Although the diagnosis and treatment of disorders associated with hypogonadism were discussed in another chapter (see Chapter 29), they will be mentioned here because these conditions may present as primary amenorrhea. Because breast development is the first sign of estrogen exposure in puberty, patients without secondary sexual characteristics typically have primary, not secondary, amenorrhea (Fig 30.1). It is helpful to categorize the causes of amenorrhea in the absence of breast development on the basis of gonadotropin status.
Gonadal dysgenesis is a term typically used to describe abnormal development of the gonads, typically resulting in streak gonads. Gonadal dysgenesis is associated with high levels of LH and FSH because the gonad fails to produce the steroids and inhibin that would normally feed back to the pituitary gland to suppress pituitary production of LH and FSH. Karyotypic abnormalities are common in women with primary amenorrhea associated with gonadal failure (Table 30.1).
In one series, approximately 30% of patients with primary amenorrhea had an associated karyotypic abnormality (3). Turner syndrome (45,X) and its variants represent the most common form of hypergonadotropic hypogonadism in women with primary amenorrhea.
Secondary sexual characteristics Present Primary Pregnancy hCG −hCG +Yes No Physical exam • If risk of endometrial  scarring, advise HSG  saline hysterogram or  hysteroscopy &  culture’s to exclude  Asherman's, cervical  stenosis and infection Normal Abnormal – consider karyotype TSH, PRL, FSH, clinical evaluation of estrogen status Abnormal TSH Normal TSH Normal PRL High PRL Hyperprolactinemia Absent Physical exam Normal Normal or low Absent uterus FSH level High Karyotype • 5α-reductase deficiency • 17–20 lyase deficiency • 17α-hydroxylase deficiency (all with XY karyotype) • Kallman's syndrome • Physiologic delay • Disorders of low estrogen status before puberty • XX • Y line • Turner (XO) • Hyperthyroidism • Hypothyroidism • Mlerian anomaly • Androgen insensitivity • True hermaphrodite
Figure 30.1 Decision tree for evaluation of amenorrhea. FSH, follicle-stimulating hormone; HCG, human chorionic gonadotropin; HSG, hysterosalpingogram; TSH, thyroid-stimulating hormone; PRL, prolactin; CT, computed tomography; MRI, magnetic resonance imaging; EEG, electroencephalogram; SHG, saline hysterogram.
Normal PRL Normal FSH Normal estrogen Low estrogen Neurological exam. CT/MRI, EEG Normal • Feedback disorders hypothalmic dysfunction • Obesity • Cushing's syndrome • Androgen-secreting adrenal tumors • Congenital adrenal hyperplasia • Ovarian neoplasm • Granulosa cell androgen-secreting • Chronic disease pulmonary renal liver diabetes • Addison's disease • Hypothalmic dysfunction • Anorexia • Exercise-induced • Stress • Pseudocyesis • Malnutrition High FSH • Ovarian insufficiency-45 XO, mosaic FMR1 premutation   chromosomal radiation chemotherapy infections autoimmune • Galactosemia • Idiopathic Abnormal • Pituitary-hypothalmic lesions tumors infection infarction pituitary failure Sheehan's • Diabetic vasculitis • Toxic-lead • Chronic anovulatory • Polycystic ovarian syndrome • Idiopathic
Table 30.1 Amenorrhea Associated with a Lack of Secondary Sexual Characteristics 5α-reductase deficiency, 17, 20-lyase deficiency, or 17α-hydroxylase deficiency in XY individual