What laboratory tests are used to diagnose menopause?

Laboratory Testing for Menopause Diagnosis

In most clinical scenarios, menopause should be diagnosed clinically based on age and amenorrhea duration, without routine laboratory testing. Laboratory tests are only indicated in specific circumstances when menopausal status is uncertain and has treatment implications.

When Laboratory Testing is NOT Needed

For women ≥60 years old, no laboratory testing is required—they are considered postmenopausal by age alone. 1

For women <60 years old who have been amenorrheic for ≥12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression, no laboratory testing is needed—clinical criteria alone establish menopause. 1

When Laboratory Testing IS Indicated

Laboratory testing should be performed in the following specific situations:

1. Women <60 Years Taking Tamoxifen or Toremifene

• Measure FSH and plasma estradiol levels to confirm postmenopausal status 1
• Both values must be in the postmenopausal range 1

2. Women with Chemotherapy-Induced Amenorrhea

• Amenorrhea after chemotherapy is NOT a reliable indicator of menopausal status 1
• Ovarian function may remain intact or resume despite amenorrhea 1
• Serial measurements of FSH and/or estradiol are required if considering aromatase inhibitor therapy 1

3. Monitoring During Endocrine Therapy Transitions

Monitor estradiol and FSH/LH levels in women <60 years who are: 1

• Amenorrheic for ≤12 months prior to starting adjuvant endocrine therapy 1
• Amenorrheic after tamoxifen +/- ovarian function suppression 1
• Switching from tamoxifen to an aromatase inhibitor 1
• Being taken off ovarian function suppression 1
• Prior to next dose of GnRH agonist, particularly in women <45 years 1

Critical Limitations of FSH Testing

FSH measurements have significant limitations and should be interpreted with extreme caution:

• FSH levels fluctuate markedly during the menopausal transition—a single elevated FSH does not reliably indicate menopause 2, 3, 4, 5
• Ovulatory cycles can occur even after postmenopausal FSH levels are documented 4
• In one study, 40.6% of women with elevated FSH had normal values on subsequent testing 6
• At least two consecutive elevated FSH measurements are required before considering a woman postmenopausal 6
• The commonly cited FSH cutoff of 40 IU/L is inappropriate by itself for clinical determination 5

When Menopausal Status CANNOT Be Determined

It is not possible to assign menopausal status to women receiving LHRH agonists or antagonists (GnRH agonists). 1 Testing should be deferred until after discontinuation of these medications.

Specific Laboratory Tests to Order

When testing is indicated based on the criteria above:

• Follicle-stimulating hormone (FSH) 1
• Estradiol 1
• LH (in specific monitoring situations) 1

Both FSH and estradiol must be in the postmenopausal range to confirm menopausal status. 1

Important Clinical Pitfalls

• Aromatase inhibitors can stimulate ovarian function—if vaginal bleeding occurs while on an AI, immediate physician contact is required 1
• Single FSH measurements are unreliable during the perimenopausal transition due to marked hormonal fluctuations 3, 4
• Estradiol levels may remain normal or even elevated until late perimenopause despite rising FSH 3
• FSH testing should preferably be done in women ≥50 years, as there is greater likelihood of true postmenopausal status 6