Pharmacy and Medical Editor: Jay W. Marks, MD

GENERIC NAME: conjugated estrogens

BRAND NAME: Premarin

DRUG CLASS AND MECHANISM: Estrogens are one of the two major classes of female hormones. (Progestins comprise the second major class). Estrogens are used primarily to treat the symptoms of menopause and states in which there is a deficiency of estrogen, for example, in women who have had their ovaries removed.

Conjugated estrogens are a mixture of several different estrogens (estrogen salts) that are derived from natural sources and blended to the approximate composition of estrogens in the urine of pregnant mares. The main components are sodium estrone sulphate and sodium equilin sulfate. Estrogens have widespread effects on many tissues in the body. Estrogens cause growth and development of the female sexual organs and maintain female sexual characteristics such as the growth of underarm and pubic hair, body contours and skeleton. Estrogens also increase secretions from the cervix and growth of the inner lining of the uterus (endometrium).

PRESCRIPTION: Yes.

GENERIC AVAILABLE: No.

PREPARATIONS: Tablets: 0.3, 0.45, 0.625, 0.9, and 1.25 mg. Vaginal cream: 0.625 mg per gm of cream. Injection: 25 mg

STORAGE: Conjugated estrogen tablets and cream should be stored at room temperature, between 15-30°C (59-86°F). The injection should be stored between 2° and 8°C (36° and 46°F).

PRESCRIBED FOR: Conjugated estrogens are used for treating the symptoms of menopause including hot flashes, vaginal dryness, and vaginal atrophy. They also are used as therapy when the body does not produce enough estrogen due to castration (removal of the ovaries), ovarian failure or underdevelopment of hormone-secreting organs (hypogonadism). Conjugated estrogens also may be beneficial in treating advanced prostate and breast cancer. Although estrogens are approved for preventing osteoporosis, other drugs are more commonly prescribed for this purpose. Intravenous conjugated estrogens are used for treating abnormal uterine bleeding due to hormonal imbalance.

DOSING: To minimize side effects, the lowest effective oral dose of conjugated estrogens is used. The usual starting dose for treating symptoms associated with menopause and for preventing postmenopausal osteoporosis is 0.3 mg/day. The dose should be increased based on response. Conjugated estrogens may be administered in a continuous or cyclical interval (i.e., 25 days on treatment then 5 days off treatment).

Hypogonadism is treated with doses of 0.3 mg or 0.625 mg daily with a cyclical interval of 25 days on treatment followed by 5 days off treatment. The dose for women who have been castrated or have ovarian failure is 1.25 mg daily in a cyclical interval of three weeks on treatment and one week off treatment. In reality, most women take estrogens continuously since during the week off treatment, symptoms return because of the lack of estrogen. For treatment of breast cancer, the recommended dose is 10 mg daily for three months.

Abnormal uterine bleeding due to hormonal imbalance is treated with one 25 mg intravenous or intramuscular injection. Another injection may be given in 6-12 hours if needed.

The vaginal cream is used for treating vulvar and vaginal atrophy, and the recommended dose is ½ to 2 g daily.

DRUG INTERACTIONS: Estrogens increase the liver's ability to manufacture factors that promote the clotting of blood. Because of this, patients receiving warfarin (Coumadin), a drug that thins the blood and prevents clotting by reducing clotting factors, need to be monitored for loss of the blood thinning effect if treatment with an estrogen is begun.

Rifampin (Rifadin), barbiturates, carbamazepine (Tegretol), griseofulvin (Grifulvin), phenytoin (Dilantin), St. John's wort and primidone all increase the elimination of estrogen by enhancing the liver's ability to eliminate estrogens. Use of any of these medications with estrogens may result in a reduction of the beneficial effects of estrogens. Conversely, drugs such as erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox), and ritonavir (Norvir) may reduce the elimination of estrogens by the liver as and lead to increased levels of estrogens in the blood. Grapefruit juice also may increase levels of estrogen by increasing the absorption of estrogens from the intestine. Increased levels of estrogens in the blood may result in more estrogen-related side effects.

PREGNANCY: Estrogens should not be given to pregnant women due to the risk of harm to the fetus.

NURSING MOTHERS: Estrogens are secreted in breast milk and cause unpredictable effects in the infant. They should not be taken by women who are breast-feeding.

SIDE EFFECTS: Common side effects of conjugated estrogens include headache, abdominal pain, nervousness, nausea, back pain, joint pain and vaginal bleeding. Patients may also experience 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.

From the Doctors at MedicineNet.com

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