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Pathogenesis and causes of spontaneous primary ovarian insufficiency (premature ovarian failure)

Corrine K Welt, MD
Section Editors
Robert L Barbieri, MD
William F Crowley, Jr, MD
Deputy Editor
Kathryn A Martin, MD


Primary hypogonadism in women is defined as ovarian failure accompanied by high serum follicle-stimulating hormone (FSH) concentrations. Premature ovarian failure (POF), now referred to as primary ovarian insufficiency (POI), is defined as primary hypogonadism in a woman under the age of 40 years.

POI is characterized by loss of oocytes, lack of folliculogenesis and ovarian estrogen production, and infertility. Transient or partial resumption of ovarian activity has been documented in over 50 percent of women based upon hormonal measurements, pelvic ultrasonography, or conception [1,2].

There are several known causes of ovarian failure, including chromosomal defects like Turner syndrome and fragile X syndrome premutation carriers, exposure to radiation and certain drugs, and autoimmune disease. The list of mutations that can cause ovarian failure has increased rapidly, as discoveries from the human genome project and next generation sequencing increase our understanding of the factors involved in ovarian development. Unfortunately, the etiology remains unknown in approximately 75 to 90 percent of cases [3].

The pathogenesis and causes of POI will be reviewed here (table 1); its evaluation and treatment are discussed separately. (See "Clinical manifestations and evaluation of spontaneous primary ovarian insufficiency (premature ovarian failure)" and "Management of spontaneous primary ovarian insufficiency (premature ovarian failure)".)


Normal ovarian development is dependent on a carefully timed cascade of events; as a result, there are multiple potential etiologies for ovarian dysfunction. Pathophysiologically, these defects can be divided into two major categories:

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Literature review current through: Sep 2017. | This topic last updated: Jul 01, 2017.
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