High‡Androgen resistance*There is necessarily an arbitrary component to this type of table. It is based on current experience and should be subject to changes according to further clinical evidence. †Blood sample classification based on at least two separate morning blood samples. ‡"High" luteinising hormone level is defined as > 1.5 times the upper limit of the eugonadal reference range for young men. §Hypergonadotropic and hypogonadotropic hypogonadism are also referred to as primary and secondary hypogonadism, respectively. Compensated Leydig cell failure is a form of partial androgen deficiency in which androgen replacement is often beneficial. **Elevated testosterone is defined as above the upper limit of the eugonadal reference range for young men. Back to text 3: Androgen treatment modalities7-13 Testosterone implants Fused cylindrical pellets of pure crystalline testosterone that form a subdermal depot Provide stable, physiological levels of testosterone for 4-6 months following a single implantation of four 200 mg (800 mg) implants Implantation uses a trochar and cannula technique under office sterile conditions, and requires local anaesthesia Main adverse effect is extrusion of implants via the insertion site 1-2 months after implantation Extrusion rate (about 10%) depends on operator experience and patient's physical activity Minor adverse effects related to the minor office surgery (bleeding, infection) are infrequent (<5%) Should only be used for patients who have demonstrated satisfactory tolerance of androgen effects with shorter-acting preparations Transdermal testosterone Administered daily via androgen-impregnated adhesive skin patches or hydroalcoholic gels (not yet available in Australia) Other depot testosterone formulations Newer injectable esters (testosterone undecanoate, testosterone buciclate) Testosterone-laden biodegradable microspheres Both these formulations deliver stable, physiological testosterone levels for 2-3 months following injection Oral testosterone undecanoate Useful where parenteral testosterone is undesirable (eg, bleeding disorders or anticoagulation) or poorly tolerated Administered as 160-240 mg (four to six 40 mg capsules), divided into 2-4 doses per day Second-line formulation for routine ART, because of frequency of administration, high hepatic load, gastrointestinal intolerance, and higher cost Back to text

Ann J Conway · David J Handelsman · Douglas W Lording · Bronwyn Stuckey · Jeffrey D Zajac

Editorial Erectile dysfunction in the Australian community This problem is both increasingly recognised and increasing in prevalence with the ageing of our population MJA 1999; 171: 342-343 Erectile dysfunction (ED) is the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual activity.1 Worldwide, 100 million men are estimated to have some degree of ED, with around 30 million men in the United States1 and around one million men in Australia affected. With our ageing, but relatively fit, population the incidence of ED is certain to escalate. The first major community-based study on ED was the Massachusetts Male Aging Study (MMAS),2 an observational study (conducted from 1987 to 1989) of a random sample of men aged between 40-70 years living in and around Boston, Massachusetts. This study yielded, for the first time, an understandable concept of ED; comparable studies in Australia have been singularly lacking. The first report on the prevalence of ED in our community was a study by Chew et al from the Keogh Institute for Medical Research in Perth3 (formerly the Reproductive Medicine Research Institute). The generalisability of this 1996 study was limited as it only included men who presented to general practices in Perth. The South Australian community study by Pinnock and colleagues in this issue of the Journal,4 which recruited men from the general community through a 1997 household survey, provides data that are, firstly, drawn from a more general community sample than the one in the Perth study, and secondly, more suited to our own demographic situation than data from overseas surveys. The South Australian study confirms that age is the strongest contributing demographic factor to ED, with 60 years of age being the turning point where desire exceeds potency and sexual frequency diminishes.4 The MMAS found that 52% of men aged between 40 and 70 years had some form of ED, with almost 60% of 60-year-old men having this complaint.2 Both studies found that sexual function was also affected by risk factors such as smoking, hypertension, obesity and a high total cholesterol level with a low concentration of high density lipoprotein. Vigorous exercise was found to be protective. The Perth study also found diabetes mellitus (types 1 and 2) to be significant contributors to ED. It should be noted that Pinnock et al used a questionnaire based on the UCLA Prostate Cancer Index that covered sexual function parameters including desire and orgasm, frequency of intercourse, prostate surgery and erectile function. As this index has not been validated in patients who do not have prostate cancer, its use in a randomly based population study represents a methodological flaw. A more appropriate questionnaire for this study would have been the better-known International Index of Erectile Function (IIEF),5 a 15-question survey that includes similar parameters, assesses intercourse and overall satisfaction, but excludes questions related to prostate cancer. The higher incidence of ED reported in the South Australian study4 compared with the MMAS2 probably reflects improvements in public awareness and keenness to discuss and report ED over the past 10 years. The study by Pinnock et al4 clearly shows that cardiovascular disease and ED have similar risk factors and present in a similar age group. Thus, it seems possible that, by improving their risk factor profile, men may benefit both their cardiovascular health and their sexual function. Pinnock et al also suggest non-cancer prostate surgery appears a more important contributor to ED than previously recognised. Erectile dysfunction is clearly an established and recognised male health problem -- one that is decreasingly being regarded as an inevitable consequence of ageing. The estimated 10% of men currently seeking help will increase, as