Ragnheiður Valdimarsdóttir: Polycystic ovary syndrome and pregnancy complications: Focus on hyperandrogenism and comorbidity

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women, affecting their lives in many ways. PCOS is characterised by ovulatory dysfunction, polycystic ovary morphology and hyperandrogenism, either clinical or biochemical. Women with PCOS face a higher risk of obstetric complications than women without PCOS. There are many factors that contribute to these complications, such as metabolic disturbances, insulin resistance, chronic inflammation, hyperandrogenism and factors related to infertility.

The overall aim of the research presented in this thesis was to study factors that might affect the association between PCOS and pregnancy complications. The thesis consists of matched cohort studies based on data from the Uppsala Biobank of Pregnant Women (Papers I and II) and national register-based cohort studies (Papers III and IV). In the first two studies, we included women with PCOS (n = 159) and BMI-matched controls (n = 320), and the aim was to study the effect of high anti-Müllerian hormone (AMH) and testosterone on pregnancy complications. The third study (n = 138 219) explored whether the association between PCOS and preeclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of preeclampsia. In the fourth study (n = 281 806), the aim was to explore association and risk estimates for pregnancy outcomes in women with either or both PCOS and gestational diabetes mellitus (GDM).

The main results were that women with PCOS have higher levels of AMH and testosterone and a higher free androgen index during second trimester pregnancy than non-PCOS controls. High AMH levels were not associated with adverse pregnancy outcome or birthweight. PCOS women with the highest testosterone levels had the highest risk for preeclampsia. Compared to non-PCOS controls, women with PCOS have increased risk of preeclampsia, especially the more severe subtypes of preeclampsia, early onset or with a birth of an infant born small for gestational age. With available data, we were unable to determine whether hyperandrogenism affects the risk of preeclampsia. The combination of PCOS and GDM exacerbates the risk of adverse pregnancy outcomes for both mother and infant compared with women with either PCOS or GDM alone.

In conclusion, the research presented in this thesis adds important information about the association of PCOS and the more severe subtypes of preeclampsia and underpins the importance of an increased awareness of PCOS in antenatal care along with early screening for diabetes and hypertensive disorders.