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Ovarian Age-Related Responsiveness to Human Chorionic Gonadotropin

Departments of Obstetrics and Gynecology (T.P., R.K., J.S.T.) and Clinical Chemistry (A.R.), Oulu University Hospital, FIN-90014 Oulu, Finland

Address all correspondence and requests for reprints to: Prof. Juha S. Tapanainen, Department of Obstetrics and Gynecology, Oulu University Hospital, P.O. Box 5000, University of Oulu, FIN-90014 Oulu, Finland. E-mail: juha.tapanainen{at}oulu.fi.

Human fertility starts to decline after the age of 30 yr, but the change in ovarian endocrine function, i.e. estrogen biosynthesis, with advancing age is not well understood. To study age-related changes in androgen secretion and ovarian capacity to synthesize/release androgens in response to human chorionic gonadotropin (hCG) stimulation, 44 healthy women (aged 20–44 yr) were investigated. Just before a single im injection of 5000 IU hCG, blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), and estradiol (E₂) assays were collected. Further samples were taken at 24, 48, 72, and 96 h. The responses of 17-OHP, A, and T to hCG, i.e. areas under the curves (AUC; 96 h), correlated negatively with age (17-OHP: r = -0.427; P = 0.004; A: r = -0.266; P = 0.081; T: r = -0.354; P = 0.018). Despite a decreasing capacity of the ovaries to secrete these estrogen precursors, the basal serum levels of E₂ remained unchanged. This may be due to the rise in serum FSH levels observed as early as after the age of 25 yr [25 yr: FSH, 5.1 ± 0.5 (±SE) U/liter; >25 yr: FSH, 7.7 ± 0.9 U/liter; P = 0.01]. No correlation was found between age and serum inhibin B levels. In conclusion, ovarian androgen secretion capacity starts to decline as early as before the age of 30 yr. Despite that, circulating E₂ levels remain normal for years, possibly due to compensatory mechanisms, reflected by the gradual rise in serum FSH levels.

This work was supported by grants from the Academy of Finland, the Sigrid Jusélius Foundation, the Research Foundation of Orion Corp., and Oulu University Hospital.

Abbreviations: A, Androstenedione; AUC, area under the curve; E₂, estradiol; hCG, human chorionic gonadotropin; 17-OHP, 17-hydroxyprogesterone; P, progesterone; T, testosterone.

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