Progesterone

Progesterone is a hormone that occurs naturally in women and is essential for the receptivity of the uterine lining, implantation of the embryo and successful pregnancy. Low progesterone or an inadequate response to progesterone can lead to infertility and pregnancy loss. Progesterone is used in various contraceptive preparations to prevent ovulation and fertilization, and in other formulations to promote and support pregnancy. It is usually administered as a solution for parenteral use or in the form of a capsule.

Pharmacodynamics

Progesterone binds and activates its nuclear receptor, PR, which plays an important role in signaling stimuli that maintain the endometrium during its preparation for pregnancy. The progesterone receptor is a member of the ligand-dependent transcription factor family of the nuclear/steroidal hormone receptor, which is expressed primarily in female reproductive tissue as well as in the central nervous system. As a result of its binding to the steroid hormone progesterone associated with it, the progesterone receptor modulates the expression of genes that regulate the development, differentiation and proliferation of target tissues. In humans, PR is highly expressed in stromal cells (connective tissue cells) during the secretory phase and during pregnancy.

Progesterone can prevent pregnancy by altering the consistency of cervical mucus so that it is unfavorable for sperm penetration and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. When used properly, the first-year failure rate for oral contraceptives with progestin alone is about 0.5%. However, the typical failure rate is estimated to be about 5% due to delayed or missed pills.

Pharmacokinetics

Progesterone is present 96%-99% bound to serum proteins, mainly serum albumin (50%-54%) and transcortin (43%-48%). Progesterone is metabolized mainly by the liver. After oral administration, the major plasma metabolites found are 20 a-hydroxy-Δ4 a-prenolone and 5 a-dihydroprogesterone. Progesterone metabolites are excreted mainly by the kidneys.

Interactions

Since progesterone is a naturally occurring hormone, interactions are not expected.

Only forms of progesterone indicated on the product labeling for pregnant women should be used. Some forms of progesterone should not be used in pregnancy.

Progesterone in high doses is an antifertility drug, and high doses are expected to affect fertility until the end of pregnancy. Progesterone contraceptive should not be used during pregnancy.

Progesterone has been shown to induce or promote the formation of tumors of the ovaries, uterus, breast, and genital tract in animals. However, these findings have limited applicability to humans.

Progesterone may pass into breast milk and should therefore not be taken during lactation.

Toxicological data

LD50 (rat, intraperitoneal): 327 mg/kg-1