The role of menopausal hormone therapy in preventing osteoporotic fractures: a critical review of the clinical evidence.

Osteoporosis is a common disease resulting in millions of potentially preventable fractures each year. Women are disproportionately affected by osteoporosis compared to men, with loss of gonadal functioning and aging being the 2 most important contributing factors to osteoporosis. For many decades, menopausal hormone therapy (HT) has been the mainstay for the prevention and treatment of osteoporosis among menopausal women. While recent randomized trial data have confirmed findings from observational studies concerning HT's protective effect on osteoporosis, they showed that HT increases the risks of breast cancer, venous thromboses, stroke, and coronary heart disease. With a strong body of evidence showing the benefit of HT in preventing osteoporotic fractures, the challenge facing clinicians is not whether HT helps to prevent osteoporotic fractures, but whether HT's fracture-prevention benefits outweigh its risks. With several medications now available having efficacy comparable to HT in preventing fractures, decisions about therapy for osteoporosis or osteopenia should take into consideration bone mineral density, other risk factors for osteoporotic fracture, and a careful examination of the benefits and risks of each treatment option. After a brief discussion of the epidemiology and pathophysiology of osteoporosis, we review the evidence from observational studies and randomized studies examining the impact of menopausal hormone therapy on osteoporosis. We focus on whether there are specific subgroups of women that accrue greater or smaller benefit from HT in terms of osteoporotic fracture reduction. We then expand our perspective to include clinical endpoints other than osteoporosis, presenting a framework for factoring in the many risks and benefits of HT. We conclude that all women should be informed of all alternative treatment options and allowed to make an informed treatment decision according to their personal risks, preferences, values, and willingness to tolerate the risks of treatment.