more men will seek help in the future. Doctors will need to improve their skills in obtaining patients' sexual histories as more men request help. A full assessment of men, with emphasis on cardiovascular risk factors, will help direct the consultation to discussion of sexual matters -- it makes good sense to combine cardiac and sexual issues. Sildenafil is the first effective oral medication for ED, and its arrival on the market was well timed with the increasing interest in ED and the increasing numbers of men wanting a simpler treatment. Initial media interest over coital deaths associated with sildenafil has abated, and the drug is now accepted as a safe treatment when prescribed within the recommended guidelines. These guidelines advise caution when prescribing sildenafil to male cardiac patients who may not be fit enough to engage in sexual activity. Sildenafil is also absolutely contraindicated in men receiving nitrate therapy and those who use amyl nitrite "poppers". When sildenafil is contraindicated or fails to achieve the desired result, the use of injectable vasoactive agents is appropriate. Penile injection therapy is still considered the "gold standard", having been used for over 10 years. Alprostadil is the only approved injectable prostaglandin medication available on the Pharmaceutical Benefits Scheme. Alprostadil is also available as an intra-urethral pellet. Vacuum erection devices have been available for over 20 years and are still an acceptable choice for some men. Penile prostheses may be used in more difficult cases. The Australian community-based studies on male sexual function show a pattern similar to that in overseas studies, and highlights two important points in this era of increasing demand for treatment for ED: Doctors need to understand "normal" sexual function for men at different age groups, as knowing the effects of ageing on sexuality is important when counselling patients and advising on treatment; and Knowing that an apparently healthy patient presenting with ED may have underlying cardiovascular disease can advantage the patient's health outcome, and conversely, reducing a patient's cardiovascular risk factors may benefit both cardiovascular health and sexual function; the implications for sexual function may add weight to the arguments against obesity, smoking and excessive alcohol intake. Michael P Lowy Sexual Health Physician Australian Centre for Sexual Health St Luke's Hospital Complex, Sydney, NSW NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Chew KK, Earle CM, Stuckey BGA, et al. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): A17. Pinnock CB, Stapleton AMF, Marshall VR. Erectile dysfunction in the community: a prevalence study. Med J Aust 1999; 171: 353-357. Rosen RC, Riley A, Wagner G, et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. J Urol 1997; 49: 822-830.

Michael P Lowy

Research Erectile dysfunction in the community: a prevalence study Carole B Pinnock, Alan M F Stapleton and Villis R Marshall MJA 1999; 171: 353-357 For editorial comment see Lowy Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Urology Abstract Objective: To investigate the prevalence of erectile dysfunction (ED) in the South Australian community, and the influence of demographic and other risk factors. Design: Survey by mailed questionnaire (based on the University of California, Los Angeles prostate cancer index) of a subset (men who agreed to participate) of a probability sample of the South Australian community who completed a multiuser interview survey. Participants and setting: Men over the age of 40 in South Australia. Main outcome measures: Sexual desire, orgasm, ability to have an erection, adequacy (firmness) of erections for intercourse, frequency of erections when wanted, frequency of intercourse, nocturnal or morning erections, and history of prostate surgery; total sexual function score based on these. Results: 612 men (86.7%) agreed to answer the sexual function survey; 427 (69.8%) returned questionnaires. ED was strongly correlated with age in all seven domains of sexual function. Erections inadequate for intercourse affected 3% of 40-49-year-olds, increasing to 64% of 70-79-year-olds. The frequency of intercourse considered normal for age by men 50-69 years was 1-6 times weekly; the disparity between this and reported frequency increased in men over 60 years, as did the difference between sexual desire and potency. A history of vigorous exercise was protective across all ages. High triglyceride levels, blood pressure medication and non-cancer surgery for prostate disease were independent predictors of poor sexual function at older ages. High cholesterol level was an independent predictor of impotence. Conclusions: We found similar or higher levels of ED than in comparable overseas studies. Disparity between potency and desire was greatest, and hence the age group in whom demand for treatment may be highest, in those 60 years and older. Cardiovascular risk factors were predictors of ED in these older men, suggesting that prevention may benefit sexual function. Non-cancer prostate surgery may be a greater contributor to ED than previously realised. Introduction Establishing the prevalence of erectile dysfunction (ED) in the community is difficult,1 but important for understanding the need for services, establishing functional expectations of men as they age and for determining the influence of demographic and preventable risk factors. An understanding of community prevalence of ED is useful when evaluating treatments for prostate disease which carry high risks of ED. Community prevalence has been examined in international, but not Australian, studies.1-4 One Australian study of ED prevalence in a Perth general practice population has been reported in conference proceedings.5 We undertook this study to establish the prevalence of erectile dysfunction among Australian men, and to investigate the influence of risk factors. Methods Questions were included in the spring 1997 Omnibus survey, a multiple-user household interview survey which provides a representative sample of the South Australian population. We have reported the methods of and results from this annual survey previously.6-8 The Omnibus survey included questions about age, educational