Exp Clin Endocrinol Diabetes 2005; 113 - V4_39
DOI: 10.1055/s-2005-862823

A common SNP in exon 10 of the follicle stimulating hormone receptor is a major determinant of length and hormonal dynamics of womens menstrual cycles

RR Greb 1, K Grieshaber 1, J Gromoll 2, B Sonntag 1, E Nieschlag 2, L Kiesel 1, M Simoni 2
  • 1Universitätsklinikum Münster, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Münster
  • 2Universitätsklinikum Münster, Institut für Reproduktionsmedizin, Münster

Data from ovarian hyperstimulation cycles suggest that follicle stimulating hormone (FSH) action is modulated by a frequent polymorphism of the FSH receptor gene exchanging Asn to Ser at codon 680. Women homozygous for the Ser680 variant, display an attenuated FSH receptor function. We hypothesized, that the FSH receptor genotype influences also the normal, ovulatory menstrual cycle, with different ovarian and hormonal dynamics.

Follicular growth and pituitary/ovarian hormone levels were monitored from the midluteal phase until the subsequent ovulation in 12 and 9 women genotyped as homozygous Asn/Asn and Ser/Ser, respectively.

The mean area under the curve of FSH levels between the luteo-follicular transition and ovulation was almost 30% greater in subjects with the Ser680 compared to the Asn680genotype (P<0.002) with significantly higher FSH levels between dayLH-18 and dayLH 0 but not before dayLH-18. This was accompanied by significantly lower progesterone, estradiol and inhibin A levels in the luteal-follicuar transition in the Ser680group. A significantly higher number of antral follicles and higher Inhibin B levels were recorded in the Ser680 group but no differences were observed in estradiol levels and growth velocities of dominant follicles during the follicular phase. The mean duration between completion of luteolysis and the subsequent midcycle LH peak was significantly longer in women with the Ser680 compared to Asn680 genotype (13.6±1.01 vs. 11.3±0.61 days, respectively, P<0.05). with a significant difference in total menstrual cycle length (28.7 vs. 25.7 days, respectively, P<0.05).

Therefore, the Ser680 genotype results in a higher ovarian threshold to FSH, a decreased negative feedback signal to the pituitary and a longer duration of the menstrual cycle and might confer an evolutionary advantage, by decreasing the overall number of pregnancies and risks associated with pregnancies.