Primary Ovarian Insufficiency in Adolescents and Young Women

This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed.

ABSTRACT: Primary ovarian insufficiency is the depletion or dysfunction of ovarian follicles with cessation of menses before age 40 years. There is no consensus on criteria to identify primary ovarian insufficiency in adolescents, and delay in diagnosis is common. Health care providers who make this clinical diagnosis should be mindful of the sensitive nature of this medical condition. Patients and their families should be counseled on the effect of the patient’s condition on future fertility, on the risk of comorbidities associated with primary ovarian insufficiency, and on the condition’s potential for genetic inheritance. Psychologic counseling also should be offered because impaired self-esteem and emotional distress have been reported after diagnosis of primary ovarian insufficiency. Once primary ovarian insufficiency is diagnosed, patients should be evaluated at least annually. The goals of hormonal therapy extend beyond simply symptom relief to levels that support bone, cardiovascular, and sexual health. Referrals to a reproductive endocrinology and infertility specialist should be made when desired by the patient and family to further discuss available reproductive treatments.

Chromosomal Abnormalities

A common cause of primary ovarian insufficiency in adolescents is gonadal dysgenesis, with or without Turner syndrome PubMed] “>3. When adolescents present with prienorrhea and no associated comorbidities, 50% are found to have abnormal karyotypes. Among younger women (aged 30 years or younger) with secondary amenorrhea, 13% also have been noted to have an abnormal karyotype PubMed] [Full Text] “>5. Although pubertal and growth delays are common in this group, many affected females may first be recognized at the time of evaluation for menstrual abnormalities.

Fragile X Syndrome

Fragile X syndrome is the most common form of hereditable mental retardation. Among females with primary ovarian insufficiency and a normal karyotype, 6% have a premutation in the FMR1 gene PubMed] [Full Text] “>5. Although the onset of menstruation appears to be normal among premutation carriers in adolescence, approximately 1% of premutation carriers will experience their final menses before age 18 years PubMed] “>10. If a woman has a personal or family history of ovarian failure or an elevated follicle-stimulating hormone (FSH) level before age 40 years without a known cause, fragile X premutation carrier testing should be offered PubMed] [Obstetrics & Gynecology]”>11.


There is no consensus on criteria to identify primary ovarian insufficiency in adolescents, and delay in diagnosis is common. Box 1 for a reasonable approach to diagnosis and initial evaluation.) Although some adolescent females will report hot flushes or vaginal symptoms like dryness or dyspareunia, the most common presenting symptom of prienorrhea. Among patients with amenorrhea, the incidence of primary ovarian insufficiency ranges from 2% to 10% PubMed] “>3. Abnormal bleeding patterns also may include oligomenorrhea (bleeding that occurs less frequently than every 35 days), nonstructural causes of abnormal uterine bleeding (eg, ovulatory dysfunction, iatrogenic, or not yet classified), or polymenorrhea (bleeding that occurs more often than every 21 days) PubMed] [Full Text] “>1. Because irregular menstrual cycles are both common during early adolescence and an initial symptom of early primary ovarian insufficiency, diagnosis can be difficult in this population. Although less than 10% of women who present with abnormal menses will ultimately be found to have primary ovarian insufficiency, the condition has such detrimental consequences on bone health that early diagnosis of this condition is important Full Text] “>12. Therefore, in young females it is important to evaluate amenorrhea or a change from regular to irregular menses for 3 or more consecutive months in the absence of hormonal preparations such as oral contraceptives (OCs) for all potential causes, including pregnancy, polycystic ovary syndrome, hypothalamic amenorrhea, thyroid abnormalities, hyperprolactinemia, and primary ovarian insufficiency PubMed] [Full Text] “>1 Full Text] “>12. Inquiries should be made about family medical history because females with a family history of early menopause are at risk of primary ovarian insufficiency PubMed] [Obstetrics & Gynecology]”>13.