progesterones

Progesterone is a steroid hormone of the pregnane class produced mainly by the corpus luteum of the ovary, with placental production during pregnancy. It is also synthesized in smaller amounts by the adrenal glands. In medicine, the term progesterone broadly refers to natural progesterone and to synthetic compounds known as progestins or progestogens, which mimic its effects.

Biochemistry and mechanism: Progesterone is derived from cholesterol and acts primarily through intracellular progesterone receptors (PR-A and PR-B). Binding of progesterone to these receptors regulates gene expression, promoting the secretory transformation of the endometrium and preparing the uterus for implantation. It also helps maintain pregnancy by reducing uterine contractility and provides negative feedback on the hypothalamic-pituitary axis, reducing gonadotropin release.

Physiology: During the menstrual cycle, luteal progesterone dominates the second half, supporting a receptive endometrium. In pregnancy, placental progesterone supports the uterus and prevents contractions.

Medical uses: Progesterone or progestins are used for contraception (in combination with estrogens or alone in progestin-only methods), to treat abnormal uterine bleeding and endometriosis, and in hormone replacement therapy to counter estrogen effects during menopause. In assisted reproduction, luteal phase support may use exogenous progesterone. Formulations vary and include oral, vaginal, and transdermal routes.

Progestins versus natural progesterone: Synthetic progestins differ in receptor binding and pharmacokinetics; some have androgenic or glucocorticoid activity in addition to progestogenic effects. The choice of agent depends on the indication and patient risk factors.

Safety: Common side effects include fatigue, mood changes, weight gain, and breast tenderness. Thromboembolic risk is higher with estrogen-containing regimens; liver disease, undiagnosed vaginal bleeding, and pregnancy are contraindications for progesterone therapies.