Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome

Context: Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. Objective: To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Design and methods: Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Results: Circulating concentrations of testosterone (T) (P= 0.026), free T (FT) (P= 0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P= 0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S ≥ 11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Conclusion: Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation.