Progestogens — progesterone derivatives
ATC code: G03DA04 (Progesterone, micronized)
Brand names
Prometrium, Crinone, Endometrin
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.
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.
First line
Standard for luteal phase support in ART per 2019. Vaginal forms 200 mg three times daily from embryo transfer day until 8–12 weeks of pregnancy. Cochrane meta-analyses favor the vaginal route over oral and find it comparable to IM injectable.
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.
Individual decision
Progesterone for threatened miscarriage in patients with confirmed fetal heartbeat is debated. The PRISM trial (NEJM 2019, over 4,100 patients) in women with threatened miscarriage and recurrent loss showed a small benefit of vaginal progesterone 400 mg twice daily — a 3 % absolute increase in live birth (70 % → 73 %). No significant effect in patients without recurrent loss. NG126 2021 supports use in this narrow subgroup. In most patients, the cause is embryonic chromosomal abnormality, and progesterone does not help in that scenario.
Not recommended
— Micronized progesterone for premenstrual syndrome in women without MHT indications: Micronized progesterone (Utrogestan, Prajisan) is routinely prescribed in Russia and CIS to reproductive-age women with PMS, irregular cycles, perceived luteal-phase progesterone deficiency, and premenstrual mastalgia – without confirmed luteal-phase pathology or MHT indication. Practice Bulletin 73 (2014), ISPMD Consensus (2017), and Green-top 48 (2016) do not support this. First-line for physical PMS symptoms is luteal-phase SSRIs or drospirenone-containing COCs; for severe PMDD – continuous SSRIs. Progesterone monotherapy for PMS is not listed in these documents.
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.
An endogenous hormone present in milk in small amounts. Compatible with breastfeeding.
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.
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.
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.
An endogenous hormone present in milk in small amounts. Compatible with breastfeeding.
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.