Conjugated estrogens / medroxyprogesterone Side Effects
Commonly reported side effects of conjugated estrogens/medroxyprogesterone include: depression, headache, nausea, and mastalgia. Other side effects include: dizziness, and peripheral edema. See below for a comprehensive list of adverse effects.
For the Consumer
Applies to conjugated estrogens / medroxyprogesterone: oral tablet
In addition to its needed effects, some unwanted effects may be caused by conjugated estrogens / medroxyprogesterone. 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 conjugated estrogens / medroxyprogesterone:Less common:
- Bloating or swelling of the face, arms, hands, lower legs, or feet
- blood in the urine
- blurred vision
- chest pain
- clear or bloody discharge from the nipple
- cough or hoarseness
- dimpling of the breast skin
- fast, irregular, pounding, or racing heartbeat or pulse
- feeling faint, dizzy, or lightheaded
- feeling of warmth or heat
- fever or chills
- flushing or redness of the skin, especially on the face and neck
- inverted nipple
- lower back or side pain
- lump in the breast or under the arm
- pain during sexual intercourse
- painful or difficult urination
- persistent crusting or scaling of the nipple
- pounding in the ears
- redness or swelling of the breast
- severe cramping of the uterus
- sore on the skin of the breast that does not heal
- thick, white vaginal discharge with no odor or with a mild odor
- tingling of the hands or feet
- unusual weight gain or loss
- vaginal bleeding that is unusual and heavy
- vaginal or genital itching
- vaginal yeast infection
- Absent, missed, or irregular menstrual periods
- acid or sour stomach
- breast pain or tenderness
- darkened urine
- decreased vision or other changes in vision
- difficulty with speaking
- double vision
- inability to move the arms, legs, or facial muscles
- inability to speak
- loss of appetite
- pain or discomfort in the arms, jaw, back, or neck
- pain or feeling of pressure in the pelvis
- pain, redness, or swelling in the arm or leg
- painful or tender cysts in the breasts
- pains in the stomach, side, or abdomen, possibly radiating to the back
- slow speech
- sudden shortness of breath or troubled breathing
- unexpected or excess milk flow from the breasts
- yellow eyes or skin
Minor Side Effects
Some of the side effects that can occur with conjugated estrogens / 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:More common:
- Back pain
- excess gas in the stomach or intestines
- lack or loss of strength
- Blemishes on the skin
- body aches or pain
- difficulty with moving
- dry skin
- dryness of the vagina
- excessive muscle tone
- feeling paranoid
- flu-like symptoms
- fullness or swelling of the breasts
- hair loss or thinning of the hair
- headache, severe and throbbing
- leg cramps
- loss of bladder control
- menstrual periods that are longer or heavier
- muscle pain or stiffness
- pain in the joints
- pain or tenderness around the eyes and cheekbones
- pimples or acne
- quick to react or overreact emotionally
- rapidly changing moods
- sore mouth or tongue
- stuffy or runny nose
- tender, swollen glands in the neck
- tightness of the chest or wheezing
- trouble with sleeping
- trouble with swallowing
- vaginal discharge that is clear or white
- voice changes
- white patches in the mouth or on the tongue
- Changes in appetite
- hives or welts
- inability to have or keep an erection
- increased hair growth, especially on the face
- increased interest in sexual intercourse
- loss in sexual ability, desire, drive, or performance
- loss of scalp hair
- pain in the ankles or knees
- painful, red lumps under the skin, mostly on the legs
- patchy brown or dark brown discoloration of the skin
- redness of the skin
- weight changes
For Healthcare Professionals
Applies to conjugated estrogens / medroxyprogesterone: oral tablet
General side effects have included headache (28% to 36%), abdominal pain (16% to 23%), asthenia (6% to 10%), back pain (13% to 16%), and flu-like symptoms (10% to 13%), pelvic pain (4% to 5%), infection (14% to 18%), and generalized pain (11% to 13%).[Ref]
The manufacturer recommends close observation if conjugated estrogens must be used in patients who may be particularly sensitive to fluid retention because of underlying asthma, epilepsy, migraine, heart disease, and renal dysfunction.[Ref]
Metabolic side effects of estrogen have included increased serum triglyceride levels resulting in pancreatitis in patients with familial lipoprotein metabolic defects. However, metabolic effects in patients treated with conjugated estrogens include generally favorable alterations in plasma lipid profiles. Specifically, increased HDL and decreased cholesterol and LDL levels occur.
