A Common Single Nucleotide Polymorphism in Exon 10 of the Human Follicle Stimulating Hormone Receptor Is a Major Determinant of Length and Hormonal Dynamics of the Menstrual Cycle

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Abstract
Context: FSH is essential for follicular maturation. Data from ovarian hyperstimulation cycles suggest that FSH action is attenuated by a frequent single nucleotide polymorphism of the FSH receptor gene exchanging Asn for Ser at codon 680. Objective: We hypothesized that the FSH receptor genotype influences menstrual cycle dynamics. Design: Menstrual cycle was monitored from the midluteal phase through ovulation until the consecutive menstruation. Setting: The study was conducted at the University research center. Subjects: Women homozygous for the Asn680 (n = 12) and Ser680 (n = 9) variants with normal menstrual cycles volunteered for the study. Interventions: There were no interventions. Main Outcome Measurements: Follicular growth, serum LH, FSH, estradiol, progesterone, inhibin A, inhibin B and antimullerian hormone were measured. Results: During the luteo-follicular transition, serum levels of estradiol, progesterone, and inhibin A were significantly lower, and FSH started to rise earlier in the Ser680/Ser680 group. FSH levels were steadily and significantly higher, and the mean area under the FSH curve was 31% greater in this group (P < 0.002). No differences were observed in estradiol, inhibin B, and growth velocities of dominant follicles. The time from luteolysis to ovulation was significantly longer in women with the Ser680/Ser680 (13.6 ± 1.01 d) compared with Asn680/Asn680 (11.3 ± 0.61 d, P < 0.05) genotype with a significant difference in total menstrual cycle length (29.3 vs. 27.0 d, respectively; P < 0.05). Conclusions: The FSH receptor Ser680/Ser680 genotype is associated with higher ovarian threshold to FSH, decreased negative feedback of luteal secretion to the pituitary during the intercycle transition, and longer menstrual cycles.

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