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Progesterone, micronized

Progestogens — progesterone derivatives

ATC code: G03DA04

Brand names: Prometrium, Crinone, Endometrin

Updated · Methodology

Indications

A

Endometrial protection during estrogen MHT

First line

First-line for endometrial protection during estrogen MHT per NAMS 2022, IMS 2016, BMS 2024. A progestogen is mandatory in women with an intact uterus. Compared with synthetic progestins, micronized progesterone has a more favorable profile for breast cancer risk and thromboembolism. Dose 100–200 mg at bedtime, cyclically (12–14 days per month) or continuously.

Sources

  1. Menopause: The 2022 hormone therapy position statement of The North American Menopause Society (2022)
  2. Climacteric: The impact of micronized progesterone on the endometrium: a systematic review (2016)
  3. Climacteric: 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy (2016)
  4. Post Reproductive Health: Hormone replacement therapy after myocardial infarction: British Menopause Society Tool for Clinicians (2024)
  5. JAMA: Effects of Hormone Replacement Therapy on Endometrial Histology in Postmenopausal Women (1996)
  6. International Journal of Cancer: Breast cancer risk in relation to different types of hormone replacement therapy in the E3N‐EPIC cohort (2004)
A

Menopausal symptoms

First line

In women with an intact uterus on MHT, micronized progesterone provides endometrial protection and offers mild anxiolytic and sleep-promoting effects, often welcomed by patients. French E3N and EPIC data suggest lower breast cancer risk with micronized progesterone in MHT versus synthetic progestins.

As part of MHT combined with estrogens, in women with a uterus.

Sources

  1. Menopause: The 2022 hormone therapy position statement of The North American Menopause Society (2022)
  2. Breast Cancer Res Treat: Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. (2008)
  3. Menopause: Different regimens of menopausal hormone therapy for improving sleep quality: a systematic review and meta-analysis. (2022)
  4. BMJ Open: Breast and endometrial safety of micronised progesterone versus norethisterone acetate in menopausal hormone therapy (PROBES): study protocol of a double-blind randomised controlled trial. (2024)

ICD-10: N95.1 · ICD-11: GA30

B

Threatened miscarriage

Individual decision

Micronized progesterone is recommended in threatened miscarriage for a specific subgroup: women with vaginal bleeding and at least one previous miscarriage ( NG126, FIGO 2023, ). The regimen is vaginal 400 mg twice daily up to 16 weeks of pregnancy. In the PRISM trial (NEJM 2019, over 4000 women) there was no significant effect in the overall population, but in this subgroup live birth increased (roughly from 70 to 73–75%). Outside this subgroup, routine use is not justified. The decision is individualized with an obstetrician.

Sources

  1. New England Journal of Medicine: A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy (2019)
  2. Health Technology Assessment: Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT (2020)
  3. Cochrane Database of Systematic Reviews: Progestogens for preventing miscarriage: a network meta-analysis (2021)
  4. NICE NG126 Ectopic pregnancy and miscarriage: diagnosis and initial management (: NICE NG126 Ectopic pregnancy and miscarriage: diagnosis and initial management (обновление 2021/2023) (2021)

ICD-10: O20.0 · ICD-11: JA40.0

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Alternative reproductive and gynecological medicine

Not recommended

Micronised progesterone is a form of the hormone used in reproductive medicine for well-defined indications, such as luteal-phase support during IVF. In alternative and off-protocol approaches it gets promoted more broadly – as a remedy for any infertility, for anti-ageing, or for general hormonal balancing. No convincing benefit has been shown for these expanded uses, and there is no solid evidence behind them. For a specific problem with conception or the menstrual cycle, the right approach is worked out with a gynaecologist after assessment, not through a one-size-fits-all regimen.

Sources

  1. Cochrane Database of Systematic Reviews: Progestogens for preventing miscarriage: a network meta-analysis (2021)
  2. Am J Obstet Gynecol: Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence. (2020)
  3. Menopause Int: Compounded or confused? Bioidentical hormones and menopausal health. (2011)
  4. PLOS ONE: Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis (2020)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Bio-identical analogue of endogenous progesterone. Binds progesterone receptors in endometrium, myometrium, breast, and CNS. Suppresses endometrial proliferation and stimulates secretory transformation. Through the hepatic metabolite allopregnanolone, exerts anxiolytic and sedative effects — hence oral capsules are taken at bedtime. Oral capsules (Utrogestan, Prajisan) and vaginal forms exist; the vaginal route is often preferable for bioavailability and tolerability.

Safety

Contraindications

  • Hypersensitivity
  • Undiagnosed vaginal bleeding
  • Severe hepatic impairment
  • Thrombophlebitis, thromboembolic conditions
  • Hormone-dependent tumors (relative)
  • Suspected or confirmed ectopic pregnancy
  • Incomplete abortion

Serious adverse effects

  • Thromboembolic events (lower risk than synthetic progestins)
  • Cholestasis, hepatic dysfunction (rare)
  • Allergic reactions

Common adverse effects

  • Drowsiness, dizziness (after oral capsules)
  • Breast tenderness
  • Mood swings
  • Nausea
  • Bloating
  • Menstrual disturbance
  • Vaginal irritation (vaginal forms)

Pregnancy: can you take Progesterone, micronized?

Use in pregnancy (luteal support in ART, prevention of preterm birth with short cervix) is evidence-based. Routine progesterone use in pregnancy without specific indication is not recommended.

Breastfeeding: can you take Progesterone, micronized?

An endogenous hormone present in milk in small amounts. Compatible with breastfeeding.

Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Oral capsules at bedtime — sedation supports sleep and minimizes daytime drowsiness. Vaginal forms 1–3 times daily depending on indication. After insertion, the patient lies down for 30 minutes — improves retention.

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Frequently asked

What is Progesterone, micronized used for?

Progesterone, micronized is evaluated for the following indications with varying evidence strength: Endometrial protection during estrogen MHT (evidence tier A), Luteal phase support in ART (evidence tier A), Menopausal symptoms (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Progesterone, micronized?

Common side effects of Progesterone, micronized (≥ 1 in 100): Drowsiness, dizziness (after oral capsules), Breast tenderness, Mood swings, Nausea, Bloating, Menstrual disturbance. See the Safety section for uncommon and serious reactions.

Is Progesterone, micronized safe during pregnancy?

Use in pregnancy (luteal support in ART, prevention of preterm birth with short cervix) is evidence-based. Routine progesterone use in pregnancy without specific indication is not recommended.

Is Progesterone, micronized compatible with breastfeeding?

An endogenous hormone present in milk in small amounts. Compatible with breastfeeding.

Who should not take Progesterone, micronized?

Progesterone, micronized is contraindicated in: Hypersensitivity; Undiagnosed vaginal bleeding; Severe hepatic impairment; Thrombophlebitis, thromboembolic conditions; Hormone-dependent tumors (relative). Full list in the Safety section.

Other drugs in this group

Red clover (Trifolium pratense), Tibolone, Tongkat ali (Eurycoma longifolia), Ulipristal acetate, Cyproterone acetate, Estradiol, Ethinylestradiol + Gestodene, Levonorgestrel