FSH Elevation in Ovarian Failure
Yes, FSH will be elevated in ovarian failure—this is the diagnostic hallmark of the condition. Premature ovarian insufficiency (POI) is defined by two elevated FSH levels in the menopausal range (typically >40 IU/L, though some labs use >20 IU/L as threshold), measured at least 4 weeks apart, in women under age 40 with amenorrhea lasting ≥4 months 1.
Diagnostic Criteria
The diagnosis of POI requires both clinical and biochemical confirmation:
- Two separate FSH measurements in the menopausal range (>40 IU/L by most assays), obtained at least 4 weeks apart 1
- Amenorrhea for ≥4 months in women under age 40 1
- Low estradiol levels (<50 pmol/L) accompanying the elevated FSH 2
The elevated FSH represents the pituitary's compensatory response to loss of negative feedback from declining ovarian follicles 3, 2.
Mechanism of FSH Elevation
FSH rises because of loss of ovarian feedback mechanisms:
- Depletion of primordial follicles leads to decreased inhibin B and AMH production 1, 4
- Loss of negative feedback on the hypothalamic-pituitary axis results in increased FSH secretion 4
- Studies show that women with imminent ovarian failure have higher FSH pulse amplitudes and enhanced pituitary sensitivity to GnRH 4
- The monotropic rise in FSH is the hallmark of the menopausal transition 1
Clinical Context Matters
FSH interpretation depends on the clinical scenario:
In Functional Hypothalamic Amenorrhea (FHA)
- FSH levels are typically LOW, not elevated 1
- FHA patients show low gonadotropins, especially LH 1
- About 82% of FHA patients have an LH to FSH ratio <1 1
- This contrasts sharply with POI where FSH is markedly elevated 1
In Cancer Survivors
- Elevated FSH confirms POI in survivors treated with gonadotoxic therapy 1
- Risk increases with alkylating agents and ovarian radiation exposure 1
- FSH should be measured in conjunction with estradiol for accurate diagnosis 1
Important Caveats
FSH elevation alone is not sufficient for diagnosis:
- Timing matters: If measuring in women with oligomenorrhea, FSH should be checked during early follicular phase (days 2-5) 1
- Fluctuations occur: Some women with elevated FSH may have intermittent ovarian function, with occasional follicle development and even rare spontaneous pregnancies (5% of cases) 3, 5
- Occult ovarian failure exists: Some women maintain regular menses despite elevated FSH, representing compensated granulosa cell dysfunction 6
- Repeat testing is mandatory: A single elevated FSH is insufficient; two measurements separated by at least 4 weeks are required 1
Differential Diagnosis
Always exclude other causes before confirming POI:
- Perform karyotype in women <30 years to exclude Turner syndrome and other chromosomal abnormalities 3, 2
- Check thyroid function and autoimmune markers, as 50% may have associated autoimmunity 6
- Consider FMR1 premutation testing (fragile X syndrome) 3
- Rule out iatrogenic causes: chemotherapy, radiation, bilateral oophorectomy 1, 3, 2
The bottom line: Elevated FSH (>40 IU/L on two occasions ≥4 weeks apart) combined with amenorrhea ≥4 months in women <40 years definitively confirms ovarian failure and distinguishes it from hypothalamic causes where FSH would be low 1, 2.