There's no question hormone replacement therapy (HRT) can help control many of the acute symptoms of fluctuating and declining hormone levels in and around the time of menopause. It's also true that HRT can counter some of the long-term effects of diminished estrogen production in postmenopausal women. However, HRT is also associated with side effects--some quite serious. Whether a woman should begin (or continue) HRT depends in large part on her individual risks factors for those serious side effects and complications. It's a decision that must be made individually, based on consultation with a healthcare provider who can assess the woman's history and help her understand her own personal levels of risk.

The major short-term benefits of HRT

Hormone replacement therapy is very effective in the management of certain short-term menopausal symptoms, especially hot flashes, urogenital atrophy, and psychological effects.

Hot flashes -- Hot flashes (or flushes) are sudden feelings of intense body heat lasting anywhere from 30 seconds to 30 minutes. They are often accompanied by profuse sweating and followed by chills. Hot flashes occurring at night can result in night sweats and disrupt normal sleep patterns. Hot flashes occur in up to 85% of perimenopausal women are the most common menopausal symptom for which women seek treatment. A number of non-medical, non-hormonal interventions such as dietary changes, wearing lightweight clothing, and lowering room temperatures may be successful in the management of hot flashes, but up 25% of women are sufficiently discomforted that they seek medical relief. HRT is of clinically proven value in treating hot flashes.

Urogenital atrophy -- Estrogen plays an important role in the maintenance of a woman's urogenital health. The tissues of the vulva, vagina, urethra, and bladder, as well as the pelvic musculature that supports the internal urogenital organs, require estrogen for optimal function. HRT can prevent the thinning of vulvar and vaginal tissues and prevent the estrogen-deficient degradation of urogenital tissues that can lead to urinary incontinence.

Psychological benefits -- Estrogen has a number of positive effects on the brain and nervous system. The mood swings, fuzzy thinking, and short-term memory defects that sometimes accompany menopause can be mollified by HRT. Wulf Utian, MD, in his book Managing Your Menopause describes a "mental tonic effect" attributable to estrogen replacement therapy that includes a feeling of overall well-being and revitalization, leading to "better performance of daily duties and greater enjoyment of daily pleasures." Estrogen is also credited with a positive therapeutic effect on minor depression related to menopausal changes (although not on major depression).

Major long-term benefits of HRT

Osteoporosis -- Osteoporosis describes the gradual loss of bone density. In the most extreme cases, bones may be weakened to the point that the stresses of normal everyday physical activity are enough to cause bones to break. Osteoporosis affects an estimated 25 million women in the U.S., causing 250,000 hip fractures each year. About 20% of women with hip fracture die within the first month of their injury. Estrogen is highly effective in countering the osteoporotic effect of declining estrogen production, and there are other drugs that can help as well. Women hoping to avoid osteoporosis are also advised to maintain a diet high in calcium and vitamin D and to get plenty of weight-bearing exercise.

Cardiovascular disease (CVD) -- The cardio-protective effect of HRT is somewhat controversial, but the majority of commentators still appear to believe in it. Recently the American Heart Association revised its recommendations, advising that HRT not be initiated in peri- and postmenopausal women solely for the primary prevention of heart disease. 'Primary prevention' refers to the prophylactic use of HRT in women who do not currently have any signs or symptoms of CVD. A large ongoing study known as the Women's Health Initiative is expected to provide more definitive answers about the cardiovascular benefits of HRT in the near future.

Quality of life (QOL) -- Although HRT is thought by many to prolong the lives of postmenopausal women, the magnitude of this effect is at best one to three years. What's far more important is the overall effect of HRT on QOL. The short- and long-term salutary effects conferred by HRT translate into improved quality of life for many peri- and postmenopausal women. Not every woman needs HRT, and there are nonhormonal options to address many of the hormone-related problems of menopause. But for women who suffer particular harsh effects from declining estrogen production, HRT can be a Godsend.

The downside of HRT

Lila Nachtigall, MD--a prominent menopause expert and advocate of HRT--categorizes the risks of HRT as nuisance side effects, serious side effects, and complications. nuisance side effects include but are not limited to nausea, headache, weight gain, fluid retention, breast tenderness, unpredictable breakthrough bleeding, the return of menstruation, a bloated feeling and gassiness, and vaginal irritation and secretions. Among the serious side effects, she lists liver problems (which are rare), gall bladder disease (which usually occurs only in women with specific risk factors for gall bladder disease), high blood pressure, and fibroids (usually regrowth of existing fibroids that shrank after menopause). And among the potential complications of HRT, Nachtigall also lists endometrial cancer, breast cancer, and thromboembolic disease.

