How do you differentiate between Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) blood work?

Differentiating FSH and LH Blood Work

What They Are and What They Do

FSH (Follicle-Stimulating Hormone) and LH (Luteinizing Hormone) are both gonadotropins secreted by the anterior pituitary gland that regulate reproductive function, but they have distinct roles: FSH primarily drives follicular development and spermatogenesis, while LH triggers ovulation in females and stimulates testosterone production in males. 1

In Males

• LH stimulates Leydig cells in the testes to produce testosterone, which is essential for male sexual function and secondary sex characteristics 1
• FSH acts on Sertoli cells to support spermatogenesis and sperm maturation 1
• In hypogonadotropic hypogonadism (HH), both LH and FSH are deficient, leading to low testosterone and impaired sperm production 1

In Females

• FSH drives the growth and maturation of ovarian follicles during the follicular phase 2
• LH triggers ovulation at mid-cycle and maintains the corpus luteum during the luteal phase 2
• The LH surge at mid-cycle is the defining hormonal event of ovulation 2

Normal Reference Ranges and Patterns

Baseline Levels

• In normal adult females during the early follicular phase, FSH levels are typically higher than LH levels 2
• Normal ranges vary by menstrual cycle phase, age, and sex 3, 2
• In prepubertal children, FSH levels may rise earlier (ages 5-8 years) than LH levels (ages 9-10 years) 3

The FSH:LH Ratio

• A normal FSH:LH ratio is approximately 1.0 to 2.5 in most clinical contexts 1, 4, 5
• An LH:FSH ratio >2.0 strongly suggests PCOS (polycystic ovary syndrome) 1, 4
• An LH:FSH ratio <1.0 (or FSH:LH ratio >2.5) suggests functional hypothalamic amenorrhea (FHA) or diminished ovarian reserve 1, 4, 5

Clinical Interpretation by Condition

Elevated Both FSH and LH

• Primary ovarian insufficiency (POI) or primary testicular failure causes elevated FSH and LH due to loss of negative feedback from the gonads 6, 3
• In gonadal dysgenesis, FSH typically elevates before LH, especially in younger patients (ages 4.8-10.9 years) 3
• LH levels provide stronger discrimination than AMH when distinguishing POI from isolated elevated FSH 6

Low or Low-Normal Both FSH and LH

• Hypogonadotropic hypogonadism (central hypogonadism) presents with deficient LH and FSH secretion, resulting in low testosterone in males and amenorrhea in females 1, 4
• Functional hypothalamic amenorrhea (FHA) shows low-normal LH and FSH levels (e.g., LH 4.8 IU/L, FSH 4.7 IU/L) with an LH:FSH ratio of approximately 1.0 4
• Severe FHA can present with both LH and FSH <2 IU/L, representing profound hypothalamic suppression 4

Discordant FSH and LH Levels

• FSH secretion has some autonomy from hypothalamic control, while LH is more tightly regulated by GnRH pulsatility 7
• An elevated FSH:LH ratio ≥3.6 with normal day 3 FSH predicts poor ovarian response to stimulation 5
• In rare cases of pure gonadal dysgenesis with concurrent illness, FSH may remain elevated while LH decreases, creating an FSH:LH ratio of 10 (versus normal 2-2.5) 7

Diagnostic Algorithms by Clinical Scenario

Evaluating Amenorrhea

1. Measure FSH, LH, estradiol, and testosterone (with SHBG) simultaneously 1, 4
2. If FSH and LH are both elevated: consider primary ovarian insufficiency; check for gonadal dysgenesis if age <40 years 6, 3
3. If FSH and LH are both low-normal with low estradiol: consider FHA; assess for energy deficit, excessive exercise, or psychological stress 1, 4
4. If LH:FSH ratio >2 with normal or elevated androgens: consider PCOS 1, 4

Evaluating Male Infertility

1. Check morning testosterone, LH, FSH, and prolactin 1
2. If testosterone is low with low/low-normal LH: measure prolactin to exclude hyperprolactinemia; consider MRI if prolactin is elevated 1
3. If both LH and FSH are deficient: diagnose hypogonadotropic hypogonadism; refer to endocrinology for gonadotropin replacement therapy 1
4. Treatment for HH involves hCG to normalize testosterone first, then adding FSH or FSH analogues to optimize spermatogenesis 1

Distinguishing FHA-PCOM from PCOS

• This is a critical diagnostic pitfall: 41.9-46.7% of women with FHA have polycystic ovarian morphology (PCOM) on ultrasound 1, 4
• Key differentiators favoring FHA-PCOM over PCOS include: clear history of caloric restriction/energy deficit, LH:FSH ratio <1, very high SHBG, low androgens with very low Free Androgen Index, and thin endometrium 1, 4
• FHA-PCOM patients still demonstrate core FHA features: low gonadotropins, hypoestrogenism (low estradiol), and normal insulin sensitivity 1, 4

Common Pitfalls and Caveats

Timing Matters

• In females, FSH and LH must be measured on cycle day 2-4 (early follicular phase) for accurate interpretation of baseline ovarian reserve 5
• Mid-cycle LH surge can cause 10-20 fold elevations that are physiologic, not pathologic 2

Age-Related Considerations

• FSH may be a more sensitive early marker than LH in prepubertal children with gonadal dysgenesis 3
• In delayed puberty, gonadotropin levels should be interpreted relative to stage of sexual development, not just chronological age 3

Differential Regulation

• FSH and LH are differentially regulated: FSH has partial autonomy from GnRH, while LH is more GnRH-dependent 7
• Systemic illness, medications (especially glucocorticoids), and critical illness can suppress LH more than FSH 1, 7

Treatment Implications

• Exogenous testosterone suppresses both LH and FSH through negative feedback, potentially causing azoospermia; it should never be prescribed to men interested in fertility 1
• For hypogonadotropic hypogonadism, sequential therapy (hCG first, then add FSH) is more effective than simultaneous initiation 1