Bone Abstracts

Currently menopausal hormone treatment (HT) is not recommended for the prevention of chronic disease. This recommendation is based on reputable science relying largely on the Women’s Health Initiative (WHI), a large methodologically sound, long-term, randomized clinical trial (RCT) of 27 347 women age 50–79 years. A RCT is considered level two evidence in the hierarchy of evidence only below a systematic review of several RCTs. The WHI HT trials were designed to determine the risks and benefits of HT when taken for chronic disease prevention by predominantly healthy postmenopausal women. Specific targets for age were instituted to insure a wide representative sample of postmenopausal women. At the time the WHI was designed (1990–1992), menopausal HT had been increasingly viewed as a way to prevent chronic diseases of aging, including coronary heart disease (CHD) and cognitive impairment. Women with an intact uterus received conjugated equine estrogen (CEE; 0.625 mg/day) plus medroxyprogesterone acetate (MPA; 2.5 mg/day) or placebo. Women with prior hysterectomy received CEE or placebo. The intervention lasted a median of 5.6 years in the CEE+MPA trial and 7.2 years in the CEE-alone trial with 13 years of cumulative follow-up. During the intervention phase of CEE+MPA trial, the hazard ratio (HR) for the primary endpoints were CHD, HR=1.18; 95% CI, 0.95–1.45 and invasive breast cancer, HR=1.24; 95% CI, 1.10–1.53. Additional risks included an increased stroke, pulmonary embolism, deep vein thrombosis (DVT), dementia, gall bladder disease and urinary incontinence. For the CEE trial, the HR for the primary endpoints were CHD, HR=0.94; 95% CI, 0.78–1.14 and breast cancer, HR=0.79; 95% CI, 0.6–1.02. In the post-intervention period the increased risk of breast cancer in the CEE + MPA trial persisted and in CEE-alone, the decreased risk was statistically significant. Of importance, however, the risk of stroke, DVT, gall bladder and urinary incontinence remained elevated among women randomized to CEE-alone. These risks outweighed observed benefits for hip fracture, diabetes and vasomotor symptoms. In summary, in both HT trials, the observed increased risk of stroke and DVT as well as gall bladder disease and urinary incontinence remain a concern in both younger and older women on both regimens. The risks of HT outweigh benefits for chronic disease prevention.