Note: This document contains side effect information about conjugated estrogens / medroxyprogesterone. Some of the dosage forms listed on this page may not apply to the brand name Premphase.
Applies to conjugated estrogens/medroxyprogesterone: oral tablet
Oral route (Tablet)
Estrogen with or without progestin should not be used for the prevention of cardiovascular disease or dementia. Increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years) using estrogen alone have been reported. Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years) using estrogen combined with progestin have been reported. An increased risk of developing probable dementia in postmenopausal women 65 years or older has also been reported in women receiving estrogen alone or estrogen combined with progestin. Unopposed estrogens increase the risk of endometrial cancer. Adding a progestin will reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Diagnostic measures should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. Risks should be assumed to be similar for other doses, combinations, and dosage forms of estrogens and progestins. Estrogens, with or without progestins, should be prescribed at the lowest effective doses and for the shortest duration possible.
Along with its needed effects, conjugated estrogens / medroxyprogesterone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking conjugated estrogens / medroxyprogesterone:
Incidence not known
Some side effects of conjugated estrogens / medroxyprogesterone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Incidence not known
Applies to conjugated estrogens / medroxyprogesterone: oral tablet
The most commonly reported adverse events have included abdominal pain, asthenia, back pain, headache, flatulence, nausea, depression, pruritus, breast pain, dysmenorrhea, and leukorrhea.
The Women's Health Initiative (WHI) sub-study reports an increased risk of deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women 50 to 79 years old with a duration of 5.6 years of daily conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg use compared with placebo. The WHI estrogen-alone study reported increased risks of stroke and DVT during 7.1 years of daily conjugated estrogen treatment.
-Stroke Risk (WHI substudy; conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg daily): A statistically significant increased stroke risk: 33 versus 25 per 10,000 women-years
-Coronary Heart Disease (WHI substudy; conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg): A statistically non-significant increased risk: 41 versus 34 per 10,000 women-years
-Venous Thromboembolism (VTE): (WHI substudy; conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg): A statistically significant (VTE) risk: 35 versus 17 per 10,000 women-years. Specifically, DVT: 26 versus 13 per 10,000 women-years and PE:18 versus 8 per 10,000 women-years
The Heart and Estrogen/Progestin Replacement Study (HERS) demonstrated no cardiovascular benefit in postmenopausal women with established coronary heart disease (CHD) taking daily conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg (average follow-up of 4.1 years). In the HERS II study, an open label extension of HERS, an additional 2.7 years of follow-up showed rates of CHD remained comparable to placebo.
Common (1% to 10%): Chest pain, generalized edema, hypertension, vasodilation, edema
Uncommon (0.1% to 1%): Palpitation
Postmarketing reports: Deep and superficial venous thrombosis, pulmonary embolism, superficial thrombophlebitis, myocardial infarction, stroke, increase in blood pressure
Common (1% to 10%): Breast neoplasm
Uncommon (0.1% to 1%): Endometrial hyperplasia
Postmarketing reports: Ovarian cancer, endometrial hyperplasia, endometrial cancer, breast cancer
Breast Cancer: An increased risk of breast cancer was reported in the WHI substudy of daily conjugated estrogen 0.626 mg-medroxyprogesterone 2.5 mg use. After a mean follow-up of 5.6 years, the risk was 41 versus 33 cases per 10,000 women. In the women taking conjugated estrogen-medroxyprogesterone, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage. Metastatic disease was rate and not different compared to placebo.
Ovarian Cancer: A statistically non-significant risk of ovarian cancer was reported in the WHI substudy of daily conjugated estrogen 0.626 mg-medroxyprogesterone 2.5 mg use. After a mean follow-up of 5.6 years, the risk was 4 versus 3 cases per 10,000 women. A large meta-analysis showed a significant increased risk of ovarian cancer in women using both estrogen-alone and estrogen plus progestin. The duration of hormone therapy use associated with an increased risk of ovarian cancer is unknown.
Very common (10% or more): Breast pain (up to 36%)
Common (1% to 10%): Breast enlargement
Uncommon (0.1% to 1%): Breast engorgement
Postmarketing reports: Breast tenderness, breast enlargement, breast pain, nipple discharge, galactorrhea, fibrocystic breast changes, changes in libido
Very common (10% or more): Dysmenorrhea (up to 13%)
Common (1% to 10%): Pelvic pain, cervix disorder, leukorrhea, menstrual disorder, metrorrhagia, suspicious PAP smear, vaginal moniliasis, vaginitis, uterine spasm, vaginal hemorrhage
Uncommon (0.1% to 1%): Menorrhagia, urinary incontinence, hematuria, urinary tract infection, vaginal dryness
Postmarketing reports: Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, vaginal candidiasis, amenorrhea, changes in cervical secretion
Postmarketing reports: Anaphylaxis, angioedema, hypersensitivity
Common (1% to 10%): Decreased glucose tolerance (hyperglycemia), weight gain
Uncommon (0.1% to 1%): Increased appetite
Postmarketing reports: Appetite changes, weight increases and decreases, glucose intolerance, increased triglycerides
Very common (10% or more): Abdominal pain (up to 17%)
Common (1% to 10%): Diarrhea, dyspepsia, eructation, flatulence, nausea
Frequency not reported: Gallbladder disease
Postmarketing reports: Nausea, vomiting, abdominal pain, bloating, increased incidence of gallbladder disease, pancreatitis ischemic colitis
Common (1% to 10%): Pruritus, Rash
Uncommon (0.1% to 1%): Acne, alopecia, dry skin, sweating, skin discoloration
Postmarketing reports: Chloasma or melasma that may persist when drug is discontinue, erythema multiforme, erythema nodosum, loss of scalp hair, hirsutism, pruritus, urticaria, rash, acne
Common (1% to 10%): Back pain, arthralgia, leg cramps
Postmarketing reports: Arthralgia
In the WHIMS (Women's Health Initiative Memory Study) an ancillary study of WHI, the absolute risk of probable dementia for conjugated estrogen 0.625 mg-medroxyprogesterone 2.5 mg was 45 versus 22 cases per 10,000 women-years. These studies were conducted in women 65 to 79 years old and therefore it is unknown if this risk applies to younger postmenopausal women.
Very common (10% or more): Headache (up to 19%)
Common (1% to 10%): Migraine, dizziness, hypertonia
Postmarketing reports: Headache, migraine, dizziness, exacerbation of chorea, exacerbation of epilepsy, growth potentiation of benign meningioma
Common (1% to 10%): Emotional lability, depression, Insomnia, nervousness, anxiety
Postmarketing reports: Mental depression, mood disturbances, anxiety, irritability, dementia
Postmarketing reports: Cholestatic jaundice
Common (1% to 10%): Pharyngitis, sinusitis
Postmarketing reports: Asthma exacerbation
Common (1% to 10%): Asthenia, pain
Common (1% to 10%): Flu syndrome
Uncommon (0.1% to 1%): Infection, moniliasis
Medically reviewed by BestRx Medical Team Last updated on 1/1/2020.
Source: Drugs.com Premphase