This review examines a number of areas of postconceptive fertility regulation, focusing on promising new antiprogestational agents. Pregnancy is dependent upon the availability of progesterone for the uterus and its withdrawal results in the breakdown of the secretory endometrium. Its availability can be interferred with at several levels and the new methods which allow for progesterone inhibition must be tested for possible defeminizing properties or for serious side effects. In the evaluation of contragestational agents, several areas must be taken into consideration--assessment of biological activities, dose requirements and mode of action, duration of effects, route of administration, and drug tolerance and side effects. The failure to maintain progesterone in the blood at levels required for pregnancy maintenance may be due to a decrease in progesterone secretion by the ovary or to an increased rate of metabolism and excretion of circulating progesterone. The various substances discussed do either 1 or the other; however even when a compound is known to result in a decrease in the rate of progesterone secretion, the process by which it does this may not be known. Prostaglandins seem to affect myometrial contraction, luteinizing hormone releasing hormones can inhibit steroid production or interfere with LH binding to its receptor, and immunization against hCG is a successful immunological approach to conception. Lithospermic acid is another substance which interferes with gonadotropin support of the ovary and has good potential. Other compounds that interfere with progesterone secretion act to inhibit steroidogenesis in the ovary and placenta; such substances include aminoglutethimide, oxymetholone, trilostane, azastene, and danazol. Another progesterone-suppression method would remove a sufficient amount of progesterone from the body to cause endometrium involution and promote contractility of the myometrium. Progesterone antagonists include ORF 9361, R3434, Anordrin, ORF 3858, and other estrogens, triazole compounds, ORF 5513, trichosanthin, and zoapatanol.
|Original language||English (US)|
|Number of pages||14|
|Journal||Research frontiers in fertility regulation : RFFR / PARFR|
|State||Published - Feb 1 1981|
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