Cycrin Side Effects
Generic Name: medroxyprogesterone
Note: This page contains information about the side effects of medroxyprogesterone. Some of the dosage forms included on this document may not apply to the brand name Cycrin.
For the Consumer
Applies to medroxyprogesterone: oral tablet
Other dosage forms:
In addition to its needed effects, some unwanted effects may be caused by medroxyprogesterone (the active ingredient contained in Cycrin). In the event that any of these side effects do occur, they may require medical attention.
Major Side Effects
You should check with your doctor immediately if any of these side effects occur when taking medroxyprogesterone:Incidence not known:
- Abdominal or stomach pain
- absent, missed, or irregular menstrual periods
- blurred vision
- breast pain or tenderness
- changes in skin color
- clay-colored stools
- dark urine
- decrease in amount of urine
- difficulty swallowing
- dizziness or lightheadedness
- eye pain
- fast heartbeat
- hives or welts, itching, redness, swelling, or skin rash
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- loss of appetite
- menstrual changes
- noisy, rattling breathing
- pain in the chest, groin, or legs, especially the calves
- pain, tenderness, or swelling of the foot or leg
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- severe, sudden headache
- shortness of breath
- slurred speech
- stopping of menstrual bleeding
- sudden loss of coordination
- sudden, severe weakness or numbness in the arm or leg
- sudden, unexplained shortness of breath
- swelling of the fingers, hands, feet, or lower legs
- troubled breathing at rest
- unexpected or excess milk flow from the breasts
- unpleasant breath odor
- unusual tiredness or weakness
- vaginal bleeding or spotting
- vision changes
- vomiting of blood
- weight gain
- yellow eyes or skin
Minor Side Effects
Some of the side effects that can occur with medroxyprogesterone may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:Incidence not known:
- Blemishes on the skin
- feeling sad or empty
- hair loss, thinning of hair
- increased hair growth, especially on the face
- lack of appetite
- loss of interest or pleasure
- sleepiness or unusual drowsiness
- trouble concentrating
- trouble sleeping
- weight changes
For Healthcare Professionals
Applies to medroxyprogesterone: compounding powder, intramuscular suspension, oral tablet, subcutaneous suspension
Cushing's syndrome is uncommon and appears to be associated with a long duration of therapy and moderate to high doses of medroxyprogesterone (the active ingredient contained in Cycrin) Doses used for hormonal replacement therapy and for long-term contraception are not associated with Cushing's syndrome.
Medroxyprogesterone has mild glucocorticoid activity. In cases of medroxyprogesterone-induced Cushing's syndrome, low cortisol and adrenocorticotrophic hormone (ACTH) levels with a reduced pituitary-adrenal reserve have been documented. Acute adrenal insufficiency may ensue following withdrawal of medroxyprogesterone.[Ref]
Endocrine side effects have included breast tenderness, galactorrhea with or without hyperprolactinemia, prevention of lactation, hirsutism, and Cushing's syndrome.[Ref]
Weight gain is more frequently encountered than weight loss during medroxyprogesterone (the active ingredient contained in Cycrin) 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.
Data regarding the effect of medroxyprogesterone on lipid profiles have been conflicting. Some studies report possible negative effects on lipid profiles while others have documented a reduction in total and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol levels.[Ref]
Metabolic side effects have included weight changes (increases and decreases), glucose intolerance, and changes in serum cholesterol concentrations.[Ref]
Genitourinary side effects have been relatively common and included primarily menstrual changes such as amenorrhea, irregular bleeding, spotting, and heavy bleeding. Vaginal cysts, dyspareunia, and changes in cervical erosion and secretions have also been reported. While endometrial hyperplasia has been reported, medroxyprogesterone (the active ingredient contained in Cycrin) tended to have a favorable effect on the endometrium. Changes in libido and anorgasmia have also occurred.[Ref]
Withdrawal bleeding is a common complaint among postmenopausal women receiving sequential (10 to 14 days per cycle) medroxyprogesterone therapy. In postmenopausal women receiving continuous medroxyprogesterone and estrogen therapy, 75% or more are amenorrheic by one year of therapy.
In women receiving medroxyprogesterone for contraception, more than 50% are amenorrheic by one year of therapy.
In women on estrogen replacement therapy, the addition of medroxyprogesterone or other progestin for at least 10 to 14 days of each cycle significantly reduces the risk of endometrial hyperplasia and, thus, the risk of endometrial carcinoma. Low-dose continuous medroxyprogesterone therapy also reduces the risk of endometrial hyperplasia associated with the use of unopposed estrogen.