Metabolic side effects of medroxyprogesterone have included weight changes (increases and decreases), glucose intolerance, and changes in serum cholesterol concentrations.[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.
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]
Cardiovascular side effects of estrogens have included increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism.
Cardiovascular side effects of medroxyprogesterone 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 reported. 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]
A number of studies have suggested that the risk of endometrial carcinoma is removed (or delayed) by the administration of progestins in combination with estrogen therapy.
The risk of breast cancer due to use of conjugated estrogens is controversial. Meta analysis of epidemiological data supports a modest risk increase associated with long-term hormone replacement therapy (HRT).
A study of Swedish women has reported that a 10% increase in the relative risk of breast cancer may occur and that the risk is related to increasing duration of estrogen use had a 70% greater relative risk of breast cancer than controls. That study, however, examined use of a variety of estrogen preparations of which estradiol was the most frequently prescribed. In addition, women who took progestins did not demonstrate a decreased risk of breast cancer and may even have been at higher risk.
The Toronto Breast Cancer Study has reported that women who receive unopposed conjugated estrogens for less than 15 years are not at increased risk of breast cancer. In that study, an increase in the risk of breast cancer for women who used conjugated estrogens form more than 15 years was not ruled out.
The Case Control Surveillance Study reported "no evidence that the use of unopposed conjugated estrogens increases the risk of breast cancer, even after long duration of use or long latent intervals, but the possibility of a modest increase (less than doubling) could not be excluded."
Follow-up data to the Nurses' Health Study of 1992 concluded, however, that there is an increased risk of breast cancer in women taking estrogen replacement therapy and that the risk is not reduced by concurrent use of progestins. (In that study, greater risk was associated with advanced age and prolonged duration of hormonal therapy.)
A study of middle-aged women in the Puget Sound area concluded that "on the whole, the use of estrogen with progestin HRT [hormone replacement therapy] does not appear to be associated with an increased risk of breast cancer in middle-aged women."
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 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 New Zealand study 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.
A prospective cohort study (11 years) of 37,105 women by Gapstur et al evaluated the histology of the breast cancer in women with ever HRT use. Little evidence of association was found between duration of ever HRT use and the incidence of ductal carcinoma in situ or invasive ductal/lobular carcinoma. The duration of ever HRT use was associated with risk of invasive carcinoma with a favorable prognosis [relative risk (RR) = 1.81, 95% confidence interval (CI), 1.07 to 3.07 for HRT use less than or equal to 5 years and RR = 2.65, CI, 1.32 to 5.23 for HRT use > 5 years, p = 0.005]. The relative risk of invasive carcinoma with a favorable prognosis for current users (adjusted for age and other risk factors) was 4.42, CI, 2.00 to 9.76 for less than or equal to 5 years and 2.63, CI 1.18 to 5.89 for > 5 years). Risk of invasive ductal or lobular carcinoma for current users less than or equal to 5 years was RR = 1.38, CI, 1.03 to 1.85.[Ref]
Oncologic side effects of unopposed estrogen therapy have included an increased risk of endometrial carcinoma and breast cancer.[Ref]
Gastrointestinal side effects of conjugated estrogen therapy have included nausea and vomiting. Some studies have demonstrated a 2 to 4 fold increase in gallbladder disease in postmenopausal women taking estrogen therapy.
Gastrointestinal side effects of medroxyprogesterone have included nausea, abdominal pain, bloating, and anorexia in up to 5% of patients treated.
