Provera Side Effects
Generic name: medroxyprogesterone
Medically reviewed by Drugs.com. Last updated on Feb 12, 2024.
Note: This document provides detailed information about Provera.
For healthcare professionals
Applies to medroxyprogesterone: compounding powder, intramuscular suspension, oral tablet, subcutaneous suspension Side Effects associated with medroxyprogesterone. Some dosage forms listed on this page may not apply specifically to the brand name Provera.
For healthcare professionals
Applies to medroxyprogesterone: compounding powder, intramuscular suspension, oral tablet, subcutaneous suspension.
Gastrointestinal adverse events
- Very common (10% or more): Abdominal pain/discomfort (up to 11.2%)
- Common (1% to 10%): Nausea, bloating, abdominal distention, diarrhea, vomiting, constipation
- Uncommon (0.1% to 1%): Dry mouth
- Postmarketing reports: Gastrointestinal disturbances, rectal bleeding[Ref]
Genitourinary
- Very common (10% or more): Amenorrhea (up to 68%), bleeding (up to 57.3%), uterine bleeding irregularities (up to 35%)
- Common (1% to 10%): Dysmenorrhea, leukorrhea, vaginitis, intermenstrual bleeding, urinary tract infection, vaginal candidiasis, vaginitis, vaginitis bacterial, abnormal cervix smear, metrorrhagia, menometrorrhagia, menstruation irregular, vaginal hemorrhage, erectile dysfunction, genitourinary tract infection, pelvic pain, dyspareunia
- Frequency not reported: Uterine cervical erosions, cervical discharge, vulvovaginal dryness, premenstrual syndrome, vaginal cyst, ovarian cyst, lack of return to fertility, sensation of pregnancy
- Postmarketing reports: Unexpected pregnancy, uterine hyperplasia, oligomenorrhea, prolonged anovulation[Ref]
Metabolic
- Very common (10% or more): Increase weight (up to 37%)
- Common (1% to 10%): Increased appetite, decreased appetite
- Uncommon (0.1% to 1%): Diabetes mellitus exacerbated, hypercalcemia, fluid retention
- Frequency not reported: Elevations of serum calcium and potassium levels, exacerbation of diabetes mellitus
- Postmarketing reports: Decreased glucose tolerance, changes in appetite, excessive thirst[Ref]
Weight gain is more frequently encountered than weight loss during medroxyprogesterone therapy. In women using intramuscular medroxyprogesterone for contraception, the mean weight gain after one year of therapy is 2.5 kg. After two, four, and six years, patients gain a mean of 3.7, 6.3, and 7.5 kg, respectively.[Ref]
Nervous system
- Very common (10% or more): Nervousness (10.8%)
- Common (1% to 10%): Dizziness
- Rare (less than 0.1%): Cerebral infarction, somnolence
- Frequency not reported: Loss of concentration, adrenergic-like effects, migraine, seizure, VII th nerve paralysis, syncope
- Postmarketing reports: Paralysis, facial palsy, paresthesia, drowsiness[Ref]
Other
- Very common (10% or more): Headache (up to 16.5%)
- Common (1% to 10%): Asthenia, fatigue, edema /fluid retention, breast pain, breast tenderness
- Frequency not reported: Chills, fever, vertigo, breast atrophy, breast mass, nipple exudate bloody, breast enlargement
- Postmarketing reports: Changes in breast size[Ref]
Cardiovascular
- Common (1% to 10%): Hot flashes
- Uncommon (0.1% to 1%): Cardiac failure congestive, thrombophlebitis
- Rare (less than 0.1%): Myocardial infarction, embolism, thrombosis, blood pressure increased
- Frequency not reported: Tachycardia, palpitations
- Postmarketing reports: Deep vein thrombosis, varicose veins[Ref]
The majority of cases of thromboembolic disease during hormonal therapy have been attributed to estrogens and not to progestogens. However, it has been demonstrated that this drug, at least at high doses, can produce a hypercoagulable state. Whether or not this contributes to the development of thrombotic events remains unknown.[Ref]
Dermatologic
- Common (1% to 10%): Acne, no hair growth/alopecia, rash, hyperhidrosis
- Uncommon (0.1% to 1%): Hirsutism, urticaria, pruritus, chloasma
- Frequency not reported: Lipodystrophy acquired, dermatitis, ecchymosis, scleroderma, skin striae, erythema multiforme, erythema nodosum
