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Weight gain accompanied by an increased tendency for central fat distribution is common among women in midlife. These changes are a result of aging, decreasing estrogen levels after menopause, and other unique influences in menopausal women that interfere with the adoption of healthy lifestyle measures. Central obesity, in particular, results in several adverse metabolic consequences, including dysglycemia, dyslipidemia, hypertension, and cardiovascular disease. Given that cardiovascular disease is the leading cause of death in postmenopausal women, the importance of weight management in midlife cannot be overemphasized. In addition, weight gain in midlife contributes to other health risks including cancer, arthritis, mood disorders, and sexual dysfunction. It is imperative that primary care physicians screen midlife women for overweight/obesity and offer appropriate advice and referral. In addition to counseling regarding lifestyle change, behavioral modification, and psychological support, it is important to address the unique barriers to adoption of healthy lifestyle measures in postmenopausal women, including the presence of vasomotor symptoms, mood disorders, and sleep disturbance. When indicated, menopausal hormone therapy should be considered to manage bothersome symptoms. Despite its favorable influence on body fat distribution, menopausal hormone therapy cannot be recommended as a treatment for central obesity in midlife women.