Chapter 051. Menstrual Disorders and Pelvic Pain (Part 3)

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Algorithm for evaluation of amenorrhea. β-hCG, human chorionic gonadotropin; PRL, prolactin; FSH, follicle-stimulating hormone; TSH, thyroidstimulating hormone. Hypogonadotropic Hypogonadism Low estrogen levels in combination with normal or low levels of LH and FSH are seen with anatomic, genetic, or functional abnormalities that interfere with hypothalamic GnRH secretion or normal pituitary responsiveness to GnRH. Although relatively uncommon, tumors and infiltrative diseases should be considered in the differential diagnosis of hypogonadotropic hypogonadism (Chap. 333). These disorders may present with primary or secondary amenorrhea. They may occur in association with other features suggestive of hypothalamic or pituitary dysfunction such as short stature, diabetes insipidus,...

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Chapter 051. Menstrual Disorders and Pelvic Pain (Part 3) Algorithm for evaluation of amenorrhea. β-hCG, human chorionic gonadotropin; PRL, prolactin; FSH, follicle-stimulating hormone; TSH, thyroid- stimulating hormone. Hypogonadotropic Hypogonadism Low estrogen levels in combination with normal or low levels of LH and FSH are seen with anatomic, genetic, or functional abnormalities that interfere with hypothalamic GnRH secretion or normal pituitary responsiveness to GnRH. Although relatively uncommon, tumors and infiltrative diseases should be considered in the differential diagnosis of hypogonadotropic hypogonadism (Chap. 333). These disorders may present with primary or secondary amenorrhea.
They may occur in association with other features suggestive of hypothalamic or pituitary dysfunction such as short stature, diabetes insipidus, galactorrhea, or headache. Hypogonadotropic hypogonadism may also be seen following cranial irradiation. In the postpartum period, it may be due to pituitary necrosis (Sheehan syndrome) or lymphocytic hypophysitis. Because reproductive dysfunction is commonly associated with hyperprolactinemia, either from neuroanatomic lesions or medications, prolactin should be measured in all patients with hypogonadotropic hypogonadism (Chap. 333). Isolated hypogonadotropic hypogonadism (IHH) is more common in men than women and is often associated with anosmia. IHH generally presents with primary amenorrhea. A number of genetic causes of IHH have been identified (Chaps. 340 and 341). Functional hypothalamic amenorrhea (HA) is caused by a mismatch between energy expenditure and energy intake. Leptin secretion may play a key role in transducing the signals from the periphery to the hypothalamus in HA. The hypothalamic-pituitary-adrenal axis may also play a role. The diagnosis of HA can generally be made on the basis of a careful history, physical examination, and the demonstration of low levels of gonadotropins and normal prolactin levels. Eating disorders and chronic disease must be specifically excluded (Chap. 76). An atypical history, headache, signs of other hypothalamic dysfunction, or
hyperprolactinemia, even if mild, necessitates cranial imaging with CT or MRI to exclude a neuroanatomic cause. Hypergonadotropic Hypogonadism Ovarian failure is considered premature when it occurs in women younger than age 40. Ovarian failure is associated with the loss of negative-feedback restraint on the hypothalamus and pituitary, resulting in increased FSH and LH levels. FSH is a better marker of ovarian failure as its levels are less variable than LH. As with natural menopause, premature ovarian failure (POF) may wax and wane, and serial measurements may be necessary to establish the diagnosis. Once the diagnosis of POF has been established, further evaluation is indicated because of other health problems that may be associated with POF. For example, POF is seen in association with a variety of chromosomal abnormalities including Turner syndrome, autoimmune polyglandular failure syndromes, radio- and chemotherapy, and galactosemia. In the majority of cases, however, a cause is not determined. The recognition that early ovarian failure occurs in premutation carriers of the fragile X syndrome is important because of increased risk of severe mental retardation in male children with FMR1 mutations. Hypergonadotropic hypogonadism occurs rarely in other disorders, such as mutations in the FSH or LH receptors. Aromatase deficiency and 17α-hydroxylase deficiency are associated with elevated gonadotropins with hyperandrogenism and
hypertension, respectively. Gonadotropin-secreting tumors in women of reproductive age generally present with high, rather than low, estrogen levels and cause ovarian hyperstimulation or dysfunctional bleeding. Amenorrhea Caused by Ovulatory Disorders: Treatment Amenorrhea is almost always associated with chronically low levels of estrogen, whether it is caused by hypogonadotropic hypogonadism or ovarian failure. Development of secondary sexual characteristics requires gradual titration of estradiol replacement with eventual addition of a progestin. Symptoms of hypoestrogenism can be treated with hormone replacement therapy or oral contraceptive pills. Patients with hypogonadotropic hypogonadism who are interested in fertility require treatment with pulsatile GnRH or exogenous FSH and LH, whereas patients with ovarian failure can consider oocyte donation, which has a high chance of success in this population. Polycystic Ovarian Syndrome (PCOS) This is diagnosed based on the presence of clinical or biochemical evidence of hyperandrogenism in association with amenorrhea or oligomenorrhea. Symptoms generally begin shortly after menarche and are slowly progressive. Lean patients with PCOS generally have high LH levels in the presence of normal to low levels of FSH and estradiol. The LH/FSH abnormality is less pronounced in obese patients in whom insulin resistance is a more prominent feature. Most
patients also have a polycystic ovarian morphology on ultrasound, although there is controversy as to whether this morphology in combination with hyperandrogenism is sufficient for the diagnosis of PCOS.