- Postmarketing reports: Axillary swelling, excessive sweating and body odor, dry skin, melasma[Ref]
Musculoskeletal
- Common (1% to 10%): Leg cramps, arthralgia, back pain, limb pain, pain in extremity
- Uncommon (0.1% to 1%): Muscle spasms
- Frequency not reported: Gluteal infiltration and abscess formation
- Postmarketing reports: Chest pain, osteoporosis including osteoporotic fractures, loss of bone mineral density, scleroderma[Ref]
Psychiatric
- Common (1% to 10%): Depression, insomnia, anxiety, irritability, decreased libido
- Uncommon (0.1% to 1%): Euphoria, changes in libido
- Rare (less than 0.1%): Confusion
- Frequency not reported: Anorgasmia, emotional disturbance, affective disorder,
- Postmarketing reports: Increased libido[Ref]
Respiratory
- Common (1% to 10%): Bronchitis, influenza, nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection
- Uncommon (0.1% to 1%): Pulmonary embolism
- Frequency not reported: Dysphonia
- Postmarketing reports: Dyspnea, asthma, hoarseness[Ref]
Endocrine
- Uncommon (0.1% to 1%): Corticoid-like effects
- Frequency not reported: Cushingoid syndrome, galactorrhea
- Postmarketing reports: Prevention of lactation with or without hyperprolactinemia[Ref]
Hepatic
- Uncommon (0.1% to 1%): Abnormal hepatic function, jaundice cholestatic
- Postmarketing reports: Abnormal liver function test, abnormal hepatic enzyme[Ref]
Hypersensitivity
- Frequency not reported: Allergic reactions including angioedema, anaphylactic reaction, anaphylactoid reaction[Ref]
Immunologic
- Frequency not reported: White blood cell count increased, platelet count increased
- Postmarketing reports: Anemia, blood dyscrasia[Ref]
Local
- Frequency not reported: Injection site abscess, injection site infection, injection site nodule/lump, injection site pain/tenderness, injection site persistent atrophy/indentation/dimpling[Ref]
Ocular
- Frequency not reported: Retinal embolism and thrombosis, cataract diabetic, visual impairment[Ref]
Renal
- Frequency not reported: Glycosuria[Ref]
Oncologic
- Postmarketing reports: Cervical cancer, breast cancer, endometrial hyperplasia, breast lumps or nipple bleeding, nipple discharge[Ref]
A significant increase in the incidence of breast cancer in beagle dogs in addition to an apparent increase in the incidence of endometrial cancer in rhesus monkeys was noted in early animal carcinogenicity studies.[Ref]
References
1. (2001) "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn
2. (2001) "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn
3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
4. Cerner Multum, Inc. "Australian Product Information."
5. (2022) "Product Information. MedroxyPROGESTERone Acetate (medroxyPROGESTERone)." Greenstone LLC
6. (2022) "Product Information. depo-subQ provera 104 (medroxyPROGESTERone)." Pfizer U.S. Pharmaceuticals Group
7. Fraser IS (1986) "Menstrual changes associated with progestogen-only contraception." Acta Obstet Gynecol Scand Suppl, 134, p. 21-7
8. Kora S, Virkar K (1975) "Incidence of pregnancy, changes in menstrual pattern, and recovery of endometrial function after discontinuation of medroxyprogesterone acetate therapy." Fertil Steril, 26, p. 121-5
9. Sapire KE (1991) "A study of bleeding patterns with two injectable contraceptives given postpartum and the effect of two non-hormonal treatments." Adv Contracept, 7, p. 379-87
10. Belsey EM (1991) "Menstrual bleeding patterns in untreated women and with long-acting methods of contraception. Task Force on Long-Acting Systemic Agents for Fertility Regulation." Adv Contracept, 7, p. 257-70
11. Fraser IS (1983) "A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives." Contraception, 28, p. 385-97
12. Mukherjea M, Mukherjee P, Biswas R (1980) "Long-term contraception with Depo-Provera: a clinical evaluation." Int J Fertil, 25, p. 122-6
13. Woodruff JD, Pickar JH (1994) "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone." Am J Obstet Gynecol, 170, p. 1213-23
14. Archer DF, Pickar JH, Bottiglioni F (1994) "Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate." Obstet Gynecol, 83, p. 686-92
