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.
BACKGROUND
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.


METHODS
Menstrual cycle was monitored from the midluteal phase through ovulation until the consecutive menstruation.


METHODS
The study was conducted at the University research center.


METHODS
Women homozygous for the Asn680 (n = 12) and Ser680 (n = 9) variants with normal menstrual cycles volunteered for the study.


METHODS
There were no interventions.


METHODS
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.
Greb
R R
RR
Department of Obstetrics and Gynecology, Münster University Hospital, Domagkstrasse 11, D-48149 Münster, Germany.
Grieshaber
K
K
Gromoll
J
J
Sonntag
B
B
Nieschlag
E
E
Kiesel
L
L
Simoni
M
M
D000293:Adolescent; D000328:Adult; D005091:Exons / Q000235:genetics; D025461:Feedback, Physiological / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008597:Menstrual Cycle / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011962:Receptors, FSH / Q000235:genetics*
D011962:Receptors, FSH