How do hormone levels, such as Follicle-Stimulating Hormone (FSH), estrogen, and Anti-Müllerian Hormone (AMH), indicate perimenopause?

Determining Perimenopause with Hormone Levels

Hormone levels are unreliable for diagnosing perimenopause because FSH, estradiol, and AMH fluctuate markedly and unpredictably during this transition, making single measurements or even serial measurements poor indicators of menopausal status. 1, 2

Why Hormone Testing Fails in Perimenopause

FSH Fluctuations Make It Unreliable

• FSH levels during perimenopause can swing from postmenopausal ranges back down to premenopausal ranges within weeks, and ovulatory cycles can occur even after observing postmenopausal FSH levels 1, 3
• Women in perimenopause show FSH patterns ranging from low premenopausal levels during ovulatory cycles to transient episodes with postmenopausal FSH levels, with no predictable progression 3
• The heterogeneity of FSH represents a mixture of ovulatory and anovulatory cycles, with ovulatory cycles showing little FSH increase while anovulatory cycles show markedly elevated FSH 2
• FSH measurement has little to no value in assessing perimenopausal women because it cannot be interpreted reliably 1

Estradiol Is Equally Unpredictable

• Estradiol levels remain relatively unchanged or actually rise during perimenopause until the late transition, despite rising FSH, presumably due to FSH stimulation of remaining follicles 4
• Perimenopausal women can have postmenopausal FSH levels occurring simultaneously with high estrogen levels for 2-9 weeks at a time 3
• Approximately one-third of perimenopausal cycles show a major estradiol surge occurring during the luteal phase (termed "LOOP" events), adding further unpredictability 5

AMH Has Limited Clinical Utility

• AMH shows promise as a marker of ovarian reserve and correlates with follicle numbers, but there is a wide range of normal values in healthy young adult women, making interpretation difficult 6
• AMH levels decline with age and reach undetectable levels at menopause, but normative data in various age groups remain limited 6, 2
• For women under age 25, AMH can fluctuate significantly throughout the menstrual cycle, requiring extra caution in interpretation 6

The Clinical Approach: Rely on Menstrual History, Not Hormones

Primary Diagnostic Criteria

• Base the diagnosis of perimenopause on menstrual cycle changes: onset of menstrual irregularity in women over age 40-45 is the key clinical marker 4, 2
• Look for specific patterns: irregular cycle length, skipped periods, changes in flow, or cycles occurring after 3+ months of amenorrhea 6
• Document symptoms of estrogen fluctuation: hot flashes, night sweats, sleep disturbances, and mood changes 6

When Hormone Testing May Be Considered

Reserve FSH and estradiol testing for specific clinical scenarios only:

• Women with menstrual dysfunction suggesting premature ovarian insufficiency (under age 40) 6
• Women desiring assessment of fertility potential who need counseling about timing of conception 6
• Women on medications that affect interpretation (tamoxifen, toremifene, or chemotherapy) where serial measurements may help assess ovarian function 7

Testing Protocol When Indicated

• If testing is performed, measure FSH and estradiol together on cycle day 2-5 of the early follicular phase (if oligomenorrheic) or randomly if amenorrheic 6
• Recognize that a single elevated FSH does not confirm perimenopause, as levels can return to normal and ovulation can resume 1, 3
• Serial measurements over time may show the pattern of increasing FSH variability characteristic of perimenopause, but still cannot reliably predict timing of menopause 2, 5

Critical Pitfalls to Avoid

• Never use a single FSH or estradiol measurement to counsel women about fertility status during perimenopause—ovulatory cycles can occur even after postmenopausal hormone levels 1, 3
• Do not assume amenorrhea with elevated FSH means permanent menopause until 12 months have passed without menses in women under 60 7
• Avoid testing FSH in women taking oral contraceptives or hormone replacement therapy, as results are uninterpretable; ideally wait 2 months after discontinuation 6
• FSH alone is particularly unreliable in women on tamoxifen or after chemotherapy—these populations require specialized assessment 7

Age-Specific Considerations

• Women over age 60 do not require hormone testing for menopause diagnosis—age and amenorrhea are sufficient 7
• Women under 60 with 12 months of amenorrhea can have FSH and estradiol measured to confirm postmenopausal status, but this is confirmatory rather than diagnostic of the perimenopausal transition itself 7
• The average age of follicle depletion to approximately 100 primordial follicles per ovary (triggering menstrual irregularity) is around age 45 2