Menopausal hormone therapy (MHT) reduces the risk of developing osteoporosis, fractures, obesity and type II diabetes, yet it is only approved for short-term therapy due to the serious risks associated with long-term therapy (e.g., increased risks of breast cancer, stroke, and heart attacks). To target these indications associated with menopause, it will be necessary to develop safer MHT regimens that can be used as continuous therapy. There are two current strategies for developing safer MHT: First, estrogens have been combined with the selective estrogen receptor modulator, bazedoxifene, which prevents estrogen binding to ERα, thereby blocking the proliferative effects on the uterus. However, this combination is approved only for short-term treatment of hot flashes. Second, ERβ-selective agonists have been developed; unfortunately, ERβ agonists may not be effective for osteoporosis, weight gain or diabetes because ERα is the major active ER in both bone and adipose tissue. UC Berkeley researchers have discovered a compound that acts as a reprogramming ERα coligand that could improve safety profile of MHT. The compound was found to bind of to a different site on ERα and reprograms the actions of estradiol. This compound represents a new class of drugs that can be combined with existing estrogens to produce safer MHT regimen for long-term treatment to safely prevent chronic diseases associated with menopause.