Polycystic ovary syndrome (PCOS) and obesity– two main threats on women’s reproductive and metabolic health

The work of our research team focuses on polycystic ovary syndrome (PCOS), which is the most common hormonal disorder in fertile aged women, affecting 10-18% of them. The syndrome is characterized by hyperandrogenism and chronic oligo-anovulation and is also the most common cause of anovulatory infertility. PCOS is not only a gynecological disorder, as it associates also with several co-morbidities, such as type 2 diabetes, hypertension, dyslipidemia, stroke, and endometrial cancer as well as psychological burden. Obesity and weight gain together with oxidative stress and the insulin resistance typical of the syndrome seem to be the pivotal derangements in PCOS, but the role of hyperandrogenism as a metabolic risk is still under debate.

Decreasing insulin resistance by the way of weight loss or by the use of insulin sensitizing drugs, such as metformin, has been shown to improve both the reproductive and metabolic disorders linked to the syndrome.

The oral contraceptive pills (OCPs) are commonly used to treat the most disabling symptoms of PCOS, hirsutism or oligoamenorrhoea. OCPs are known to induce some unfavourable metabolic effects in healthy women, especially on glucose metabolism and oxidative stress. The women with PCOS may have an increased risk for adverse metabolic outcomes when exposed to OCPs, but there are no studies on the metabolic effects of different preparations in PCOS in a long run.

Recent meta-analyses have also suggested that PCOS per se is associated with an increased risk of pregnancy complications, such as hypertensive disorders and gestational diabetes, but the respective significance of obesity, weight gain through life, hyperandrogenism and the syndrome per se regarding these risks remains to be clarified.

PCOS is a complex disorder influenced by both environmental and genetic factors, but genetic factors explain less than 10 % of the cases. The prevalence of PCOS varies (5 to 18%) between different ethnic groups, suggesting that there may be true ethnic differences, translating into different incidence and severity of clinical, endocrinal and metabolic disturbances and their correlates. Responses to treatment modalities may also differ. Ethnicity- specific guidelines are therefore needed to identify anthropometric thresholds for appropriate screening, diagnosis as well as preventive action and treatment in different ethnic groups.

Anti-Müllerian hormone (AMH) is expressed from growing antral follicles and its serum levels strongly correlate with antral follicle count. Women with PCOS display 2-3 times higher AMH levels than those observed in other women and AMH may have an important role in the pathophysiology of PCOS. AMH levels associate with insulin resistance, but the results regarding the relationship between metabolic risk factors and AMH remain controversial. AMH levels are also commonly used as an indicator for ovarian reserve and as a predictor for age of menopause. The process of ovarian aging (expressed by AMH decline) and of emergence of cardiovascular risk factors seem to occur simultaneously in the perimenopausal transition. However, up to now, there are few studies on the relationship between AMH serum levels with reproductive lifelong capacity on one hand, and with metabolic risks on the other hand, either in healthy women or in women with PCOS.

The prevalence of obesity has doubled during the last ten years and seems to continue rising. Especially childhood obesity is a huge increasing health problem. Obesity in adulthood has been widely shown to increase the risk of infertility and childlessness but there is limited data concerning the association of childhood growth patterns and obesity with fertility later in life. Our projects aim to clarify the association of obesity and weight gain from birth until age 46 with reproductive capacity both in men and women, focusing especially on the impact of weight development in infancy and adolescence.

Main focuses of our research team

• The metabolic and reproductive effects of insulin sensitizers agents in PCOS
• The respective roles hyperandrogenism, obesity and weight gain through life in the development of the syndrome and of its reproductive and metabolic complications, including pregnancy complications and health of the newborn
• The impact of hormonal contraceptives on metabolic risks linked to PCOS
• The role of AMH in reproductive and metabolic aging
• The impact of obesity and weight gain from birth until age 46 regarding reproductive capacity in men and women, independently of PCOS
• The realization of comparative ethnic studies to establish specific cut-off for hormonal and metabolic parameters in PCOS women of different ethnicities

Materials and methods

Most of our epidemiological studies are performed in the 1966 and 1986 Northern Finland Birth Cohorts (http://www.oulu.fi/nfbc/node/44315). In addition, we have several collaboration projects including Nordic and Indian populations of women with PCOS. Last, we have run and are still running several RCTs and follow-up studies.