Initial laboratory evaluation for suspected primary ovarian insufficiency includes measurements of basal FSH and basal estradiol levels and tests to rule out causes such as pregnancy, thyroid disease, and hyperprolactinemia. Gonadotropin and estradiol values may be altered by concomitant use of hormonal preparations and thus should only be obtained in patients who are not taking hormonal medications, including OCs. If gonadotropins are elevated into the menopausal range (typically, basal FSH levels will be greater than 30–40 mIU/mL, depending on the laboratory used), a repeat FSH measurement is indicated in 1 month. If the result indicates that FSH is elevated, a diagnosis of primary ovarian insufficiency can be established. Estradiol levels of less than 50 pg/mL indicate hypoestrogenism.
Surrogate markers of ovarian reserve (presence of regular menses, serial serum estradiol levels, and antral follicle count by transvaginal ultrasonography) are highly variable and are not predictive of future fertility or hormonal production in young women who have undergone treatment for cancer PubMed] «>6 PubMed] «>7, but are currently undergoing investigation. Once a diagnosis of primary ovarian insufficiency is established, further testing, including karyotype, adrenal antibodies, FMR1 premutation, and pelvic ultrasonography, may be indicated to investigate possible etiologies of primary ovarian insufficiency.
Treatment
Optimal treatment of an adolescent in whom primary ovarian insufficiency is diagnosed requires special sensitivity to both the physical and emotional needs of young women receiving this diagnosis during a time of significant developmental changes. Patients may be emotionally unprepared and may require more information and understanding to process the immediate and long-term implications of this disorder.
Hormonal Therapy
Once pubertal development is complete, ongoing hormonal therapy will be necessary for long-term health. Hormonal support involves daily therapy with the goal of maintenance of normal ovarian functioning levels of estradiol. Transdermal, oral, or occasionally transvaginal estradiol in doses of 100 micrograms daily is the therapy of choice to mimic a physiologic dose range and to achieve symptomatic relief. The addition of cyclic progesterone for 10–12 days each month is protective against endometrial hyperplasia and endometrial cancer, risks of unopposed estrogen. Oral estradiol may be used, but it increases the potential for thromboembolism relative to transdermal estradiol due to the first-pass effect on the liver. Oral contraceptives contain higher doses of estrogen than are necessary for hormonal therapy; therefore, they are not recommended as first-line hormonal therapy.
Fertility and Contraception
Fertility may persist even when few functional follicles 
are present. Because of occasional spontaneous resumption of ovarian function, there is a 5–10% chance of spontaneous pregnancy despite a diagnosis of primary ovarian insufficiency PubMed] «>10. Unless pregnancy is desired, a discussion of effective contraception should take place. Although OCs are commonly prescribed in this situation, the use of barrier methods or an intrauterine device is encouraged PubMed] [Full Text] «>1. If a patient chooses a nonestrogen method of contraception, estrogen also should be administered to preserve bone mineral density and prevent other adverse effects of hypoestrogenemia. A missed menstrual cycle should warrant a pregnancy test.
Associated Comorbidities
Primary ovarian insufficiency increases the risk of bone loss, CV disease, and endocrine disorders. Health care providers also should be aware of the potential psychologic effects of priily members and patients on the risk of associated comorbidities.
Bone Loss
Loss of ovarian function at an early age affects bone architecture at the very time when bone accrual is at its maximum. There are no published data to support specific recommendations for dual-energy X-ray absorptiometry scanning in adolescents with estrogen deficiency. Although some experts suggest monitoring bone density annually in adolescents with estrogen deficiency during early to mid puberty to document peak bone accrual and then every 2 years in late adolescence, others do not because the implications of a low bone mineral density result in this population are unclear given the low risk of fracture and the potential for long-term treatment of low bone mass. To date, long-term use of bisphosphonates is not recommended in the adolescent population because of uncertain adverse effects and safety profiles. Further research in this area is needed.