attainment, marital status, household income, area of residence, blood pressure group (low, normal, borderline, high), cholesterol group (low, normal, high), alcohol intake by frequency (days per week) and volume (standard drinks per day when drinking), doctor's report of high triglyceride levels, body mass index (BMI), whether vigorous exercise was undertaken in the past two weeks, current and previous smoking status, and number of cigarettes per day usually smoked. Also included were questions about the presence of lower urinary tract symptoms (LUTS) such as nocturia, frequency, urgency, and a visit to a doctor for LUTS, as reported previously.6 In addition, men aged 40 years and over were asked if they would be prepared to answer a further, mailed questionnaire on urological issues. This comprised an introductory letter explaining the purpose of the survey,7 questions on sexual function and one on history of prostate surgery. To provide an indication of men's expectations of intercourse frequency across age groups, the first question asked what frequency of intercourse the respondent considered normal for a man of his age. Respondents were then offered the opportunity to return the questionnaire without answering further questions if they considered these too intrusive. Sexual function questions were derived from the UCLA (University of California, Los Angeles) prostate cancer index developed by Litwin et al.9,10 These applied to the previous three months and covered seven domains: (i) sexual desire, (ii) orgasm, (iii) ability to have an erection, (iv) frequency of erections when wanted, (v) frequency of intercourse, (vi) frequency of morning or nocturnal erections, and (vii) firmness of erections. The first six of these had five response options ("nil", "poor", "fair", "good", "very good" for domains i-iii; "never had an erection when I wanted one", "less than half the time when I wanted one", "about half the time I wanted one", "whenever I wanted one" for domain iv; "once or more daily", "1-6 times weekly", "1-3 times monthly", "less than once a month", "not at all" for domain v; "never", "seldom [less than a quarter of the time]", "not often [less than half the time]", "often [more than half the time]", "very often [more than 75% of the time]" for domain vi), while the seventh had four ("no erections at all", "not firm enough for any sexual activity", "firm enough for masturbation and foreplay only", "firm enough for intercourse"). Additional questions involved history of prostate surgery (for cancer and for non-cancerous conditions). Ethical consideration for the study was by Repatriation General Hospital's Research Ethics Committee. Analysis We defined sexual dysfunction as a response of one of the two lowest response categories (eg, "nil" or "poor") in each of the first six domains. Confidence intervals were adjusted for a design effect of 1.1 to allow for clustering.11 Dysfunction in the seventh domain (firmness of erections) was termed "impotence", defined as "usual quality of erections during the past three months not firm enough for intercourse" (corresponds with National Institutes of Health definition)12 -- one of the three lowest response options for this domain. A total erectile function score was derived by adding scores for each of the seven domains. The resulting score out of a possible 34 was expressed as a percentage; a score of 0 indicated worst possible function and 100% indicated best possible function in all domains. The reliability coefficient (Cronbach's alpha) of this seven-item score was 0.940. The association of demographic and cardiovascular risk factors with total sexual function (expressed as a continuous variable) and with impotence (a dichotomous variable) was examined after allowing for the effects of age by means of analysis of variance and logistic regression. For analysis, data were weighted by household size, age, sex and geographic region to benchmarks derived from the resident South Australian population in August 1996. We used SPSS for Windows13 for statistical analysis. Results The numbers and age breakdown of respondents are shown in Box 1. The mean age of respondents was 57.5 years (standard error, 0.58). Of the 745 men aged 40 years and over who responded to the Omnibus survey (representing a response rate of 70.8%), 612 (82.1%) agreed to complete a further, mailed questionnaire on urological issues. These questionnaires were returned by 427 respondents (69.8%), 371 (86.9%) of whom agreed to answer the full questionnaire. Box 1 shows that the age distribution was the same in all of these groups. We weighted further analyses to reflect the age distribution in the South Australian community; marginal totals thus do not correspond to the totals in Box 1. A comparison of respondents who agreed to answer the sexual function questions with those who did not agree to a further survey, did not respond to the mailed form or did not agree to answer the sexual function questions showed no significant differences in age, marital status, blood pressure, cholesterol and triglyceride levels, blood pressure medication or visit to a doctor for LUTS. Men who answered the sexual function questions were more likely to report vigorous exercise in the past two weeks (25.0% v 15.4%; P = 0.001), and more likely to drink alcohol five or more times per week (34.2% v 25.3%; P = 0.026) than those who did not answer these questions. Frequency of intercourse The frequency of intercourse considered by respondents as normal for their age, shown in Box 2(a), and actual reported frequency of intercourse were strongly correlated (Spearman's correlation coefficient, 0.62; P < 0.0001). Most 40-60-year-olds considered that intercourse 1-6 times per week was normal for their age and most reported this frequency of intercourse. In older men, however, a discrepancy emerged: most 70-79-year-olds considered 1-3 times per month to be normal for their age, but most reported an actual frequency of less than once per month. Box 2(b) illustrates this more clearly. In younger age groups, the reported frequency approximated that considered normal for age, but in older age groups it was substantially lower. Similarly, Box 2(c) shows that, while potency exceeds desire in men aged 40-59 years, after age 60 years