estrogens conjugated (Premarin)

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 approximate the composition of estrogens in the urine of pregnant horses. 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).

Premarin

GENERIC AVAILABLE: No.

Yes.

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.

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 continuously or in a cyclical fashion (i.e., 25 days on treatment then 5 days off treatment).

Hypogonadism is treated cyclically with doses of 0.3 mg or 0.625 mg daily for 25 days followed by 5 days off treatment.

The dose for women who have had their ovaries removed or have ovarian failure is 1.25 mg daily for three weeks followed by 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.

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 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.

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

Estrogens are secreted in breast milk and may cause unpredictable effects in the infant. Estrogens may also reduce the quality of breast milk. They should not be taken by women who are breastfeeding.

What preparations of estrogens conjugated are available?

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 per vial

How should I keep estrogens conjugated stored?

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