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Primary ovarian insufficiency

Last updated: May 8, 2025

Summarytoggle arrow icon

Primary ovarian insufficiency (POI) is impaired ovarian function before the age of 40 years due to a defect in the ovaries that decreases follicle numbers or results in an insufficient follicular response to gonadotropin stimulation (i.e., hypergonadotropic hypogonadism). The underlying etiology is unknown in 70% of cases; known etiologies include genetic disorders, autoimmune diseases, and iatrogenic causes (e.g., chemotherapy or pelvic surgery). Because ovarian insufficiency affects ovulation and estrogen production, symptoms include amenorrhea or abnormal uterine bleeding, and climacteric symptoms. Unlike premature menopause, ovarian function in POI may not have permanently ceased; function is intermittent, and individuals may become pregnant, although infertility is common. POI is often discovered during diagnostics for amenorrhea; a low estradiol level with elevated FSH suggests POI. If FSH is normal or low, secondary ovarian insufficiency (inadequate gonadotropic stimulation of the ovaries by the hypothalamus and/or pituitary glands, i.e., hypogonadotropic hypogonadism) should be considered. POI is confirmed if values remain abnormal when repeated at least a month later. Assessment for the underlying cause involves genetic studies and, potentially, autoantibodies. Management of POI includes long-term hormone replacement therapy (HRT), management of infertility, and ongoing monitoring for the development of complications of POI (e.g., cardiovascular disease and osteoporosis).

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Etiologytoggle arrow icon

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Pathophysiologytoggle arrow icon

Follicular dysfunction or depletion → estrogen levels → reduced feedback inhibition of estrogen on FSH and LH FSH and LH (usually FSH > LH)

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Clinical featurestoggle arrow icon

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Diagnosistoggle arrow icon

POI is often detected on diagnostic studies for amenorrhea.

Approach [1][2][3]

  • Initial diagnostic studies, including FSH and estradiol
  • Repeat in one month if results are abnormal. POI is likely if: [1][5]
  • Evaluate for underlying causes.
  • Refer patients who want to preserve fertility to a reproductive endocrinologist for additional evaluation, including ovarian reserve testing. [1][3]

If estradiol is low but FSH is normal or low, assess for secondary ovarian insufficiency. [2]

Hormonal contraception can affect gonadotropin and estradiol values; stop any exogenous hormones before obtaining diagnostic studies. [1]

Initial diagnostic studies [1][2][3]

See also “Diagnostics for amenorrhea.”

Evaluation of underlying causes [1][5]

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Differential diagnosestoggle arrow icon

Secondary ovarian insufficiency

Secondary ovarian insufficiency is impaired ovarian function due to inadequate gonadotropic stimulation of the ovaries by the hypothalamus and/or pituitary glands (i.e., hypogonadotropic hypogonadism). [7]

Etiology

See “Ovulatory dysfunction” for hypogonadotropic causes of hypogonadism.

Diagnosis [2][7]

Management

The differential diagnoses listed here are not exhaustive.

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Managementtoggle arrow icon

The following outlines management of postpubertal individuals with POI; refer patients who have not completed puberty to a specialist for management.

Approach [1][3][5]

HRT [11]

Individuals who do not wish to become pregnant require contraception, since spontaneous pregnancy occurs in up to 10% of individuals with POI, and HRT does not provide adequate contraception. [2][11]

Reassure patients that HRT has not been associated with breast cancer when used before the age of menopause. [5]

Ongoing management [1]

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Complicationstoggle arrow icon

We list the most important complications. The selection is not exhaustive.

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