Lifestyle modifiable reproductive and metabolic disease in women

A major public health concern and prevention opportunity

Diet and physical activity have profound health impacts across the lifespan. Weight is escalating with reduced physical activity and increased caloric intake. Obesity now causes more ill health than undernutrition and it is driving non-communicable diseases internationally.1 Young women have the highest rate of weight gain, with unprecedented reproductive health implications. Metabolic, mental health and musculoskeletal complications are all increased in obesity, as is malignancy. The greatest effects fall increasingly on low and middle income countries, and on poorer people within all countries, mirroring the underlying socio-economic determinants.1 In Australia, Aboriginal and Torres Strait Islander women present a key risk group. With established obesity being exceedingly difficult to treat, public health obesity prevention initiatives are now prioritised internationally. These initiatives need to be population wide and we align with the National Health and Medical Research Council (NHMRC) Obesity Case for Action and propose that young women of reproductive age, especially those of low socio-economic status and of Aboriginal and Torres Strait Islander background, are an important target group for obesity prevention.

Observational studies highlight the prevalence of excess weight, with less than 40% of the Australian adult population within a healthy weight range,2 similar to many developed countries. The progression towards overweight and obesity at a younger age is equally concerning, with the most accelerated weight gain occurring in those aged 20–40 years.2 Weight gain in women is progressive and estimated to be just under a kilogram per year.3 The highest rate of weight gain occurs in younger reproductive-aged women, confirming that they are a vulnerable, high risk population group. In Aboriginal and Torres Strait Islander women obesity is higher across all reproductive age groups.4

The causes for all women are complex, yet they appear to be primarily environmental, exacerbated by low socio-economic status.1 An increase in the availability of energy-dense convenience food coupled with the fact that 93% of women do not meet the recommended serves of fruit or vegetables are key factors for weight gain. More than half of reproductive-aged women do not meet physical activity recommendations,5 with high risk periods, including pregnancy and postpartum, where physical activity declines further. These factors drive increasing weight, and the reversal of these trends underpins the national recommendations for lifestyle modification and obesity prevention initiatives.

Adverse lifestyles and excess weight have reproductive complications for women, such as polycystic ovary syndrome, infertility, pregnancy complications and impaired breastfeeding. The in utero environment in obese mothers also has significant adverse health implications for the next generation.6 Psychosocial implications of obesity include impact on self-esteem, body image, sexuality, mood and quality of life. Metabolic complications include gestational diabetes mellitus (GDM), metabolic syndrome, hypertension, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).7 Musculoskeletal and respiratory diseases and cancer are also increased.7 Here, we focus on the reproductive and metabolic implications of excess weight — highlighting that those at the highest metabolic risk are women presenting early with reproductive complications — providing prevention opportunities.

Reproductive health implications of excess weight in women, such as polycystic ovary syndrome (PCOS), are often poorly appreciated. PCOS, which is increasingly prevalent, is now estimated at 12–21%8 and arises from a complex interaction between genetic and environmental factors. Recent genome-wide association screening has identified overexpression of multiple genes, including those linked to insulin resistance and diabetes.9 Further studies are now being undertaken. Inherited factors may include polycystic ovary morphology, hyperandrogenism, insulin resistance or insulin signalling defects.10 These factors are exacerbated by obesity, which in itself is influenced by genetic and environmental factors.

Diagnosis of PCOS is based on oligo- or anovulation, hyperandrogenism, and polycystic ovaries on ultrasound, yet metabolic features are integral and independent of weight status. Women with PCOS have higher rates of obesity, which further exacerbates metabolic risk. PCOS is underpinned by intrinsic insulin resistance and hyperandrogenism, both of which are exacerbated by obesity.8

PCOS has key metabolic features, including metabolic syndrome, T2DM, increased cardiovascular risk profiles and increased CVD.8 Women with PCOS have threefold higher GDM prevalence rates and fourfold higher T2DM with earlier onset, compared with women without PCOS.11 Weight loss and exercise improve clinical outcomes and are the recommended first-line treatment for this syndrome.8 PCOS presents in adolescence and provides an early opportunity for targeted prevention of weight gain and metabolic features in this high risk group.8 Aboriginal and Torres Strait Islander women also have higher rates of PCOS and of obesity with significant health implications and a high priority for healthy lifestyles.8

Obesity also affects fertility and pregnancy. Young women with obesity are more likely to experience difficulties with conception, largely related to oligo- or anovulation and decreased oocyte quality.12 Obesity decreases pregnancy rates and live births and reduces responsiveness to assisted reproduction.13 Lifestyle interventions and weight loss often restore ovulation and may improve outcomes with ovulation induction. However, benefits in assisted reproduction in obese women remain controversial,14,15 potentially strengthening the argument for obesity prevention.