15. Kaunitz AM (1994) "Long-acting injectable contraception with depot medroxyprogesterone acetate." Am J Obstet Gynecol, 170, p. 1543-9
16. Leiman G (1972) "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol, 114, p. 97-102
17. Barnes RB, Roy S, Lobo RA (1985) "Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women." Obstet Gynecol, 66, p. 216-9
18. Amatayakul K, Sivasomboon B, Thanangkul O (1980) "A study of the mechanism of weight gain in medroxyprogesterone acetate users." Contraception, 22, p. 605-22
19. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE (1989) "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception, 39, p. 619-32
20. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D (1986) "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet, 24, p. 291-6
21. Teichmann AT, Wander HE, Cremer P, et al. (1987) "Medroxyprogesterone acetate and lipid metabolic changes." Arzneimittelforschung, 37, p. 573-77
22. Who Task Force on Long-acting Agents for Fertility Regulation (1986) "Metabolic side-effects of injectable depot-medroxyprogesterone acetate, 150 mg three-monthly, in undernourished lactating women." Bull World Health Organ, 64, p. 587-94
23. Luciano AA, De Souza MJ, Roy MP, Schoenfeld MJ, Nulsen JC, Halvorson CV (1993) "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women." J Reprod Med, 38, p. 207-14
24. Grady D, Yaffe K, Kristof M, Lin F, Richards C, Barrett-Connor E (2002) "Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study." Am J Med, 113, p. 543-8
25. Astedt B, Jeppsson S, Pandolfi M (1972) "Fibrinolytic activity of veins during use of depot medroxyprogesterone acetate as a contraceptive." Fertil Steril, 23, p. 489-92
26. Yamamoto H, Noguchi S, Miyauchi K, Inaji H, Imaoka S, Koyama H, Iwanaga T (1991) "Changes in hematologic parameters during treatment with medroxyprogesterone acetate for breast cancer." Jpn J Cancer Res, 82, p. 420-5
27. Fukutomi T, Nanasawa T, Yamamoto H, Adachi I, Watanabe T (1990) "The induction of a hypercoagulable state by medroxyprogesterone acetate in breast cancer patients." Jpn J Surg, 20, p. 665-70
28. Skouby SO, Gram J, Andersen LF, Sidelmann J, Petersen KR, Jespersen J (2002) "Hormone replacement therapy: Estrogen and progestin effects on plasma C-reactive protein concentrations." Am J Obstet Gynecol, 186(5 Pt 1), p. 969-977
29. Farag NH, Nelesen RA, Parry BL, Loredo JS, Dimsdale JE, Mills PJ (2002) "Autonomic and cardiovascular function in postmenopausal women: The effects of estrogen versus combination therapy." Am J Obstet Gynecol, 186(5 Pt 1), p. 954-61
30. (2002) "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial." JAMA, 288, p. 321-33
31. (2002) "Hormone replacement therapy." Med Lett Drugs Ther, 44, p. 78
32. Bosch X (2002) "Depo-Provera contraceptive may increase risk of cardiovascular disease." BMJ, 325, p. 513
33. Cundy T, Evans M, Roberts H, Wattie D, Ames R, Reid IR (1991) "Bone density in women receiving depot medroxyprogesterone acetate for contraception [published erratum appears in BMJ 1991 Jul27;303(6796):220]." BMJ, 303, p. 13-6
34. Cundy T, Farquhar CM, Cornish J, Reid IR (1996) "Short-term effects of high dose oral medroxyprogesterone acetate on bone density in premenopausal women." J Clin Endocrinol Metab, 81, p. 1014-7
35. Paiva LC, PintoNeto AM, Faundes A (1998) "Bone density among long-term users of medroxyprogesterone acetate as a contraceptive." Contraception, 58, p. 351-5
36. Nand SL, Wren BG, Gross BA, Heller GZ (1999) "Bone density effects of continuous estrone sulfate and varying doses of medroxyprogesterone acetate." Obstet Gynecol, 93, p. 1009-13
37. Bjorn I, Bixo M, Nojd KS, Nyberg S, Backstrom T (2000) "Negative mood changes during hormone replacement therapy: A comparison between two progestogens." Am J Obstet Gynecol, 183, p. 1419-26
38. Siminoski K, Goss P, Drucker DJ (1989) "The Cushing syndrome induced by medroxyprogesterone acetate." Ann Intern Med, 111, p. 758-60
