Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: A study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles

This study sought to compare circulating and follicular fluid (FF) concentrations of dimeric inhibin A and B utilizing specific two-site ELISAs for these hormones in normal older and younger ovulatory women. Methods: Normally ovulating women age 40-45 (n=10) and 20-25 (n=13) were studied throughout the follicular phase with daily blood sampling, transvaginal ultrasound examinations, and dominant follicle aspiration. When the dominant follicle reached a mean diameter of 16 mm or serum estradiol (E(2)) was greater than or equal to 550 pmol/L, 10,000 IU of hCG was administered intramuscularly followed 32 hours later by transvaginal follicle aspiration. Serum and FF samples were analyzed for E(2), FSH, and inhibin A and B. Daily hormone levels were compared by ANOVA, and mean results were compared using t-tests. Results: Older women developed a dominant follicle sooner, meeting criteria for hCG cycle day 10.6+/-0.4 vs. 14.5+/-1.0 p<0.001. As expected, the older group had higher maximal serum FSH concentrations compared to the younger women (11.4+/-0.5 vs. 8.0+/-0.4 IU/L, p<0.001). We compared hormone concentrations from days - 1 to 3 (where day 0 = day of maximal FSH concentration). E(2) concentration was higher in the older women (p=0.002), and there was no significant difference in inhibin A secretion (p=0.61). In contrast, mean inhibin B concentration was significantly lower in the older women (p=0.04). On the day of aspiration of the dominant follicle, serum inhibin B was decreased in the older subjects (42.6+/-6.5 vs. 153.1+/-53 pg/ml, p=0.02), whereas older subjects had higher levels of inhibin A (106+/-16 vs. 60.4+/-9.4 pg:ml, p=0.04) and similar E(2) levels (665+/-35.2 vs. 687+/-92 pmol/L, p=0.83). There were no differences in FF concentrations of inhibin B (164+/-31 vs. 174+/-37 ng/ml, p=0.85), inhibin A (317.7+/-38 vs. 248+/-57 ng/ml, p=0.16), or E(2) (2074+/-294 vs. 2474+/-338 nmol/L, p=0.82) in the older and younger women. Conclusion: Follicular phase inhibin B secretion is decreased in older ovulatory women who demonstrate a monotropic FSH rise, whereas inhibin A secretion is similar to that in younger women. The dominant follicle in these older women appears to be normal in terms of FF E(2) and inhibin content. We speculate that decreased inhibin B secretion most likely reflects a diminished follicular pool in older women and may be an important regulator of the monotropic FSH rise.