Indicated in a woman with a uterus for:

Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause

Prevention of Postmenopausal Osteoporosis

Estrogen Plus Progestin Therapy:

• Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia
• Increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo
• The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer
• Increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women

Estrogen-Alone Therapy:

• There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
• Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia
• Increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo
•  Increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens

PREMPRO or PREMPHASE therapy should not be used in women with any of the following conditions:

• Undiagnosed abnormal genital bleeding

• Known, suspected, or history of breast cancer

• Known or suspected estrogen-dependent neoplasia

• Active DVT, PE, or a history of these conditions

• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions

• Known anaphylactic reaction or angioedema to PREMPRO/PREMPHASE

• Known liver dysfunction or disease

• Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

• Known or suspected pregnancy

A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases.

Retinal vascular thrombosis has been reported in women receiving estrogens.

In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis.

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens.

Estrogens may be poorly metabolized in women with impaired liver function.

A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.

Cases of anaphylaxis, which developed within minutes to hours after taking PREMPRO or PREMPHASE and require emergency medical management, have been reported in the postmarketing setting.

Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.

Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.

Estrogens plus progestins may cause some degree of fluid retention. Women with conditions that might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogens plus progestins are prescribed.

If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.

Inducers of CYP3A4, such as St. John’s wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects.

Aminoglutethimide administered concomitantly with MPA may significantly depress the bioavailability of MPA.

PREMPRO and PREMPHASE should not be used during pregnancy.

PREMPRO and PREMPHASE should not be used during lactation.

GoToSource

• Use in patients under the age of 18. GoToSource

• Alzheimer’s disease. GoToSource

• Androgenic alopecia. GoToSource

• Colorectal cancer. GoToSource 

• Hypoactive sexual desire disorder. GoToSource 

• Anti-aging therapy. GoToSource

Breast cancer, uterine cancer, stroke, heart attack, blood clots, dementia and gallbladder disease. GoToSource

Pulmonary emboli (blockage in lung artery) and deep vein thrombosis (blood clot that forms in a vein deep inside the body). GoToSource

Ovarian cancer. GoToSource 

Nephrolithiasis (kidney stones). GoToSource

Increase seizure activity in women with epilepsy. GoToSource

Endometrial cancer. GoToSource

Hypertension (high blood pressure). GoToSource

Exacerbation of asthma. GoToSource

Worsening of coronary atherosclerosis in patients with diabetes or impaired glucose tolerance. GoToSource

Exacerbation of migraine. GoToSource

Systemic lupus erythematosus flares. GoToSource

Liver tumors. GoToSource

Increased risk of cataracts. GoToSource

Lawsuits filed for breast cancer, heart attacks and strokes.