Conjugated Estrogens (Cenestin, Enjuvia, Estrace, and Others)

  • Pharmacy Author:
    Omudhome Ogbru, PharmD

    Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.

  • Medical and Pharmacy Editor: Jay W. Marks, MD
    Jay W. Marks, MD

    Jay W. Marks, MD

    Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

What are the side effects of conjugated estrogens?

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.

What drugs interact with conjugated estrogens?

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.

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