Detailed Drug Information:

DRUG CLASS AND MECHANISM: Estrogens occur in nature in severalforms. In women with active menstrual cycles, the ovaries produce between70 and 500 micrograms of estradiol daily. This is converted to estrone andto a lesser extent estriol. After menopause, estrone is the most activecirculating estrogen. (After menopause estrone is made in the adrenalglands.) Estrogens cause growth and development of female sex organs andmaintain sex characteristics, including underarm and pubic hair and the shape of body contours and skeleton. Estrogens also increase secretionsfrom the cervix and growth of the inner lining of the uterus(endometrium). Estrogens reduce LDL-cholesterol ("bad"cholesterol) and increase HDL-cholesterol ("good" cholesterol)concentrations in the blood. Estrogens, when taken alone or in combinationwith a progestin, have been shown to reduce the risk for hip fracture dueto osteoporosis by 25%.

PREPARATIONS: Tablets, micronized: 0.5mg, 1mg, 2mg; Vaginal cream: 0.01%;Continuous release skin patch: 14 mcg/day, 0.05 mg/day, 0.1 mg/day.

STORAGE: All forms should be stored between 15° (59°F)and 30°C (86°F).

PRESCRIBED FOR: Estradiol is prescribed for symptomatictreatment of the usual symptoms associated with menopause (hot flashes,vaginal dryness, etc.), prevention of bone fractures associated withosteoporosis, reduction of the risk of heart attacks and strokes, anddysfunctional (excessive and painful) uterine bleeding. The vaginal creamis prescribed for vaginal or vulvar atrophy associated with menopause.

DOSING: Estradiol tablets are generally prescribed once daily.In some patients, a so-called cyclic regimen is used, wherein estradiol isgiven daily for 23 consecutive days, followed by 5 days of no medication,after which the cycle resumes.

The adhesive part of the patch should be applied to a dry, hairless,clean part of the trunk, but not on the breasts. It should not be placedonto irritated or damaged skin. Sites of application should be rotated,with at least one week between repeated applications to any one site. Thepatch should be applied immediately after removing the protective layer,and pressure should be applied to the patch when it is attached for about10 seconds.

DRUG INTERACTIONS: Estrogens can inhibit the metabolism ofcyclosporine, resulting in increased cyclosporine blood levels. Suchincreased blood levels can result in kidney and/or liver damage. If thiscombination cannot be avoided, cyclosporine concentrations can bemonitored, and the dose of cyclosporine can be adjusted to assure that itsblood levels are not elevated.

Estrogens appear to increase the risk of liver disease in patientsreceiving dantrolene through an unknown mechanism. Women over 35 years ofage and those with a history of liver disease are especially at risk.

Estrogens increase the liver's ability to manufacture clotting factors.Because of this, patients receiving warfarin (Coumadin) need to bemonitored for loss of anticoagulant (blood thinning) effect if an estrogenis added when warfarin is already being taken.

Rifampin, barbiturates, carbamazepine (Tegretol), griseofulvin,phenytoin (Dilantin) and primidone, can all increase the elimination ofestrogen by enhancing the liver's ability to metabolize it. Concurrent usemay result in reduction of the beneficial effects of estrogens.

PREGNANCY: Estrogens are contraindicated during pregnancy due toan increased risk of fetal abnormalities.

NURSING MOTHERS: Estrogens are secreted in milk and causeunpredictable effects in the infant. Estrogens generally should not beused by women if they are breast-feeding.

SIDE EFFECTS: Among the most common endocrine side effects are break-through bleeding or spotting, loss of periods or excessively prolonged periods, breast pain, breast enlargement, and changes insexuality (increase or decrease in libido). Abdominal pain may indicatethe development of gallstones or occasionally hepatitis. Migraineheadaches have been associated with estrogen therapy. Estrogens can causesodium and fluid retention. Melasma, tan or brown patches, may develop onthe forehead, cheeks, or temples. These may persist even after theestrogen is stopped. Conjugated estrogens may cause an increase in thecurvature of the cornea. Patients with contact lenses may developintolerance to their lenses.

Blood clots are an occasional but serious adverse effect and aredose-related. (The higher the dose, the more likely the clots.) Cigarettesmokers are at a higher risk for clots, and, therefore, patients requiringestrogen therapy are strongly encouraged to quit smoking.

Estrogens can promote a buildup of the uterine lining (endometrialhyperplasia) and increase the risk of endometrial carcinoma. At diagnosis,endometrial cancers in estrogen recipients are generally of an earlierstage and a lower grade. Survival is also is better in women exposed toestrogens than in those not exposed to estrogens. The addition of aprogestin to estrogen therapy prevents endometrial carcinoma.

Conflicting data exists on the association between estrogens and breast cancer. There may be a small increase in risk. The effect of concomitantprogestin therapy on the risk of estrogen-induced breast carcinoma isunclear.