Laboratory Testing to Confirm Menopause
No reliable laboratory tests are available to confirm definitive loss of fertility or menopause in most clinical situations, and the diagnosis should be made on clinical grounds alone. 1
Age-Based Diagnostic Approach
Women ≥60 Years Old
- No laboratory testing is required or recommended 2
- Age alone is sufficient for clinical diagnosis of menopause 2
- This represents the most straightforward scenario where labs add no value
Women <60 Years Old with Amenorrhea ≥12 Months
- FSH and estradiol testing may be considered but are not reliable 1
- Both FSH and estradiol must be in the postmenopausal range to suggest menopausal status 3, 2
- However, FSH levels fluctuate dramatically during the menopausal transition, with postmenopausal values potentially returning to premenopausal ranges 4, 5
- Ovulation can occur even after observing postmenopausal FSH levels 5
- The commonly cited FSH cutoff of 40 IU/L is inappropriate by itself for determining postmenopausal status 6
Special Populations Where Testing IS Indicated
Women on Tamoxifen or Toremifene
- Measure both FSH and plasma estradiol levels 3, 2
- Both must be in postmenopausal ranges to confirm status 3
- FSH alone is unreliable in this population 2
- This is one of the few scenarios where hormonal testing is actually recommended by guidelines
Women with Chemotherapy-Induced Amenorrhea
- Amenorrhea after chemotherapy is NOT a reliable indicator of menopausal status 3
- Serial measurements of FSH and/or estradiol are required if considering aromatase inhibitor therapy 3
- Serial estradiol measurements are more useful than FSH to determine return of ovarian function 2
- Monitor estradiol and FSH/LH levels in women <60 years who are amenorrheic for ≤12 months prior to starting adjuvant endocrine therapy 3
Women on GnRH Agonists/Antagonists
- It is not possible to assign menopausal status while receiving these medications 3, 2
- Testing should be deferred until after discontinuation 3
- Aromatase inhibitors can stimulate ovarian function, making hormone interpretation unreliable 3, 2
Common Pitfalls to Avoid
- Do not rely on a single FSH measurement: 40.6% of women with elevated FSH had normal values on subsequent testing 7
- Do not use FSH alone in women on hormonal contraceptives: DMPA users showed 40.6% had FSH return to normal after one elevated measurement 7
- Do not assume elevated FSH means permanent menopause: FSH can fluctuate abruptly between postmenopausal and premenopausal ranges during the transition 4, 5
- Do not test FSH in women on depot medroxyprogesterone acetate unless ≥50 years old: There is greater likelihood of true postmenopause at this age 7
Practical Clinical Algorithm
For routine menopause diagnosis:
- Age ≥60 years: No testing needed 2
- Age <60 years with 12 months amenorrhea: Clinical diagnosis based on menstrual history alone 1
- Age <60 years on tamoxifen/toremifene: Order FSH and estradiol; both must be postmenopausal 3, 2
- Post-chemotherapy considering aromatase inhibitors: Serial FSH and estradiol measurements 3, 2
- On GnRH agonists: Defer testing until after medication discontinuation 3
The median age of menopause is approximately 51 years in North America but can range from 40-60 years 1. The median age of definitive loss of natural fertility is 41 years but can range up to 51 years 1. Given this variability and the unreliability of hormonal testing, contraceptive protection should continue until age 50-55 years or confirmed menopause by clinical criteria 1.