Concomitant with increasing weight in reproductive years, larger proportions of women are entering pregnancy overweight or obese — 60% of women gain excessive gestational weight and 65% retain excess weight postpartum.16 Maternal overweight and obesity have adverse maternal and neonatal outcomes in pregnancy with lifelong impacts on infants of obese mothers. Maternal outcomes include increased risk of miscarriage, GDM, hypertension, pre-eclampsia, induction of labour and caesarean delivery.17 Infants are at increased risk of birth defects, perinatal death, macrosomia, birth trauma and obesity in childhood. Recent large population-based cohort studies highlight that a reduction in pre-pregnancy weight is associated with improved pregnancy outcomes; however, there are no randomised controlled trials in this area.6

Additionally, excess gestational weight gain has adverse implications in pregnancy, linked to poor maternal and neonatal outcomes, independent of the underlying maternal body mass index.16 International initiatives to limit excess gestational weight gain show modest weight benefits; however, the impact on maternal and neonatal complications is limited to date.5 These complications highlight the public health imperative for healthy lifestyles before and during pregnancy.18

Metabolic complications of obesity are arguably the most recognised. The Australian Diabetes, Obesity and Lifestyle Study — the first national study of the prevalence and impact of diabetes in Australia — reported that 6.8% of women over the age of 25 years had T2DM and that an additional 15.4% of women either had impaired glucose tolerance or impaired fasting glucose.19 Aboriginal and Torres Strait Islander women experience this risk at an even younger age than the national average. For example, in the Northern Territory, in Aboriginal and Torres Strait Islander women of reproductive age (15–34 years), the rates of pre-existing diabetes are as high as 6.1% and the rates of impaired glucose tolerance are 8%.20 The rates of T2DM in Australia overall have doubled over 20 years,19 largely attributable to rising obesity, sedentary lifestyle and poor dietary habits. Lifestyle intervention has been shown to be at least as effective as pharmacological interventions in preventing T2DM.21

Metabolic syndrome occurs in 11–27% of Australian women, depending on the diagnostic criteria, and is higher in Aboriginal and Torres Strait Islander women at 28–41%.22 Women with metabolic syndrome have an eightfold increased risk of CVD.23 A report in 2010 by the Australian Institute of Health and Welfare noted that 37% of female deaths in Australia were attributable to CVD, making it the leading cause of death for Australian women.24 A significant proportion of Australian women have metabolic risk factors for CVD: 48% have dyslipidaemia, 27% have hypertension, 7% have T2DM19 and 15% smoke regularly. These risk factors are largely modifiable and can be optimised with a healthy lifestyle to reduce the risk of CVD.

Early reproductive complications in women herald a high risk and earlier onset of subsequent metabolic complications in those with PCOS, GDM, pre-eclampsia and high gestational weight gain. This presents an opportunity for early recognition of women at risk from a young reproductive age and for early intervention.

Overall, the increasing economic and public health costs of obesity underpin a global consensus on the urgency and priority of low cost, effective population obesity prevention strategies, with a clear need for early intervention. The NHMRC Obesity Case for Action, on evidence translation in obesity, recommends that reproductive-aged women before conception and during pregnancy are a priority target group.16 This aligns with the recommendations of the World Health Organization and the United States Institute of Medicine highlighting this life stage as a vital window for intervention to reduce non-communicable diseases. Capitalising on this in young women provides prevention opportunities for both mothers and babies. Also, as the mother retains a central role in family lifestyle behaviour25 and parental modelling influences children’s lifestyle behaviour, targeting young reproductive-aged women may have broader family and community impacts.26 Initiatives in this area also must focus on Aboriginal and Torres Strait Islander women at even higher risk.16

The rationale for obesity prevention is clear. It requires lower effort and cost compared with treating established obesity, needs only minor energy balance adjustments and has broad population relevance. Effective system-wide strategies are needed to prevent weight gain, with the potential for major benefits to physical, metabolic and reproductive health. Moving forward, learnings from Australia’s exceptional public health track record on smoking and road deaths should be heeded. A broad multifaceted public health approach is needed with targeted interventions, education, support, approaches to enabling systems and ultimately regulation, if we are to halt the rising obesity rates and adverse implications for chronic disease. We propose that within the national obesity prevention strategy, reproductive-aged women, especially Aboriginal and Torres Strait Islander women, are a vital target group in improving the health and wellbeing of Australian women and their families.