Metabolism of endogenous and exogenous reproductive hormones

During the ovulatory menstrual cycle, estradiol is produced by the functioning ovary. Ninety-five percent of circulating serum estradiol originates from the ovary with the maturing follicle or corpus luteum. Estradiol production rates increase by at least fivefold from baseline in a natural ovarian cycle [1], with serum levels ranging from about 30 pg/mL during menses to about 200 pg/mL at ovulation. In contrast to estradiol, less than half of estrone is produced by direct ovarian secretion. Estrone is converted from estradiol by 17beta-estradiol dehydrogenase in the liver and other tissues [2]. Estrone is also produced by the conversion of estrone sulfate to estrone by the adrenal, and by the aromatization of androstenedione whose concentration also peaks at mid-cycle. There is a major decrease in serum estrogens in the perimenopause and in the immediate postmenopausal period [3] with little change occurring in the subsequent years. After the final menstrual period, there is very little ovarian contribution to serum concentrations of sex steroids. Women with a history of bilateral oophorectomy show little difference in serum levels of estrone, estradiol, or testosterone when compared with women undergoing a natural menopause [4]. Androstenedione levels were actually higher in women with oophorectomy that their menopausal cohort. This is perhaps counterintuitive [5], but highlights the very low metabolic activity of the postmenopausal ovary.