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.

Progesterone
Clinical data
Trade namesPrometrium, Utrogestan, Endometrin, others
Other namesP4; Pregnenedione; Pregn-4-ene-3,20-dione
AHFS/Drugs.comMonograph
MedlinePlusa604017
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.Tooltip aqueous solution)
Intrauterine (IUDTooltip intrauterine device)
Drug classProgestogen; Antimineralocorticoid; Neurosteroid
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityOral: <2.4%
Vaginal (micronized insert): 4–8%
Protein binding98–99%:
Albumin: 80%
CBGTooltip Corticosteroid-binding globulin: 18%
SHBGTooltip Sex hormone-binding globulin: <1%
• Free: 1–2%
MetabolismMainly liver:
5α- and 5β-reductase
3α-Tooltip 3α-Hydroxysteroid dehydrogenase and 3β-HSDTooltip 3β-Hydroxysteroid dehydrogenase
20α-Tooltip 20α-Hydroxysteroid dehydrogenase and 20β-HSDTooltip 20β-Hydroxysteroid dehydrogenase
Conjugation
17α-Hydroxylase
21-Hydroxylase
CYPsTooltip CYP (e.g., CYP3A4)
MetabolitesDihydroprogesterones
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
IVTooltip Intravenous injection: 3–90 minutes
ExcretionBile and urine
Identifiers
  • (8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC21H30O2
Molar mass314.469 g·mol−1
3D model (JSmol)
Specific rotation[α]D25 = +172 to +182° (2% in dioxane, β-form)
Melting point126 °C (259 °F)
  • CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C
  • InChI=InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1 N
  • Key:RJKFOVLPORLFTN-LEKSSAKUSA-N Y
  (verify)

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.

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