desire exceeds potency. Prevalence of erectile dysfunction Erectile dysfunction was strongly correlated with age across all seven domains (Box 3). The prevalence of impotence (defined above) increased sharply from 3% in 40-49-year-olds to 42% in 60-69-year-olds and 64% in 70-79-year-olds. Other domains of sexual function, including morning or nocturnal erections, followed this pattern of steep decline in the fifth and sixth decades. Total sexual function scores ranged from 17% to 97%, with a mean of 68.1% (standard error, 1.1); 21% of respondents had a score of 50% or less. The sexual function score was also strongly correlated with age (Pearson's correlation coefficient, 0.63; P < 0.0001). Demographic risk factors Age, income, education, marital status, area of residence, occupation and country of birth were examined for their association with total sexual function and impotence. By far the strongest contributor to total sexual function score was age, and so the contribution of other factors was examined singly after first accounting for the effects of age in analysis of variance models, including first-order interactions (sexual function) and logistic regression (impotence). Where factors or their first-order interactions were significant, a combined model was examined. A summary of these analyses is given in Box 4. Men with lower socioeconomic status (income, education, occupation) tended to have lower sexual function, and this association was seen particularly in older men. In the 70-79 years age group, the total sexual function score varied from 47.1 in the lowest education category to 61.7 in the highest. Sexual function tended to be lower in Australian-born than overseas-born respondents. When tested in a model containing cardiovascular risk factors, this association remained. No demographic factors, apart from age, were significant contributors to impotence. Cardiovascular and other risk factors The cardiovascular risk factors shown in Box 4, as well as presence of LUTS, doctor visit for LUTS and surgery for prostate disease (cancer or non-cancer), were examined for their effects on total sexual function and impotence, as described for demographic factors. A number of factors were significantly (P < 0.05) associated with decreased sexual function after controlling for the effects of age. For total sexual function, these were ever having smoked, taking blood pressure medication and having had surgery for non-cancer prostate disease. A history of vigorous exercise was protective. Risk factors for impotence were high body mass index, high levels of triglycerides and cholesterol, and surgery for non-cancer prostate disease. Again, a history of vigorous exercise was protective. When combined models were constructed with these factors, the number that remained independently significant was reduced (Box 4). For total sexual function, these were vigorous exercise, high triglyceride levels, blood pressure medication, and surgery for non-cancer prostate disease. The combined model for total sexual function explained 55% of the variance. The observed power was low for all non-significant factors. The effects of cardiovascular risk factors were stronger in older age groups. For example, men in their 60s with high triglyceride levels had a total sexual function score of 41% (95% CI, 31%-52%), compared with 64% (95% CI, 59%-70%) for men of the same age who did not have this risk factor. Discussion Few international or Australian studies of the prevalence of sexual dysfunction have surveyed the general community.1 Our study was based on a representative sample of the South Australian community, and employed rigorous methods which have been previously used in other prevalence studies.1,8 The study was undertaken before the recent introduction of the drug oral sildenafil for erectile dysfunction. The subsample who answered questions on sexual function were similar in terms of most demographic and risk factor variables tested, but did report undertaking more vigorous exercise, and more frequent alcohol consumption. They may therefore reflect a more physically active subgroup, and our estimates of erectile dysfunction are likely to be conservative. Relative to other studies with comparable methods and measures of sexual dysfunction, the prevalences we found were similar or higher. For example, a study of frequency of sexual activity reported that 34.7% of married 60-65-year-old people did not have sexual intercourse within the preceding month,14 while we found that 34.3% of 60-69-year-old men reported having intercourse "less than once a month". A survey of 1240 men attending general practices in Perth found a 45% prevalence of "complete ED [erectile dysfunction]" in 70-79-year-old men,5 compared with our finding of impotence in 64.2%, and 64.3% in a study by Diokno et al.15 The frequently quoted Massachusetts Male Aging Study reports a prevalence of complete impotence of 9.6% for a 40-70-year-old population;2 the corresponding figure in our study was 16%. As expected, frequency of intercourse considered normal for age was strongly correlated with the frequency of intercourse reported (Figure 2). Solstad and Hertoft found that, while 40% of interviewed Danish men reported some kind of sexual dysfunction, only 7% considered their problems abnormal for their age,16 implying that men tend to see their own functional level as normal. Nevertheless, in our study, the discrepancy between reported frequency of intercourse and that considered normal for age increased with age. It was greatest in men 70 years and older, suggesting that it is older men who may be most concerned about their sexual function. Consistent with this, potency exceeded desire in younger age groups, but the relationship was reversed in men aged 60 years and over. About one in five men over the age of 50 experience good to very good sexual desire, but nil to poor erectile function; these men may be more likely to seek treatment. If the goal of treatment is to achieve perceived "normal function for this age", this may be a frequency of intercourse of 1-3 times monthly for 70-79-year-olds and weekly in the case of 40-69-year-olds. The effects of demographic risk factors such as income and education were more apparent in older age groups and were consistent