Postmarketing reports have included ischemic colitis.[Ref]
Cases of oral pigmentation and ischemic colitis have been reported rarely.[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]
Genitourinary side effects of conjugated estrogens-medroxyprogesterone have included mastodynia (12% to 38%). Dysmenorrhea and pelvic pain have also been reported.
Conjugated estrogens may also cause abnormal uterine bleeding (which must be carefully distinguished from bleeding related to endometrial carcinoma). In addition, conjugated estrogens may increase the size of preexisting uterine leiomyomata. Several cases of pseudoincontinence (excessive vaginal discharge perceived by patients as urinary incontinence) have been reported in premenopausal women who have undergone hysterectomy oophorectomy and received postoperative conjugated estrogens.
Genitourinary side effects of medroxyprogesterone have included primarily menstrual changes such as amenorrhea, irregular bleeding, spotting, and heavy bleeding. Changes in libido and anorgasmia may also occur.[Ref]
Cushing's syndrome is uncommon and appears to be associated with a long duration of therapy and moderate to high doses of medroxyprogesterone. 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 ensure following withdrawal of medroxyprogesterone.[Ref]
Endocrine side effects of estrogen have included increased levels of thyroxin-binding globulin, leading to an increase in total thyroid serum levels and a decrease in resin uptake of T3. Free thyroid hormone levels remain unchanged. Other endocrine effects include decreased fasting plasma glucose.
Endocrine side effects of medroxyprogesterone have included breast tenderness, galactorrhea with or without hyperprolactinemia, prevention of lactation, hirsutism, and Cushing's syndrome.[Ref]
Dermatologic side effects of conjugated estrogens have included pruritus and rash (5% to 10%).
Dermatologic side effects of medroxyprogesterone have included acne, reduced hair growth, alopecia, melasma, chloasma, rash, excessive sweating, dry skin, scleroderma, erythema multiforme, and erythema nodosum. Melasma may persist following discontinuation of therapy.[Ref]
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 greater than 2 years 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]
Musculoskeletal side effects of medroxyprogesterone have included changes in bone mineral density. Such effect are thought to be due to medroxyprogesterone induced estrogen deficiency. Arthralgias and leg cramps have also been reported.[Ref]
Nervous system side effects have included headache, migraine, dizziness, mental depression, exacerbation of chorea, mood disturbances, anxiety, irritability, exacerbation of epilepsy, dementia, and growth potentiation of benign meningioma. A case of chorea has been reported in association with conjugated estrogen therapy.[Ref]
Hepatic side effects of estrogen therapy have included cases of focal nodular hyperplasia, liver cell adenomas, hepatic hemangiomas and well differentiated hepatocellular carcinomas.
Hepatic side effects associated with medroxyprogesterone therapy have included elevations in liver function tests, jaundice, cholestatic jaundice, and cholelithiasis.[Ref]
Many of the reports of hepatic tumors have occurred in women taking long-term oral contraceptives. However, some tumors have been reported in women taking isolated estrogen therapy.[Ref]
Hypersensitivity side effects of conjugated estrogen have included anaphylaxis. Some of these reactions may have been associated with the dyes contained in some conjugated estrogen formulations.
Hypersensitivity side effects of medroxyprogesterone have included urticaria, angioneurotic edema, and anaphylaxis or anaphylactoid reactions[Ref]
Rare cases of exacerbations of pulmonary lymphangioleiomyomatosis have occurred. In addition, combinations of high-dose conjugated estrogens and progestin have been reported to increase the hypoxic ventilatory response.[Ref]
Respiratory side effects of conjugated estrogens-medroxyprogesterone have included pharyngitis (11% to 13%), rhinitis and sinusitis (5% to 8%).[Ref]
Other side effects of estrogen therapy have included a possible increase the risk of "fibrocystic breast disease" by as much as twofold.[Ref]
Psychiatric side effects of conjugated estrogens have included cases of rapid mood cycling in patients with severe depression.[Ref]
Hematologic side effects of conjugated estrogens have included hypercoagulability.
