Effects of the FSH-β-Subunit Promoter Polymorphism-211G→T on the Hypothalamic-Pituitary-Ovarian Axis in Normally Cycling Women Indicate a Gender-Specific Regulation of Gonadotropin Secretion

Context: A polymorphism in the FSHB promoter (-211G -> T, rs10835638) was found to be associated with decreased FSH, elevated LH, reduced testosterone, and oligozoospermia in males. Although FSH is pivotal for ovarian function, no data on consequences of FSHB -211G -> T are available in females. Objective: We studied the effects of FSHB -211G -> T on the hypothalamic- pituitary-ovarian axis in women. Design and Setting: In a university-based in vitro fertilization unit, women undergoing standardized diagnostics were genotyped and compared with a fertile control group. Patients: The study group consisted of 365 thoroughly characterized women with normal menstrual cycle intervals and proven ovulation, with predominantly male-factor infertility. The independently recruited control group included 438 women with proven fertility and no history of abortions. Main Outcome Measures: Distribution of alleles and genotypes were compared between the study group and controls. In the study group, associations of endocrine parameters with FSHB -211G -> T were assessed. Results: Allele and genotype frequencies were not significantly different between the study population and controls (T-allele: 14.4 vs. 16.6%; TT-homozygotes: 2.5 vs. 3.2%). The FSHB -211G -> T TT-genotype was strongly associated with elevated FSH (TT-homozygosity effect 2.05 U/liter, P = 0.003). LH increased with the number of T-alleles (1.30 U/liter per T-allele, P < 0.001). Additionally, FSHB -211G -> T was associated with reduced progesterone (-1.96 ng/ml per T-allele, P = 0.047). Conclusions: This is a report on phenotypic consequences of FSHB -211G -> T on the hypothalamic-pituitary-ovarian axis in women. The findings, partially contradictory to those in men, point to a gender-specific compensatory mechanism of gonadotropin secretion, probably involving progesterone. (J Clin Endocrinol Metab 98: E82-E86, 2013)