with lower sexual function in lower socioeconomic groups. No reason is immediately apparent for the lower sexual function of Australian-born men compared with their overseas-born counterparts. Cardiovascular and medical risk factors reflected a conventional pattern.1,17 Predictors of low total sexual function scores after controlling for age only were smoking, blood pressure medication, high triglyceride levels and non-cancer prostate surgery, while a history of vigorous exercise provided a protective effect. In a combined model, smoking was no longer significant. Predictors of impotence after controlling for age only were high body mass index, high triglyceride levels, high cholesterol level, surgery for non-cancer prostate disease, while vigorous exercise was again protective. In a combined model, only high cholesterol remained significant. However, it is likely that small numbers of respondents limited the power of our study to investigate all these factors simultaneously. Our findings suggest that men experience poor sexual function as a deficit in the same age ranges in which cardiovascular risk factors are major determinants of that function, raising the possibility of prevention. It would be interesting to know whether, for men 60 years and over, improving cardiovascular risk factor profile would also reduce the prevalence of sexual dysfunction. Also of interest is the consistent and independent effect of non-cancer prostate surgery on sexual function. While its effects are small relative to age, it may point to a higher impotence rate than is commonly believed to result from this type of surgery,18 and this warrants further investigation. Acknowledgements We thank Living Health and Quitline for generously sharing their data on cardiovascular risk factors, and the AntiCancer Foundation for funding the prostate cancer questions. We would also like to thank the Behavioural Epidemiology Unit, South Australian Department of Human Services, and Lynne Giles, Flinders University, for assistance with aspects of the statistical analyses. References Bortolotti A, Parazzini F, Colli E, Landoni M. The epidemiology of erectile dysfunction and its risk factors. Int J Androl 1997; 20: 323-334. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54-61. Helgason AR, Adolfsson J, Dickman P, et al. Factors associated with waning sexual function among elderly men and prostate cancer patients. J Urol 1997; 158: 155-159. Jonler M, Moon T, Brannan W, et al. The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol 1995; 75: 651-655. Chew K, Burio C, Stuckey B, Jamrozik K. Erectile dysfunction in general medical practice. A study in Perth, Australia. Int J Impotence Res 1997; 9 (Suppl 1): S36. Pinnock C, Marshall V. Troublesome urinary symptoms in the community: a prevalence study. Med J Aust 1997; 167: 72-75. Weller D, Pinnock C, Silagy C, et al. Prostate cancer testing in South Australian men: influence of sociodemographic factors, health beliefs and lower urinary tract symptoms. Aust N Z J Public Health 1998; 22: 400-402. Pinnock C, Weller D, Marshall V. Self-reported prevalence of prostate specific antigen (PSA) testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Litwin MS, Hays RD, Fink A, et al. Quality-of-life outcomes in men treated for localized prostate cancer. JAMA 1995; 273(2): 129-35. [See comments.] Litwin MS, Nied RJ, Dhanani N. Health-related quality of life in men with erectile dysfunction. J General Intern Med 1998; 13: 159-166. Kish L. Estimates of unit variance: design effect. Survey sampling. New York: John Wiley and Sons, 1965: 257-263. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83-88. SPSS for Windows [computer program], version 6.1. Chicago, Ill: SPSS Inc, 1996. Marsiglio W, Donnelly D. Sexual relations in later life: a national study of married persons. J Gerontol 1991; 46(6): S338-S344. Diokno AC, Brown MB, Herzog AR. Sexual function in the elderly. Arch Intern Med 1990; 150: 197-200. Solstad K, Hertoft P. Frequency of sexual problems and sexual dysfunction in middle-aged Danish men. Arch Sexual Behavior 1993; 22: 51-58. Helgason AR, Adolfsson J, Dickman P, et al. Waning sexual function -- the most important disease-specific distress for patients with prostate cancer. Br J Cancer 1996; 73: 1417-1421. Clinical practice guidelines for the management of uncomplicated lower urinary tract symptoms in men. Canberra: National Health and Medical Research Council, 1997. (Received 30 Nov 1998, accepted 28 Jun 1999) Authors' details Repatriation General Hospital, Daw Park, Adelaide, SA. Carole B Pinnock, PhD, Principal Research Scientist, Division of Surgery; Alan M F Stapleton, PhD, FRACS, Director, Urology Unit; Villis R Marshall, MD, FRACS, Head, Division of Surgery, and Head, Department of Surgery, Flinders Medical Centre. Reprints will not be available from the authors. Correspondence: Dr C B Pinnock, Division of Surgery, Repatriation General Hospital, Daws Road, Daw Park, SA 5041. carole.pinnockAThealth.sa.gov.au Back to text Back to text Back to text Back to text

Carole B Pinnock · Villis R Marshall

Prostate-specific antigen testing for prostate cancer: the case for informed consent Informed consent should be obtained before testing asymptomatic men MJA 1998; 169: 9-10 The prostate-specific antigen (PSA) test is only the first step in screening asymptomatic men for prostate cancer. Its lack of specificity usually necessitates transrectal ultrasound-guided multiple biopsies for confirmation of the diagnosis. These procedures will discover a large number of cancers, many of which, viewed from one perspective, will be potentially curable by surgery1 or radiotherapy. However, epidemiological evidence suggests that most cancers localised to the prostate will not cause clinically significant disease for at least 10 years.2 PSA-based screening presents unique difficulties because at present there is no means to distinguish those cancers which will impair health to a degree that justifies the risk of iatrogenic morbidity of investigation (biopsy-related sepsis) and curative treatment (incontinence, impotence, and radiation damage to adjacent organs). This issue of the Journal includes four pertinent articles: the incidence of prostate cancer and the prevalence of PSA testing are described and