Endometriosis remains an enigma despite having been extensively studied. Its aetiology remains unclear, although there is a positive correlation with retrograde menstruation, probably with a background genetic predisposition. Traditionally, the symptoms of endometriosis are said to be pelvic pain and infertility, but, while a causal link between these symptoms and the disease is sometimes clear, the link is not always established. Treatment aimed at eliminating endometriotic deposits is effective in controlling symptoms in a proportion of patients, but recurrence is common.

Endometriosis is considered difficult to diagnose because the extent of the disease (endometriotic deposits and scar tissue) does not correlate with symptoms. The only accepted diagnostic test is direct visualisation (usually laparoscopically) by an experienced surgeon.1 Arguably, as endometriosis can be diagnosed in up to 40% of menstruating women at laparoscopy,2 it may be detected in all women at some stage of their reproductive lives, only to regress spontaneously in some. In addition, some symptoms associated with endometriosis are common. For instance, dysmenorrhoea occurs in up to 60% of women with regular menses3 and infertility occurs in about 15% of the population (of whom 30% have endometriosis).4 Hence, common conditions (mild endometriosis) may be associated with common symptoms (eg, dysmenorrhoea) by chance, not causally. The enormous variation in symptomatic expression and lack of clear correlation with the extent of endometriosis suggest the need for epidemiological studies of each symptom and of women with either mild or severe disease. This would exclude the possibility that mild endometriosis may be a normal finding in women. Epidemiological studies of women with endometriosis associated with dysmenorrhoea may find a causal link only in women with progressive dysmenorrhoea.

In addition, epidemiological studies confined to specific symptoms causally associated with endometriosis (eg, dyspareunia and endometriosis in the uterosacral ligaments, progressive dysmenorrhoea and American Fertility Society stage III and IV endometriosis5) may result in consistent findings of the role of genes in disease development. 6

From observations that pregnancy resolves symptoms, particularly of dysmenorrhoea, "mimicking pregnancy" became a treatment option. Medications that resulted in amenorrhoea (such as GnRH analogues, danazol and high-dose progestogens) have been used. These work by antagonising the growth-promoting effect of oestrogens or reducing the oestrogenic stimulus for growth, as well as increasing apo-ptosis. Each of these medications has been shown in a recent Cochrane meta-analysis of randomised controlled trials to be equally effective in control of dysmenorrhoea, dyspareunia and pelvic pain, and in decreasing the bulk of endometriotic tissue.7 However, the follow-up period in these trials was usually only three to six months. Annual recurrence rates of endometriosis after treatment are generally accepted to be of the order of 10%.8 Hence, further trials with longer follow-up, and possibly comparisons with the oral contraceptive pill (which has a better side-effect profile than the other drugs), in three-monthly cycles, would be beneficial. That medical therapies are not effective for infertility associated with mild endometriosis has been well established in large-scale, randomised controlled trials.9

Another Cochrane review showed that laparoscopic ablation or excision of the endometriotic tissue is effective in treating endometriosis associated with pelvic pain. However, this conclusion was based on one randomised controlled trial10 and further trials are needed to confirm this finding. Similarly, further evidence to support the effectiveness of laparoscopic surgery for subfertility associated with endometriosis is needed to support the beneficial finding in one randomised controlled trial. This is the aim of a protocol developed by the Cochrane Library.11

While the above conclusions are based on Cochrane reviews of the best available evidence, doubt remains. All trials are subject to a chance of showing a real effect when there is a probability that there is no effect. Continued development of well conducted randomised trials will reduce the probability of an incorrect conclusion. In addition, expert opinion based on the current extensive body of literature, and taking into account the basic mechanisms of the disease process of endometriosis, will help distinguish the causal relationship between each symptom associated with endometriosis. In turn this would lead to improved clinical outcomes for patients with associated dysmenorrhoea, chronic pelvic pain, dyspareunia and infertility.

It is argued that current evidence for effective treatment of each of the symptoms associated with endometriosis could be further improved by further randomised controlled trials with clearly defined patient groups (eg, chronic pelvic pain in association with mild endometriosis, in-vitro fertilisation for three to five years of infertility associated with mild endometriosis). In addition, if results of epidemiological studies show no probable causal link between endometriosis and dysmenorrhoea then therapeutic regimens targeted at both symptom relief and monitoring progression of the disease may be more efficacious than excision of endometriotic tissue alone.

While many of our current treatment regimens are effective in some patients, continued improvement in long term health outcomes for women with endometriosis requires a mindset open to critical evaluation.