Professor Juha Tapanainen is the Chair of the University Department of Obstetrics and Gynecology, University of Helsinki, Finland, the Past Chairman of ESHRE; he is also a member of the Centre for Research Excellence in Polycystic Ovary Syndrome (CRE in PCOS) International Advisory Panel. Juha tells us about his latest findings.
The majority of women with polycystic ovary syndrome (PCOS) are overweight or obese, and present with risk factors for several metabolic derangements including hypertension, dyslipidemia, metabolic syndrome, cardiovascular diseases (CVDs) and gestational and type 2 diabetes (T2DM)1, 2. Whether these unfavorable hormonal and metabolic derangements and outcomes translate into higher risk for CVD events later in life is not known. For instance, many of the risk factors are known to contribute and promote the development of CVDs, but so far there is not strong evidence supporting the fact that the risk for CVD is related to PCOS per se.
PCOS being common diagnosis, it is crucial to evaluate the benefits of screening for metabolic derangements (dyslipidemina, glucose tolerance) in this population, especially in times when the resources of healthcare systems are scarce in many countries. In a large population-based follow-up cohort, the Northern Finland Birth Cohort 1966, our group could show that PCOS per se significantly increased the risk of T2DM in overweight/obese but not in normal weight women with PCOS. The increase in weight in early adulthood was the most important risk factor associated with the development of T2DM3. Furthermore, in a large cross-over study including 1327 women with PCOS from Finland, Sweden, Norway and Denmark, we could show that lipid profiling was required only when women with PCOS develop T2DM or hypertension. Inversely, lipid profiling rarely changed the clinical care of low risk PCOS patients before the age of 35, especially in the normal-weight women4. These results support the view that OGTT-screening should be targeted to overweight/obese women with PCOS rather than to all women with PCOS. Furthermore, the extensive monitoring of lipid profiles suggested by international PCOS guidelines does not seem to be necessary in low risk PCOS women.
The inhibition of cholesterol biosynthesis by statins could decrease androgen synthesis in ovarian theca cells by decreasing the availability of cholesterol. Given the worsened lipid profile in PCOS, the question is whether or not statin therapy could effectively relieve hyperandrogenism bringing additional benefit particularly in women with PCOS. Indeed, several studies have been designed to approach this question, and many of them have revealed a decrease in serum testosterone levels.
Our research groups in Oulu and Helsinki, Finland, conducted a randomised, double-blind, placebo-controlled study on atorvastati5. Women with PCOS were treated with atorvastatin (20 mg/d) or placebo for six months. We did not observe any improvement in serum androgen levels, but atorvastatin therapy improved chronic inflammation and lipid profile. However, insulin resistance worsened significantly. As overweight/obese women with PCOS have an increased risk of developing T2DM, our recommendation is that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease, and not only because of PCOS.
More than 100 million women of fertile age use oral contraceptives worldwide and combined hormonal contraceptives (CHCs) are commonly used in PCOS to improve menstrual irregularity and to manage hyperandrogenic symptoms, acne and hirsutism, as CHCs effectively reduce androgen action on sebaceous glands and hair follicles6. Despite the efficacy of CHCs in treating these symptoms the results of some7,8,9,10 but not all11 previous studies suggested that oral CHCs worsen glucose metabolism, while transdermal and vaginal contraceptives was not found to have any effect12,13,14,15.
To further clarify the role of CHCs in glucose metabolism our group investigated the effect of alternative administration routes of CHCs on androgen secretion, chronic inflammation, glucose tolerance and lipid profile16. In this randomised open-label study healthy women used oral contraceptive pills, transdermal contraceptive patches or contraceptive vaginal rings continuously for nine weeks. As expected androgen profile improved in all three study groups, but insulin sensitivity was reduced independently of the administration route. Although the long-term consequences of these metabolic alterations remain unclear, there is increasing data that a long-term use of CHCs may lead to prediabetes and even to T2DM. The reliable contraception is always a priority, but the present findings emphasise the importance of monitoring glucose metabolism during CHC use and the possibility of considering alternative contraception methods in women with high risk of metabolic derangements.
These studies suggest that screening for disorders of lipid or glucose metabolism should be targeted to high risk women with PCOS with high risk metabolic profile, mainly in overweight or obese women. Moreover, when treating patients with PCOS, we should always consider whether the medication is justified and, if so, whether the chosen drug is the best possible for the patient. When and if the medication is indicated despite its possible side effects a regular follow-up should be programmed, especially for women with increased metabolic risks. References are here.
Professor Tapanainen’s co-authors on this article are Dr Laure Morin-Papunen, Associate Professor, Head of Reproductive Medicine; and Dr Terhi Piltonen, Associate Professor, Consultant, Department of Obstetrics and Gynecology, Oulu University Hospital, Finland.