Endocrine Abstracts

Background: Recently, a single nucleotide polymorphism (SNP) in the FSHB promoter (−211G>T, rs10835638) was found to be associated with lower serum FSH levels and oligozoospermia in males. In contrast, a SNP in the FSH-receptor gene (FSHR, 2039A>G, rs6166) was previously shown to be associated with FSH levels in women only.

Subjects and methods: One thousand two hundred and thirteen male partners in infertile couples without known causes for male infertility and 365 thoroughly characterised women with normal menstrual cycle intervals and proven ovulation were genotyped for both SNPs by TaqMan assay. Associations between genotypes and clinical parameters were evaluated.

Results: In males, the FSHB −211G>T T-allele showed significant dosage effects for FSH (−0.51 U/l per T-allele), LH (0.28 U/l) and bi-testicular volume (−3.2 ml). In contrast, The FSHR 2039A>G G-allele exhibited non-significant trends for associations with higher FSH and reduced testicular volumes. However, in the combined model, FSHR 2039A>G significantly modulated the more dominant effect of FSHB −211G>T on serum FSH and testicular volume among the T-allele carriers.

In contrast, in women the FSHB −211G>T T-allele was associated with both higher FSH (0.99 U/l) and LH levels (1.30 U/l) and with reduced progesterone (−1.96 ng/ml). The FSHR 2039A>G G-allele was associated with higher FSH levels (0.35 U/l per G-allele). Numbers were too small to calculate combined SNP effects.

Conclusions: The SNPs in the FSHB and FSHR genes have significant impact on reproductive parameters in both sexes and the combinatory effects of variants in hormone and receptor are an unparalleled example in endocrinology. Gender specific mechanisms, probably involving progesterone in females, may explain the partially opposing findings concerning FSHB −211G>T. Oligozoospermic patients carrying unfavourable variants affecting FSH action may benefit from FSH treatment and women undergoing IVF may receive tailored ovarian stimulation in the future.