Medroxyprogesterone acetate (MPA) is a synthetic progestin used orally (Provera) for secondary amenorrhea, abnormal uterine bleeding, endometrial protection in HRT, and endometriosis. The injectable long-acting form (Depo-Provera) is a widely used contraceptive given every 3 months. It is also used in the treatment of endometrial and renal cell carcinoma and in the management of endometriosis-associated pain.
Reduces menstrual bleeding (many users become amenorrheic)3,5
Oral form protects endometrium when combined with estrogen in HRT
Treatment of abnormal uterine bleeding
What to watch for
Irregular menstrual bleeding and spotting (common initially)
Amenorrhea (50% of users by 1 year on Depo-Provera)
Weight gain (average 5–8 lbs over 2 years with Depo-Provera)
Known or suspected pregnancy
Active thrombophlebitis or current thromboembolic disorders
The bottom line
Evidence rating strong. Most-documented uses: highly effective injectable contraception (>99%), only 4 injections per year for contraception, reduces menstrual bleeding (many users become amenorrheic). 10 sources indexed (2015–2024), with 5 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
A synthetic progestogen that binds to progesterone receptors, transforming a proliferative endometrium into a secretory one and preventing endometrial hyperplasia. For contraception, Depo-Provera suppresses the hypothalamic-pituitary-ovarian axis, inhibiting gonadotropin secretion and preventing ovulation. Also thickens cervical mucus and alters the endometrium to prevent implantation. Has mild glucocorticoid and anti-estrogenic activity.
Class
Progestin Hormone
Absorption
Fat-soluble; take with food
Dosing
Dosing & protocol.
Common range
Oral: 2.5–10 mg daily for 10–14 days per cycle; Depo-Provera: 150 mg IM or 104 mg subcutaneously every 3 months (as prescribed by your physician)
Recommended form
Oral tablet (Provera) or intramuscular/subcutaneous injection (Depo-Provera)
Oral tablets can be taken with or without food. Depo-Provera injection forms a depot that slowly releases medication over 3 months.
Safety
Full safety detail.
Side effects
Irregular menstrual bleeding and spotting (common initially)
Amenorrhea (50% of users by 1 year on Depo-Provera)
Weight gain (average 5–8 lbs over 2 years with Depo-Provera)
Headache
Mood changes and depression
Bone mineral density loss with prolonged injectable use
Delayed return to fertility after injectable discontinuation (average 10 months)
Breast tenderness
Contraindications
Known or suspected pregnancy
Active thrombophlebitis or current thromboembolic disorders
Depot medroxyprogesterone acetate (DMPA) is associated with a measurable but largely reversible decrease in bone mineral density during use. Adequate calcium intake (1000-1300 mg/day) is recommended for women on DMPA to support bone health, alongside vitamin D and weight-bearing exercise.
Recommendation: Aim for 1000-1300 mg/day total calcium from diet plus supplements while on DMPA. Split supplemental doses (500 mg or less per serving) for best absorption, and take with vitamin D.
Vitamin D adequacy is essential for the bone-protective effect of calcium during DMPA use. Without adequate vitamin D, dietary calcium cannot be efficiently absorbed and DMPA-related bone loss is more pronounced.
Recommendation: Take vitamin D3 800-2000 IU/day while on DMPA, targeting serum 25(OH)D above 30 ng/mL. Take with a fatty meal at any time of day.
Vitamin K2 complements calcium and vitamin D for bone protection during DMPA use by activating osteocalcin and matrix Gla protein. Although direct DMPA-K2 trials are limited, the mechanism and extrapolation from postmenopausal osteoporosis data supports use.
Recommendation: Vitamin K2 (MK-7 90-180 mcg/day) is a reasonable addition to calcium and vitamin D for women on long-term DMPA. Take with a fatty meal. Avoid if you also take warfarin.
Magnesium plays a structural and signaling role in bone health and supports the calcium-vitamin D-PTH axis. Although direct DMPA trials are limited, magnesium adequacy is reasonable for women on long-term DMPA, especially given the BMD concern.
Recommendation: Aim for daily magnesium needs from diet plus modest supplements during long-term DMPA use. Magnesium glycinate or citrate are well tolerated; take in the evening for sleep benefit.
DMPA can cause or worsen low mood in some users, and depleted B6 status (common in women on hormonal contraception) may contribute. Modest B6 supplementation supports neurotransmitter synthesis and may improve tolerability.
Recommendation: Consider B6 25-50 mg/day (as pyridoxine or P5P) during DMPA use, especially if you experience low mood or irritability. Take with or without food at any time of day.
Zürcher A, Knabben L, von Gernler M et al.. Depot medroxyprogesterone acetate and breast cancer: a systematic review. Archives of gynecology and obstetrics. 2024
Dianat S, Fox E, Ahrens KA et al.. Side Effects and Health Benefits of Depot Medroxyprogesterone Acetate: A Systematic Review. Obstetrics and gynecology. 2019
Silva P, Qadir S, Fernandes A et al.. Dietary intake and eating behavior in depot medroxyprogesterone acetate users: a systematic review. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2018
Brind J, Condly SJ, Mosher SW et al.. Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis. Issues in law & medicine. 2015
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
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