Hematologic side effects of medroxyprogesterone have included rare reports of hematologic dyscrasias. Hypercoagulability with or without thromboembolic activity has been reported.[Ref]
1. "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
2. "Product Information. Prempro (conjugated estrogens-medroxyprogesterone)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
3. 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
4. Pripp U, Hall G, Csemiczky G, Eksborg S, Landgren BM, SchenckGustafsson K "A randomized trial on effects of hormone therapy on ambulatory blood pressure and lipoprotein levels in women with coronary artery disease." J Hypertens 17 (1999): 1379-86
5. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
6. Grodstein F, Stampfer MJ, Manson JE "Postmenopausal estrogen and progestin use and the risk of cardiovascular disease." N Engl J Med 335 (1996): 453-61
7. 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
8. 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
9. Harrison RF, Magill P, Kilminster SG "Impact of a new formulation of low-dose micronised medroxyprogesterone and 17-beta estradiol on lipid profiles in menopausal women." Clin Drug Invest 16 (1998): 93-9
10. Kaunitz AM "Long-acting injectable contraception with depot medroxyprogesterone acetate." Am J Obstet Gynecol 170 (1994): 1543-9
11. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn, Kalamazoo, MI.
12. Teichmann AT, Wander HE, Cremer P, et al. "Medroxyprogesterone acetate and lipid metabolic changes." Arzneimittelforschung 37 (1987): 573-77
13. 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
14. Leiman G "Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure." Am J Obstet Gynecol 114 (1972): 97-102
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. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E "Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women." JAMA 280 (1998): 605-13
18. 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
19. The Writing Group for the PEPI Trial "Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial." JAMA 273 (1995): 199-208
20. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
21. Crane MG, Harris JJ "Estrogens and hypertension: effect of discontinuing estrogens on blood pressure, exchangeable sodium, and the renin-aldosterone system." Am J Med Sci 276 (1978): 33-55
22. Schwartz J, Freeman R, Frishman W "Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women." J Clin Pharmacol 35 (1995): 1-16
23. Wren BG, Routledge DA "Blood pressure changes: oestrogens in climacteric women." Med J Aust 2 (1981): 528-31
24. 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
25. Herrington DM "The HERS Trial results: paradigms lost?" Ann Intern Med 131 (1999): 463-6
26. Grady D, Rubin SM, Petiti DB, et al. "Hormone therapy to prevent disease and prolong life in postmenopausal women." Ann Intern Med 117 (1992): 1016-36
27. Rosenberg L, Slone D, Shapiro S, Kaufman D, Stolley PD, Miettinen OS "Noncontraceptive estrogens and myocardial infarction in young women." JAMA 244 (1980): 339-42
28. Stampfer MJ, Colditz GA, Willett WC, et al. "Postmenopausal estrogen and cardiovascular disease. Ten-year follow-up from the Nurses' Health Study." N Engl J Med 325 (1991): 756-62
29. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
30. Crane MG, Harris JJ, Winsor W 3d "Hypertension, oral contraceptive agents, and conjugated estrogens." Ann Intern Med 74 (1971): 13-21
31. Barrett-Connor E, Wingard DL, Criqui MH "Postmenopausal estrogen use and heart disease risk factors in the 1980s. Rancho Bernardo, Calif, revisited." JAMA 261 (1989): 1095-2100
32. Jick H, Dinan B, Rothman KJ "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA 239 (1978): 1407-8
33. 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
34. Stanford JL, Weiss NS, Voigt LF, Daling JR, Habel LA, Rossing MA "Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women." JAMA 274 (1995): 137-42
35. Gordon J, Reagan JW, Finkle WD, Ziel HK "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate." N Engl J Med 297 (1977): 570-1
