Other Hormonal Factors The secretion of hypothalamic neuromodulators can be altered by feedback from abnormal levels of peripheral hormones. Excesses or deficiencies of thyroid hormone, glucocorticoids, androgens, and estrogens can cause menstrual dysfunction. Excess secretion of GH, TSH, ACTH, and prolactin from the pituitary gland can cause abnormal feedback inhibition of GnRH secretion, leading to amenorrhea. Growth hormone excess causes acromegaly, which may be associated with anovulation, hirsutism, and polycystic-appearing ovaries as a result of stimulation of the ovary by IGF-1. More commonly, GH excess is accompanied by amenorrhea, low gonadotropin levels, and elevated prolactin levels. Acromegaly is recognized by enlargement of facial features, hands, and feet; hyperhidrosis; visceral organ enlargement; and multiple skin tags. Cushing disease is caused by an ACTH-secreting pituitary tumor, which is manifested by truncal obesity, moon facies, hirsutism, proximal weakness, depression, and menstrual dysfunction.
Evaluation for Women with Amenorrhea in the Presence of Normal Pelvic Anatomy and Normal Secondary Sexual Characteristics
A pregnancy test (urine or serum human chorionic gonadotropin [hCG]) should be performed in a reproductive-age woman who has amenorrhea with normal secondary sexual characteristics and a normal pelvic examination. If the results of the pregnancy test are negative, the evaluation of amenorrhea is as follows: 1.
Clinical assessment of estrogen status 2.
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Vaginal ultrasound for assessment of antral follicle count in the ovaries can be considered (may help establish the diagnosis of PCOS or suggest POI) 6.
Imaging of the pituitary and hypothalamic assessment if prolactin is elevated or if hypothalamic amenorrhea is suspected (particularly if CNS symptoms are present or there is no clear explanation for hypothalamic amenorrhea).
Assessment of Estrogen Status
The presence of vaginal dryness or hot ﬂashes increases the likelihood of a diagnosis of hypoestrogenism. A sample of vaginal secretions can be obtained during the physical examination, and mucosal estrogen response can be demonstrated by the presence of superficial cells. A serum estradiol level higher than 40 pg/mL is considered indicative of significant estrogen production, but interassay discrepancies often exist and serum estrogen levels can vary greatly on a day-today basis for a given woman. Vaginal ultrasound demonstrating a thin endometrium suggests that a patient is hypoestrogenic, unless there is reason to suspect that the patient lacks functional endometrium. A DEXA (dual-energy x-ray absorptiometry) scan to determine bone mineral density should be considered for a patient in whom long-term hypoestrogenism is suspected.
There is little utility in routine performance of a progestogen challenge test to determine the patient’s estrogen status. False positives and false negatives are common.
Consideration should be given to thyroid disorders and hyperprolactinemia in women with amenorrhea because of the relatively common incidence of these conditions.
1. Sensitive TSH assays can be used to evaluate hypothyroidism and hyperthyroidism.
Further evaluation of a thyroid disorder is required if abnormalities in TSH levels are found. Mild degrees of thyroid dysfunction are unlikely to cause amenorrhea. Given the general health implications of thyroid dysfunction and readily available treatments, routine assessment of TSH is reasonable for women with amenorrhea.