compared in Western Australia3 (Threlfall et al) and New South Wales4 (Smith & Armstrong); reasons for PSA tests being ordered by general practitioners (GPs) in central Sydney are reported5 (Ward et al); and the prevalence of PSA testing among South Australian men is given, together with findings concerning men's understanding of the immediate consequences of having a PSA test6 (Pinnock et al). PSA tests were the sixth most frequent pathology item ordered by GPs in the June quarter of 1996,5 but their use has fallen since the peak in 1995.3,4 This may indicate that GPs are adopting a more discerning approach, in line with guidelines that recommend against the use of PSA tests to screen for prostate cancer.7 However, in the period 1992-1996, it is clear that GPs and asymptomatic men adopted the test enthusiastically. Medicare data show that one in every four Australian men (27%) aged at least 50 years had a PSA test in 1995 or 19964 and, in a random survey of households in South Australia carried out in 1996, 28% of men aged 50 years or older without prostate cancer reported having a PSA test in the preceding 12 months.6 A high proportion of PSA tests were ordered by GPs for screening ("routine for age") or in response to patient request.5,6 Men over 70 years old have been tested as frequently as younger men4,6 -- but the older the man when prostate cancer is detected, the less likely it is that a benefit from early intervention is possible.8 In South Australia, there was an association between PSA testing and visiting a doctor for urinary symptoms.6 PSA testing is not recommended for men presenting with uncomplicated lower urinary tract symptoms (because such symptoms are unlikely to be indicative of localised prostate cancer),6,9 but it is understandable that GPs may order the test because the question of prostate disease has been raised during the consultation. It is evident that PSA tests have been carried out without the consequences of an abnormal test result being adequately explained.6 GPs need a clear-cut structured framework within which the paucity of good scientific evidence and the potential harms and benefits can be discussed with patients. Most GPs will have had difficulty reconciling the negative evidence relating to the cost-benefit of PSA testing with their natural inclination to detect and treat cancer at an early stage. However, in asymptomatic people the balance of harm versus benefit must demonstrably be more clearly in favour of benefit than in usual clinical practice. In the United States, where enthusiasm for both case-finding by PSA testing and treatment by radical prostatectomy occurred some years earlier than in Australia, there appears to have been a small fall in mortality from prostate cancer in the period 1990-1995.10 Interpretation of this fall is far from clear, but it may be attributable to the dramatic increase in use of radical prostatectomy11 or other therapeutic advances in the 1980s. Conclusive evidence of reduced mortality from prostate cancer as a result of PSA screening must await the completion of randomised controlled trials. From an intention-to-treat analysis of men aged 50-79 years with clinically localised prostate cancer in the population-based US Surveillance, Epidemiology, and End Results (SEER) Program, no advantage in 10-year disease-specific survival was found for either radical prostatectomy or radiotherapy compared with conservative management for men with tumours with a Gleason score of 2-4 (well differentiated).12 For men with tumours with a Gleason score of 5-7 (moderately differentiated) there was an advantage for radical prostatectomy but not for radiotherapy -- this may reflect the fact that patients selected for surgery excluded those whose general health, and therefore prognosis, was already bad when prostate cancer was diagnosed. The 10-year disease-specific survival was better for men with tumours with a Gleason score of 8-10 (poorly differentiated) treated by either radical prostatectomy or radiotherapy compared with conservative management. Because of the way screening for breast and cervical cancers has been promoted, the general public will perceive that finding a cancer earlier is beneficial because treatment is more likely to be effective. However, using the PSA test for detecting prostate cancer in asymptomatic men is not analogous to mammography for early detection of breast cancer in asymptomatic women. Apart from the unproven benefit, there is a need for universally applied guidelines for the management of men with an abnormal test result, comparable with those built into the mammographic screening program. Such guidelines would include counselling and provision for a multidisciplinary approach when a decision is being made about the best course of management. At present, the cascade of events following an abnormal PSA test result proceeds without the man always making an informed choice before the test. Indeed, when men are given prior information about the PSA test and its characteristics, the consequences of having a raised PSA level, follow-up diagnostic procedures, treatment options and side effects, they are less likely to decide to have the test.13 GPs have a professional responsibility to give appropriate advice based on current evidence and, where there is uncertainty, this should be conveyed. Obtaining informed consent is accepted in the context of an invasive procedure. Given the medical uncertainties, the invasive nature of the confirmatory and therapeutic procedures that will be required if the test is positive, and the possibility of doing more harm than good, informed consent should be obtained from asymptomatic men before ordering a PSA test. Margaret McCredie Professorial Research Fellow, Department of Preventive and Social Medicine University of Otago, Dunedin, New Zealand, and Cancer Epidemiology Research Unit, NSW Cancer Council, Woolloomooloo, NSW Brian Cox Senior Research Fellow, Department of Preventive and Social Medicine University of Otago, Dunedin, New Zealand Kaye KW. Prostate cancer: enthusiasm for screening. Med J Aust 1995; 162: 540-541. Johansson J-E, Adami H-O, Andersson S-O, et al. