Laboratory Testing for Menopause Diagnosis
In most clinical situations, menopause should be diagnosed based on clinical criteria (age and menstrual history) without laboratory testing, as FSH and estradiol levels fluctuate unpredictably during the menopausal transition and cannot reliably confirm menopausal status. 1, 2, 3
When Laboratory Testing IS Indicated
Laboratory testing should be reserved for specific clinical scenarios where confirmation is medically necessary:
Cancer-Related Indications
- Women taking tamoxifen or toremifene: Measure FSH and plasma estradiol to confirm postmenopausal status before considering aromatase inhibitor therapy 4
- Post-chemotherapy amenorrhea: Serial measurements of FSH and/or estradiol are required, as amenorrhea alone is unreliable for determining menopausal status 5, 4
- Women <60 years with amenorrhea ≤12 months: Monitor estradiol and FSH/LH before starting adjuvant endocrine therapy 4
What to Order When Testing Is Indicated
- Both FSH and estradiol must be measured together 5, 4
- Both values must be in the postmenopausal range to confirm menopausal status 4
- Typical postmenopausal values: FSH >35-40 mIU/mL, estradiol <20-30 pg/mL 6, 3
Why Routine Testing Is Not Recommended
FSH and Estradiol Fluctuate Dramatically
- In regularly cycling women over 45 years, 7% had postmenopausal FSH levels and 39% had elevated FSH, yet they continued menstruating 1
- 40.6% of women with one elevated FSH measurement had normal FSH on subsequent testing 6
- Postmenopausal FSH levels can be followed by normal ovulation, indicating potential fertility 2
- FSH can rise 10-15 fold after menopause, but individual measurements during perimenopause are unreliable 2
Clinical Diagnosis Is More Reliable
- Diagnosis should be based on menstrual history and age 3
- Women ≥45 years with 12 months of amenorrhea can be diagnosed clinically without testing 1, 3
Special Situations Where Testing Cannot Be Interpreted
Medications That Invalidate Testing
- Women on LHRH/GnRH agonists or antagonists: Cannot assign menopausal status; defer testing until after discontinuation 4
- Women on depot medroxyprogesterone acetate (DMPA): Require at least two consecutive elevated FSH measurements (≥50 years old preferred for testing) 6
- Women on hormone replacement therapy: Estrogen administration should be guided by clinical response, not serum hormone levels 7
Prior Cancer Treatment
- FSH is not reliable after chemotherapy or pelvic radiation 5
- Serial measurements are required if considering changes in endocrine therapy 5, 4
Critical Pitfalls to Avoid
- Never rely on a single FSH or estradiol measurement during the menopausal transition 6, 2
- Do not assume amenorrhea equals menopause in women with prior chemotherapy 5, 4
- Do not test women on GnRH agonists as results are uninterpretable 4
- Remember that elevated FSH does not rule out future ovulation or fertility 2
- If vaginal bleeding occurs while on aromatase inhibitors, immediate physician contact is required as these drugs can stimulate ovarian function 4