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Ovarian Follicular Concentrations of Activin, Follistatin, Inhibin, Insulin-Like Growth Factor I (IGF-I), IGF-II, IGF-Binding Protein-2 (IGFBP-2), IGFBP-3, and Vascular Endothelial Growth Factor in Spontaneous Menstrual Cycles of Normal Women of Advanced Reproductive Age¹

University of Washington (N.A.K., D.E.B., W.J.B., M.R.S.), Seattle, Washington 98105; Northwestern University (T.K.W.), Chicago, Illinois 60208; University of Michigan (V.P.), Ann Arbor, Michigan 48109; and Stanford University (L.C.G.), Stanford, California 94305

Address all correspondence and requests for reprints to: Nancy A. Klein, M.D., 4225 Roosevelt Way NE, Suite 305, Seattle, Washington 98105. E-mail: nklein{at}u.washington.edu

Previous studies indicate that the menstrual cycles of older reproductive age women are characterized by a selective elevation of FSH associated with early development and ovulation of a dominant follicle. Several intraovarian hormones and growth factors have been identified that appear to serve important paracrine roles. The purpose of this study was to examine follicular fluid (FF) hormones and growth factors in the dominant follicle of unstimulated cycles of older, ovulatory women. We aspirated FF from the preovulatory dominant follicle in natural menstrual cycles of older subjects (age, 40–45 yr; n = 20) and younger controls (age, 20–25 yr; n = 19). FF was analyzed for estradiol, progesterone, testosterone, androstenedione, inhibin A and B, total activin A, total follistatin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3, and vascular endothelial growth factor (VEGF) concentrations. We found that the dominant follicles from older women contain normal concentrations of steroids, inhibin A and B, IGF-II, IGFBP-2, and IGFBP-3; increased concentrations of follistatin, activin A, and VEGF; and decreased concentrations of IGF-I. Therefore, under the influence of elevated FSH, the dominant follicle in older women is highly competent in terms of hormone and growth factor secretion. We postulate that elevated FF activin may be related to the early ovulation observed in older women, whereas elevated VEGF may be related to the meiotic spindle abnormalities observed in the oocytes of older reproductive age women.

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