Primary Ovarian Insufficiency

Abstract

A 30-year-old woman presents with a history of no menses since she stopped taking oral contraceptives 6 months ago in order to conceive. She had undergone puberty that was normal in both timing and development, with menarche at 12 years of age. At 18 years of age, she started taking oral contraceptives for irregular menses. She reports stress at work. Her weight is 59 kg, and her height 1.66 m; her body-mass index (the weight in kilograms divided by the square of the height in meters) is 21.3. There is no galactorrhea, hirsutism, or acne. The pelvic examination is normal, a pregnancy test is negative, the prolactin level is normal, and the follicle-stimulating hormone (FSH) level is in the menopausal range. How should she be evaluated and treated? THE CLINICAL PROBLEMThe ovary is unique in the endocrine system in that an entirely new secretory structure is developed within it each month -the graafian follicle, which arises from a microscopic primordial follicle. Menopause, defined as the permanent cessation of menses, results from the depletion of potentially functional primordial follicles. The mean (±SD) age at the time of natural menopause is 50±4 years. 1 Menopause before the age of 40 years is considered to be premature.Primary ovarian insufficiency is the preferred term for the condition that was previously referred to as premature menopause or premature ovarian failure; other terms used for this condition include primary ovarian failure and hypergonadotropic hypogonadism, as well as the misnomer, gonadal dysgenesis. 2,3 The condition is considered to be present when a woman who is less than 40 years old has had amenorrhea for 4 months or more, with two serum FSH levels (obtained at least 1 month apart) in the menopausal range. 4,5 The condition differs from menopause in that there is varying and unpredictable ovarian function in approximately 50% of cases, and about 5 to 10% of women conceive and deliver a child after they have received the diagnosis. 4,6-9 Thus, the term "primary ovarian insufficiency," as originally suggested by Albright, meets the need to describe a continuum of impaired ovarian function rather than a dichotomous state. 2,3 This term may also be less stigmatizing than the terms that were used previously.Address reprint requests to Dr. Nelson at the Integrative Reproductive Medicine Unit, NICHD-Intramural Research Program on Reproductive and Adult Endocrinology, CRC, Rm. 1-3330, 10 Center Dr., MSC-1103, Bethesda, MD 20892, or at lawrence_nelson@nih.gov. Dr. Nelson reports being an inventor on three United States patents directed to MATER (a potential antigen in autoimmune primary ovarian insufficiency) and its applications (U.S. patent numbers 7,189,812; 7,217,811; and 7,432,067), as well as one pending United States patent application (U.S. patent application number 11/586,160) and foreign counterparts. No other potential conflict of interest relevant to this article was reported. Primary ovarian insufficiency occurs through two major mechanisms: follicle dysfunction and foll...