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA 1992; 267: 2192-2196. Threlfall TJ, English DR, Rouse IL. Prostate cancer in Western Australia: trends in incidence and mortality from 1985 to 1996. Med J Aust 1998; 169: 21-24. Smith DP, Armstrong BK. Prostate-specific antigen testing in Australia and association with prostate cancer incidence in New South Wales. Med J Aust 1998; 169: 17-20. Ward JE, Gupta L, Taylor NJ. Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer? Med J Aust 1998; 169: 29-31. Pinnock CB, Weller DP, Marshall VR. Self-reported prevalence of prostate-specific antigen testing in South Australia: a community study. Med J Aust 1998; 169: 25-28. Australian Health Technology Advisory Committee. Prostate cancer screening. Canberra: AGPS, 1996. Fleming C, Wasson JH, Albertsen PC, et al. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. Prostate Patient Outcomes Research Team. JAMA 1993; 269: 2650-2658. National Health and Medical Research Council. Clinical practice guidelines. The management of uncomplicated lower urinary tract symptoms in men. Canberra: AGPS, 1996. Mettlin CJ, Murphy GP. Why is the prostate cancer death rate declining in the United States? Cancer 1998; 82: 249-251. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994; 343: 251-254. Lu-Yao GL, Yao S-L. Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet 1997; 349: 906-910. Flood AB, Wennberg JE, Nease RF, et al. The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team. J Gen Intern Med 1996; 11: 342-349. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Margaret McCredie · Brian Cox

Management of localised prostate cancer: state of the art The decision to treat should be based on the age of the patient and the grade of the cancer MJA 1998; 169: 11-12 We know that the incidence of prostate cancer increases with age and that many men "die with, but not from, prostate cancer".1 This has made the medical community concerned that, because of the high prevalence of comorbid illnesses among elderly men, many cancers detected by screening based on prostate-specific antigen (PSA) testing will be clinically insignificant, and that most patients would be overtreated. Unfortunately, we are also faced with the reality that approximately 2500 men succumb to prostate cancer annually, and many, particularly younger men, in fact "die of the disease and not with it".2 Most patients with localised prostate cancer will be given three management options: watchful waiting, radiotherapy, or radical surgery. Watchful waiting is defined as no initial treatment, with regular patient surveillance (which involves frequent consultations, digital rectal examinations and PSA testing) and commencement of androgen ablative therapy when clinical progression occurs. The success of watchful waiting depends on the predicted biological aggression of the cancer (related to the histological grade), as well as on the age and the associated comorbid illnesses of any individual patient. A pooled analysis of 828 patients treated conservatively in six non-randomised studies concluded that histologic grade was an important determinant of outcome. The 10-year cause-specific survival of patients with well or moderately differentiated cancers was 87%, compared with only 36% for those with poorly differentiated disease (who were at high risk of cancer progression and death).3 The cancer had metastasised by 10 years in 19% of men with well differentiated disease and 42% of men with moderately differentiated disease, despite the satisfactory cause-specific survival. Although watchful waiting may be an appropriate treatment choice for men with life expectancy of less than 10 years with well or moderately differentiated cancers, the outcome at 15 years may be less favourable. In another series, among men who survived more than 10 years from their initial diagnosis, prostate cancer was the direct or contributing cause of death in 63%.4 A report from the Connecticut Tumour Registry has shown that in men diagnosed with moderately differentiated cancer there is a modest, but not insignificant, risk of death from prostate cancer (28%) at 15 years with conservative treatment, and a potential loss of 4-5 years of life.5 Both mortality and potential years of life lost were even higher in men diagnosed with poorly differentiated disease. Contemporary radiotherapy offers an alternative to radical surgery for men who prefer not to undergo surgery or who have comorbidities which increase the risks of surgery. It also offers a chance of local tumour control to men with locally advanced cancer deemed unsuitable for curative surgery. There has been debate over the contribution of radiotherapy because surgery achieves higher rates of clinical and biochemical freedom of disease in the long term (although there have been no valid prospective, randomised controlled trials which directly compare these two treatments). However, the apparent advantage of surgery could be a reflection of the use of radiotherapy in patients with more advanced disease than those for whom radical prostatectomy would be contemplated. Success with radiotherapy has been shown to be dependent on both the stage and grade of the cancer. Fifteen-year cause-specific survival rates varied from 84% for low-stage to 52% for high-stage clinically localised cancers, and from 85% for well differentiated to 32% for poorly differentiated cancers.6 Traditional external beam radiotherapy involves a treatment course lasting up to seven or eight weeks. Acute proctitis and cystitis occurs in most patients, and there is a 2%-3% risk of long term rectal morbidity (diarrhoea, rectal bleeding) and a 30%-60% risk of permanent impotence. There are increasingly convincing data to support the hypothesis that local control and disease-free survival rates in patients with apparently localised disease improve with increasing radiation dose.7 Current research strategies are therefore aimed at increasing radiation dose without increasing surrounding normal tissue damage. This may be achieved by three-dimensional conformal therapy or brachytherapy, either alone or in combination with external beam radiotherapy. Another approach is to use androgen ablation to shrink the tumour, and then to deliver radiotherapy to maximise tumour cell kill.8 All these techniques have shown encouraging preliminary results, but follow-up has been relatively short. Improvements