36. Lavecchia C "Depot-medroxyprogesterone acetate, other injectable contraceptives, and cervical neoplasia." Contraception 49 (1994): 223-30
37. Jordan A "Toxicology of depot medroxyprogesterone acetate." Contraception 49 (1994): 189-201
38. Palmer JR, Rosenberg L, Clarke EA, Miller DR, Shapiro S "Breast cancer risk after estrogen replacement therapy: results from the Toronto Breast Cancer Study." Am J Epidemiol 134 (1991): 1386-95
39. Skegg DC, Noonan EA, Paul C, Spears GF, Meirik O, Thomas DB "Depot medroxyprogesterone acetate and breast cancer." JAMA 273 (1995): 799-807
40. Chilvers C "Breast cancer and depot-medroxyprogesterone acetate - a review." Contraception 49 (1994): 211-22
41. Shapiro S, Kelly JP, Rosenberg L, Kaufman DW, Helmrich SP, Rosenshein NB, Lewis JL Jr, Knapp RC, Stolley PD, Schottenfeld D "Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens." N Engl J Med 313 (1985): 969-72
42. Persson I, Adami HO, Bergkvist L, Lindgren A, Pettersson B, Hoover R, Schairer C "Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study." BMJ 298 (1989): 147-51
43. Spengler RF, Clarke EA, Woolever CA, Newman AM, Osborn RW "Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases." Am J Epidemiol 114 (1981): 497-506
44. Buring JE, Bain CJ, Ehrmann RL "Conjugated estrogen use and risk of endometrial cancer." Am J Epidemiol 124 (1986): 434-41
45. "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
46. Hoover R, Glass A, Finkle WD, Azevedo D, Milne K "Conjugated estrogens and breast cancer risk in women." J Natl Cancer Inst 67 (1981): 815-20
47. 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
48. "Breast cancer and depot-medroxyprogesterone acetate: a multinational study. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 338 (1991): 833-8
49. "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
50. 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
51. Thomas DB, Persing JP, Hutchinson WB "Exogenous estrogens and other risk factors for breast cancer in women with benign breast diseases." J Natl Cancer Inst 69 (1982): 1017-25
52. Kaufman DW, Palmer JR, de Mouzon J, Rosenberg L, Stolley PD, Warshauer ME, Zauber AG, Shapiro S "Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study." Am J Epidemiol 134 (1991): 1375-85
53. 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
54. Colditz GA, Hankinson SE, Hunter DJ, et al. "The use of estrogens and progestins and the risk of breast cancer in postmenopausal women." N Engl J Med 332 (1995): 1589-93
55. Lumbiganon P "Depot-medroxyprogesterone acetate (DMPA) and cancer of the endometrium and ovary." Contraception 49 (1994): 203-9
56. "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
57. "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
58. Antunes CM, Strolley PD, Rosenshein NB, Davies JL, Tonascia JA, Brown C, Burnett L, Rutledge A, Pokempner M, Garcia R "Endometrial cancer and estrogen use. Report of a large case-control study." N Engl J Med 300 (1979): 9-13
59. Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C "The risk of breast cancer after estrogen and estrogen-progestin replacement." N Engl J Med 321 (1989): 293-7
60. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
61. "Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives" Lancet 2 (1984): 1207-8
62. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9
63. Perusse R, Morency R "Oral pigmentation induced by Premarin." Cutis 48 (1991): 61-4
64. Boston Collaborative Drug Surveilance Program "Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy." N Engl J Med 290 (1974): 15-9
65. McClennan BL "Ischemic colitis secondary to Premarin: report of a case." Dis Colon Rectum 19 (1976): 618-20
66. Husson RN, Mueller BU, Farley M, Woods L, Kovacs A, Goldsmith JC, Ono J, Lewis LL, Balis FM, Brouwers P, Avramis VI, Churc "Zidovudine and didanosine combination therapy in children with human immunodeficiency virus infection." Pediatrics 93 (1994): 316-22
