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

J Clin Endocrinol Metab. 2005 Aug;90(8):4866-72. doi: 10.1210/jc.2004-2268. Epub 2005 May 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Exons / genetics
  • Feedback, Physiological / genetics
  • Female
  • Genotype
  • Humans
  • Menstrual Cycle / genetics*
  • Menstrual Cycle / physiology
  • Polymorphism, Single Nucleotide*
  • Receptors, FSH / genetics*

Substances

  • Receptors, FSH