Synthetic progestational hormones and their principle indications in gynecology

Progestins have been synthesized from a variety of sources and have diverse actions and therapeutic applications. No synthetic progestin possesses all the properties of natural progesterone. They are use in place of progesterone because they are not catabolized as rapidly by the liver. Progestins belong to 4 main classes: derivatives of 19-nortestosterone of 19-norprogesterone of 17-hydroxyprogesterone and isomers of progesterone. Progestins have progestational properties especially expressed in modifications of the cervical mucus. Some have estrogenic properties at high doses. All especially the 19-norsteroids have antiestrogenic properties and some have the antiandrogenic properties of progesterone. The 19-norsteroids have androgenic effects and may induce acne seborrhea and an anabolizing effect with weight gain. Progestins like progesterone have antigonadotropic and antiovulatory effects which account for their use in contraception. The metabolic effects of progestins depend on the specific progestin the dose and the duration of use. At high doses progestins disturb hepatic function. Low-dose progestins have very little effect on lipid metabolism while higher doses diminish the high density lipoprotein fraction of cholesterol and exercise a hypotriglyceridic effect. The 19-norsteroids taken orally or injected have a particularly strong effect. Spellacy reports that some progestins such as norgestrel ethinodiol acetate and medroxyprogesterone acetate alter glucose tolerance in 10% of cases. Low dose progestins appear to have very little or no effect on carbohydrate metabolism. Sodium retention has been observed with norethisterone norgestrel ethinodiol diacetate and chlormadinone. Some norsteroids induce and augmentation of hepatic angiotensinogen and plasma renin activity. Studies have shown no modifications of coagulation factors after long durations of use. Only medroxyprogesterone can cause a slight diminution of fibrinolytic activity. In prescribing progestins the pharmacologic effects and desirable or undesirable secondary effects of the agent must be considered. Progestins can be used to establish a regular menstrual cycle in parapubescent girls to treat significant menorrhagia caused by endometrial hyperplasia to treat the relative hyperestrogenism of the premenopause and assure a regular cycle until the menopause and to establish regular cycles in cases of luteal insufficiency or irregular ovulation. Symptomatic hemostatic treatment of metrorrhagia or menorrhagia allows a respite during which clinical explorations can be made. Essential dysmenorrhea results from excessive synthesis of estrogen-dependent endometrial prostaglandins and can be treated by a combination of estrogen and progestin. Progestins are used to treat uterine fibromyomas especially moderately sized myomas in premenopausal women. Certain forms of endometriosis benefit from continuous treatment with a progestin having antiestrogenic properties. Progestins with antiandrogenic properties can be used in treatment of precocious puberty acne seborrhea and hirsutism. Progestins may provide some protection against breast cancer and possibly against benign breast disease as well as against endometrial cancer.