Progesterone

Mechanism

Progesterone binds the nuclear progesterone receptor isoforms PR-A and PR-B, which act as ligand-activated transcription factors on progesterone response elements. In the oestrogen-primed endometrium this converts proliferative endometrium to secretory endometrium, which is the basis of the labelled endometrial-hyperplasia indication. At usual doses it also suppresses pituitary gonadotrophin secretion, preventing follicular maturation and ovulation. Its hepatic metabolites include allopregnanolone, a positive allosteric modulator of the GABA-A receptor, which is the published mechanistic account of the sedation reported with oral dosing; no trial on file measured that link directly.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

• Prevention of endometrial hyperplasia in non-hysterectomised postmenopausal women receiving conjugated oestrogens — the FDA-labelled indication.
• Induction of withdrawal bleeding in secondary amenorrhoea — the second FDA-labelled indication, and the indication of the intramuscular oil injection alongside abnormal uterine bleeding due to hormonal imbalance.
• Vasomotor symptoms have been studied in randomised placebo-controlled trials in perimenopausal women; the 2023 Phase III Canada-wide trial (n=189) missed its primary endpoint (rate ratio 0.79, 95% CI 0.54–1.15, p=0.222), with secondary measures of perceived night sweats and sleep favouring progesterone.
• Vaginal progesterone has been studied for prevention of preterm birth in women with a sonographic short cervix; an individual-patient-data meta-analysis of randomised trials reported reduced preterm delivery and neonatal morbidity.
• Breast cancer incidence on combined menopausal hormone therapy has been studied observationally by progestagen type; the E3N cohort reported a relative risk of 1.00 (0.83–1.22) for oestrogen plus progesterone versus 1.69 (1.50–1.91) for oestrogen plus other progestagens.

Half-life, storage & sport

Elimination half-life

22.78 h (terminal t½, oral 200 mg soft micronised capsule) (human, oral) — study. From a randomised open-label crossover study in 16 healthy postmenopausal women (aged 45–60) comparing hard and soft micronised capsules by oral and vaginal route. Same study, same population: hard capsule oral t½ 26.12 h; vaginal t½ 20.66 h (soft) and 20.21 h (hard). The US label reports absorption only — oral Cmax 17.3 ± 21.9 ng/mL at 100 mg, 38.1 ± 37.8 ng/mL at 200 mg, 60.6 ± 72.5 ng/mL at 300 mg, Tmax 1.5–2.3 h, 96–99% protein bound, hepatic metabolism to pregnanediols and pregnanolones with biliary and urinary excretion of conjugates — and states no half-life. Older literature quotes a much shorter elimination half-life for intravenous progesterone; those are different routes and are not interchangeable with the figure above. No intramuscular half-life is on file here.

Storage

not on file — no stability record found.

In sport (WADA)

not recorded as a yes or no — Progesterone is an endogenous steroid but is not an anabolic androgenic steroid and is not a hormone or metabolic modulator as those classes are defined on the Prohibited List. Not listed under S1 (anabolic agents) or S4 (hormone and metabolic modulators) of the current WADA Prohibited List. the list WADA publishes a prohibited list, not a permitted list, so absence is inferred from the list rather than stated by WADA. We could not extract the machine-readable text of the current list PDF during this review; the class structure was read from WADA's Prohibited List page. Treat the scope above as unverified against the PDF text.

The half-life on file is 22.8 h, measured orally. No dosing schedule could be read from this record, so the curve below is one dose drawn from the moment it is given. Nothing here says how often it is repeated.

The rise is not modelled and the axis is not a blood level. No absorption rate constant and no volume of distribution are on file, so each dose appears at full height the instant it is given, and the axis is percent of this compound's own peak.

Reported adverse effects

• Boxed warning on the US label: oestrogens with progestins should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative reported increased myocardial infarction, stroke, invasive breast cancer, pulmonary embolism and deep vein thrombosis — but that trial used conjugated oestrogens plus medroxyprogesterone acetate, not micronised progesterone, and the label states the relevance of the findings to other products has not been established.

  reversibility not on file

• Endometrial-protection trial, 200 mg with conjugated oestrogens: headache 31%, breast tenderness 27%, depression 19%, dizziness 15%, abdominal bloating 12% (US label).

  reversibility not on file

• Secondary amenorrhoea trial, 400 mg: dizziness 24%, abdominal pain 20%, headache 16%, breast pain 16% (US label).

  reversibility not on file

• Sedation and dizziness are why the labelled oral regimens are taken at bedtime; the label directs taking the capsule with water while standing if swallowing is difficult.

  reversibility not on file

• The capsules contain peanut oil and are contraindicated in peanut allergy.

  reversibility not on file

• Labelled contraindications: undiagnosed abnormal genital bleeding; known, suspected or past breast cancer; active deep vein thrombosis or pulmonary embolism; active or recent arterial thromboembolic disease; liver dysfunction or disease; known or suspected pregnancy (for the menopausal indications).

  reversibility not on file

• In the 2023 perimenopausal RCT no serious adverse events occurred; mild-to-moderate side effects were numerically more frequent on progesterone (22 vs 8) without reaching significance.

  reversibility not on file

Literature on file 9

• human RCT
  Oral micronized progesterone for perimenopausal night sweats and hot flushes: a Phase III Canada-wide randomized placebo-controlled 4 month trial (Scientific Reports, 2023) graded on: a randomised trial — “randomized placebo-controlled 4 month trial”
• human RCT
  Pharmacokinetics of hard micronized progesterone capsules via vaginal or oral route compared with soft micronized capsules in healthy postmenopausal women: a randomized open-label clinical study graded on: a randomised study — “randomized open-label clinical study”
• human observational
  Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and meta-analysis of individual patient data graded on: a synthesis of human studies — “systematic review”
• human observational
  Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study graded on: an observational human design — “cohort”
• human RCT
  FDA approval graded on: an FDA approval (), which requires adequate and well-controlled human investigations — “”

Not graded

4 citations whose study design could not be read from the title. Left ungraded rather than guessed at.

• not graded
  PROMETRIUM (progesterone) capsules — US prescribing information (DailyMed SPL)
• not graded
  Progesterone Injection USP in Sesame Oil, for intramuscular use — US label
• not graded
  Author Correction to the Phase III Canada-wide oral micronized progesterone trial (Scientific Reports, 2024)
• not graded
  The Prohibited List — World Anti-Doping Agency

Identity

Also called

• micronised progesterone
• micronized progesterone
• P4
• Utrogestan
• Prometrium

Listed prices 21

What 4 shops we track listed for Progesterone, read from their own public catalogues on 2026-09-14. We take no commission on these and they are not ranked by any payment — how vendors are scored.