[29] DMPA, under brand names such as Depo-Provera and Depo-SubQ Provera 104, is used in hormonal birth control as a long-lasting progestogen-only injectable contraceptive to prevent pregnancy in women.

Since Norplant and ParaGard allow no scope for user error, their much higher 1995 NSFG failure rates were attributed by Trussell to contraceptive overreporting at the time of a conception leading to a live birth.

[60] Proponents of bioidentical hormone therapy believe that progesterone offers fewer side effects and improved quality of life compared to MPA.

[75][76] At high doses for the treatment of breast cancer, MPA can cause weight gain and can worsen diabetes mellitus and edema (particularly of the face).

However, the study population did show a slightly increased risk of breast cancer in recent users (DMPA use in the last four years) under age 35, similar to that seen with the use of combined oral contraceptive pills.

[73] DMPA has been associated in multiple studies with a higher risk of venous thromboembolism (VTE) when used as a form of progestogen-only birth control in premenopausal women.

[4][99][98] DMPA may cause reduced bone density in premenopausal women and in men when used without an estrogen, particularly at high doses, though this appears to be reversible to a normal level even after years of use.

On 17 November 2004, the United States Food and Drug Administration put a black box warning on the label, indicating that there were potential adverse effects of loss of bone mineral density.

[101] However, a 2008 Committee Opinion from the American Congress of Obstetricians and Gynecologists (ACOG) advises healthcare providers that concerns about bone mineral density loss should neither prevent the prescription of or continuation of DMPA beyond two years of use.

[111] The World Health Organization issued statements in February 2012 and July 2014 saying the data did not warrant changing their recommendation of no restriction – Medical Eligibility for Contraception (MEC) category 1 – on the use of DMPA in women at high risk for HIV.

[115][116] In January 2015, the Faculty of Sexual & Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists issued a statement reaffirming that there is no reason to advise against use of DMPA in the United Kingdom even for women at 'high risk' of HIV infection.

While a study showed "no significant difference in birth weights or incidence of birth defects" and "no significant alternation of immunity to infectious disease caused by breast milk containing DMPA", a subgroup of babies whose mothers started DMPA at two days postpartum had a 75% higher incidence of doctor visits for infectious diseases during their first year of life.

[120] A larger study with longer follow-up concluded that "use of DMPA during pregnancy or breastfeeding does not adversely affect the long-term growth and development of children".

[7][8] In the FDA product label for oral MPA (Provera), it is stated that overdose of an estrogen and progestin may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding.

[158] In addition, since the medication suppresses estrogen levels as well, MPA can produce strong functional antiestrogenic effects similarly, and has been used to treat estrogen-dependent conditions such as precocious puberty in girls and endometriosis in women.

[175][176] In fact, likely due to its suppressive actions on androgen levels, it has been reported that MPA is generally highly effective in improving pre-existing symptoms of hirsutism in women with the condition.

[161] As an agonist of the GR, MPA has glucocorticoid activity, and as a result can cause symptoms of Cushing's syndrome,[185] steroid diabetes, and adrenal insufficiency at sufficiently high doses.

[195] MPA was found to significantly reduce seizure incidence when added to existing anticonvulsant regimens in 11 of 14 women with uncontrolled epilepsy, and has also been reported to induce anesthesia in animals, raising the possibility that it might modulate the GABAA receptor similarly to progesterone.

[199] MPA weakly stimulates the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1).

[200] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone, dydrogesterone, and other progestins such as medroxyprogesterone acetate and norethisterone in clinical studies.

[210] With intramuscular administration of 150 mg microcrystalline MPA in aqueous suspension, the medication is detectable in the circulation within 30 minutes, serum concentrations vary but generally plateau at 1.0 ng/mL (2.6 nmol/L) for 3 months.

[211] The particle size of MPA crystals significantly influences its rate of absorption into the body from the local tissue depot when used as a microcrystalline aqueous suspension via intramuscular injection.

[217] With intramuscular administration, the high levels of MPA in the blood inhibit luteinizing hormone and ovulation for several months, with an accompanying decrease in serum progesterone to below 0.4 ng/mL.

[211] Hot flashes are rare while MPA is found at significant blood levels in the body, and the vaginal lining remains moist and creased.

[14][15][224][225] It was first introduced on 18 June 1959 by Upjohn in the United States under the brand name Provera (2.5, 5, and 10 mg tablets) for the treatment of amenorrhea, metrorrhagia, and recurrent miscarriage.

[233] Upjohn sought FDATooltip Food and Drug Administration approval of intramuscular DMPA as a long-acting contraceptive under the brand name Depo-Provera (150 mg/mL MPA) in 1967, but the application was rejected.

[234] A subcutaneous formulation of DMPA was introduced in the United States as a contraceptive under the brand name Depo-SubQ Provera 104 (104 mg/0.65 mL MPA) in December 2004, and subsequently was also approved for the treatment of endometriosis-related pelvic pain.

[11][12][129] Brand names of MPA in combination with CEEs as oral tablets in different countries include Prempro, Premphase, Premique, Premia, and Premelle.

[248] Points in the controversy included: DMPA was studied by Upjohn for use as a progestogen-only injectable contraceptive in women at a dose of 50 mg once a month but produced poor cycle control and was not marketed for this use at this dosage.

[271][272] It was formulated as an oral medication at very high dosages, and was thought to inhibit the signaling of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, with a mechanism of action that was said to be similar to that of corticosteroids.