Progesterone
Progesterone is a natural female sex hormone used as bioidentical replacement in menopausal hormone therapy (in combination with estradiol), in luteal-phase support during IVF, and in selected gynaecological indications. Available as oral micronised capsules and vaginal gels, capsules or inserts.
- Chemical formula
- C21H30O2
- CAS number
- 57-83-0
- ATC code
- G03DA04
- Molecular weight
- 314.46 g/mol
- Drug class
- Progestogen / hormone replacement
- Also known as
- Prometrium, Utrogestan, Crinone, Endometrin
What is it?
Progesterone is the principal endogenous progestogen, produced primarily by the corpus luteum and placenta. The clinically used form is micronised progesterone, which improves oral absorption of the natural molecule. Marketed as Prometrium (US, Canada) and Utrogestan (Europe) for oral capsules, Crinone gel and Endometrium inserts for vaginal use. Generic micronised progesterone is widely available. It is on the WHO Essential Medicines List as part of HRT.
Mechanism of action
Progesterone binds to progesterone receptors and modulates gene expression in reproductive and other tissues. In menopausal hormone therapy, it counteracts estrogen-driven endometrial proliferation, preventing hyperplasia and endometrial cancer in women with an intact uterus receiving estradiol. It also has metabolites with mild GABAergic activity (allopregnanolone), explaining sedation that often accompanies oral dosing.
Pharmacokinetics
Oral micronised progesterone is rapidly absorbed but undergoes extensive first-pass metabolism, producing relatively low and variable plasma levels and significant sedative metabolites. Vaginal administration bypasses first pass and produces stable, locally elevated endometrial levels with lower systemic exposure. Half-life of plasma progesterone is short (a few hours); vaginal forms maintain effective endometrial concentrations through once or twice daily dosing.
Indications
Progesterone is approved for endometrial protection in postmenopausal women receiving estrogen, secondary amenorrhoea, luteal-phase support in IVF/ART, and prevention of preterm birth in women with short cervix (vaginal forms). According to current menopause guidelines, micronised progesterone is preferred over synthetic progestins (medroxyprogesterone, norethindrone) because of evidence suggesting lower breast cancer and cardiovascular risk.
Safety profile
Common adverse effects include drowsiness (especially with bedtime oral dosing), dizziness, breast tenderness, mood changes and breakthrough bleeding. Vaginal forms may cause local irritation or discharge. Sedation from oral dosing is often used therapeutically by recommending evening administration. According to evidence to date, micronised progesterone in HRT carries less breast cancer signal than older synthetic progestins, though long-term combined HRT still carries a small increased risk.
Products containing this ingredient
Frequently asked questions
Why is micronised progesterone preferred over older progestins for HRT? ▾
Observational studies of European HRT cohorts suggest that micronised progesterone is associated with a lower breast cancer signal and more favourable cardiovascular profile than synthetic progestins like medroxyprogesterone acetate. According to current menopause guidelines, micronised progesterone is preferred when available, though evidence quality is mixed.
Why is progesterone often taken at bedtime? ▾
Oral micronised progesterone undergoes extensive first-pass metabolism, generating allopregnanolone and other GABAergic metabolites that often cause drowsiness. Bedtime dosing turns this into a clinical advantage by aiding sleep. According to the prescribing information, the sedative effect is usually mild but is enough that morning dosing or driving immediately after dosing is generally avoided.
Is vaginal progesterone the same as oral? ▾
Same molecule, different pharmacology. Vaginal progesterone produces high local endometrial levels with lower systemic exposure, which is preferred for IVF luteal-phase support, prevention of preterm birth and some HRT regimens. Oral produces more systemic exposure including sedative metabolites. According to current practice, the choice depends on the clinical indication.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.