Pregnancy should be considered as the number one cause of secondary amenorrhea.

The differential diagnosis includes polycystic ovarian disease (most common ovarian cause), chronic anovulation, structural changes (cervical stenosis and Asherman’s syndrome), adrenal or thyroid dysfunction, endometrial atrophy (i.e., continuous progesterone use), pituitary prolactinoma, gestational trophoblastic disease, and nutritional disorders.

Occurs before the age of 40 years.

Tests to order: pregnancy test (negative), follicle-stimulating hormone (FSH) (>40 IU/L), estradiol (<12 pg/mL), serum antimüllerian hormone (low), prolactin level (normal), transvaginal ovarian ultrasound (small to absent ovaries with minimal follicular activity).

Tests to consider: karyotype (Turner’s syndrome—45,XO, trisomy X, Swyer’s syndrome—XY gonadal dysgenesis, or mosaicism), thyroid peroxidase antibodies (positive in autoimmune thyroiditis), fragile X mutation (FMR-1 gene mutation positive), celiac antibodies, adrenal antibodies, B12, adrenocorticotropic hormone stimulation test, and baseline dual X-ray absorptiometry (may be low in estrogen-deficient women).

The time before and after the last period, when hormone fluctuations occur.

Diagnosis is made clinically; no serologic testing can predict the time of menopause.

A persistent elevation in FSH [and luteinizing hormone (LH)] can signal that menopause is imminent.