Which laboratory tests should be obtained to evaluate a woman's menopausal status?

Laboratory Assessment of Menopausal Status

When Laboratory Testing is NOT Required

For women aged 60 years or older, no laboratory testing is needed—age alone establishes postmenopausal status. 1

• Women who have undergone bilateral oophorectomy require no hormonal testing regardless of age 1
• Women under 60 with 12 months of amenorrhea and no exposure to chemotherapy, tamoxifen, toremifene, or ovarian-suppressing agents can be diagnosed clinically without mandatory laboratory confirmation, though testing adds diagnostic certainty 1

When Laboratory Testing IS Required

For women under 60 years with amenorrhea, measure both FSH and estradiol—both must be in the postmenopausal range to confirm menopause. 2, 1

Specific Populations Requiring Testing:

• Women on tamoxifen or toremifene (age <60): FSH alone is unreliable; both FSH and plasma estradiol must be in postmenopausal ranges 2, 1
• Women with chemotherapy-induced amenorrhea: Amenorrhea does not reliably indicate menopause; serial measurements of FSH and/or estradiol are required if considering aromatase inhibitor therapy 2, 1
• Women with amenorrhea <12 months (age <60): Monitor estradiol and FSH/LH levels before starting adjuvant endocrine therapy 2

Recommended Laboratory Tests

Order FSH and estradiol together when testing is indicated. 2

• FSH and estradiol are the primary hormones for assessing menopausal status 3
• LH may be added for serial assessment in women who become amenorrheic with chemotherapy, particularly when considering aromatase inhibitor therapy 3
• Both FSH and estradiol must be in the postmenopausal range to confirm diagnosis 2

Timing of Testing:

• For women with oligomenorrhea (not amenorrhea), measure FSH and estradiol during the early follicular phase (days 2-5) 1
• For indeterminate results, repeat measurements at least 4 weeks apart 1

Critical Limitations and Pitfalls

FSH measurement alone is unreliable during the menopausal transition because levels fluctuate dramatically—postmenopausal FSH levels can be followed by normal ovulation. 4, 5

• FSH levels may rise into the postmenopausal range and then fall back to reproductive levels, even in women who subsequently ovulate 4, 5
• Estradiol levels can be markedly elevated during perimenopause despite elevated FSH 6, 7
• Perimenopausal women demonstrate hyperestrogenism, hypergonadotropism, and decreased luteal progesterone simultaneously 6

Situations Where Testing Cannot Determine Menopausal Status:

It is impossible to assign menopausal status to women receiving LHRH agonists or antagonists (GnRH agonists)—defer testing until after discontinuation of these medications. 2, 1

• Aromatase inhibitors can stimulate ovarian function, making hormone interpretation unreliable 2, 3
• If vaginal bleeding occurs while on an aromatase inhibitor, immediate physician contact is required 2
• Serial estradiol measurements are more useful than FSH for detecting return of ovarian function after chemotherapy 1

Clinical Algorithm

For women <60 years:

1. Confirm 12 months of amenorrhea 1
2. Order FSH and estradiol together 2
3. Use local laboratory definitions of postmenopausal ranges 1
4. Both values must be in postmenopausal range to confirm diagnosis 2
5. If on tamoxifen/toremifene or post-chemotherapy, consider serial measurements rather than single values 1
6. Monitor for clinical symptoms suggesting persistent ovarian function 1

For women ≥60 years:

• No testing required; diagnose based on age 1