The etiology of primary ovarian insufficiency (POI) may be genetic, autoimmune, or iatrogenic. Genetic conditions include 45,X, 46,XX and 46,XY POI, and POI associated with galactosemia and FMR premutations. Women with autoimmune polyglandular syndromes 1 and 2 may develop autoimmune POI, as may those who receive chemotherapy or radiotherapy. Hypogonadism in POI can result in reduced rates of bone mass accrual in adolescents and young women, and low bone density for age in older women. Measures to optimize bone density in women with POI include attention to lifestyle measures and hormone replacement. Resistance training and adequate calcium and vitamin D supplementation are essential, as is replacement of estrogen/progestin. Estrogen/progestin replacement may be problematic in women with estrogen-sensitive breast cancer who developed POI in the course of therapy for cancer. In these instances, bisphosphonates are an option. In particular, zoledronic acid has been used successfully in conjunction with chemotherapy, tamoxifen, and aromatase inhibitors.
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