Medroxyprogesterone
Medroxyprogesterone acetate (MPA) is a synthetic progestin used as oral therapy (Provera) for menstrual cycle disorders and as part of menopausal HRT, and as a long-acting injectable contraceptive (Depo-Provera) given every 12 weeks. It has anti-estrogenic and anti-gonadotrophic effects.
- Chemical formula
- C22H32O3
- CAS number
- 520-85-4
- ATC code
- G03DA02
- Molecular weight
- 344.49 g/mol
- Drug class
- Progestin
- Also known as
- Provera, Depo-Provera, MPA, Medroxyprogesterone Acetate
What is it?
Medroxyprogesterone acetate (MPA) is a synthetic progestin in clinical use since 1959, on the WHO Essential Medicines List. It is marketed as Provera (oral tablets) for HRT and gynaecological indications, and as Depo-Provera (intramuscular or subcutaneous depot injection) for long-acting contraception. MPA was the dominant HRT progestin during the era of the Women's Health Initiative trial. Authorised generic medroxyprogesterone is widely available across both routes.
Mechanism of action
MPA binds progesterone receptors and produces strong progestational effects: thickening cervical mucus, inhibiting ovulation, thinning the endometrium and reducing hot flashes. It has weak androgenic and corticosteroid activity but minimal estrogenic effect. The injectable depot (Depo-Provera) maintains effective serum levels for 12–14 weeks per dose, providing one of the most reliable user-independent contraceptive options.
Pharmacokinetics
Oral MPA is well absorbed but undergoes substantial first-pass metabolism, producing relatively low and variable plasma levels. The half-life of oral MPA is ~12–17 hours, supporting once-daily dosing in HRT. The intramuscular depot (Depo-Provera 150mg) maintains effective levels for 12–14 weeks; the subcutaneous depot 104mg is given every 12 weeks. Hepatic CYP3A4 metabolism predominates with renal excretion of metabolites.
Indications
MPA is approved for amenorrhoea, abnormal uterine bleeding due to hormonal imbalance, prevention of endometrial hyperplasia in postmenopausal women receiving estrogen, and prevention of pregnancy (depot formulation). According to current menopause guidelines, micronised progesterone is now generally preferred over MPA for HRT because of evidence suggesting lower breast cancer and cardiovascular risk, but MPA remains widely used and available.
Safety profile
Common adverse effects of oral MPA include irregular bleeding, breast tenderness, mood changes, fluid retention and weight gain. Depo-Provera additionally carries reversible bone mineral density loss with prolonged use, so use beyond 2 years is reviewed against alternatives. The Women's Health Initiative trial linked MPA-containing combined HRT to increased breast cancer and cardiovascular risk relative to placebo, which has shaped contemporary preference for micronised progesterone in HRT.
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Frequently asked questions
Why is medroxyprogesterone less commonly used in HRT now? ▾
The Women's Health Initiative trial in 2002 found that combined HRT containing oral conjugated estrogens plus MPA was associated with a small increase in breast cancer, stroke and venous thromboembolism. Since then, observational data have suggested better outcomes with bioidentical micronised progesterone, which has shifted prescribing patterns. According to current menopause guidelines, micronised progesterone is the preferred progestogen when available, with MPA remaining an option.
How long can Depo-Provera be safely used? ▾
Depo-Provera produces reversible decreases in bone mineral density during use, which mostly recover after stopping. According to the prescribing information, use beyond 2 years should be reviewed against alternatives, particularly in adolescents and women at risk of osteoporosis. For most women without bone risk factors, longer use is reasonable when contraception preference favours the once-quarterly dosing.
Is Provera the same as natural progesterone? ▾
No — Provera is medroxyprogesterone acetate, a synthetic progestin with progesterone-like activity but different pharmacology, including weak androgenic and corticosteroid effects. Bioidentical natural progesterone (Prometrium, Utrogestan) is structurally identical to endogenous hormone and has a different metabolic profile. According to current menopause guidelines, micronised progesterone is generally preferred for bioidentical HRT.
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