39. Spellacy WN, Buhi WC, Birk SA (1975) "Stimulated plasma prolactin levels in women using medroxyprogesterone acetate or an intrauterine device for contraception." Fertil Steril, 26, p. 970-81
40. Grenfell A, Rudenski A, Watts M, Wiltshire C, Day JL, Gray IP (1990) "Cushing's syndrome and medroxyprogesterone acetate" Lancet, 336, p. 256
41. Donckier JE, Michel LA, Buysschaert M (1990) "Cushing syndrome and medroxyprogesterone acetate" Lancet, 335, p. 1094
42. Wortsman J, Hirschowitz JS (1980) "Galactorrhea and hyperprolactinemia during treatment of polycystic ovary syndrome." Obstet Gynecol, 55, p. 460-3
43. Learoyd D, McElduff A (1990) "Medroxyprogesterone induced Cushing's syndrome." Aust N Z J Med, 20, p. 824-5
44. Chaudhury RR, Chompootaweep S, Dusitsin N, Friesen H, Tankeyoon M (1977) "The release of prolactin by medroxy-progesterone acetate in human subjects." Br J Pharmacol, 59, p. 433-4
45. Riippa P, Kauppila A, Sundstrom H, Vihko R (1984) "Hepatic impairment during simultaneous administration of medroxyprogesterone acetate and tamoxifen in the treatment of endometrial and ovarian carcinoma." Anticancer Res, 4, p. 109-12
46. Meyer WJ, 3d Wiener I, Emory LE, Cole CM, Isenberg N, Fagan CJ, Thompson JC (1992) "Cholelithiasis associated with medroxyprogesterone acetate therapy in men." Res Commun Chem Pathol Pharmacol, 75, p. 69-84
47. Zacest R, Cushway A, Haines C, Cox LW (1982) "Hypersensitivity reaction to Depo-Provera" Med J Aust, 1, p. 12
48. Brooks GG (1974) "Anaphylactoid shock with medroxyprogesterone acetate: A case report." J La State Med Soc, 126, p. 397-9
49. Liang AP, Levenson AG, Layde PM, Shelton JD, Hatcher RA, Potts M, Michelson MJ (1983) "Risk of breast, uterine corpus, and ovarian cancer in women receiving medroxyprogesterone injections." JAMA, 249, p. 2909-12
50. (1984) "Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet, 2, p. 1207-8
51. (1991) "Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet, 338, p. 833-8
52. (1992) "Depot-medroxyprogesterone acetate (DMPA) and risk of invasive squamous cell cervical cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Contraception, 45, p. 299-312
53. (1991) "Depot-medroxyprogesterone acetate (DMPA) and risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer, 49, p. 191-5
54. (1991) "Depot-medroxyprogesterone acetate (DMPA) and risk of endometrial cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer, 49, p. 186-90
55. (1991) "Depot-medroxyprogesterone acetate (DMPA) and risk of liver cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer, 49, p. 182-5
56. Oberle MW, Rosero-Bixby L, Irwin KL, Fortney JA, Lee NC, Whatley AS, Bonhomme MG (1988) "Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica." Int J Epidemiol, 17, p. 718-23
57. Jordan A (1994) "Toxicology of depot medroxyprogesterone acetate." Contraception, 49, p. 189-201
58. Lumbiganon P (1994) "Depot-medroxyprogesterone acetate (DMPA) and cancer of the endometrium and ovary." Contraception, 49, p. 203-9
59. Chilvers C (1994) "Breast cancer and depot-medroxyprogesterone acetate - a review." Contraception, 49, p. 211-22
60. Lavecchia C (1994) "Depot-medroxyprogesterone acetate, other injectable contraceptives, and cervical neoplasia." Contraception, 49, p. 223-30
61. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB (1995) "Depot medroxyprogesterone acetate and breast cancer." JAMA, 273, p. 799-807
Frequently asked questions
- How long after having a Depo Provera shot can you have unprotected sex?
- My stool has changed color. What does it mean?
- Why is my poop green? What does this mean?
More about Provera (medroxyprogesterone)
- Check interactions
- Compare alternatives
- Pricing & coupons
- Reviews (317)
- Drug images
- Dosage information
- During pregnancy
- Generic availability
- Support group
- Drug class: contraceptives
- Breastfeeding
- En español
Patient resources
Professional resources
Other formulations
Related treatment guides
Further information
Provera side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Some side effects may not be reported. You may report them to the FDA.
