The aging ovary.

During reproductive life, ovarian steroid biosynthesis is gonadotropin dependent and occurs in theca and granulosa cells. In the menopausal ovary, there is atresia of ovarian follicles, with sparing of the androgen-producing theca-interstitial cell component. The aging ovary, therefore, produces significantly reduced amounts of estrogen, with continued, though decreased, androgen production. After menopause, ovarian estradiol biosynthesis is minimal, with circulating estrogen being derived principally from peripheral aromatization of ovarian and adrenal androgens. Androgen biosynthesis from the adrenal gland, in addition to that from the ovary, decreases with age. Although ovarian androgen production declines with age, there is not an abrupt decrease as is seen with ovarian estrogen levels at the time of menopause. The biological activity of these steroids, either before or after menopause, depends on the amount of steroid available in the unbound fraction. To this end, sex hormone-binding globulin (SHBG) levels are an important determinant of hormone action. Not only does the concentration of SHBG influence the biological effect of testosterone and estradiol, but these steroids also regulate SHBG concentrations.