In patients in whom abnormal bleeding persists or is severe, the possibility of an organic pathology should be considered and ruled out.[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.
International long-term studies designed to assess the risk of medroxyprogesterone (the active ingredient contained in Cycrin) in humans, sponsored by the World Health Organization, failed to find an increased risk of cancer in users of medroxyprogesterone. Overall, there was no significant increase in the risk of breast cancer, cervical cancer, or epithelial ovarian cancer. Data from these studies did, however, support a significant (8-fold) reduction in the incidence of endometrial cancer among medroxyprogesterone users.
A study from New Zealand has suggested that women taking depot medroxyprogesterone acetate may be at higher risk for breast cancer during the first 5 years, but therapy for more than 5 years confers no increased risk of breast cancer.[Ref]
Oncologic side effects possibly associated with medroxyprogesterone have been the topic of considerable debate. Data from some animal studies suggested an increased risk of breast and endometrial cancer. The current consensus is that the carcinogenic potential of medroxyprogesterone is no greater than that of other hormonal contraceptives.[Ref]
The majority of cases of thromboembolic disease during hormonal therapy have been attributed to estrogens and not to progestins. However, it has been demonstrated that medroxyprogesterone (the active ingredient contained in Cycrin) at least at high doses, can produce a hypercoagulable state. Whether or not this contributes to the development of thrombotic events remains unknown.
Because medroxyprogesterone can cause edema, it should be used cautiously in patients with underlying disease (like migraine headaches, asthma, heart disease, renal dysfunction, or seizure disorders) which may be exacerbated by edema or fluid retention.[Ref]
Cardiovascular side effects have included thromboembolic disorders such as thrombophlebitis, deep vein thrombosis, pulmonary embolism, cerebrovascular accidents, and retinal thrombosis. In addition, edema, hypertension, tachycardia, and syncope have been noted.[Ref]
Musculoskeletal side effects have included changes in bone mineral density and leg cramps.[Ref]
Reductions in bone mineral density and osteoporosis have been attributed to medroxyprogesterone. Such effects are probably due to medroxyprogesterone-induced estrogen deficiency.
Conflicting data concerning the effects of medroxyprogesterone on bone mineral density have been reported.
In one study, women 25 to 51 years of age receiving medroxyprogesterone 150 mg intramuscularly every three months for five or more years for long-term contraception had a reduction in bone mineral density compared with premenopausal controls. However, bone mineral density in the treatment group was still significantly greater than that observed in postmenopausal controls.
A study of 200 women who received medroxyprogesterone 150 mg intramuscularly every three months for a median duration of 12 years (range 2 to 26 years) reported that bone density was significantly reduced in medroxyprogesterone users. However, bone mineral density in women starting depot medroxyprogesterone after the age of 20 years and using it for 15 or fewer years was greater than the remainder of the cohort.
A study to determine the potential for postmenopausal fracture due to residual effects of depot medroxyprogesterone in former users reported the risk to be small and unlikely to have substantial impact in postmenopausal women. No significant differences in bone density were found, however, women who had used depot medroxyprogesterone for >2 yeas had a trend toward lower bone densities.
Bone density in 185 women receiving long-term depot medroxyprogesterone for a mean of 5 years (range of 1-16 years) was only minimally below the normal population despite decreased estrogen levels.[Ref]
Dermatologic side effects have included acne, reduced hair growth, alopecia, melasma, chloasma, rash, excessive sweating, dry skin, scleroderma, erythema multiforme, and erythema nodosum.[Ref]
Nervous system side effects have included headache, asthenia, dizziness, depression, somnolence, and insomnia. Paresthesias, convulsions, and facial palsy have been reported although causality is unknown.[Ref]
Gastrointestinal side effects have occurred in up to 5% of patients and included nausea, abdominal pain, bloating, and anorexia.[Ref]
Hepatic side effects have included elevations in liver function tests, jaundice, cholestatic jaundice, and cholelithiasis.[Ref]
