Snapshot A 22-year-old female presents with increased hair growth. She reports having to shave frequently above the lip, chin, chest, and lower back. She also states not having her menses over a period of four months. Prior to this, she had a regular menses. The patient's weight is 168 lbs (76.2 kg) and height 5 feet and 1 inch (154.9 cm). On physical examination, there is increased hair above the lip and chin area. There is also acne on the cheeks and forehead. Hyperpigmented plaques of the skin are found in the back of the neck. Bilateral enlarged ovaries are palpated on pelvic examination. β-hCG is negative and LH:FSH is 3. (Polycystic ovarian syndrome) SUMMARY Absence of menses > 3 months in those with regular menses or absence of menses > 6 months in those with irregular menses Etiology pregnancy (most common) hypothalamic dysfunction e.g., functional hypothalamic amenorrhea, benign or malignant hypothalamic tumors, and systemic illness functional hypothalamic amenorrhea also known as functional hypothalamic GnRH deficiency excludes pathological disease risk factors eating disorders, excessive exercise, and stress hypothalamic tumors include craniopharyngiomas infiltrative disease affecting the hypothalamus include Langerhans cell histiocytosis and sarcoidosis pituitary dysfunction e.g., prolactin-secreting pituitary adenoma and pituitary infarct (Sheehan syndrome) thyroid disorder e.g., hypothyroidism and severe hyperthyroidism polycystic ovarian syndrome (most common reproductive disorder in women) ovarian dysfunction e.g., primary ovarian insufficiency and ovarian malignancy uterine disorders e.g., Asherman syndrome obesity Presentation Symptoms and physical examination findings will be dependent on the etiology of secondary amenorrhea e.g., patient with eating disorder (functional hypothalamic amenorrhea), hirsutism, or obesity (polycystic ovarian syndrome) History e.g., eating disorder, excessive exercise, hyperandrogenism, visual defects, vaginal dryness, and hot flashes Physical Exam e.g., body mass index, acne, hirsutism, acanthosis nigricans, vitiligo, galactorrhea, and signs of estrogen deficiency on pelvic examination Studies β-hCG best initial test Follicle-stimulating hormone (FSH), prolactin (PRL), and thyroid-stimulating hormone (TSH) order after ruling out pregnancy assesses primary ovarian insufficiency, hyperprolactinemia, and thyroid abnormalities (e.g., severe hyperthyroidism and hypothyroidism) Testosterone should be ordered if there is evidence of hyperandrogenism Progesterone challenge test presence of withdrawal bleeding suggests endogenous estrogen exposure absence of bleeding suggests hypoestrogenism or outflow tract obstruction Estrogen-progesterone challenge test presence of withdrawal bleeding suggests inadequate estrogen next step is ordering an FSH absence of bleeding suggests outflow tract obstruction or scarring of the endometrium Differential Diagnosis Pregnancy Contraceptive use Excessive exercise/physical stress Refer to introduction for causes of secondary amenorrhea Treatment Treatment depends on etiology of disease as a rule of thumb, treat underlying pathology examples include functional hypothalamic amenorrhea lifestyle modification e.g., decreasing exercise and increasing caloric intake in patients with exercise excess primary ovarian insufficiency estrogen and progresterone therapy Asherman syndrome hysteroscopic lysis of adhesions afterwards, place patient on estrogen therapy to stimulate regrowth of the endometrium Complications Infertility Decreased bone density in patients with inadequate estrogen