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Am Fam Physician. 2000;61(1):203-204

Hormone replacement therapy (HRT) is standard treatment for menopausal symptoms, but the long-term benefits and risks remain uncertain. Contradicting evidence has added to the confusion.

Stuenkel and Barrett-Connor conducted a computer-based search (1990 to 1999 literature) to provide up-to-date recommendations for HRT. One use of HRT is relief of menopausal symptoms. Estrogen is the gold standard for treatment of hot flashes. No evidence has shown the benefit of estrogen-progestin combination therapy over unopposed estrogen therapy in reducing vasomotor symptoms. In women with vaginal dryness or urinary symptoms, topical estrogen therapy is as effective as systemic therapy. Local estrogen therapy is available in vaginal creams and other preparations, such as a silastic vaginal ring that requires replacement every three months. Vaginal estrogen therapy reduces the incidence of urinary tract infection, but the effect of HRT on urinary incontinence is less clear.

Research on the cognitive and depressive symptoms occurring in perimenopausal and postmenopausal women have not shown a clear beneficial effect of HRT on anxiety, cognitive symptoms or affective disorders. Evidence demonstrates that unopposed estrogen therapy reduces depressed moods more than the combination of estrogen with progesterone. Androgen replacement therapy may be associated with the greatest benefit.

Estrogen is the treatment of choice in preventing postmenopausal osteoporosis and osteoporosis-induced fractures. The timing of the initiation of HRT may be highly important, with more lifetime benefit occurring in women taking estrogen continuously from the start of menopause and only minimal difference in women starting therapy at 60 years of age. The National Osteoporosis Foundation has recently recommended starting HRT after the age of 60. Although 0.625 mg of conjugated equine estrogen daily or its equivalent is the standard dosage for the prevention of bone loss, recent studies support the use of lower dosages, such as 0.3 mg of esterified estrogen, 0.5 mg of micronized estradiol or 0.3 mg of conjugated equine estrogens. The most common progestin therapy provides no added benefit to unopposed estrogen therapy, but the addition of androgens to the standard regimen may increase bone formation. Calcium supplementation may augment estrogen's beneficial effects on bone. Other approved medications to prevent or treat osteoporosis include alendronate, raloxifene and calcitonin.

The use of HRT appears to decrease low-density lipoprotein cholesterol levels and increase high-density lipoprotein cholesterol levels, and has also demonstrated positive changes in apolipoprotein and homocysteine levels, endothelial function and vascular reactivity. Results from clinical studies on the effect of estrogen in cardiovascular disease remain unclear. A major study showed an increase in short-term cardiac morbidity and mortality rates in women with preexisting coronary heart disease who received HRT for secondary prevention. Longer studies are needed to clarify this question.

The ability of HRT to reduce dementia remains uncertain because of the brevity and small sizes of the studies recently reported. Further study is also needed on the effect of HRT on colon cancer risk.

Several risks are associated with HRT (see the accompanying table). These risks include endometrial cancer with unopposed estrogen therapy in women who have not undergone a hysterectomy, and a possible increased risk of breast cancer in women taking HRT for five years or longer. Other risks include gall bladder disease, venous thromboembolic episodes, a possibly higher risk of systemic lupus erythematosus and an increased risk of asthma.

Liver disease
Undiagnosed vaginal bleeding
Prior deep venous thrombosis
Prior pulmonary embolism
Estrogen-dependent cancer

In conclusion, the authors state that the medical management of menopausal women should be individualized, based on the specific desires of the patient and the anticipated risks and benefits of the therapy. The only clear indications for HRT are to relieve menopausal symptoms and to prevent or treat vertebral fractures.

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