What tests are necessary to diagnose amenorrhea?

Diagnostic Testing for Amenorrhea

The essential tests to diagnose amenorrhea include a pregnancy test (urine hCG), serum prolactin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), followed by a progesterone challenge test if initial labs are normal. 1, 2

Initial Mandatory Laboratory Tests

All patients presenting with amenorrhea require the following baseline tests:

• Pregnancy test (urine or serum hCG) - Must be performed first to exclude pregnancy, the most common cause of amenorrhea 1, 3, 4
• Serum prolactin level - To identify hyperprolactinemia and potential pituitary adenoma 1, 2, 4
• Thyroid-stimulating hormone (TSH) - To detect thyroid dysfunction 1, 2, 4
• Follicle-stimulating hormone (FSH) - To differentiate ovarian failure from hypothalamic/pituitary dysfunction 1, 2
• Luteinizing hormone (LH) - To assess gonadotropin status and identify patterns suggestive of polycystic ovary syndrome 1, 2

History and Physical Examination Components

The clinical evaluation must include specific targeted elements:

Menstrual and reproductive history:

• Age at menarche, cycle length and characteristics, onset/severity of dysmenorrhea 5
• Gravidity, parity, pregnancy outcomes and complications 5
• Duration of amenorrhea (primary vs. secondary) 1, 2

Review of systems emphasizing:

• Symptoms of thyroid disease, galactorrhea, hirsutism 5
• Pelvic or abdominal pain, dyspareunia 5
• Eating and exercise habits, psychosocial stressors, body weight changes 2
• Vasomotor symptoms (hot flashes suggesting hypoestrogenism) 2

Physical examination must include:

• Height, weight, and BMI calculation 5
• Thyroid examination for enlargement, nodules, or tenderness 5
• Clinical breast examination and assessment for galactorrhea 5
• Assessment for signs of androgen excess (hirsutism, acne) 5
• Pelvic examination when indicated (see below) 5

Progesterone Challenge Test

If pregnancy test, prolactin, and TSH are normal:

• Administer progesterone (medroxyprogesterone acetate 10 mg daily for 5-10 days) to determine outflow tract patency and estrogen status 4
• Positive test (withdrawal bleeding occurs) indicates adequate estrogen and patent outflow tract, suggesting anovulation (commonly polycystic ovary syndrome) 4
• Negative test (no bleeding) indicates either hypoestrogenism or outflow tract obstruction 4

Additional Testing Based on Initial Results

If prolactin is elevated:

• Brain MRI to evaluate for pituitary adenoma 6, 2

If TSH is abnormal:

• Complete thyroid function panel (free T4) 2

If FSH is elevated (>40 mIU/mL):

• Indicates primary ovarian insufficiency 1, 2
• Karyotype analysis if patient is under 30 years old to identify Turner syndrome or other chromosomal abnormalities 1, 2

If FSH is low or normal with negative progesterone challenge:

• Suggests hypothalamic or pituitary dysfunction 1, 4
• Consider evaluation for functional hypothalamic amenorrhea (eating disorders, excessive exercise, stress) 2, 4

If hyperandrogenism is suspected clinically:

• Serum testosterone, DHEA-sulfate, and 17-hydroxyprogesterone 2

Imaging Studies

Pelvic ultrasound indications:

• Primary amenorrhea with absent uterus (to confirm Müllerian agenesis) 3
• Suspected polycystic ovary syndrome 2
• Evaluation for outflow tract obstruction 5

When pelvic examination is necessary:

• Primary amenorrhea to assess for anatomic abnormalities (imperforate hymen, transverse vaginal septum) 5, 3
• Suspected outflow tract obstruction 5
• Note: Pelvic examination is NOT required before initiating most hormonal contraceptives 5

Bone Density Assessment

DXA scan indications in amenorrheic patients:

• History of amenorrhea ≥6 months with low energy availability, eating disorder, or BMI <17.5 kg/m² 5
• History of stress fractures 5
• Athletes with oligomenorrhea/amenorrhea and other Female Athlete Triad risk factors 5

Sites to scan:

• Adults ≥20 years: posteroanterior lumbar spine, total hip, femoral neck 5
• Adolescents <20 years: posteroanterior lumbar spine and whole body (head excluded) 5

Common Pitfalls to Avoid

• Never skip the pregnancy test - even in patients who deny sexual activity, as this is the most common cause of amenorrhea 1, 3, 4
• Do not order all tests simultaneously - follow the algorithmic approach to avoid unnecessary testing and cost 1, 2
• Do not assume infertility - patients with primary ovarian insufficiency can maintain unpredictable ovarian function 1, 2
• Do not overlook eating disorders - functional hypothalamic amenorrhea requires specific evaluation for disordered eating and carries risk for decreased bone density 1, 2