Risks and Benefits of Hormone Replacement Therapy

Hot flashes. Night sweats. Vaginal dryness and discomfort. These common, unpleasant signs of menopause affect about 75 percent of all U.S. women at midlife, and there’s no doubt about the most effective treatment for them: hormone replacement therapy, also known as menopausal hormonal therapy.

But, in 2002, preliminary findings from the hormone therapy arm of the Women’s Health Initiative (WHI) sounded an alarm that warned against hormone replacement therapy use. The WHI, conducted by the National Institutes of Health, included two large, long-term randomized clinical trials designed to determine whether hormone therapy could counteract or lessen the onset of age-related disease in postmenopausal women.

Instead, the studies found an increased risk of breast cancer, heart disease, stroke, gall-bladder disease and blood clots in the legs and lungs among participants who took certain forms of hormone replacement therapy for more than five years. Researchers stopped both trials early, and prescriptions for hormonal therapy plummeted. (The researchers, however, continued to gather observational data on participants even after the hormones were stopped.)

Six years later, a second analysis of the WHI data suggested that hormone replacement therapy’s potential harms were overstated for healthy women younger than 60. Why the change in viewpoint? Several reasons:

The 27,234 WHI participants’ average age was 63—a good 10 to 15 years older than the average woman in her 40s or 50s who seeks hormone replacement therapy for relief. The average age of menopause is 51.

At the start of the trials, many participants already had high blood pressure, were current or former smokers and were obese —all risk factors that might have influenced outcomes.

When researchers took a second look at the data, they realized that the timing of hormone replacement therapy made a big difference in its risks and benefits. The greater the gap between the last menstrual period and the start of hormone therapy, the greater the risk for heart disease, strokes, and dementia.

In the study arm of WHI that reported increased cardiovascular risk and cancer, the researchers used only one form of hormone, oral Prempro (Premarin and Provera) or Premarin alone. Women today have more hormone options—including a variety of estrogens and progesterones, as well as different modes of delivery and lower doses—that may have fewer risks, which vary by therapy.

WHI wasn’t designed to look at the short-term use of hormone therapy for relief of menopausal symptoms; it was designed to investigate the prevention of disease over the long term.

What we now know

Based on the reanalysis, it turns out that the benefits of symptom relief can outweigh the risks in healthy women younger than 60 who start hormone replacement therapy at the onset of natural menopause and use it for less than five years. Some studies have found a slight dip in cardiovascular risk for women under age 60, but cardiovascular risk persists in older women. Breast cancer risk increases with longer-term use (more than five years) of certain types of hormone replacement therapy.

Studies have shown that hormone replacement therapy can reduce hot-flash frequency and severity by 75 percent to 87 percent, respectively. Some research suggests that certain types of hormone replacement therapy prescribed to relieve hot flashes and night sweats—called vasomotor symptoms—may also help improve the following menopause-associated conditions:

• Genitourinary symptoms, such as urinary incontinence and frequency

• Vaginal dryness and irritation and painful intercourse

• Sleep disturbances

• Joint pain

• Anxiety and mild to moderate depressive symptoms

• Bone loss and fractures

A new age of hormone therapy

Most experts now agree that hormone replacement therapy’s risks depend on a woman’s age, the duration between her last period and treatment, and the length of time she uses hormone replacement therapy. “Healthy women in their 50s have a low risk of developing complications from menopausal hormonal therapy,” says Wen Shen, M.D., M.P.H., assistant professor of gynecology and obstetrics at Johns Hopkins University School of Medicine in Baltimore. “For most women within 10 years of menopause onset, it turns out that menopausal hormonal therapy at low doses is a good option for the relief of significant menopausal symptoms.”

Within the past three years, the Endocrine Society, the North American Menopause Society (NAMS) and the American College of Obstetricians and Gynecologists (ACOG) have released guidelines suggesting that hormone replacement therapy is safe and effective to treat vasomotor symptoms. The groups also agree that doctors should prescribe hormone replacement therapy only to relieve moderate to severe vasomotor symptoms and not to prevent osteoporosis, heart disease, dementia or other chronic conditions—although new guidelines may be forthcoming.