Laboratory Testing for Menopause Status
Primary Diagnostic Approach: Age-Based Algorithm
For women aged 60 years or older, no laboratory testing is required—menopause is diagnosed clinically based on age alone. 1, 2
For women under 60 years with amenorrhea of 12 months or longer, measure both FSH and estradiol levels to confirm postmenopausal status, with FSH in the postmenopausal range and low estradiol supporting the diagnosis. 1, 2 The combination of elevated FSH and low estradiol provides stronger diagnostic certainty than either marker alone. 2
Core Laboratory Tests
Follicle-Stimulating Hormone (FSH)
- Elevated FSH indicates declining ovarian follicular activity and is the most established indirect marker of follicular function. 1, 3
- FSH should be measured during the early follicular phase (days 2-5) in women with oligomenorrhea rather than complete amenorrhea. 2
- Critical limitation: FSH is unreliable in women with prior chemotherapy, pelvic radiation exposure, or those taking tamoxifen. 1, 2
- During the menopausal transition, FSH levels fluctuate markedly, making single measurements unreliable guides to menopausal status. 3
Estradiol
- Postmenopausal-range estradiol confirms ovarian failure and should be measured concurrently with FSH. 1, 2
- Estradiol levels remain relatively unchanged or may even rise until late perimenopause, despite elevated FSH. 3
- Serial estradiol measurements are particularly useful for perimenopausal/premenopausal women who became amenorrheic and later develop bleeding, to determine return of ovarian function. 1, 2
Luteinizing Hormone (LH)
- LH is measured as part of comprehensive hormonal assessment and is elevated in the postmenopausal state. 1
- Serial LH assessment alongside FSH and estradiol is recommended when considering aromatase inhibitor therapy in women who become amenorrheic with chemotherapy. 2
Prolactin
- Prolactin should be measured to exclude hyperprolactinemia as a cause of amenorrhea. 1
When Laboratory Testing Is Actually Indicated
Laboratory confirmation is not routinely required for diagnosing menopause in most clinical scenarios. 1 The diagnosis is primarily clinical, based on menstrual history and age. 4
Specific Indications for Testing:
- Women aged 40-45 years with menopausal symptoms 5
- Women under 40 years with suspected premature ovarian insufficiency 5
- Women under 60 years with 12+ months of amenorrhea requiring confirmation 1, 2
- Women on tamoxifen or toremifene under age 60 (require both FSH and estradiol in postmenopausal ranges, as FSH alone is unreliable) 2
Special Populations Requiring Modified Approach
Women on Endocrine Therapy
- Women on LHRH agonists/antagonists cannot be assigned menopausal status while on these medications. 1, 2
- These women require oophorectomy or serial FSH/estradiol measurements if considering aromatase inhibitors. 1
- Aromatase inhibitors can stimulate ovarian function, making hormone level interpretation unreliable. 2
Post-Chemotherapy Patients
- Premenopausal women post-chemotherapy require serial FSH/estradiol measurements to ensure postmenopausal status before aromatase inhibitor use. 1
- FSH is not a reliable marker in this population; serial estradiol measurements are more useful. 2
Premature Ovarian Insufficiency (POI)
- Requires two elevated FSH measurements in the menopausal range, taken at least 4 weeks apart, plus oligo/amenorrhea for ≥4 months. 2
Complementary Laboratory Assessment
Beyond reproductive hormones, additional testing may be warranted:
- Thyroid function tests to exclude thyroid disease mimicking menopausal symptoms 1
- Full blood count, liver and renal function tests, alkaline phosphatase, and calcium levels 1
- 25-OH vitamin D levels if high risk for deficiency 1
Critical Clinical Pitfalls
Avoid relying on single hormone measurements during the menopausal transition, as hormone levels fluctuate markedly during this period. 3, 4 Serial measurements taken 4+ weeks apart provide more reliable information when results are indeterminate. 2
Do not order FSH testing in women aged 60 or older—it adds no diagnostic value and age alone is sufficient. 1, 2
Never attempt to determine menopausal status in women actively receiving ovarian suppression therapy, as accurate assessment is impossible while on these medications. 2