What labs are used to assess ovarian function?

Laboratory Assessment of Ovarian Function

The core laboratory tests for assessing ovarian function are FSH and estradiol measured during the early follicular phase (cycle days 2-5), with AMH and transvaginal ultrasound for antral follicle count providing additional reserve assessment. 1, 2

Primary Hormone Panel

FSH (Follicle-Stimulating Hormone)

• FSH is the hallmark marker for ovarian function assessment and should be measured during cycle days 2-5 of the menstrual cycle 3, 1
• Elevated FSH indicates diminished ovarian reserve, with levels showing minimal day-to-day variation during this window (coefficient of variation 14.8%) 4, 5
• For women with amenorrhea, FSH should be measured randomly rather than waiting for a specific cycle day 3
• FSH levels remain consistent across cycle days 2-5, making any of these days acceptable for testing 5

Estradiol

• Estradiol must be measured concurrently with FSH during the early follicular phase to properly interpret FSH results 1, 2
• Normal FSH with elevated estradiol may mask diminished ovarian reserve, as rising estradiol can suppress FSH through negative feedback 1
• Estradiol shows greater variability than FSH between cycle days 2-5 (coefficient of variation 31.1%), with significant increases by days 4-5 4, 5
• In older reproductive-age women (40-45 years), estradiol levels increase significantly from day 1 to day 4, unlike younger women 6

LH (Luteinizing Hormone)

• LH should be measured when clinically indicated to provide additional context for ovarian function 2
• The combination of FSH and LH on cycle day 1 provides the best prediction of reproductive age differences 6
• LH levels remain relatively stable during ovarian function assessment, showing less diagnostic utility than FSH 6

Additional Ovarian Reserve Markers

Anti-Müllerian Hormone (AMH)

• AMH represents the best endocrine marker for assessing age-related decline in ovarian reserve in healthy women 3
• AMH provides additional information on ovarian reserve but should not be used alone due to limited normative data 2
• No recommendations exist for using AMH in diagnosing premature ovarian insufficiency, as its diagnostic value remains unestablished 3

Antral Follicle Count (AFC)

• Transvaginal ultrasound with AFC is the most established method for assessing ovarian reserve in adult women 3, 1
• AFC shows strong positive correlation with AMH levels 1
• AFC <5 follicles and ovarian volume <3 cm³ indicates diminished ovarian reserve 1

Special Clinical Contexts

Premature Ovarian Insufficiency (POI) Evaluation

• For suspected POI, assess menstrual history, FSH, estradiol, AMH levels, and AFC via transvaginal ultrasound 1
• Laboratory evaluation is not recommended as primary surveillance in asymptomatic at-risk women; testing should be triggered by menstrual changes or POI symptoms 3

Post-Chemotherapy or Cancer Survivors

• Female cancer survivors treated with gonadotoxic therapies require regular ovarian function assessment 1
• Higher risk occurs with alkylating agents, cyclophosphamide, procarbazine, or pelvic radiotherapy 1
• Amenorrhea after chemotherapy does not confirm menopause, as ovarian function may resume 2

Critical Testing Limitations

• FSH is unreliable in women taking tamoxifen, toremifene, or LHRH agonists/antagonists 3, 2
• Menopausal status cannot be determined while receiving ovarian function suppression 3
• Aromatase inhibitors can stimulate ovarian function; vaginal bleeding while on AI requires immediate physician contact 3

Timing and Monitoring Protocols

When to Monitor Estradiol and FSH/LH

• Women under age 60 who are amenorrheic for ≤12 months prior to adjuvant endocrine therapy 3
• Women amenorrheic after chemotherapy or after tamoxifen +/- ovarian function suppression 3
• After switching from tamoxifen to an aromatase inhibitor, or if discontinued from ovarian function suppression 3
• Prior to next dose of GnRH agonist, particularly in women under age 45 3

Oligomenorrhea vs. Amenorrhea

• For oligomenorrhea, measure FSH and estradiol during early follicular phase (days 2-5) 3
• For amenorrhea, measure FSH and estradiol randomly 3

Common Pitfalls to Avoid

• Do not rely on FSH alone without concurrent estradiol measurement, as elevated estradiol can falsely normalize FSH 1, 2
• Do not assume amenorrhea equals menopause in women with prior chemotherapy or pelvic radiation 2
• Do not test FSH in women currently on tamoxifen or ovarian suppression therapy, as results will be unreliable 3, 2
• Do not wait for cycle day 3 specifically; any day between cycle days 2-5 is acceptable for FSH testing 5