Androgenic alopecia associated with the HSD3B1 (1245a>c) in overweight women with polycystic ovarian syndrome

Abstract

HSD3B1 (1245A>C) has been mechanistically linked to polycystic ovarian syndrome (PCOS) because it encodes an altered enzyme that augments dihydrotestosterone synthesis from non-gonadal precursors. We postulated that women inheriting the HSD3B1 1245C allele would exhibit specific phenotypic variances in women with PCOS. A cross-sectional study conducted in a university-associated tertiary care medical center. A total of 472 Taiwanese women with PCOS were enrolled according to the Rotterdam criteria. HSD3B1 genotype was determined in all patients to correlate with various phenotypic outcomes, including androgenic alopecia (AGA), acne, hirsutism, obesity, hypertension, and laboratory evidences of androgen excess and dyslipidemia. Databases of 1000 Genomes Project and Taiwan BioBank were applied to compare the frequency of the C allele of HSD3B1 among different populations. The presence of AGA was higher in women with HSD3B1 variant AC or CC genotype (23.2%), compared to that with wild-type AA genotype (13.5%, p= 0.068). The association between HSD3B1 genotype and the presence of AGA is especially stronger in overweight women with PCOS (OR: 3.53, P=0.009) but not in those normal-weight women with PCOS (OR: 1.087, P=0.883). In PCOS women with AGA, compared to those without AGA, we found a significantly higher BMI (26.9 vs. 23.0 kg/m2, p=0.0004), lower HDL-C levels (47.5 vs. 50.5 mg/dL, p=0.008), higher triglyceride (TG) levels (119.9 vs. 88.4 mg/dL, p<0.0001), lower sex hormone binding globulin (SHBG) levels (30.6 vs. 37.3 nmol/L, p=0.002), and higher proportion of hypertension (17.6 vs. 9.0%, p=0.049). The strong association between the presence of AGA and the HSD3B1 AC/CC genotypes still existed (OR: 2.312, P=0.021) by using stepwise logistic regression analysis after considering confounders as age, BMI, levels of fasting sugar, HDL-C, TG, free androgen index and SHBG, and the presence of hypertension. The frequency of the C allele among Taiwanese women with PCOS was 6.4%, which was much lower than that observed in the individuals of European ancestry (34%), but similar to the prevalence of that observed in the general Taiwanese population (6.6%). The presence of AGA in women with PCOS associates with the higher risk of metabolic disturbances as higher BMI and TG levels, higher risk of hypertension, but lower HDL and SHBG levels. Although the frequency of HSD3B1 1245C allele are not significant different between women with PCOS and normal population, the inheritance of such variant type in overweight women with PCOS comprise significantly higher risk of AGA phenotype than those women with wild type of HSD3B1.