Hematologic side effects have included rare reports of hypercoagulability with and without thromboembolic activity.[Ref]
Hypersensitivity side effects have been uncommon but have included urticaria, angioneurotic edema, and anaphylaxis or anaphylactoid reactions.[Ref]
Local side effects associated with intramuscular administration of medroxyprogesterone (the active ingredient contained in Cycrin) have included pain, change in skin color, residual lumps, and sterile abscesses at the injection site.[Ref]
Ocular side effects have included visual disturbances such as sudden loss of vision (partial or complete), sudden onset of proptosis, diplopia, or migraine have been reported. Therapy should be withdrawn in the presence of papilledema or retinal vascular lesions.[Ref]
Psychiatric side effects have included dysphoric symptoms similar to premenstrual syndrome (PMS).[Ref]
1. Donckier JE, Michel LA, Buysschaert M "Cushing syndrome and medroxyprogesterone acetate" Lancet 335 (1990): 1094
2. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
3. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
4. Spellacy WN, Buhi WC, Birk SA "Stimulated plasma prolactin levels in women using medroxyprogesterone acetate or an intrauterine device for contraception." Fertil Steril 26 (1975): 970-81
5. Wortsman J, Hirschowitz JS "Galactorrhea and hyperprolactinemia during treatment of polycystic ovary syndrome." Obstet Gynecol 55 (1980): 460-3
6. Learoyd D, McElduff A "Medroxyprogesterone induced Cushing's syndrome." Aust N Z J Med 20 (1990): 824-5
7. Siminoski K, Goss P, Drucker DJ "The Cushing syndrome induced by medroxyprogesterone acetate." Ann Intern Med 111 (1989): 758-60
8. Grenfell A, Rudenski A, Watts M, Wiltshire C, Day JL, Gray IP "Cushing's syndrome and medroxyprogesterone acetate" Lancet 336 (1990): 256
9. Chaudhury RR, Chompootaweep S, Dusitsin N, Friesen H, Tankeyoon M "The release of prolactin by medroxy-progesterone acetate in human subjects." Br J Pharmacol 59 (1977): 433-4
10. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32
11. Teichmann AT, Wander HE, Cremer P, et al. "Medroxyprogesterone acetate and lipid metabolic changes." Arzneimittelforschung 37 (1987): 573-77
12. Kaunitz AM "Long-acting injectable contraception with depot medroxyprogesterone acetate." Am J Obstet Gynecol 170 (1994): 1543-9
13. Barnes RB, Roy S, Lobo RA "Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women." Obstet Gynecol 66 (1985): 216-9
14. Who Task Force on Long-acting Agents for Fertility Regulation "Metabolic side-effects of injectable depot-medroxyprogesterone acetate, 150 mg three-monthly, in undernourished lactating women." Bull World Health Organ 64 (1986): 587-94
15. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6
16. Amatayakul K, Sivasomboon B, Thanangkul O "A study of the mechanism of weight gain in medroxyprogesterone acetate users." Contraception 22 (1980): 605-22
17. Luciano AA, De Souza MJ, Roy MP, Schoenfeld MJ, Nulsen JC, Halvorson CV "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women." J Reprod Med 38 (1993): 207-14
18. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
19. Kora S, Virkar K "Incidence of pregnancy, changes in menstrual pattern, and recovery of endometrial function after discontinuation of medroxyprogesterone acetate therapy." Fertil Steril 26 (1975): 121-5
20. Archer DF, Pickar JH, Bottiglioni F "Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate." Obstet Gynecol 83 (1994): 686-92
21. Sapire KE "A study of bleeding patterns with two injectable contraceptives given postpartum and the effect of two non-hormonal treatments." Adv Contracept 7 (1991): 379-87
22. Fraser IS "A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives." Contraception 28 (1983): 385-97
23. Woodruff JD, Pickar JH "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone." Am J Obstet Gynecol 170 (1994): 1213-23
24. Belsey EM "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 (1991): 257-70
25. Fraser IS "Menstrual changes associated with progestogen-only contraception." Acta Obstet Gynecol Scand Suppl 134 (1986): 21-7
26. Mukherjea M, Mukherjee P, Biswas R "Long-term contraception with Depo-Provera: a clinical evaluation." Int J Fertil 25 (1980): 122-6
27. Lumbiganon P "Depot-medroxyprogesterone acetate (DMPA) and cancer of the endometrium and ovary." Contraception 49 (1994): 203-9
28. "Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 338 (1991): 833-8
29. Liang AP, Levenson AG, Layde PM, Shelton JD, Hatcher RA, Potts M, Michelson MJ "Risk of breast, uterine corpus, and ovarian cancer in women receiving medroxyprogesterone injections." JAMA 249 (1983): 2909-12
