We use essential cookies (authentication, your saved goals/stack) by default. With your permission we’ll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more about cookies
Progesterone — bioidentical (micronized) progesterone; Prometrium / Utrogestan
The endogenous steroid hormone, sold as a prescription bioidentical (micronized) drug (Prometrium / Utrogestan). It is the essential ENDOMETRIAL-PROTECTION half of menopausal hormone therapy — it opposes estrogen to prevent endometrial hyperplasia/cancer — and is used for luteal support in IVF and to treat secondary amenorrhea. Oral micronized progesterone is also widely used OFF-LABEL for menopausal SLEEP and hot flashes, because a metabolite (allopregnanolone) is GABA-active and sedating. Randomized trials support these specific indications; in early-pregnancy bleeding (PRISM) benefit was limited to women with prior miscarriages. It is NOT a general healthy-population enhancer, and the breast-cancer signal from older synthetic progestins (WHI) should not be assumed for micronized progesterone, where data suggest it is more breast- and metabolically neutral but longer-term evidence is limited. Prescription-only and NOT a dietary supplement; OTC 'progesterone creams' absorb erratically and are not equivalent.
Prescription medication — not a dietary supplement
Progesterone is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Progesterone studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1976–2026 with a typical study size of 310 participants.
Based on 563 studies · 76 meta-analyses · 455 RCTs · 28,478 total participants
Confidence
High confidenceBy outcome
For its specific indications the evidence is real and randomized: the PEPI trial established that adding a progestogen (including micronized progesterone) protects the endometrium from estrogen-driven hyperplasia, a Cochrane review of 94 RCTs supports progesterone for IVF luteal-phase support, and placebo-controlled RCTs show oral micronized progesterone improves menopausal sleep (Caufriez 2011) and reduces vasomotor symptoms (Hitchcock & Prior 2012). In early-pregnancy bleeding (PRISM) benefit was confined to women with prior miscarriages. But these benefits are indication-specific — not a general healthy-population enhancer — it is prescription-only with dose-related sedation, mood and breast-tenderness trade-offs, and long-term breast-outcome data on MICRONIZED (vs synthetic) progesterone remain more limited, keeping the score moderate.
589 rigorous studies
482 randomized trials · 83 meta-analyses · 24 systematic reviews
Our evidence rating for Progesterone is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
196 trials ongoing or recruiting · 684 completed on ClinicalTrials.gov
211 of the completed trials have posted results
Registered trials show research momentum for Progesterone, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Progesterone is the endogenous steroid hormone (pregn-4-ene-3,20-dione) produced chiefly by the corpus luteum after ovulation and by the placenta in pregnancy.
It prepares and stabilizes the endometrium, supports early pregnancy, and acts in the brain partly through its neurosteroid metabolite allopregnanolone, a positive allosteric modulator of the GABA-A receptor — which is why oral progesterone is sedating.
The pharmaceutical entry here is bioidentical micronized progesterone (brand Prometrium / Utrogestan): the same molecule as the body's own, micronized and oil-suspended to improve absorption, and taken orally (also used vaginally in assisted reproduction). It is a prescription drug, not a dietary supplement.
Its evidence is genuinely strong but indication-bounded.
First and most important, progesterone is the essential endometrial-protection component of menopausal hormone therapy: estrogen given alone to a woman with a uterus drives endometrial hyperplasia and raises endometrial-cancer risk, and adding a progestogen prevents that.
The PEPI trial randomized postmenopausal women to estrogen alone or estrogen plus a progestogen (including micronized progesterone) and showed that the progestogen arms protected the endometrium where unopposed estrogen produced hyperplasia — the foundational reason any woman with a uterus on systemic estrogen also needs progesterone.
Second, progesterone is standard luteal-phase support in IVF/assisted reproduction: a large Cochrane systematic review (van der Linden 2015, 94 RCTs) found luteal-phase support with progesterone improved pregnancy outcomes versus placebo.
Third, oral micronized progesterone is widely used off-label for menopausal sleep and vasomotor symptoms.
