Ovarian Failure

Primary ovarian failure is associated with elevated plasma gonadotropin levels and can result from several causes. The most frequent cause is gonadal dysgenesis, in which the germ cells are absent and the ovary is replaced by a fibrous streak. A 45,X karyotype is found in about half of women with this disorder, and most have somatic defects, including short stature, webbed neck, shield chest, and cardiovascular defects, collectively termed the Turner phenotype. The remainder of women with X chromosome abnormalities have chromosomal mosaicism with or without associated structural abnormalities of the X. Approximately 90% of women with gonadal dysgenesis due to partial or complete deletion of the X never have menstrual bleeding, and the remaining 10% have sufficient follicles to experience menses and, rarely, fertility; the menstrual and reproductive lives of such individuals are invariably brief.

One-tenth of individuals identified as having bilateral streak gonads have a normal 46,XX or 46,XY karyotype and are said to have pure gonadal dysgenesis. These individuals have either normal or above-average stature, owing to failure of estrogen-mediated epiphyseal closure in the presence of a normal chromosomal constitution. Pure gonadal dysgenesis does not constitute a phenotypic or chromosomally homogeneous disorder.

Other causes of ovarian failure and amenorrhea include deficiency of the CYP17 gene that encodes 17-α hydroxylase and 17,20-lyase activities, premature ovarian failure, the resistant-ovary syndrome, and ovarian failure secondary to chemotherapy or radiation therapy for malignancy. 17-Hydroxylase deficiency is a rare, autosomal recessive disorder characterized by primary amenorrhea, sexual infantilism, and hypertension, the latter due to increased production of desoxycorticosterone (DOC); women with 17,20-lyase deficiency have primary amenorrhea and sexual infantilism with normal blood pressure. The diagnosis of premature ovarian failure or premature menopause applies to women who cease menstruating before age 40. The ovaries in such women are similar to those of postmenopausal women, containing few or no follicles as the result of accelerated follicular atresia. Premature ovarian failure due to ovarian antibodies may be one component of polyglandular failure, together with adrenal insufficiency, hypothyroidism, and other autoimmune disorders. A rare form of ovarian failure is the resistant-ovary syndrome, in which the ovaries contain many follicles that are arrested in development prior to the antral stage, possibly because of resistance to the action of FSH in the ovary. A subset of these individuals have mutations in FSH or its receptor. To differentiate this disorder from the 46,XX variety of pure gonadal dysgenesis, which is also associated with sexual immaturity, it is necessary to perform ovarian biopsy or genetic testing. Women with ovarian failure who desire pregnancy have been treated with hormone replacement and transfer of donor embryos to the uterine cavity or fallopian tubes.