Side Effects of Premarin (conjugated estrogens)

WARNING

ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA

Estrogen-Alone Therapy

Endometrial Cancer

• 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.
• Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Cardiovascular Disorders and Probable Dementia

• Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.
• The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo.
• The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an 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.
• Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estrogen Plus Progestin Therapy

Cardiovascular Disorders and Probable Dementia

• Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.
• The WHI estrogen plus progestin substudy reported increased risks of 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 CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.
• The WHIMS estrogen plus progestin ancillary study of the WHI, reported an 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.

Breast Cancer

• The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.
• In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other 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 consistent with treatment goals and risks for the individual woman.

Common side effects of conjugated estrogens are:

• headache,
• abdominal pain,
• nervousness,
• nausea,
• back pain,
• joint pain and
• vaginal bleeding.

Other side important effects include:

• vaginal spotting,
• loss of periods or
• excessively prolonged periods,
• breast pain,
• breast enlargement and
• an increase or decrease in sexual drive.

Effects of estrogen on the skin include rash, and melasma (tan or brown patches) that may develop on the forehead, cheeks, or temples and may persist even after estrogens are stopped.

In the eyes, conjugated estrogens may cause an increase in the curvature of the cornea, and, as a result, patients with contact lenses may develop intolerance to their lenses.

Estrogens may increase calcium levels in the blood (hypercalcemia) in patients with breast and bone cancer.

Some patients may experience increased blood pressure and triglyceride levels.

There is an increased risk of cholesterol gallstones among men and women taking estrogens.

Estrogens also may inhibit the flow of bile from the liver (cholestasis) and uncommonly cause jaundice.

Estrogens can cause salt (sodium) and water retention (edema). Therefore, patients with heart failure or reduced function of their kidneys who are taking estrogens should be carefully observed for retention of water and its complications.

Blood clots in the legs or lungs occasionally occur in women taking conjugated estrogens. This potentially serious complication of estrogen therapy is dose-related, that is, it occurs more commonly with higher doses. Therefore, the lowest effective doses that relieve symptoms should be used.

Cigarette smokers are at a higher risk for blood clots. Therefore, patients requiring estrogen therapy should quit smoking.

Estrogens can promote a build up of the lining of the uterus (endometrial hyperplasia) and increase the risk of endometrial cancer. (Women who have undergone surgical removal of the uterus--hysterectomy--are not susceptible to endometrial hyperplasia.) The addition of a progestin to estrogen therapy prevents the development of endometrial cancer.

The Women's Health Initiative found that postmenopausal women (50-79 years old) taking conjugated estrogens, 0.625 mg daily, in combination with medroxyprogesterone, 2.5 mg daily, for five years, had an increased risk of heart attacks, stroke, breast cancer, and blood clots, while postmenopausal women taking conjugated estrogens without progesterone experienced only increased strokes but not increased blood clots, heart disease, or breast cancer.

There was an increased risk of impaired cognition and/or dementia among women over age 65 treated with either estrogens or estrogens and medroxyprogesterone.