Conjugated Estrogens

Conjugated estrogens are mixtures of man-made or natural estrogens used as an external source and replacement for the natural female hormone. 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).

Menopausal women produce less estrogen which leads to symptoms of hot flashes, vaginal dryness, shrinking in vaginal tissue and painful intercourse. Using conjugated estrogens can help treat such symptoms in menopausal women. Conjugated estrogens can also help in prevention of bone loss in menopausal women.

Examples of oral conjugated estrogens are:

• Enjuvia,
• Cenestin, and
• Premarin.

Premarin vaginal cream is a topical form of estrogen.

Enjuvia and Cenestin are synthetic conjugated estrogens produced from plant material.

Premarin is derived from natural sources and blended to approximate the composition of estrogens found in urine of pregnant horses.

There are many side effects of conjugated estrogens. Common side effects of conjugated estrogens are nausea, headache, pain, swelling of breasts, weight change, abdominal pain, anxiety, edema, vaginal bleeding, and mood disturbances.

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 (deep vein thrombosis or DVT) or lungs (pulmonary embolism) 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 to 79 years old) taking conjugated estrogens, 0.625 mg daily, in combination with medroxyprogesterone (Provera, Depo-Provera, Depo-Sub Q Provera 104), 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.

Medications like St. John's Wort, phenobarbital, carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol), and rifampin (Rifadin) can accelerate the breakdown of conjugated estrogens, leading to low levels of absorbed drug and reduced effectiveness. Grapefruit juice and medications like erythromycin, clarithromycin (Biaxin, Biaxin XL), ketoconazole (Nizoral, Extina, Xolegel, Kuric), and ritonavir can slow down the breakdown of conjugated estrogens in the liver, leading to increased levels of estrogens and increased estrogen side effects.

Conjugated estrogens are available as oral tablets and topical cream.

Conjugated estrogens are not recommended during pregnancy because it may cause birth defects in the unborn. Use of conjugated estrogens is not recommended in nursing mothers because conjugated estrogens enter breast milk and may have harmful effects on the newborn. Conjugated estrogens can also affect the quality and quantity of breast milk.