Study of medroxyprogesterone: a long-acting injectable female contraceptive agent.
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A reliable radioimmunoassay (RIA) for the measurement of ethinylestradiol (EE2) in plasma after the separation of norethindrone (NET) by column chromatography has been developed. The procedure involves diethyl ether extraction, followed by celite column partition chromatography to separate NET from EE2. An antiserum against ethinylestradiol-7-(3-thiopropionic acid)-bovine serum albumin conjugate was employed. Tritiated EE2 was used as the radioligand. The separation of bound from free 3H-EE2 was carried out with dextran-coated charcoal. This RIA procedure was used to measure plasma EE2 at specified time intervals in three women following oral administration of a tablet containing EE2 (0.12 mg) and NET (1.0 mg). The results show that EE2 is rapidly absorbed after oral administration. Peak concentrations of plasma EE2 were reached within 1.0 to 1.5 hours and then declined biphasically. The EE2 alpha phase half-life values in three subjects were 1.5, 2.8 and 3.8 hours. By comparison, the half-life values for the beta phase for the same three women were 6.2, 12.3 and 14.5 hours, respectively. Plasma samples were also analyzed for NET by RIA. The half-life values for the beta phase for EE2 and NET in the three subjects were similar.
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Superactive GnRH agonists represent a new class of pharmacologic agents that inhibit reproductive function in both men and women when administered chronically. These hormonal drugs are being tested extensively as both male and female contraceptive agents, as a treatment for prostate cancer, and as a new treatment for idiopathic precocious puberty. Other potential uses include treatment for endometriosis, hirsutism, polycystic ovarian disease, and severe intractable androgen-related acne. This chapter reviews the effects of GnRH agonists on gonadotropin and steroid hormone secretion in both men and women, and assesses the potential of these agents in the varied clinical uses delineated above.
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