What investigations are recommended for a woman with secondary amenorrhea at age 40?

Investigations for Secondary Amenorrhea at Age 40

For a 40-year-old woman with secondary amenorrhea, perform a pregnancy test first, followed by serum FSH, LH, prolactin, and TSH levels, with particular attention to ruling out premature ovarian insufficiency (POI) given her age. 1, 2

Initial Mandatory Laboratory Tests

The diagnostic workup must begin systematically:

• Pregnancy test (serum or urine hCG) is the absolute first step to exclude pregnancy, regardless of patient's reported sexual activity or contraceptive use 1, 2, 3

• Serum FSH and LH levels are essential to differentiate between primary ovarian insufficiency and other causes. At age 40, elevated FSH (>40 mIU/mL) suggests POI, which requires confirmation with repeat testing 4 weeks later (two elevated values needed for diagnosis) 1, 2, 3

• Serum prolactin level to identify hyperprolactinemia, which accounts for approximately 20% of secondary amenorrhea cases. Elevated prolactin (>20 μg/L) may indicate pituitary adenoma or medication effect 1, 2, 3

• Serum TSH level to detect thyroid dysfunction, a reversible cause of amenorrhea 1, 2, 3

Additional Hormonal Testing Based on Initial Results

• Serum estradiol level should be measured when functional hypothalamic amenorrhea (FHA) is suspected, with low levels indicating hypoestrogenism 1, 2

• Testosterone and androstenedione levels if clinical signs of hyperandrogenism are present (hirsutism, acne), though PCOS is less likely as a new diagnosis at age 40 2

• LH/FSH ratio can help identify PCOS if suspected (ratio >2 suggests PCOS), though this is more relevant in younger women 2, 3

Imaging Studies

• Pelvic ultrasound is recommended to assess endometrial thickness and ovarian morphology. Thin endometrium (<5 mm) suggests estrogen deficiency, while thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen 1, 2

• Brain MRI is indicated if prolactin is elevated or if there are neurological symptoms (headaches, visual changes) suggesting pituitary pathology 1, 4

Critical Age-Specific Considerations at Age 40

At age 40, premature ovarian insufficiency is a primary concern and requires specific attention:

• POI is defined by elevated FSH within the menopausal range in patients younger than 40 years with oligo/amenorrhea 1

• Patients with POI can maintain unpredictable ovarian function and should not be presumed infertile 2, 3, 5

• Hormonal replacement therapy is indicated to reduce risk of osteoporosis, cardiovascular disease, and urogenital atrophy 1

• Karyotype testing should be performed if POI is confirmed to identify conditions like Turner syndrome variants 2

Bone Health Assessment

• DXA scan for bone mineral density is recommended for patients with amenorrhea lasting >6 months, as low estrogen levels increase risk for decreased bone mineral density and stress fractures 1, 2

History and Physical Examination Focus

While laboratory testing is paramount, the clinical assessment should specifically evaluate:

• Weight changes, eating patterns, and exercise habits to assess for FHA, which accounts for 20-35% of secondary amenorrhea cases 1, 2, 5

• Medication history, particularly antipsychotics, antiepileptics, and hormonal contraceptives that can cause amenorrhea 2

• Symptoms of galactorrhea suggesting hyperprolactinemia 1, 4

• History of cancer treatment, particularly alkylating agents or pelvic radiation, which significantly increases POI risk 6, 4

• Vasomotor symptoms (hot flashes, night sweats) suggesting estrogen deficiency from POI 5

Common Pitfalls to Avoid

• Do not assume menopause at age 40 without proper workup—this is premature ovarian insufficiency and requires different management 1

• Do not delay evaluation—over half of women with POI report visiting clinicians three or more times before appropriate testing, with 25% waiting over 5 years for diagnosis 7

• Do not forget to discontinue hormone replacement therapy or hormonal contraceptives prior to laboratory evaluation, as these will interfere with accurate hormonal assessment 6, 1

• Do not overlook eating disorders or excessive exercise even in a 40-year-old, as FHA can occur at any age 1, 5

Timing of Laboratory Testing

• Draw FSH, LH, and testosterone between days 3-6 of the menstrual cycle if any cycles are occurring, or at any time in amenorrheic patients 2

• A single prolactin measurement taken at any time of day is sufficient 1