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Using Progestins in Clinical Practice
Progestational agents have many important functions, including regulation of the menstrual cycle, treatment of dysfunctional uterine bleeding, prevention of endometrial cancer and hyperplastic precursor lesions, and contraception.
Because of the reported side effects of synthetic analogs called "progestins," there has been interest in replicating the natural hormone for clinical use. Natural progesterone is obtained primarily from plant sources and is currently available in injectable, intravaginal and oral formulations. An oral micronized progesterone preparation has improved bioavailability and fewer reported side effects compared with synthetic progestins. Adolescents and perimenopausal women may require progestational agents for the treatment of dysfunctional uterine bleeding resulting from anovulatory cycles. These agents may also be used in women at risk for endometrial hyperplasia because of chronic unopposed estrogen stimulation. Progestin-only contraceptives can be used in women with contraindications to estrogen; however, efficacy requires rigorous compliance. New progestins for use in combination oral contraceptive pills were specifically developed to reduce androgenic symptoms. It is unclear whether these progestins increase the risk of venous thromboembolic disease. Progestin-only emergency contraception offers a regimen that is more effective than combination oral contraceptive pills, with fewer reported side effects.
Progesterone is a naturally occurring steroid hormone. In nonpregnant women, the main sites of progesterone biosynthesis are the ovaries and the adrenal cortices. Despite the extensive protein binding of serum progesterone, its half-life is only about five minutes. Because of the poor oral absorption of progesterone and its susceptibility to rapid first-pass metabolism in the liver, a variety of oral, injectable and implantable synthetic analogs, called "progestins," have been developed. Progestational agents have many important clinical functions, including regulation of the menstrual cycle, prevention of endometrial hyperplasia, treatment of abnormal uterine bleeding and contraception.
Physiologic Functions of Progesterone
Progesterone plays an important role in postovulatory regulation of the menstrual cycle. Under the influence of luteinizing hormone, the corpus luteum secretes progesterone, which stimulates the endometrium to develop secretory glands. The corpus luteum produces progesterone for approximately 10 to 12 days of the cycle. If a fertilized ovum is not implanted, progesterone and estrogen levels decline sharply, resulting in menstrual bleeding. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy.
Progesterone controls the estrogen-primed endometrial glands by decreasing the number of estrogen receptors, thus preventing endometrial cancer. Progesterone also regulates mitosis in fully differentiated endometrial cells. It now appears that severely atypical endometrial lesions and early well-differentiated endometrial cancer can be reversed with high-dose progestin therapy in women of reproductive age.