Changing Clinical Views of Hormone Replacement Therapy

Overwhelming media coverage of the recent stopping of two major studies of Hormone Replacement Therapy (HRT) have physicians’ telephones ringing off their hooks; women who once faithfully believed in the cardioprotective benefits of their Hormone Replacement Therapy are now questioning whether the drugs have, in fact, put them at greater risk for heart disease, stroke, thrombosis and breast cancer.

Initial beliefs of the cardioprotective benefits of HRT were based on Harvard University’s 1976 Nurses’ Health Study, a study of 122,000 nurses that examined the long-term health effects of women taking oral contraceptives. Reduced numbers of cardiac incidents and heart disease among women taking hormones were noted, which led to a general belief that HRT was cardioprotective, and prompted the National Institutes of Health (NIH) to begin sponsoring more thorough clinical investigations to substantiate data collected during the Nurses’ Health Study.

On July 3, 2002, results of the Heart Estrogen/Progestin Replacement Study Follow-up (HERS II) appeared in the Journal of the American Medical Association, making news and generating worry among women taking HRT. HERS II continued following 2,321 postmenopausal women with diagnosed coronary artery disease who had participated in the initial HERS study. These women, at an average age of 67 years at enrollment, were assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians’ discretion during HERS II. The hormones were assigned to determine the effectiveness of HRT in the prevention of cardiac event in postmenopausal women with coronary artery disease; study results determined, in fact, an increased risk of cardiac events during the first year on HRT.

The Women’s Health Initiative (WHI), sponsored by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) made headlines that same week when it was stopped early, due to an increased risk of invasive breast cancer, coronary artery disease, stroke and pulmonary embolism in study participants. The study, blinded and placebo-controlled, involved 16,608 healthy menopausal women, ages 50-79 years with an intact uterus. A group of women enrolled in the study were randomly assigned to a daily dose of the same estrogen plus progestin combination as those in HERS, or to a placebo. This arm of the study was stopped after an average of 5.2 years of follow-up, and, in combination with the results of HERS II, was reported heavily in the media and ignited a flurry of panic among women on, or considering, the therapy for symptoms and health issues associated with menopause. (It is important to note that the estrogen-only arm of the study is still ongoing; information regarding that modality is still pending.)

Like physicians across the country, Deborah cardiologists have been fielding questions from patients who are now suddenly wondering if they’ve been unknowingly putting their health in danger, by taking a drug once thought to protect and help them. The advice they’re giving? Don’t panic.

“I’m explaining to my patients that, despite the extensive coverage in the media and the dangers that have been illustrated, individualized, monitored hormone replacement therapy can still be effective for their symptoms,” stated Maritza Cotto, MD, Attending Cardiologist, Section of Clinical Cardiology. “What we as physicians must remember, and clearly explain to our patients, is that these studies took large populations of women, at a wide range of ages and in different states of health, and administered the same therapy to all of them. The studies do not reflect how these women would have fared had their therapy been individualized, and had their hormone combination been selected based on their individual health profile.”