The estrogen agonist-antagonist raloxifene (Evista, 60 mg per day orally) prevents vertebral fractures in women with low bone mass and osteoporosis, though does not appear to reduce the risk of nonvertebral fractures (45). Raloxifene exercises estrogen-like actions on bone and lipids without stimulating the breast or endometrium. Calcitonin nasal spray (Miacalcin, 200 IU per day intranasal) is another approved treatment for established osteoporosis. Unlike most treatments for osteoporosis that inhibit bone resorption, parathyroid hormone (human recombinant PTH 1–34) (teriparatide, Forteo, 20 μg per day subcutaneously) stimulates new bone formation, resulting in significant reductions in vertebral and nonvertebral fractures (46). Recently approved for the treatment of postmenopausal osteoporosis, denosumab (Prolia) 60 mg, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand, decreases the risk of vertebral and hip fractures in postmenopausal osteoporotic women when given subcutaneously twice yearly for 36 months’ duration (47).
Cardiovascular Disease Cardiovascular disease (CVD) is the leading cause of death for women, accounting for approximately 45% of mortality. Nonmodifiable risk factors include family history and age. Modifiable risk factors include a sedentary lifestyle, obesity, and smoking. Medical conditions associated with an increased risk of heart disease include diabetes, hypertension, and hyperlipidemia. Advising women to alter modifiable risk factors for CVD and adequately treating diabetes, hypertension, and hyperlipidemia are important parts of the comprehensive care of midlife women.
As epidemiologic studies identify an approximately 50% decrease in coronary heart disease (CHD) in woman who use hormone therapy, prevention of heart disease was considered a potential benefit of postmenopausal hormones (48). This observed reduction in CHD was considered secondary to beneficial effects of hormone therapy on the vascular wall and lipid levels (49). Observational studies are prone to bias, and women who used hormone therapy were generally healthier and at lower risk for CHD than nonusers (50).
The WHI randomized controlled trial of combination hormone therapy versus placebo showed that hormone therapy did not prevent heart disease in healthy women, but instead, it increased the risk of cardiovascular events in older women (51). The WHI was a 15-year study sponsored by the National Institutes of Health that examined ways to prevent heart disease, osteoporosis, and breast and colorectal cancer in women. There were several different studies in WHI, involving more than 160,000 healthy postmenopausal women. The WHI randomized controlled trial enrolled approximately 16,000 women nationwide between the ages of 50 and 79 years. The average age of women in the study was 63 years. The major goal of the WHI clinical trial was to determine whether combined estrogen and progestin hormone therapy prevented heart disease and to evaluate associated benefits and risks. After an average of 5 years of follow-up, risks (hazard ratio) were increased for CHD (1.3), breast cancer (1.3), stroke (1.4), and pulmonary embolism (PE) (2.1), and decreased for hip fracture (0.7) and colorectal cancer (0.6) (51). The absolute excess risk per 10,000 woman-years attributable to hormone therapy was small, with seven more CHD events, eight breast cancers, eight strokes, and eight pulmonary embolisms, with six fewer colorectal cancers and five fewer hip fractures.