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Menopausal Hormone Therapy and the Role of Estrogen. Menopause is a universal experience for midlife women. The physiological decline in endogenous estrogen can be associated with vasomotor symptoms or hot flashes, sleep disruption, and mood disorders. Long-term concerns arise with sequelae of estrogen loss such as genitourinary syndrome of menopause and osteoporosis. Although the pendulum has swung widely since the 1942 approval of conjugated equine estrogens, estrogen therapy, now available in an ever-expanding menu of preparations, routes of administration, and dosing, remains the most effective means to collectively address these, and potentially, additional concerns. Refinement of knowledge of risks and benefits facilitates patient selection and counseling.