30. "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial." JAMA 288 (2002): 321-33
31. "Depot-medroxyprogesterone acetate (DMPA) and risk of endometrial cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer 49 (1991): 186-90
32. Lavecchia C "Depot-medroxyprogesterone acetate, other injectable contraceptives, and cervical neoplasia." Contraception 49 (1994): 223-30
33. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB "Depot medroxyprogesterone acetate and breast cancer." JAMA 273 (1995): 799-807
34. Jordan A "Toxicology of depot medroxyprogesterone acetate." Contraception 49 (1994): 189-201
35. "Hormone replacement therapy." Med Lett Drugs Ther 44 (2002): 78
36. "Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 2 (1984): 1207-8
37. Oberle MW, Rosero-Bixby L, Irwin KL, Fortney JA, Lee NC, Whatley AS, Bonhomme MG "Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica." Int J Epidemiol 17 (1988): 718-23
38. "Depot-medroxyprogesterone acetate (DMPA) and risk of epithelial ovarian cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer 49 (1991): 191-5
39. "Depot-medroxyprogesterone acetate (DMPA) and risk of invasive squamous cell cervical cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Contraception 45 (1992): 299-312
40. Chilvers C "Breast cancer and depot-medroxyprogesterone acetate - a review." Contraception 49 (1994): 211-22
41. "Depot-medroxyprogesterone acetate (DMPA) and risk of liver cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives." Int J Cancer 49 (1991): 182-5
42. Astedt B, Jeppsson S, Pandolfi M "Fibrinolytic activity of veins during use of depot medroxyprogesterone acetate as a contraceptive." Fertil Steril 23 (1972): 489-92
43. Farag NH, Nelesen RA, Parry BL, Loredo JS, Dimsdale JE, Mills PJ "Autonomic and cardiovascular function in postmenopausal women: The effects of estrogen versus combination therapy." Am J Obstet Gynecol 186(5 Pt 1) (2002): 954-61
44. Yamamoto H, Noguchi S, Miyauchi K, Inaji H, Imaoka S, Koyama H, Iwanaga T "Changes in hematologic parameters during treatment with medroxyprogesterone acetate for breast cancer." Jpn J Cancer Res 82 (1991): 420-5
45. Bosch X "Depo-Provera contraceptive may increase risk of cardiovascular disease." BMJ 325 (2002): 513
46. Fukutomi T, Nanasawa T, Yamamoto H, Adachi I, Watanabe T "The induction of a hypercoagulable state by medroxyprogesterone acetate in breast cancer patients." Jpn J Surg 20 (1990): 665-70
47. Skouby SO, Gram J, Andersen LF, Sidelmann J, Petersen KR, Jespersen J "Hormone replacement therapy: Estrogen and progestin effects on plasma C-reactive protein concentrations." Am J Obstet Gynecol 186(5 Pt 1) (2002): 969-977
48. Cundy T, Farquhar CM, Cornish J, Reid IR "Short-term effects of high dose oral medroxyprogesterone acetate on bone density in premenopausal women." J Clin Endocrinol Metab 81 (1996): 1014-7
49. Cundy T, Evans M, Roberts H, Wattie D, Ames R, Reid IR "Bone density in women receiving depot medroxyprogesterone acetate for contraception [published erratum appears in BMJ 1991 Jul27;303(6796):220]." BMJ 303 (1991): 13-6
50. Paiva LC, PintoNeto AM, Faundes A "Bone density among long-term users of medroxyprogesterone acetate as a contraceptive." Contraception 58 (1998): 351-5
51. Nand SL, Wren BG, Gross BA, Heller GZ "Bone density effects of continuous estrone sulfate and varying doses of medroxyprogesterone acetate." Obstet Gynecol 93 (1999): 1009-13
52. Grady D, Yaffe K, Kristof M, Lin F, Richards C, Barrett-Connor E "Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study." Am J Med 113 (2002): 543-8
53. Meyer WJ, 3d Wiener I, Emory LE, Cole CM, Isenberg N, Fagan CJ, Thompson JC "Cholelithiasis associated with medroxyprogesterone acetate therapy in men." Res Commun Chem Pathol Pharmacol 75 (1992): 69-84
54. Riippa P, Kauppila A, Sundstrom H, Vihko R "Hepatic impairment during simultaneous administration of medroxyprogesterone acetate and tamoxifen in the treatment of endometrial and ovarian carcinoma." Anticancer Res 4 (1984): 109-12
55. Zacest R, Cushway A, Haines C, Cox LW "Hypersensitivity reaction to Depo-Provera" Med J Aust 1 (1982): 12
56. Brooks GG "Anaphylactoid shock with medroxyprogesterone acetate: A case report." J La State Med Soc 126 (1974): 397-9
57. Bjorn I, Bixo M, Nojd KS, Nyberg S, Backstrom T "Negative mood changes during hormone replacement therapy: A comparison between two progestogens." Am J Obstet Gynecol 183 (2000): 1419-26
Not all side effects for Cycrin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
More about Cycrin (medroxyprogesterone)
Related treatment guides
Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.