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 (E₂) was ≤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 E₂, 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). E₂ 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 E2 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 E₂ (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 E₂ 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.