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Fertil Steril. 2016 Dec;106(7):1588-1599. doi: 10.1016/j.fertnstert.2016.09.046.

Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause.

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U.S. Food and Drug Administration, Silver Spring, Maryland.
Obstetrics, Gynecology, and Reproductive Sciences and Psychiatry, Yale University, New Haven, Connecticut.
Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Electronic address:


Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychologic impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy (HRT) to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective HRT options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ∼50 years. We address special populations of women with POI, including women with Turner syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women.


Primary ovarian insufficiency; androgen; early menopause; estrogen; hormone replacement therapy; management; menopausal hormone therapy; morbidity; mortality; premature menopause; premature ovarian failure; progestin

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