The Menopausal Patient And Hormone Replacement Therapy

Objectives

We live in a society that is slowly getting older. Two hundred years ago, 30% of women lived long enough to reach menopause, whereas 90% of today's women will experience the climacteric.1 Although menopause is not a disease, it is a relatively estrogen-deficient state. There are many consequences of a relative lack of estrogen that may affect health. Estrogen replacement therapy (ERT) and combination estrogen and progesterone therapy, also known as hormone replacement therapy (HRT), may ameliorate some adverse effects, but may in turn increase other risks.

Menopause is diagnosed by the findings of at least 6 months of amenorrhea in a woman over age 40 or amenorrhea combined with a FSH level above 40 pg/ml. Normal women experience ovarian failure at a mean age of 51 years, with 95% becoming menopausal between the ages of 45 to 55 years.2 Estrogen is the most effective treatment available for relief of the menopausal symptoms that many women experience.2

For the past three decades, long-term (>5 years) estrogen and combined estrogen-progestin therapy (HRT) have been routinely prescribed for prevention of coronary heart disease (CHD) and osteoporosis, based upon extensive observational data demonstrating a striking protective effect of estrogen on the heart and bone. However, data from the Women's Health Initiative (WHI) trials showed no cardiovascular benefit and some increase in risk. When considering whether or not to utilize HRT, it is important to weigh how a woman's quality of life may be improved and what risks are increased for her in particular in light of our best current data. Since this is a rapidly evolving field, regular review of the literature is necessary to keep abreast of new knowledge.

Risks and Benefits

Hot Flashes

Hot flashes occur in about 75% of menopausal women. Along with emotional lability, hot flashes are one of the main perimenopausal symptoms that lead women to seek HRT. Hot flashes typically begin as a sudden sensation of heat centered on the face and upper chest that rapidly becomes generalized. It lasts between two and four minutes, is often associated with profuse perspiration and occasionally palpitations, and is often followed by chills and shivering. Physiologic studies have determined that hot flashes represent thermoregulatory dysfunction; there is inappropriate peripheral vasodilatation with increased digital and cutaneous blood flow and perspiration, resulting in rapid heat loss and a decrease in core body temperature below normal. Hot flashes usually occur several times per day. Many women have profuse perspiration, which can be embarrassing in social situations. Untreated hot flashes usually stop spontaneously in five to six years, but some women continue to have them for many years. The best way to prevent or treat them in women with estrogen deficiency is to administer continuously dosed estrogen. Insomnia is twice as common a complaint in women who have hot flashes, and this problem is also ameliorated with HRT.3

Cardiovascular Disease

The Women's Health Initiative (WHI) is a set of clinical primary prevention trials, including two estrogen-progestin trials, in healthy postmenopausal women ages 50 to 79, which was scheduled to be completed in 2005. 4 However, the continuous conjugated estrogen 0.625 mg and medroxyprogesterone acetate (MPA) 2.5 mg per day versus placebo trial (n=16,000 women) was discontinued early because of an increased risk of breast cancer, CHD, stroke, and venous thromboembolism over an average follow-up of 5.2 years. Although significant benefits in the reduction in risk of fractures and colon cancer also were seen, there was concern that the risks of combined estrogen-progestin outweighed the benefits for many women. (The WHI ERT versus placebo trial in women who had undergone hysterectomy has not been discontinued, since neither an unfavorable nor favorable risk-benefit profile has been observed).4

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The Menopausal Patient And Hormone Replacement Therapy