Objective: To investigate whether genetic polymorphisms in the FSH pathway (FSHB- 211 G -> T and FSHR 2039 A -> G) affect serum levels of FSH, antimullerian hormone (AMH), and age at pubertal onset. FSH secretion and FSH signal transduction are enhanced in carriers of FSHB GG and FSHR AA, respectively. Furthermore, the combined genotype FSHB GG_FSHR AA is the most favorable for male gonadal function, but the effect of this genotype has never been evaluated in peripubertal females. AMH is a marker of ovarian function and is negatively correlated with FSH in prepubertal girls.

Design: Secondary analyses of a prospective cohort study.

Setting: General community.

Patient(s): We examined 78 healthy girls twice yearly for 6 years; the median age at baseline was 9.3 years.

Intervention(s): None.

Main Outcome Measure(s): Hormone levels were measured by immunoassays, and DNA was isolated from blood and genotyped by restriction fragment length polymorphism of polymerase chain reaction- amplified regions.

Result(s): Carriers of FSHB GG+FSHR AA had higher FSH before pubertal onset (median 2.2 vs. 1.5 IU/L) and lower AMH (13.8 vs. 19.4 pmol/L) comparedwith carriers of other genotypes. In crude analysis, girls with FSHBGG+FSHRAA entered puberty earlier, 9.7 vs. 10.6 years. However, the difference was no longer statistically significant after including interval-, right-, and left- censored data in a probit analysis.

Conclusion(s): The combined effect of FSHB GG+FSHR AA may potentiate the FSH pathway, which increases serum levels of FSH and reduces AMH. Common variations in genes regulating follicle growth may affect AMH levels independently of the number of resting primordial follicles. (Fertil Steril (R) 2013;100:1089- 95. (C) 2013 by American Society for Reproductive Medicine.)