Conjugated Estrogens

Conjugatedestrogensare 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 andpainful intercourse. Using conjugated estrogens can help treat such symptoms in menopausal women. Conjugated estrogens can also help inpreventionof bone loss in menopausal women.

Examples of oral conjugated estrogens are:

• Enjuvia,
• Cenestin, and
• Premarin.

Premarin vaginal creamis 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 ofpregnanthorses.

There are many side effects of conjugated estrogens. Common side effects of conjugated estrogens arenausea,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 withheart failureor reduced function of their kidneys who are taking estrogens should be carefully observed for retention of water and its complications.

Blood clotsin the legs (deep vein thrombosis orDVT) orlungs(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.Cigarettesmokersare at a higher risk for blood clots. Therefore, patients requiring estrogen therapy shouldquit smoking.

Estrogens can promote a build-up of the lining of the uterus (endometrial hyperplasia) and increase the risk ofendometrial 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 endometrialcancer.

The Women's Health Initiative found thatpostmenopausalwomen (50 to 79 years old) taking conjugated estrogens, 0.625 mg daily, in combination withmedroxyprogesterone(Provera,Depo-Provera,Depo-Sub Q Provera 104), 2.5 mg daily, for five years, had an increased risk ofheart attacks,stroke,breast cancer, and blood clots, while postmenopausal women taking conjugated estrogens withoutprogesteroneexperienced only increasedstrokesbut not increased blood clots,heart disease, or breastcancer.

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

Medications likeSt. 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 likeerythromycin,clarithromycin(Biaxin, Biaxin XL),ketoconazole(Nizoral,Extina,Xolegel,Kuric), andritonavircan slow down the breakdown of conjugated estrogens in theliver, 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 duringpregnancybecause it may causebirth defectsin the unborn. Use of conjugated estrogens is not recommended innursingmothers because conjugated estrogens enterbreast milkand may have harmful effects on thenewborn. Conjugated estrogens can also affect the quality and quantity of breast milk.