What blood test can confirm a menopausal state in a woman with irregular menstrual cycles, hot flashes, and mood changes?

Blood Tests to Diagnose Menopausal State

The diagnosis of menopause is primarily clinical—defined as 12 consecutive months of amenorrhea—and blood tests are generally not required for diagnosis in women over 45 years with typical symptoms. 1 However, when laboratory confirmation is needed, FSH and estradiol measured during the early follicular phase (days 3-6) are the most useful tests, though they have significant limitations during the perimenopausal transition. 2, 3

When Laboratory Testing Is Indicated

Laboratory evaluation should be reserved for specific clinical scenarios rather than routine diagnosis:

• Women under age 45 with suspected premature ovarian insufficiency or early menopause 2, 4
• Women with unclear menopausal status who are considering aromatase inhibitor therapy or other treatments requiring confirmed postmenopausal status 1, 4
• Women with amenorrhea of uncertain cause where differential diagnosis includes functional hypothalamic amenorrhea, PCOS, or other conditions 1, 2
• Women on medications (tamoxifen, chemotherapy) where clinical assessment alone is insufficient 1, 4

Primary Laboratory Tests

FSH (Follicle-Stimulating Hormone)

• FSH should be measured during the early follicular phase (days 3-6 of the menstrual cycle) when cycles are still present 2, 4
• For women with amenorrhea, FSH can be measured at any time 4
• Elevated FSH in the postmenopausal range suggests ovarian failure, but a single elevated value does not confirm menopause because FSH fluctuates widely during perimenopause 2, 3
• FSH is unreliable in women taking tamoxifen, toremifene, or LHRH agonists/antagonists 1, 4

Estradiol

• Estradiol should be measured alongside FSH during the early follicular phase to help interpret FSH results 2, 4
• Low estradiol levels in the postmenopausal range support the diagnosis of menopause 1
• Normal FSH with elevated estradiol may mask diminished ovarian reserve, so both values must be interpreted together 4
• Estradiol levels remain relatively preserved until late perimenopause despite rising FSH 3

Additional Tests Based on Clinical Context

To Rule Out Other Causes of Amenorrhea

• Prolactin should be measured to exclude hyperprolactinemia as a cause of menstrual irregularity 2, 4
• TSH (thyroid-stimulating hormone) should be checked to rule out thyroid disease that may mimic menopausal symptoms 2, 4
• LH (luteinizing hormone) can provide supplementary information, with an LH:FSH ratio <1 suggesting functional hypothalamic amenorrhea rather than menopause 1

Ovarian Reserve Markers

• Anti-Müllerian hormone (AMH) represents the best endocrine marker for age-related decline in ovarian reserve but should not be used alone for diagnosing menopause 2, 4
• AMH has wide normal ranges and fluctuates less than FSH, but no recommendations exist for using it to diagnose premature ovarian insufficiency 4
• Inhibin B levels decline with follicle depletion but are not routinely used clinically 3

Formal Diagnostic Criteria for Menopause

For women under age 60, menopause can be confirmed by:

• Amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression AND FSH and estradiol in the postmenopausal range 1
• Prior bilateral oophorectomy (surgical menopause) 1

For women age 60 and older, age alone is sufficient without laboratory testing 1

For women taking tamoxifen or toremifene and age <60 years, FSH and plasma estradiol in postmenopausal ranges are required 1

Critical Limitations and Pitfalls

When FSH Testing Is Unreliable

• FSH cannot determine menopausal status in women receiving LHRH agonists or antagonists 1, 4
• In women with chemotherapy-induced amenorrhea, FSH is unreliable because ovarian function may resume despite amenorrhea 1, 4
• Serial measurements of FSH and/or estradiol are needed if aromatase inhibitors are being considered in premenopausal women who became amenorrheic with chemotherapy 1

Hormone Fluctuations During Perimenopause

• During the menopausal transition, hormone levels vary markedly, making single measurements unreliable guides to menopausal status 3, 5
• A normal FSH level does not rule out perimenopause because levels fluctuate widely during this transition 2, 3
• FSH begins to rise years before clinical signs of menopause appear, driven by declining inhibin B levels 3

Clinical Correlation Is Essential

• Laboratory results must be interpreted alongside menstrual history and symptoms rather than in isolation 2, 5
• Menstrual irregularity (cycles <23 days or >35 days) is a key clinical indicator of perimenopause 2, 6
• Common perimenopausal symptoms include vasomotor symptoms (hot flashes, night sweats), sleep disturbances, mood changes, vaginal dryness, and sexual dysfunction 7, 6, 5
• Symptoms alone are not diagnostic and require laboratory confirmation when making management decisions that depend on menopausal status 2

Special Populations

Cancer Survivors

• Women with prior chemotherapy or pelvic radiation require serial FSH and estradiol measurements because single values are unreliable 1, 4
• Aromatase inhibitors can stimulate ovarian function; vaginal bleeding while on AI requires immediate evaluation 4
• Women under age 60 who are amenorrheic for ≤12 months prior to adjuvant endocrine therapy should be monitored 4

Young Women with Premature Ovarian Insufficiency

• Evaluation should include FSH, estradiol, AMH, and transvaginal ultrasound with antral follicle count 4
• Women with therapy-induced amenorrhea may still have intact ovarian function and should be counseled about pregnancy risk despite amenorrhea 1