Context: Single nucleotide polymorphisms altering FSH action (FSHB -211G>T, FSHR -29G>A, and FSHR 2039A>G) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls.
Objective: To investigate whether genetic polymorphisms altering FSH action affect serum levels of female reproductive hormones and breast development as early as during minipuberty.
Design: Longitudinal study.
Setting: Population-based cohort study.
Participants: A total of 402 healthy girls at 3 months of age.
Main outcome measures: Analyses of single nucleotide polymorphisms by PCR using Kompetitive Allele Specific PCR genotyping assays; identification of glandular breast tissue by palpation and measurement of the diameter. Serum levels of anti-Müllerian hormone, FSH, LH, estradiol, inhibin B, and sex hormone-binding globulin were assessed by immunoassays.
Results: FSHR -29G>A was associated with both FSH and anti-Müllerian hormone levels with an A allele effect size of -0.8 IU/L (P = .005) and 1.4 nmol/L (P = .003), respectively. FSHR 2039A>G correlated with breast tissue size with a negative additive effect of minor alleles (P = .021), whereas the effect on estradiol levels was only present in homozygotes. FSHB -211T carriers had smaller breast tissue size than girls who without a minor allele; GT+TT 10.5 (confidence interval 9.4-11.5) mm vs GG 12.1 (confidence interval 11.4-12.8) mm, P = .014.
Conclusions: Our study indicates that 3 genetic polymorphisms altering FSH action, especially FSHR -29G>A and FSHR 2039A>G, affect female hormone profile and glandular breast tissue development already during minipuberty. Thus, genetic variations of FSH signaling appear to determine the individual set point of the hypothalamic-pituitary-gonadal axis already early in life.