Most of the so-called nuisance effects of HRT either resolve on their own after a short time or can be effectively managed by adjusting the hormone dose or changing the route of hormone administration. These effects are not taken lightly because they can lead to the discontinuation of therapy, but neither do they represent a direct threat to the health and well-being of the patient receiving HRT. Of greatest concern are some of the serious side effects and irreversible complications of HRT, which we'll examine in more detail below.

Issues of greatest concern

Endometrial cancer -- It is well-established that unopposed estrogen replacement therapy (HRT with estrogen only, no progestin) can cause cancer of the uterine lining (endometrium). Estrogen promotes endometrial growth that may continue uncontrollably and turn into cancer. Fortunately, it is also well established that the addition of a progestin (a synthetic progesterone) to the HRT regimen counters the potential of unopposed estrogen to cause endometrial cancer. Progestin causes the uterine lining to break down and be shed just as in normal menstruation. HRT in women with an intact uterus, therefore, almost always means a combination of estrogen and progestin; the addition of progestin to the HRT regimen neutralizes the risk of endometrial cancer.

Breast cancer -- A woman's risk of breast cancer is related, among other things, to her lifetime exposure to estrogen. Whether HRT increases the risk of breast cancer is controversial: some experts say it definitely does; others disagree. Dr. Susan Love--a menopause expert and a breast cancer surgeon--characterizes the risk as follows: Imagine 100 women, 50 years old, who never receive HRT; of those 100 women, 10 will eventually develop breast cancer. But if every woman in that group received estrogen replacement therapy (no progestin) for at least 10 years, 15 of them would get breast cancer. And if all 100 received estrogen and a progestin for at least 10 years, the number who develop breast cancer would increase to 17. The increased risk of breast cancer with HRT is arguably small, but as Dr. Love points out, 30% of women who develop breast cancer die from it. Women who are already at risk for breast cancer, especially if one of their primary female relatives (mother, sister, or daughter) has had breast cancer, may not feel the benefits of HRT are worth the additional risk.

Gallbladder disease -- Orally administered estrogen increases the concentration of bile in the gall bladder, and women with a personal medical history of gallstones or a family history of gallbladder disease shouldn't take oral HRT. Although it is believed that transdermal delivery (patch) of HRT circumvents the problem, this has yet to be confirmed by well-designed clinical studies in an adequate number of patients.

Thromboembolic disease -- HRT increases the risk of blood clot formation. This includes thrombophlebitis (clots in veins), pulmonary emboli (clots in the lungs), and clots in the arteries of the legs. Some experts advise that a woman with any history of thromboembolic disease should not receive estrogen therapy; others think only women with repeated episodes of clotting are at risk.

Liver dysfunction -- This is a rare complication of HRT but a serious one. Women with a history of liver disorder should not receive estrogen therapy.

Hypertension (high blood pressure) -- Generally speaking, HRT does not affect blood pressure, but a few women do have what is known as an idiosyncratic or unexpected response, due largely to the action of HRT on the liver. Switching from oral HRT to transdermal delivery system is recommended for women who develop hypertension after initiating HRT because patch delivery of estrogen does not affect the liver enzymes responsible for increasing blood pressure.

Surgery/fibroids -- Fibroids are noncancerous tumor-like growths in the uterus that typically begin to appear a few years prior to menopause. They are quite common and can, in some cases, grow to distressingly large size. Fibroids tend to shrink away after menopause, but the estrogen component of HRT can restimulate their growth, causing irregular bleeding and possibly requiring surgery, either to remove the fibroid or to remove the entire uterus (hysterectomy).

Growing controversy

In recent years, a number of physician-authors writing on menopause have questioned mainstream thinking about HRT. With regard to the risk-benefit assessment, conventional practice seems to hold that the short- and long-term positive effects of HRT generally outweigh the potential risks. Critics of current practice, such as Susan Love, MD, and Christiane Northrup, MD, suggest that alternative nonhormonal therapies and interventions can achieve many of the goals of HRT without any the risks noted above. They also champion the use of alternative hormonal preparations that are closer in chemical structure and action to naturally produced hormones than many of the "name brand" versions of HRT.