A randomized, placebo-controlled crossover study (Caufriez 2011) found progesterone prevented sleep disturbances in postmenopausal women and restored normal sleep architecture, and a placebo-controlled RCT in healthy postmenopausal women (Hitchcock & Prior 2012) found oral micronized progesterone reduced vasomotor symptoms (hot flushes/night sweats) versus placebo.
Fourth, in early-pregnancy bleeding the large PRISM trial (Coomarasamy 2019, NEJM) found vaginal micronized progesterone did NOT significantly improve live births overall, but a prespecified subgroup with one or more previous miscarriages did benefit — an honest, narrow result, not a blanket 'progesterone prevents miscarriage' claim.
Progesterone also treats secondary amenorrhea by inducing a withdrawal bleed. A crucial nuance runs through all of this: micronized (bioidentical) progesterone is not the same as the older synthetic progestins.
The Women's Health Initiative breast-cancer signal came from a combined regimen using a synthetic progestin (medroxyprogesterone acetate, MPA), and observational data (the E3N cohort, Fournier 2008) found that estrogen combined with micronized progesterone was associated with little or no increased breast-cancer risk over several years, in contrast to estrogen plus synthetic progestins — so the WHI signal should be attributed to synthetic progestins, not assumed for micronized progesterone, while acknowledging that long-term randomized breast-outcome data on micronized progesterone are more limited.
The trade-offs are real: oral progesterone commonly causes drowsiness, dizziness, and fatigue (it is taken at bedtime for exactly this reason), and can cause mood changes, bloating, and breast tenderness.
Oral micronized progesterone also has low oral bioavailability because of extensive first-pass hepatic metabolism, which is part of why it is dosed relatively high and at night and why vaginal dosing is preferred for IVF.
Finally, the OTC 'progesterone creams' sold as wellness products absorb erratically and unreliably and are not equivalent to prescription oral micronized progesterone.
The score reflects strong, randomized evidence for its specific indications — endometrial protection, IVF luteal support, sleep, and vasomotor relief — set against the facts that these benefits are indication-specific rather than a general enhancement, that it is prescription-only with sedation/mood trade-offs, and that the long-term breast-safety picture for micronized progesterone, while reassuring relative to synthetic progestins, is not as deeply evidenced.
Progesterone binds the nuclear progesterone receptor and drives secretory transformation of the estrogen-primed endometrium. This opposes estrogen's proliferative drive — the basis for endometrial protection in HRT, luteal support in IVF, and the withdrawal bleed used to treat secondary amenorrhea.
Oral progesterone is metabolized to allopregnanolone, a neurosteroid that positively modulates the GABA-A receptor. This sedating, anxiolytic action explains the improvement in sleep and the drowsiness side effect — and is why oral micronized progesterone is taken at bedtime.
Oral micronized progesterone undergoes extensive first-pass hepatic metabolism, giving it low and variable oral bioavailability. This is why it is micronized and oil-suspended, dosed relatively high and at night, and why vaginal administration is preferred for IVF luteal support.
How Progesterone works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
This is the core indication — a progestogen (micronized progesterone or an alternative) is REQUIRED to protect the endometrium. Do not take systemic estrogen alone if you have a uterus.
Progesterone luteal support is standard; vaginal dosing is commonly used. Follow the fertility clinic's protocol.
PRISM found benefit only in those with one or more previous miscarriages — not a blanket treatment. Use only on obstetric advice.
Caution or avoid — discuss individualized risk. The WHI breast-cancer signal came from a SYNTHETIC progestin (MPA); micronized progesterone appears more breast-neutral observationally, but long-term randomized data are limited.
Not supported — benefits are indication-specific, not a general enhancer, and OTC progesterone creams are not equivalent to prescription micronized progesterone.
Oral progesterone is sedating via its allopregnanolone metabolite; combining it with alcohol or other CNS depressants can add to drowsiness and impairment.
Strong enzyme inducers can accelerate progesterone metabolism and lower its levels, potentially reducing endometrial protection in HRT.
