Progesterone (medication)
Progesterone (P4) is a medication and naturally occurring steroid hormone. It is a progestogen and is used in combination with estrogens mainly in hormone therapy for menopausal symptoms and low sex hormone levels in women. It is also used in women to support pregnancy and fertility and to treat gynecological disorders. Progesterone can be taken by mouth, vaginally, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device used for birth control also exist in some areas of the world.
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Trade names | Prometrium, Utrogestan, Endometrin, others |
Other names | P4; Pregnenedione; Pregn-4-ene-3,20-dione |
AHFS/Drugs.com | Monograph |
MedlinePlus | a604017 |
Routes of administration | • By mouth (capsule) • Sublingual (troche) • Topical (cream, gel) • Vaginal (capsule, tablet, gel, suppository, ring) • Rectal (suppository) • IM injection (oil solution) • SC injection (aq. soln. ) • Intrauterine (IUD ) |
Drug class | Progestogen; Antimineralocorticoid; Neurosteroid |
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Bioavailability | Oral: <2.4% Vaginal (micronized insert): 4–8% |
Protein binding | 98–99%: • Albumin: 80% • CBG : 18% • SHBG : <1% • Free: 1–2% |
Metabolism | Mainly liver: • 5α- and 5β-reductase • 3α- and 3β-HSD • 20α- and 20β-HSD • Conjugation • 17α-Hydroxylase • 21-Hydroxylase • CYPs (e.g., CYP3A4) |
Metabolites | • Dihydroprogesterones • Pregnanolones • Pregnanediols • 20α-Hydroxyprogesterone • 17α-Hydroxyprogesterone • Pregnanetriols • 11-Deoxycorticosterone (and glucuronide/sulfate conjugates) |
Elimination half-life | • Oral: 5 hours (with food) * Sublingual: 6–7 hours • Vaginal: 14–50 hours • Topical: 30–40 hours • IM: 20–28 hours • SC: 13–18 hours • IV : 3–90 minutes |
Excretion | Bile and urine |
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Formula | C21H30O2 |
Molar mass | 314.469 g·mol−1 |
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Specific rotation | [α]D25 = +172 to +182° (2% in dioxane, β-form) |
Melting point | 126 °C (259 °F) |
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Progesterone is well tolerated and often produces few or no side effects. However, a number of side effects are possible, for instance mood changes. If progesterone is taken by mouth or at high doses, certain central side effects including sedation, sleepiness, and cognitive impairment can also occur. The medication is a naturally occurring progestogen and hence is an agonist of the progesterone receptor (PR), the biological target of progestogens like endogenous progesterone. It opposes the effects of estrogens in various parts of the body like the uterus and also blocks the effects of the hormone aldosterone. In addition, progesterone has neurosteroid effects in the brain.
Progesterone was first isolated in pure form in 1934. It first became available as a medication later that year. Oral micronized progesterone (OMP), which allowed progesterone to be taken by mouth, was introduced in 1980. A large number of synthetic progestogens, or progestins, have been derived from progesterone and are used as medications as well. Examples include medroxyprogesterone acetate and norethisterone. In 2020, it was the 158th most commonly prescribed medication in the United States, with more than 3 million prescriptions.