Hyperandrogenism Synergizes With Obesity to Increase the Risk of Hypertensive Disorders of Pregnancy After Frozen...

Hyperandrogenism has been linked to increased preeclampsia risk, but its independent role remains unclear due to confounding by polycystic ovary syndrome (PCOS). This retrospective cohort study investigated whether non-PCOS hyperandrogenism is associated with hypertensive disorders of pregnancy (HDP) and adverse pregnancy outcomes in women undergoing frozen embryo transfer (FET), and whether hyperandrogenism synergizes with overweight/obesity to further increase these risks. We analyzed data from 1556 infertile women who underwent FET at Ruijin Hospital and delivered between January 2015 and December 2022. Participants were classified into four groups based on the presence of hyperandrogenism and overweight/obesity: controls (n = 1201), hyperandrogenism only (n = 116), overweight/obesity only (n = 209), and both hyperandrogenism and overweight/obesity (n = 30). Multivariable logistic regression models were used to evaluate associations with HDP and related adverse outcomes. In multivariable analyses, overweight/obesity was independently associated with an increased risk of gestational diabetes mellitus (GDM) (adjusted odds ratio [aOR] 1.62) and gestational hypertension (aOR 3.45), whereas the coexistence of overweight/obesity and hyperandrogenism was strongly associated with higher risks of preeclampsia (13.3%, aOR 7.53), preterm birth (23.3%, aOR 3.67), and cervical length shortening (CLS) (6.7%) compared to the controls. These results suggest that in women without PCOS undergoing FET, the coexistence of hyperandrogenism and overweight/obesity identifies a high-risk hypertensive phenotype characterized by a substantially elevated risk of preeclampsia. Moreover, our findings may indicate synergistic effects of endocrine and metabolic disturbances on pregnancy-related blood pressure dysregulation and could facilitate early risk stratification for HDP.