Not an adverse interaction but the intended pairing — in women with a uterus, progesterone is added specifically to oppose estrogen and protect the endometrium. Estrogen should not be taken alone in such women.
Tip: Driven by the sedating allopregnanolone metabolite of oral progesterone. Take at bedtime; avoid driving soon after dosing and avoid combining with alcohol.
Tip: Common and usually dose-related; often settles with time or a dose/regimen adjustment by the clinician.
Tip: Some women feel low or irritable on progesterone (especially sequentially). Discuss dose, route (vaginal vs oral), or progestogen choice with the prescriber.
Tip: Generally mild; report persistent or severe headache, which can warrant review.
Tip: Common when starting HRT; persistent or heavy/unexpected bleeding should be evaluated to rule out other causes.
Tip: Thrombosis risk in HRT is driven mainly by the estrogen and route; seek urgent care for leg swelling/pain, chest pain, or breathlessness. Assess personal/family clot risk before starting.
Progesterone has an evidence score of 4.4/10 — emerging evidence based on 313 indexed studies, including 1 meta-analysis. The endogenous steroid hormone, sold as a prescription bioidentical (micronized) drug (Prometrium / Utrogestan). It is the essential ENDOMETRIAL-PROTECTION half of menopausal hormone therapy — it opposes estrogen to prevent endometrial hyperplasia/cancer — and is used for luteal support in IVF and to treat secondary amenorrhea. Oral micronized progesterone is also widely used OFF-LABEL for menopausal SLEEP and hot flashes, because a metabolite (allopregnanolone) is GABA-active and sedating. Randomized trials support these specific indications; in early-pregnancy bleeding (PRISM) benefit was limited to women with prior miscarriages. It is NOT a general healthy-population enhancer, and the breast-cancer signal from older synthetic progestins (WHI) should not be assumed for micronized progesterone, where data suggest it is more breast- and metabolically neutral but longer-term evidence is limited. Prescription-only and NOT a dietary supplement; OTC 'progesterone creams' absorb erratically and are not equivalent. Representative study: PMID 26148507.
The commonly studied dose of Progesterone is Prescription-only and clinician-directed — this is a hormonal prescription drug, not a self-administered supplement, and dosing is indication-specific. For context only: for endometrial protection in menopausal hormone therapy, oral micronized progesterone is commonly ~100 mg daily (continuous-combined) or ~200 mg for ~12 days a month (sequential), taken at bedtime. For IVF luteal support, vaginal progesterone is typically used (e.g. ~90–200 mg twice or three times daily) under a fertility clinic. Doses for sleep/vasomotor use in trials were ~300 mg at bedtime. Oral micronized progesterone is dosed at night because it is sedating and because first-pass metabolism gives it low oral bioavailability.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Progesterone is before bed. Take it with food. Oral micronized progesterone is taken at BEDTIME because its GABA-active metabolite allopregnanolone is sedating — taking it earlier causes daytime drowsiness/dizziness.
Progesterone is generally safe at recommended doses, with a few precautions worth noting. The most commonly reported side effects are drowsiness / dizziness / fatigue, breast tenderness, mood changes / low mood / irritability. Use caution if any of these apply to you: Use without a prescription / without medical supervision — progesterone is a prescription hormonal drug, not a dietary supplement; Known or suspected breast cancer or other progesterone-sensitive cancer (per product labeling); Active or history of venous thromboembolism, arterial thromboembolic disease, or known thrombophilia (combined HRT context).
Quercetin
Likely helpsFlavonoid with senolytic and anti-inflammatory properties — supports immune defense, allergy relief, and exercise performance.
Soy Isoflavones
Likely helpsPlant compounds with weak estrogenic effects that support menopausal symptoms, bone health, and cardiovascular function.
DHEA
Probably helpsAdrenal hormone precursor that declines with age, supporting hormone balance, energy, and body composition.
Melatonin
Likely helpsRegulates the circadian clock to reduce sleep onset time — most effective at low doses (0.3-1mg) for jet lag and rhythm disorders.
Explore: Best supplements for Women's Health
Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 569 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
Tap node to isolate • Pinch to zoom • Tap edge for research