How to approach and interpret abnormal Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels?

Interpretation and Approach to Abnormal LH/FSH Levels

When evaluating abnormal LH and FSH levels, clinicians should measure serum LH levels in all patients with low testosterone, and measure serum prolactin in patients with low testosterone combined with low or low/normal LH levels to establish etiology and guide appropriate management. 1

Understanding Normal LH/FSH Physiology

• FSH levels vary by age, sex, and reproductive status:

  • Prepubertal children: <4 IU/L
  • Adult males: Values >4.5 IU/L may indicate abnormal spermatogenesis 2, 3
  • Adult females: Best measured between days 2-4 of menstrual cycle

    • 10 IU/L: Possible diminished ovarian reserve (especially in women <40)

    • 40 IU/L: Diagnostic of premature ovarian insufficiency (POI) or menopause 2

• LH:FSH ratio interpretation:

  • 2: Suggestive of PCOS

  • ≤1: Suggestive of functional hypothalamic amenorrhea (FHA)
  • 1-2: Indeterminate 2

Diagnostic Approach in Males

Step 1: Clinical Assessment

• Evaluate for symptoms of low testosterone: reduced energy, diminished performance, fatigue, depression, reduced motivation, poor concentration, impaired memory, irritability, infertility, reduced sex drive, erectile dysfunction 1

Step 2: Physical Examination

• Assess: body habitus, virilization status, body hair patterns, BMI/waist circumference, gynecomastia, testicular size/consistency/masses, varicocele, prostate size/morphology 1

Step 3: Laboratory Testing

• Measure serum testosterone
• If testosterone is low, measure LH (strong recommendation) 1
  • Low/normal LH with low testosterone: Suggests secondary hypogonadism
  • High LH with low testosterone: Suggests primary testicular failure
• If testosterone is low and LH is low/normal, measure prolactin (strong recommendation) 1
• Consider measuring estradiol if gynecomastia or breast symptoms present 1

Step 4: Additional Testing Based on Results

• If prolactin is elevated, repeat measurement to confirm
• If persistently elevated prolactin, refer to endocrinologist 1
• If testosterone <150 ng/dL with low/normal LH, obtain pituitary MRI regardless of prolactin level 1
• For men with FSH >4.5 IU/L, anticipate abnormal semen parameters 3
• For men with FSH >7.5 IU/L, risk of abnormal semen quality is 5-13 times higher than men with FSH <2.8 IU/L 3

Diagnostic Approach in Females

Step 1: Clinical Assessment

• Evaluate menstrual history (regularity, amenorrhea)
• Assess for symptoms of POI or menopause: hot flashes, vaginal dryness, sleep disturbances
• For prepubertal girls: monitor growth and pubertal development 1

Step 2: Laboratory Testing

• For irregular menstrual cycles, test:
  • First line: LH, FSH, estradiol, testosterone, TSH, prolactin
  • Second line (based on results): DHEAS, 17-hydroxyprogesterone, androstenedione 2
• Measure FSH and estradiol between days 2-4 of menstrual cycle for accurate assessment 2
• For fertility concerns, assess ovarian reserve with day 3 FSH, LH, estradiol, and AMH 2

Step 3: Interpretation

• FSH >40 IU/L with amenorrhea (≥3 months): Diagnostic of POI 2
• Elevated LH:FSH ratio (>2): Suggestive of PCOS 2, 4
• Low LH and FSH: Consider hypothalamic dysfunction, pituitary disorder
• In PCOS, LH levels correlate negatively with BMI (higher BMI associated with lower LH) 4

Management Recommendations

For Males:

• For men with low testosterone and abnormal LH/FSH:
  • If secondary hypogonadism: Evaluate for pituitary/hypothalamic disorders
  • If primary hypogonadism: Consider testosterone replacement if not pursuing fertility
  • For men interested in fertility with abnormal LH/FSH: Refer for reproductive health evaluation 1

For Females:

• For women with POI (FSH >40 IU/L):
  • Refer to endocrinology and/or gynecology (strong recommendation) 2
  • Hormone replacement therapy until average age of natural menopause (~51 years) 2
  • Urgent fertility consultation for women desiring future pregnancy 2
  • Bone health monitoring: Consider vitamin D, calcium levels, and bone density testing 2
  • Psychological support for emotional impact of diagnosis 2

Common Pitfalls to Avoid

• Relying on a single FSH/LH measurement (values fluctuate, especially in women)
• Not considering recent ovulation when interpreting results in women with PCOS (can normalize LH levels temporarily) 4
• Using outdated "normal" ranges for FSH in males (values >4.5 IU/L may indicate abnormal spermatogenesis) 3
• Not measuring prolactin in patients with low testosterone and low/normal LH 1
• Failing to consider body mass index when interpreting LH levels in PCOS patients 4
• Not testing FSH/LH at the appropriate time in menstrual cycle (days 2-4) for women 2