What laboratory tests should be ordered for a perimenopausal woman (approximately 40‑55 years old) to evaluate her symptoms and exclude other mimicking conditions?

Laboratory Testing for Perimenopause

Perimenopause should be diagnosed clinically based on age (40-55 years) and menstrual irregularity without routine laboratory testing. 1, 2

Primary Diagnostic Approach

• Do not order routine FSH, estradiol, LH, or other hormone panels for diagnosis in women aged 40-55 years presenting with irregular cycles, hot flashes, night sweats, or mood changes 1, 2
• The clinical history—specifically age and menstrual pattern changes—is the most accurate method of diagnosing perimenopause 2, 3
• Single hormone measurements are unreliable because FSH and estradiol levels fluctuate wildly during perimenopause, often varying dramatically from cycle to cycle 4, 3

Why Hormone Testing Fails in Perimenopause

• FSH may be elevated one month and normal the next, making it useless for diagnosis 4, 3
• Estradiol levels are often elevated rather than decreased during early perimenopause (contrary to common assumptions), remaining well-preserved until late transition 4, 3
• A single FSH measurement cannot distinguish between perimenopause and normal premenopausal status 2, 3

Essential Screening Tests (Rule Out Mimics)

These tests are mandatory to exclude conditions that mimic perimenopause:

Thyroid Function Testing

• Order TSH and free T4 in all symptomatic women, as thyroid dysfunction produces identical symptoms to perimenopause (fatigue, mood changes, menstrual irregularity, heat intolerance) 1
• Thyroid disease is common in this age group and must be excluded before attributing symptoms to perimenopause 1

Diabetes Screening

• Order fasting glucose in women with weight gain, fatigue, or metabolic symptoms 1
• Fasting glucose >7.8 mmol/L (>140 mg/dL) suggests diabetes 1

When Hormone Testing May Be Considered (Limited Scenarios)

FSH Testing (Very Limited Utility)

Only consider FSH if:

• The patient has had chemotherapy, pelvic radiation, or is taking tamoxifen (where clinical diagnosis is unreliable) 1
• You need to document premature ovarian insufficiency in a woman <40 years 1

If ordering FSH:

• Measure on cycle days 3-6 of the menstrual cycle 1
• Ideally average three samples taken 20 minutes apart 1
• FSH >35 IU/L suggests ovarian insufficiency, but levels fluctuate erratically during perimenopause 1
• A single normal FSH does not rule out perimenopause 2, 3

Estradiol Testing (Not Recommended)

• Estradiol levels are unreliable and often elevated during perimenopause 1, 4
• Only useful in amenorrheic cancer survivors to assess return of ovarian function 1

Other Hormones (Not Routinely Recommended)

• Do not order LH, prolactin, or anti-Müllerian hormone (AMH) for perimenopause diagnosis 1
• Prolactin should only be measured if galactorrhea is present, and only after excluding hypothyroidism first 1

Additional Workup for Specific Clinical Scenarios

When Menstrual Irregularities Require Further Investigation

Order these tests if clinical features suggest pathology beyond simple perimenopause:

• Mid-luteal progesterone (day 21 or 7 days before expected menses): <6 nmol/L indicates anovulation 1
• Testosterone (days 3-6 of cycle): >2.5 nmol/L suggests PCOS or other hyperandrogenic states 1
• Pelvic ultrasound if hormonal abnormalities or clinical features suggest ovarian pathology 1

Cancer Survivors

• FSH is unreliable in women with prior chemotherapy or pelvic radiation 1
• Serial estradiol levels may be used to assess ovarian function if clinically needed 1
• Post-chemotherapy patients have 33-73% risk of primary ovarian insufficiency with irregular menses but may retain fertility 1

Confirmation of Menopause

• Menopause is confirmed by 12 consecutive months of amenorrhea in the absence of chemotherapy or tamoxifen use 1
• No laboratory testing is required for this diagnosis 1, 2

Common Pitfalls to Avoid

• Do not order FSH/estradiol panels reflexively—they waste resources and provide misleading information during perimenopause 1, 2, 3
• Do not reassure patients based on a single normal FSH—levels fluctuate and a normal result does not exclude perimenopause 2, 3
• Do not attribute all symptoms to perimenopause without excluding thyroid disease and diabetes—these are common mimics that require different treatment 1
• Do not use hormone levels to decide whether to treat symptoms—treatment decisions should be based on symptom severity and patient preference, not laboratory values 5, 6