Hormone replacement therapy administration and regimens

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A. HRT should not be a universal recommendation. The benefits and risks associated with HRT must be weighed on an individual basis. A woman with significant risk factors for osteoporosis or CHD may benefit from long-term HRT. A woman with a personal or strong family history of breast cancer may not benefit from long-term HRT.

B. Hormone users have a lower risk of death (relative risk, 0.63) than nonusers. This reduction is largest in women with cardiac risk factors. The benefit decreases with use of more than 10 years (due to breast cancer deaths) but still remains significant. HRT should increase life expectancy for nearly all women. The risk of HRT outweighs the benefit only in women without risk factors for CHD or hip fracture, but who have two first-degree relatives with breast cancer.

C. Effective doses of estrogen for the prevention of osteoporosis are: 0.625 mg of conjugated estrogen, 0.5 mg of micronized estradiol, and 0.3 mg of esterified estrogen.

D. In those women with a uterus, a progestin should be given continuously (2.5 mg of medroxyprogesterone per day) or in a sequential fashion [5-10 mg of medroxyprogesterone (Provera) for 1214 days each month]. The most common HRT regimen consists of estrogen with or without progestin. The oral route of administration is preferable because of the hepatic effect on HDL cholesterol levels.

Relative and Absolute Contraindications for Hormone Replacement Therapy

Absolute contraindications

Estrogen-responsive breast cancer Endometrial cancer Undiagnosed abnormal vaginal bleeding

Active thromboembolic disease History of malignant melanoma

Relative contraindications

Chronic liver disease Severe hypertriglyceridemia Endometriosis

Previous thromboembolic disease Gallbladder disease

E. Estrogen cream. 1/4 of an applicator(0.6 mg) daily for 1-2 weeks, then 2-3 times/week will usually relieve urogenital symptoms. This regimen is used concomitantly with oral estrogen.

F. Adverse effects attributed to HRT include breast tenderness, breakthrough bleeding and thromboembolic disorders.

G. Bisphosphonates inhibit osteoclast activity. Alendronate (Fosamax) is effective in increasing BMD and reducing fractures by 40 percent. Alendronate should be taken in an upright position with a full glass of water 30 minutes before eating to prevent esophagitis. Alendronate is indicated for osteoporosis in women who have a contraindication to estrogen.

H. Raloxifene (Evista), 60 mg qd, is a selective estrogen receptor modulator, FDA-labeled for prophylactic treatment of osteoporosis. This agent offers an alternative to traditional HRT. The modulator increases bone density (although only one-half as effectively as estrogen) and reduces total and LDL cholesterol levels.

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