Normal FSH and LH Do Not Rule Out Estrogen Dominance in PCOS
Normal FSH and LH levels do not exclude estrogen dominance or PCOS, as approximately 56-65% of women with confirmed PCOS have a normal LH:FSH ratio, and biochemical hyperandrogenism is absent in 30% of PCOS cases despite meeting diagnostic criteria. 1, 2
Understanding the Hormonal Paradox in PCOS
The concept of "estrogen dominance" in PCOS is complex and not directly reflected by FSH/LH measurements:
LH:FSH ratio has poor diagnostic sensitivity - Only 35-44% of women with confirmed PCOS demonstrate the classic elevated LH:FSH ratio >2, meaning the majority have normal ratios 2, 3
Estrogen levels are typically normal-range but tonically elevated in PCOS, rather than dramatically high, and this pattern is not captured by gonadotropin measurements 2
The Rotterdam criteria require only 2 of 3 features for PCOS diagnosis: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology - notably, abnormal gonadotropins are not required 1
Why Normal Gonadotropins Don't Exclude Hormonal Dysfunction
In your specific case with PCOS, normal BMI, dyslipidemia, and letrozole treatment:
Total testosterone is abnormal in only 70% of PCOS patients, meaning 30% have normal androgen levels despite confirmed disease 2
Dyslipidemia itself indicates metabolic dysfunction driven by insulin resistance and altered sex hormone metabolism, regardless of gonadotropin levels 1, 2
Letrozole works by blocking aromatase, which converts androgens to estrogens - its therapeutic effect in PCOS is independent of baseline FSH/LH values 4, 5
The Critical Distinction: PCOS vs Functional Hypothalamic Amenorrhea
Normal-range FSH and LH can occur in both PCOS and its diagnostic opposite, functional hypothalamic amenorrhea (FHA):
FHA is characterized by low-normal LH and FSH (typically both <5 IU/L), with LH:FSH ratio approximately 1.0, low estradiol, high SHBG, and low androgens 6
PCOS with normal gonadotropins still demonstrates other features: clinical/biochemical hyperandrogenism, polycystic ovarian morphology, low SHBG, and insulin resistance 1, 2
The key differentiators are: androgen levels (elevated or normal-high in PCOS vs low in FHA), SHBG (low in PCOS vs high in FHA), and metabolic markers like dyslipidemia (present in PCOS, absent in FHA) 7, 6
Clinical Implications for Your Patient
Given your patient has PCOS with dyslipidemia and normal BMI:
Screen comprehensively for metabolic dysfunction: fasting glucose, 2-hour oral glucose tolerance test, fasting lipid panel, and consider calculated free testosterone using the Vermeulen equation 1, 2
Measure SHBG levels - Low SHBG (<30 nmol/L) supports PCOS and indicates increased bioavailable androgens even when total testosterone appears normal 7, 2
AMH levels are elevated in 92% of PCOS cases (≥35 pmol/L), though not yet recommended as a standalone diagnostic test due to lack of standardization 1, 2
Letrozole dosing may need adjustment - Studies show 5.0 mg daily produces higher pregnancy rates and more mature follicles than 2.5 mg in PCOS patients, and those with elevated LH:FSH ratio, AMH, and FAI may require higher doses 8, 9
Common Diagnostic Pitfalls to Avoid
Do not rely on LH:FSH ratio alone - It is abnormal in less than half of PCOS cases and has poor diagnostic utility 2, 3
Do not assume normal testosterone excludes PCOS - Clinical hyperandrogenism (hirsutism, acne, alopecia) plus irregular cycles is sufficient for diagnosis without any abnormal labs 2
Do not confuse normal-range gonadotropins with normal hormonal function - The presence of dyslipidemia, anovulation, and polycystic ovaries indicates significant endocrine disruption regardless of FSH/LH values 1, 2