Amenorrhea: A Systematic Approach to Diagnosis and Management

David A. Klein, MD, MPH; Scott L. Paradise, MD; Rachel M. Reeder, MD


Am Fam Physician. 2019;100(1):39-48. 

In This Article



A detailed history should include menstrual patterns (if any), pregnancy and breastfeeding history, eating and exercise habits, psychosocial stressors (e.g., perfectionist behaviors), changes in body weight, fractures, medication or substance use, chronic illness, and timing of breast and pubic hair development[2,3,6] (Table 2[1–3,5,6,10–12]). Galactorrhea, headaches, or visual field defects can indicate hypothalamic or pituitary disease,[13,14] and acne or hirsutism can indicate hyperandrogenism.[15] Vasomotor symptoms such as hot flashes or night sweats may indicate primary ovarian insufficiency.[10] A family history should include the age of menarche of relatives and any chronic disease history.[2,3]

Physical Examination

Clinicians should review trends in height, weight, and body mass index.[2,3] Normal breast development indicates the presence of circulating estrogen.[6] Atrophic vaginal mucosae suggests low estrogen, and a shortened vagina may indicate outflow tract obstruction or Müllerian agenesis.[6,16,17] Signs of virilization suggest hyperandrogenic conditions. Evidence of dysmorphism may suggest a congenital syndrome.[6,10,17]

Laboratory and Other Testing

In all cases, pregnancy should be excluded with a pregnancy test.[2,3,6] Serum patterns of follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone identify most endocrine causes of amenorrhea[2,3,6,10–12] (Figure 1[3]). Serum free and total testosterone, and dehydroepiandrosterone sulfate levels may be obtained if there is evidence of hyperandrogenism[8,15,18,19] (Table 3[2,5,6,10–12]). A 17-hydroxyprogesterone level collected at 8 a.m. assesses for late-onset congenital adrenal hyperplasia.[2,15] Low anti-Müllerian hormone correlates with ovarian reserve and may indicate primary ovarian insufficiency or menopause (Table 4).[2]

Karyotyping should also be considered in patients of short stature to evaluate for Turner syndrome.[6,20] Patients with this syndrome require screening for cardiac and renal defects, neurocognitive and behavior disorders, hypothyroidism, and hearing loss, and generally require hormone therapies for puberty induction and growth, often in consultation with a pediatric endocrinologist.[17,20,21]

Pelvic ultrasonography or magnetic resonance imaging (MRI) can identify abnormal reproductive anatomy or detect an androgen-secreting tumor.[2,15] MRI of the brain can identify pituitary and other tumors.[2,6,13] Dual energy x-ray absorptiometry can establish baseline fracture risk in patients with concerns for primary ovarian insufficiency or functional hypothalamic amenorrhea.[2,22] A hormonal challenge can be used after excluding pregnancy to determine the presence of functioning anatomy; however, the predictive value of this test on adequate endometrial estrogen exposure is inconsistent.[3,17,23] A common regimen for a hormonal challenge is 10 mg of medroxyprogesterone (Provera) orally per day for 10 days; withdrawal bleeding may indicate estrogen exposure (e.g., polycystic ovary syndrome [PCOS]) and lack of bleeding may indicate a lowestrogen condition.[2,24]