Polycystic ovary syndrome and risk of pre-eclampsia: A national register-based cohort study.

OBJECTIVE: To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre-eclampsia. DESIGN: Nationwide register-based cohort study. SETTING: Sweden. POPULATION: Nulliparous women with PCOS (n = 22 947) and non-PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997-2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti-androgenic drugs during 2005-2017 (n = 2301 among PCOS women). METHODS: The risk of pre-eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors. MAIN OUTCOME MEASURES: Overall pre-eclampsia. Early/late (delivery <34/≥34 weeks) pre-eclampsia. Pre-eclampsia with or without a small-for-gestational-age (SGA) infant. RESULTS: Compared with controls, women with PCOS had a 29% increased risk of pre-eclampsia (predictor adjusted OR 1.29, 95% CI 1.20-1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre-eclampsia seemed stronger than its association with late pre-eclampsia (predictor adjusted OR 1.64 (95% CI 1.33-2.02) and 1.26 (95% CI 1.17-1.37). Additionally, the association seemed slightly stronger between PCOS and pre-eclampsia in women with an SGA infant than without. CONCLUSIONS: Women with PCOS face an increased risk for pre-eclampsia, especially early pre-eclampsia and pre-eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre-eclampsia.

Pregnancy outcome in women with polycystic ovary syndrome in relation to second-trimester testosterone levels.

RESEARCH QUESTION: Do women with polycystic ovary syndrome (PCOS) have higher testosterone levels during pregnancy and what role does high testosterone play in the development of obstetric complications? DESIGN: Retrospective cohort study from Uppsala University Hospital, Sweden. The study population consisted of women with PCOS (n = 159) and a comparison group of women without PCOS matched for body mass index (n = 320). Plasma testosterone levels were measured in the early second trimester by liquid chromatography with tandem mass spectrometry, and women with PCOS were grouped into tertiles according to their testosterone levels. Possible associations with obstetric complications, maternal metabolic factors and offspring birth weight were explored by multivariable logistic and linear regression models. RESULTS: Compared with women who do not have PCOS, women with PCOS had higher total testosterone (median 1.94, interquartile range [IQR] 1.21-2.64 versus 1.41, IQR 0.89-1.97; P < 0.001), and free androgen index (median 0.25, IQR 0.15-0.36 versus 0.18, IQR 0.11-0.28; P < 0.001). Women with PCOS who had the highest levels of testosterone had increased risk for preeclampsia, even when adjusted for age, parity, country of birth and smoking (adjusted OR 6.16, 95% CI 1.82 to 20.91). No association was found between high testosterone in women with PCOS and other obstetric complications. CONCLUSIONS: Women with PCOS have higher levels of total testosterone and free androgen index during pregnancy than women without PCOS matched for body mass index. Preliminary evidence shows that women with PCOS and the highest maternal testosterone levels in early second trimester had the highest risk of developing preeclampsia. This finding, however, is driven by a limited number of cases and should be interpreted with caution.

Pregnancy and neonatal complications in women with polycystic ovary syndrome in relation to second-trimester anti-Müllerian hormone levels.

RESEARCH QUESTION: An association has been found between high anti-Müllerian hormone (AMH) levels during pregnancy and the development of polycystic ovary syndrome (PCOS)-like phenotypic traits in mouse offspring. The aim of this study was to determine whether AMH levels are associated with maternal testosterone levels, and whether high AMH concentration influences the risk of developing PCOS-related adverse pregnancy outcomes. DESIGN: Maternal serum AMH, testosterone and sex hormone binding globulin levels were measured in blood samples taken in early second-trimester pregnancies from women with PCOS (n = 159) and healthy controls matched for body mass index (n = 320). Possible associations with preeclampsia, gestational hypertension, gestational diabetes, preterm birth and birthweight was explored by logistic and linear regression models. RESULTS: Women with PCOS had higher AMH, higher total testosterone levels and higher free androgen index than controls (P < 0.001 for all three parameters). Among women with PCOS, high testosterone levels (B = 2.7; ß = 0.26; P = 0.001) and low first trimester body mass index (B = -0.5; ß = -0.17; P = 0.043) remained independently associated with AMH. High AMH levels were associated with decreased risk of gestational hypertension (adjusted OR 0.55; 95% CI 0.34 to 0.87), but no association was found with other adverse pregnancy outcomes or birthweight. CONCLUSIONS: Women with PCOS had higher AMH levels during pregnancy compared with controls, but high AMH was not associated with increased risk of adverse pregnancy outcomes or birthweight.