In patients who are hirsute and amenorrheic and appear to have PCOS, androgen-secreting adrenal tumors and congenital adrenal hyperplasia should be considered. Elevations in androgens (e.g., Sertoli-Leydig, hilus, and lipoid cell tumors) and estrogens (e.g., granulosa cell tumors) by ovarian tumors may lead to abnormal menstrual patterns, including amenorrhea. A history of rapid onset of hirsutism is suggestive of a tumor.
other central nervous system (CNS) lesions that disrupt the normal transport of dopamine down the pituitary stalk, and by medications that interfere with normal dopamine secretion (such as antidepressants, antipsychotics including risperidone, metoclopramide, some antihypertensives, opiates, and H2-receptor blockers).
If elevated TSH and elevated prolactin levels are found together, the hypothyroidism should be treated before hyperprolactinemia is treated. Often, the prolactin level will normalize with treatment of hypothyroidism because thyroid-releasing hormone, which is elevated in hypothyroidism, stimulates prolactin secretion.
Primary ovarian insufficiency is suggested as the preferred term for the condition that otherwise was referred to as premature ovarian failure or premature menopause (82,83). Overt primary ovarian insufficiency (POI) is defined as the presence of amenorrhea for 4 months or more accompanied by two serum FSH levels in the menopausal range for a woman who is less than 40 years of age. Ovarian “insufficiency” is suggested to be more appropriate than “failure” in part because ovarian function can wax and wane, and function can resume even after it appears that a woman transitioned into menopause. Ovarian insufficiency may be caused by decreased follicular endowment or accelerated follicular atresia (82). Over 75% of women with POI will have at least intermittent symptoms including hot ﬂushes, night sweats, and emotional lability (84). Symptoms are uncommon among women with primary amenorrhea who never received estrogen.
If the ovary does not develop or stops its hormone production before puberty, the patient will not develop secondary sexual characteristics without exogenous hormone therapy. If ovarian insufficiency begins later in life, the woman will have normal secondary sexual characteristics.
POI clearly compromises the chance of a woman conceiving with autologous oocytes. However, 5% to 10% of women with a diagnosis of premature ovarian failure achieve pregnancy, with approximately 80% of these pregnancies resulting in the delivery of a healthy child (85). It can be difficult to determine which women will be able to conceive. Published studies of testing for ovarian reserve have not specifically focused on the POI populations, and pregnancies may occur despite very unfavorable results for tests of ovarian reserve such as serum FSH, estradiol, and AMH.
POI is a heterogenous disorder with many potential causes. POI may be caused by sex chromosome disorders, mutations of single genes, and by FMR1 premutations. Radiation or chemotherapy may lead to POI. The cause of POI may be autoimmune. The cause remains unknown in a majority of cases (Table 30.3).
Sex Chromosome and Single Gene Disorders Associated with Primary Ovarian Insufficiency Deletion of the X chromosome (Turner syndrome) is associated with primary ovarian insufficiency, despite normal development of the ovaries, because of accelerated atresia of the follicles (86). Although Turner syndrome may often be associated with primary
Table 30.3 Causes of Ovarian Insufficiency or Failure after Development of Secondary Sexual Characteristics
Chromosomal etiology (e.g., Turner mosaic)
Iatrogenic causes: radiation, chemotherapy, surgical damage to ovarian blood supply or ovary