in surgical techniques, together with an increased understanding of the anatomy of the prostate, have made radical prostatectomy a popular treatment option for localised prostate cancer since the mid 1980s. A Mayo Clinic review of 3170 men treated by radical prostatectomy for clinically localised disease included 93% of men with clinically palpable disease and 25% with poorly differentiated disease. Cause-specific survival among those with palpable disease at 10 and 15 years was 90% and 82%, respectively, and 82% and 71%, respectively, among those with poorly differentiated cancers.9 The morbidity of radical surgery in an Australian setting has been discussed recently in the Journal.10 Independently administered questionnaires indicated that incontinence requiring daily pads occurred in approximately 10% of men who underwent surgery. Most of those affected required a maximum of one pad per day and the degree of inconvenience was generally low. The nerve-sparing technique may give reasonable postoperative potency rates in selected younger patients,11 but impotence occurs in most older men, and this is the issue that most affects quality of life.10 Nonetheless, men in most series indicated that they would choose to have surgery again,10 suggesting that the patients' desire to be cured of the disease outweighed the disadvantageous side effects. In a comparison of watchful waiting, radiotherapy and surgery, Surveillance, Epidemiology and End Results (SEER) data from the United States have shown that men with well differentiated cancer treated by watchful waiting have 10-year cause-specific survival rates comparable to those treated actively, while in those with moderately or poorly differentiated cancers treatment provides a survival benefit (Table).12 The gap between these groups is likely to widen further at 15 years as more men treated by watchful waiting live long enough to succumb to the disease. In most watchful waiting series, the mean age of the patients is over 70 years, and therefore few patients (5.9%-8.9%) actually survived 15 years.5,13 A recent study comparing 10-year data with 15-year data for men treated conservatively has shown a 15% reduction in cause-specific survival over the additional five years in men with well or moderately differentiated cancer,14 indicating a cumulative increase in prostate cancer mortality even in this cohort with lower grades of cancer. The hypothesis that death rates are declining as a result of increased diagnosis of localised disease treated at an earlier stage is supported by recent National Cancer Institute data showing that prostate cancer mortality in younger white men had declined by 11.7% this decade.15 It is to be hoped that randomised controlled trials currently under way will provide evidence that this is the case. A preliminary report suggests that this may be so.16 However, until the substantive results of these trials are known, men must be thoroughly counselled about the benefits and risks of early detection and treatment of prostate cancer. Aggressive, early therapy should be recommended for patients who are more likely to benefit from treatment -- those with greater than 10-year life expectancy, especially if diagnosed with a higher histological grade of cancer -- while patients less likely to benefit should be spared the morbidity of treatment. Mark Frydenberg Clinical Associate Professor, Department of Surgery, Monash University Head of Urology, Monash Medical Centre, Melbourne, VIC Gillian Duchesne Associate Professor, Department of Urology and Radiation Oncology Peter MacCallum Cancer Institute, Melbourne, VIC Phillip D Stricker Attending Urologist, Department of Urology, St Vincent's Hospital, Sydney, NSW Canstat -- Cancer in Victoria. Melbourne: Anti-Cancer Council of Victoria, 1994. Albertsen PC, Murphy-Setzko MA, Hanley JA, et al. Long term survival following conservative management of localised prostate cancer: fifteen year follow up among men aged 55-75 [abstract]. J Urol 1998; 159: 251. (Abstract No. A963.) Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative treatment of clinically localised prostate cancer. N Engl J Med 1994; 30: 242-248. Aus G, Hugosson J, Norlen L. Long term survival and mortality in prostate cancer treated with non-curative intent. J Urol 1995; 154: 466-469. Albertsen PC, Fryback DG, Storer BE, et al. Long term survival among men with conservatively treated localised prostate cancer. JAMA 1995; 274: 626-631. Bagshaw MA, Cox RS, Hancock SL. Control of prostate cancer with radiotherapy: long term results. J Urol 1994; 152: 1781-1785. Hanks GE, Martz KL, Diamond JJ. The effect of dose on local control of prostate cancer. Int J Radiat Oncol Biol Phys 1988; 15: 1299-1305. Zagars GK, Johnson DE, Von Eschenbach AC, Hussey DH. Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long term results of a prospective randomized study. Int J Radiat Oncol Biol Phys 1988; 14: 1085-1091. Zincke H, Oesterling JE, Blute ML, et al. Long term results after radical prostatectomy for clinically localised prostate cancer. J Urol 1994; 151: 1583-1586. Heathcote PS, Mactaggart PN, Boston RJ, et al. Health related quality of life in Australian men remaining disease free after radical prostatectomy. Med J Aust 1998; 168: 483-486. Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991; 145: 998-1002. Lu-Yao GL, Yao SL. Population based study of long term survival in patients with clinically localised prostate cancer. Lancet 1997; 349: 906-910. Johanssen J-E, Holmberg L, Johansson S, et al. Fifteen year survival in prostate cancer: a prospective population based study in Sweden. JAMA 1997; 277: 467-471. Adolfsson J, Steineck G, Hedlund P-O. Deferred treatment of low grade prostate cancer: actual 10 year and projected 15 year follow up of the Karolinska series [abstract]. J Urol 1998; 159: 252. (Abstract No. A965.) Mettlin CJ, Murphy GP. Why is the prostate cancer death rate declining in the United States? Cancer 1998; 82: 249-251. Charatan FB. Prostate cancer screening reduces death. BMJ 1998; 316: 1626. Reprints: Clinical Associate Professor M Frydenberg, Suite 21, Cabrini Medical Centre, Isabella Street, Malvern, VIC 3144. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Mark Frydenberg · Gillian Duchesne · Phillip D Stricker