PREMATURE OVARIAN FAILURE

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Premature ovarian failure is a condition characterized by amenorrhea, infertility, sex steroid deficiency, and elevated gonadotropins in women less than 40 years of age.71 It affects 1% of women by age 40 years and 0.1% by age 30 years.23 At one time, premature ovarian failure was considered irreversible and was described as premature menopause; however, young women with premature ovarian failure are now known to have intermittent ovarian function.70, 86

Early loss of ovarian function has significant psychosocial sequelae and major health implications. Women with premature ovarian failure have a nearly twofold age-specific increase in mortality rate107 and hence require thorough assessment, sex steroid replacement, and long-term surveillance to monitor therapy and minimize health risks in later life.

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PREMATURE OVARIAN FAILURE IS NOT MERELY AN EARLY NATURAL MENOPAUSE

The normal menopause occurs at an average age of 50 years36 and results from ovarian follicle depletion.90, 91 Normal menopause is an irreversible condition, whereas premature ovarian failure is characterized by intermittent ovarian function in one-half of young women.70 Affected women produce estrogen intermittently and may ovulate despite the presence of high gonadotropin levels.70 Pregnancies have occurred after the diagnosis of premature ovarian failure,3, 6, 48, 76, 80, 100, 111 even in

Signs and Symptoms of Spontaneous Premature Ovarian Failure

Premature ovarian failure may present as either primary or secondary amenorrhea.27, 71, 88 Women with chromosomal defects are more likely to present with primary amenorrhea, although individuals with mosaicism may have some functional gonadal tissue giving rise to various degrees of sexual development and transient menstrual cyclicity. The age of presentation of premature ovarian failure in many cases depends on the timing and rapidity of follicular atresia. In the majority of patients, ovarian

ETIOLOGY

Premature ovarian failure may occur on the basis of ovarian follicle dysfunction or ovarian follicle depletion (Table 1). Patients with follicle dysfunction have follicles remaining in the ovary70, 87 and have the theoretic possibility of having fertility restored.

NATURAL HISTORY AND PATHOPHYSIOLOGY

Follicle function requires stimulation of theca and granulosa cells by gonadotropins.37 When follicles are not functioning normally or are depleted, normal cyclic sex steroid production ceases and ovarian failure occurs.

More than one third of women with spontaneous premature ovarian failure who have a normal karyotype have structures on pelvic ultrasound examination that appear to be ovarian follicles.67 In addition, on serial blood sampling, nearly one half of these women have been found to

History and Physical Examination

A complete history should be taken regarding prior ovarian surgery, chemotherapy, or radiation. A detailed history should also be obtained regarding autoimmune disorders. Particular attention should be paid to symptoms of adrenal failure (Addison's disease), which may have a long insidious course before the disease becomes life-threatening. These symptoms include anorexia, weight loss, abdominal pain, weakness, salt craving, and increased skin pigmentation.71 Findings associated with autoimmune

MANAGEMENT

Young women find the diagnosis of premature ovarian failure particularly traumatic and need a great deal of personal and emotional support.27 Therefore, a carefully planned approach is required when informing patients of this diagnosis. It is important to emphasize that premature ovarian failure can be transient and that, in most cases, one can never be certain that there are no follicles remaining in the ovary.70

SUMMARY

In 1% of women, premature ovarian failure develops by 40 years of age,23 a condition causing amenorrhea, infertility, sex steroid deficiency, and elevated gonadotropins.71 Early loss of ovarian function has significant psychosocial sequelae and major health implications. These young women have a nearly twofold age-specific increase in mortality rate.107

Among women with spontaneous premature ovarian failure who have a normal karyotype, half have ovarian follicles remaining in the ovary that

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    Address reprint requests to Lawrence M. Nelson, MD, Section on Women's Health, DEB, NICHD, National Institutes of Health, Building 10, Room 10N262, Bethesda, MD 20892–1862

    SNK is the recipient of support by the D.B. Kaskarelis award from the Greek Obstetric and Gynecologic Society.

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