The Purpose of FSH and LH in Males
FSH (Follicle-Stimulating Hormone) and LH (Luteinizing Hormone) are essential gonadotropins that work synergistically to regulate male reproductive function: FSH acts on Sertoli cells to support all phases of sperm production and determines Sertoli cell number, while LH stimulates Leydig cells to produce testosterone, which is required for both spermatogenesis and maintenance of male secondary sexual characteristics. 1, 2
FSH's Role in Male Reproduction
Primary Functions of FSH
- FSH determines Sertoli cell number during development, which establishes the capacity for sperm production throughout a man's life 1
- FSH is required for induction and maintenance of normal sperm production by acting directly on Sertoli cells, which are the only testicular cells possessing FSH receptors 1, 2
- FSH stimulates all phases of spermatogenesis, particularly the mitotic division of spermatogonia (the earliest sperm precursor cells) 2, 3
- FSH activates cAMP-dependent protein kinase A in Sertoli cells, though the complete molecular mechanism remains incompletely understood 2
Evidence of FSH's Essential Role
- A patient with an activating mutation of the FSH receptor maintained spermatogenesis and fathered three children despite having undetectable gonadotropin levels after hypophysectomy, demonstrating that FSH alone can maintain spermatogenesis in humans 2
- However, FSH levels are negatively correlated with the number of spermatogonia—higher FSH generally indicates the testes are failing and the pituitary is compensating by producing more FSH 1
LH's Role in Male Reproduction
Primary Functions of LH
- LH stimulates Leydig cells to produce testosterone, which is the primary androgen responsible for male reproductive function 1, 4, 2
- Testosterone produced by LH stimulation is responsible for:
Intratesticular Testosterone Concentration
- Intratesticular testosterone concentrations are 50-100 times higher than serum levels and are essential for normal spermatogenesis 1
- LH stimulation maintains these high intratesticular testosterone levels independent of circulating testosterone or sex hormone-binding globulin (SHBG) levels 1
Synergistic Action: Why Both Hormones Are Required
Evidence from Experimental Studies
- Neither FSH nor LH alone achieves quantitatively normal spermatogenesis in humans 3, 5
- Studies in gonadotropin-suppressed normal men showed that:
- Selective LH replacement (with hCG) increased sperm counts to 20-50 million/mL but not to fully normal levels 6, 3, 5
- Selective FSH replacement also increased sperm counts to 20-50 million/mL but again not to fully normal levels 3
- Only combined FSH and LH replacement restored quantitatively normal sperm production in all subjects 3
Clinical Implications
- In hypogonadotropic hypogonadism, treatment with hCG followed by FSH analogues successfully initiates spermatogenesis, with 75% of men achieving sperm in ejaculate 1
- Exogenous testosterone should never be used in men desiring fertility because it suppresses both LH and FSH through negative feedback on the hypothalamus and pituitary, eliminating intratesticular testosterone production and causing azoospermia that can take months to years to recover 1, 4
Common Pitfalls and Clinical Caveats
- Male germ cells possess neither FSH nor androgen receptors—both hormones act indirectly through Sertoli cells 2
- FSH levels alone cannot predict fertility status: up to 50% of men with non-obstructive azoospermia and elevated FSH still have retrievable sperm with testicular sperm extraction 1, 7
- Men with inactivating FSH receptor mutations show variable effects on fertility, suggesting FSH's role may be partially compensated by high testosterone levels in some individuals 2
- The combination of FSH and testosterone supports qualitatively and quantitatively fully normal spermatogenesis, while either hormone alone produces suboptimal results 2, 3