What laboratory tests and interpretation criteria are used to diagnose menopause in a woman aged 45 or older with at least 12 months of amenorrhea?

Laboratory Diagnosis of Menopause

For women aged 60 years or older, no laboratory testing is required—age alone confirms menopause. 1, 2

Age-Based Diagnostic Algorithm

Women ≥60 Years

• No laboratory testing is indicated or recommended. 1, 2
• Age alone is sufficient for clinical diagnosis of postmenopausal status. 1, 2

Women <60 Years with ≥12 Months Amenorrhea

• Measure both FSH and estradiol simultaneously. 1, 3
• Both values must be in the postmenopausal range (using local laboratory reference ranges) to confirm menopause. 1, 3
• FSH alone is inadequate—estradiol must be measured concurrently to verify low ovarian function. 1
• The combination of elevated FSH and low estradiol provides stronger diagnostic certainty than either marker alone. 1

Women <60 Years with <12 Months Amenorrhea

• Monitor estradiol and FSH/LH levels if amenorrheic for ≤12 months prior to starting adjuvant endocrine therapy. 3
• Serial measurements may be necessary, as single values can be unreliable during the menopausal transition. 1

Special Populations Requiring Modified Testing

Women on Tamoxifen or Toremifene

• Both FSH and plasma estradiol must be in postmenopausal ranges to confirm menopausal status. 4, 1, 3, 2
• FSH alone is unreliable in this population because these medications alter hormone levels. 1, 3

Women After Chemotherapy

• Amenorrhea after chemotherapy does not reliably indicate menopause—ovarian function may persist or recover despite absent menses. 1, 3, 2
• FSH is not a reliable marker in this population. 1
• Serial estradiol measurements are more useful to determine return of ovarian function. 1
• If considering aromatase inhibitor therapy, confirmation requires either bilateral oophorectomy or serial measurements of both FSH and estradiol. 1, 3, 2

Women on GnRH Agonists/Antagonists

• Menopausal status cannot be determined while receiving these medications. 4, 1, 3
• Definitive determination requires oophorectomy or serial hormone testing after discontinuation. 1
• Testing should be deferred until after stopping these agents. 3

Women After Hysterectomy (with Intact Ovaries)

• Measure FSH, LH, and estradiol simultaneously in women <60 years. 1
• Postmenopausal status is defined by elevated FSH and LH together with low estradiol. 1
• FSH alone is inadequate—estradiol must be measured concurrently. 1

Critical Pitfalls to Avoid

Aromatase Inhibitor Considerations

• Aromatase inhibitors can stimulate ovarian function. 4, 3
• If vaginal bleeding occurs while on an AI, immediate physician contact is required. 4, 3
• This represents potential return of ovarian function and requires reassessment. 4

Timing of Measurements

• For women with oligomenorrhea (rather than amenorrhea), measure FSH and estradiol during the early follicular phase (days 2-5). 1
• Hormone measurements must be performed before initiating systemic therapy whose choice depends on menopausal classification. 1

Premature Ovarian Insufficiency (POI)

• POI (menopause before age 40) requires two elevated FSH measurements in the menopausal range, taken at least 4 weeks apart, plus oligo/amenorrhea for ≥4 months. 4, 1
• This differs from standard menopause diagnosis and requires serial confirmation. 4

Clinical Context

The median age of menopause is approximately 51 years, but ranges from 40-60 years. 2 Menopause is diagnosed after 12 months of amenorrhea resulting from permanent cessation of ovarian function. 5 However, there is no specific endocrine marker that reliably predicts the final menstrual period, as FSH and estradiol fluctuate markedly during the menopausal transition with both ovulatory and anovulatory cycles occurring unpredictably. 6 This is why the 12-month amenorrhea criterion combined with age-appropriate hormone levels provides the most reliable diagnostic approach. 1, 2