Administration of estrogens by any route may result in many adverse reactions, although the incidence and intensity of these reactions vary. Some of the adverse reactions seen with the administration of estrogens include:

• Central nervous system—headache, migraine, dizziness, mental depression

• Dermatologic—chloasma (pigmentation of the skin) or melasma (discoloration of the skin), which may continue when use of the drug is discontinued

• Gastrointestinal—nausea, vomiting, abdominal cramps, dermatitis, pruritus

• Genitourinary—breakthrough bleeding, withdrawal bleeding, spotting, change in menstrual flow, dysmenorrheal, premenstrual-like syndrome, amenorrhea, vaginal candidiasis, cervical erosion, vaginitis

• Local—pain at injection site, sterile abscess, redness and irritation at the application site with transdermal system

• Ophthalmic—steepening of corneal curvature, intolerance to contact lenses

• Miscellaneous—edema; changes in libido; breast pain, enlargement, and tenderness; reduced carbohydrate tolerance; venous thromboembolism;

pulmonary embolism; increase or decrease in weight; skeletal pain

Warnings associated with the administration of estrogen include an increased risk of endometrial cancer, gallbladder disease, hypertension, hepatic adenoma (a benign tumor of the liver), cardiovascular disease, increased risk of thromboembolic disease, and hypercal-cemia in those with breast cancer and bone metastases.

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