What is a Flipped LH:FSH Ratio in PCOS?
A "flipped" LH:FSH ratio in PCOS refers to an elevated ratio where LH (luteinizing hormone) is higher than FSH (follicle-stimulating hormone), typically with a ratio greater than 2:1, which is the opposite of the normal 1:1 ratio seen in healthy women. 1
The Pathophysiology Behind the Flipped Ratio
The elevated LH:FSH ratio in PCOS results from accelerated pulsatile GnRH (gonadotropin-releasing hormone) secretion, leading to:
- Hypersecretion of LH from the pituitary gland 1
- Relative hypofunction of the FSH-granulosa cell axis 1
- Ovarian theca stromal cell hyperactivity driven by excess LH, resulting in hyperandrogenism 1
- Follicular arrest and ovarian acyclicity due to inadequate FSH stimulation 1
Diagnostic Criteria and Measurement
An LH:FSH ratio >2 is considered abnormal and suggestive of PCOS, though this should be measured properly: 1
- Blood should be drawn between day 3 and 6 of the menstrual cycle (early follicular phase) 1
- Ideally calculated from an average of three measurements taken 20 minutes apart to account for pulsatile secretion 1
- Individual LH levels >11 IU/L are also considered abnormal 1
Critical Limitations of the LH:FSH Ratio
The LH:FSH ratio has poor sensitivity as a diagnostic marker and should NOT be used as the sole criterion for PCOS diagnosis. 2
Key Caveats:
- Only 35-44% of women with confirmed PCOS (by ultrasound and clinical features) actually have an elevated LH:FSH ratio 2
- The ratio varies significantly with cycle timing: In the early follicular phase, only 52% of PCOS patients maintain their elevated LH levels and ratio, while this increases significantly in the late follicular phase 3
- Total testosterone is a superior biochemical marker, being abnormal in 70% of PCOS cases 2
- The combination of testosterone, androstenedione, or LH (either alone or together) identifies 86% of PCOS women 2
Clinical Implications of the Ratio
Despite its diagnostic limitations, the LH:FSH ratio has some clinical utility:
- Patients with LH:FSH ratio ≥1 respond better to letrozole than clomiphene citrate for ovulation induction (OR 7.69, CI 3.69-16.02) 4
- The ratio does NOT predict IVF live birth rates in PCOS patients, whether using GnRH agonist or mild stimulation protocols 5
- Higher LH:FSH ratios correlate with increased insulin resistance, testosterone, and AMH levels, and decreased SHBG 6
Distinguishing PCOS from Functional Hypothalamic Amenorrhea (FHA)
An LH:FSH ratio <1 effectively rules out PCOS and suggests FHA instead, particularly when: 7
- Approximately 82% of FHA patients have an LH:FSH ratio <1 1, 7
- Both LH and FSH are low-normal (e.g., LH 4.8 IU/L, FSH 4.7 IU/L) 7
- There is clear history of energy deficit, excessive exercise, or psychological stress 7
- SHBG levels are high (opposite of PCOS) 1, 7
The FHA-PCOM Pitfall:
- 41.9-46.7% of women with FHA have polycystic ovarian morphology on ultrasound, which can lead to misdiagnosis as PCOS 7
- These patients still demonstrate low-normal gonadotropins with LH:FSH ratio <1, distinguishing them from true PCOS 1, 7
Practical Recommendations
Do not rely on LH:FSH ratio alone for PCOS diagnosis. Instead, use a comprehensive approach: 2
- Measure total testosterone as the primary biochemical marker (abnormal in 70% of cases) 2
- Check androstenedione (abnormal in 53% of cases) 2
- Assess LH levels in combination with other markers 2
- Perform pelvic ultrasound looking for >10 peripheral cysts (2-8 mm diameter) and thickened ovarian stroma 1
- Evaluate for clinical hyperandrogenism (hirsutism, acne) and menstrual irregularity 1
- Assess metabolic parameters including fasting glucose/insulin ratio and HOMA-IR 1