Which laboratory test confirms menopause in a woman with at least 12 months of amenorrhea?

Laboratory Testing to Confirm Menopause

For women under 60 years with at least 12 months of amenorrhea, measure both FSH and estradiol levels to confirm postmenopausal status, with FSH in the postmenopausal range (typically ≥40 IU/L) and low estradiol supporting the diagnosis. 1, 2

Age-Based Diagnostic Algorithm

Women 60 Years or Older

• No laboratory testing is required or recommended for menopause diagnosis in women aged 60 years or older, as age alone is sufficient for clinical diagnosis. 1, 2
• This approach is endorsed by both the National Comprehensive Cancer Network and the American College of Obstetricians and Gynecologists. 1, 2

Women Under 60 Years

• After confirming 12 months of amenorrhea, order both FSH and estradiol measurements together rather than FSH alone. 1, 2
• FSH levels in the postmenopausal range (≥40 IU/L) combined with low estradiol (<30 pg/mL) confirm menopause. 1, 3
• The combination of elevated FSH and low estradiol provides stronger diagnostic certainty than either marker alone, though FSH alone has been shown to have adequate diagnostic performance in most cases. 1, 4

Special Populations Requiring Modified Testing

Women on Tamoxifen or Toremifene

• Both FSH and plasma estradiol levels must be in postmenopausal ranges to confirm menopausal status in women under 60 taking these medications. 5, 1, 2
• FSH alone is unreliable in this population due to medication effects on hormone levels. 1

Women with Chemotherapy-Induced Amenorrhea

• Amenorrhea after chemotherapy is not a reliable indicator of menopausal status because ovarian function may remain intact or resume despite anovulation. 5, 1
• Serial measurements of estradiol are more useful than FSH to determine return of ovarian function. 1, 2
• If considering aromatase inhibitor therapy, oophorectomy or serial FSH and estradiol measurements are needed to ensure postmenopausal status. 5, 2

Women on GnRH Agonists/Antagonists

• It is not possible to assign menopausal status while receiving these medications. 5, 1
• Oophorectomy or serial hormone measurements after discontinuation are needed if definitive status determination is required. 1

Clinical Criteria That Confirm Menopause Without Testing

The following criteria establish menopause without laboratory confirmation: 5

• Prior bilateral oophorectomy
• Age ≥60 years
• Age <60 years with amenorrhea for ≥12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression (though FSH/estradiol confirmation strengthens this diagnosis)

Important Caveats and Pitfalls

FSH Variability in Perimenopause

• Single FSH measurements provide little useful information regarding menopausal status in women who are still cycling or in early transition. 6, 7
• Cross-sectional studies show that 7% of regularly cycling women over 45 have FSH levels typical of postmenopause, and levels can fluctuate dramatically from postmenopausal back to reproductive range. 6, 7
• FSH levels begin to rise approximately 2 years before the final menstrual period but reach only 50% of ultimate postmenopausal levels at the time of final menses. 7

Timing of Sample Collection

• For women with oligomenorrhea rather than complete amenorrhea, measure FSH and estradiol during the early follicular phase (days 2-5 of the cycle). 1
• If results are indeterminate, repeat measurements 4 or more weeks apart may be necessary. 1

Common Diagnostic Errors to Avoid

• Do not assume chemotherapy-induced amenorrhea equals menopause—hormone levels and absence of menses are unreliable during tamoxifen treatment. 8
• Do not rely on amenorrhea alone in women who have received chemotherapy, as premenopausal estradiol levels can occur with transient chemotherapy-induced amenorrhea. 8
• Do not attempt to determine menopausal status while patients are receiving ovarian suppression therapy, as aromatase inhibitors can stimulate ovarian function and make hormone level interpretation unreliable. 1

Practical Implementation

For routine clinical practice, follow this algorithm: 2

1. If age ≥60 years → no testing needed
2. If age <60 years with 12 months amenorrhea and no confounding medications → clinical diagnosis based on menstrual history alone is acceptable, though FSH/estradiol can confirm
3. If age <60 years on tamoxifen/toremifene → order both FSH and estradiol
4. If post-chemotherapy and considering aromatase inhibitors → serial FSH and estradiol measurements required