67. Mukherjea M, Mukherjee P, Biswas R "Long-term contraception with Depo-Provera: a clinical evaluation." Int J Fertil 25 (1980): 122-6
68. Julian TM "Pseudoincontinence secondary to unopposed estrogen replacement in the surgically castrate premenopausal female." Obstet Gynecol 70 (1987): 382-3
69. 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
70. Fraser IS "Menstrual changes associated with progestogen-only contraception." Acta Obstet Gynecol Scand Suppl 134 (1986): 21-7
71. Fraser IS "A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives." Contraception 28 (1983): 385-97
72. Kaunitz AM "Injectable depot medroxyprogesterone acetate contraception: An update for U.S. clinicians." Int J Fertil Womens Med 43 (1998): 73-83
73. 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
74. 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
75. 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
76. Molitch ME, Oill P, Odell WD "Massive hyperlipemia during estrogen therapy." JAMA 227 (1974): 522-5
77. 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
78. Virutamasen P, Leepipatpaiboon S, Kriengsinyot R, Vichaidith P, Muia PN, Sekaddekigondu CB, Mati JKG, Forest MG, Dikkeschei LD "Pharmacodynamic effects of depot-medroxyprogesterone acetate (DMPA) administered to lactating women on their male infants." Contraception 54 (1996): 153-7
79. Wortsman J, Hirschowitz JS "Galactorrhea and hyperprolactinemia during treatment of polycystic ovary syndrome." Obstet Gynecol 55 (1980): 460-3
80. Siminoski K, Goss P, Drucker DJ "The Cushing syndrome induced by medroxyprogesterone acetate." Ann Intern Med 111 (1989): 758-60
81. Learoyd D, McElduff A "Medroxyprogesterone induced Cushing's syndrome." Aust N Z J Med 20 (1990): 824-5
82. 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
83. Grenfell A, Rudenski A, Watts M, Wiltshire C, Day JL, Gray IP "Cushing's syndrome and medroxyprogesterone acetate" Lancet 336 (1990): 256
84. Donckier JE, Michel LA, Buysschaert M "Cushing syndrome and medroxyprogesterone acetate" Lancet 335 (1990): 1094
85. Cundy T, Cornish J, Roberts H, Elder H, Reid IR "Spinal bone density in women using depot medroxyprogesterone contraception." Obstet Gynecol 92 (1998): 569-73
86. The Writing Group for the PEPI Trial "Effects of hormone therapy on bone mineral density." JAMA 276 (1996): 1389-96
87. OrrWalker BJ, Evans MC, Ames RW, Clearwater JM, Cundy T, Reid IR "The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women." Clin Endocrinol 49 (1998): 615-8
88. 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
89. Gbolade B, Ellis S, Murby B, Randall S, Kirkman R "Bone density in long term users of depot medroxyprogesterone acetate." Br J Obstet Gynaecol 105 (1998): 790-4
90. Steiger MJ, Quinn NP "Hormone replacement therapy induced chorea." BMJ 302 (1991): 762
91. 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
92. 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
93. Aldinger K, Ben-Menachem Y, Whalen G "Focal nodular hyperplasia of the liver associated with high-dosage estrogens." Arch Intern Med 137 (1977): 357-9
94. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9
95. Searcy CJ, Kushner M, Nell P, Beckmann CR "Anaphylactic reaction to intravenous conjugated estrogens." Clin Pharm 6 (1987): 74-6
96. Zacest R, Cushway A, Haines C, Cox LW "Hypersensitivity reaction to Depo-Provera" Med J Aust 1 (1982): 12
97. Caucino JA, Armenaka M, Rosenstreich DL "Anaphylaxis associated with a change in premarin dye formulation." Ann Allergy 72 (1994): 33-5
98. Brooks GG "Anaphylactoid shock with medroxyprogesterone acetate: A case report." J La State Med Soc 126 (1974): 397-9
99. Jick SS, Walker AM, Jick H "Conjugated estrogens and fibrocystic breast disease." Am J Epidemiol 124 (1986): 746-51
100. Pastides H, Najjar MA, Kelsey JL "Estrogen replacement therapy and fibrocystic breast disease." Am J Prev Med 3 (1987): 282-6
101. Oppenheim G "A case of rapid mood cycling with estrogen: implications for therapy." J Clin Psychiatry 45 (1984): 34-5
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