What is the function of FSH (Follicle-Stimulating Hormone)?

What FSH Hormone Does

FSH (Follicle-Stimulating Hormone) is a glycoprotein hormone produced by the anterior pituitary gland that is essential for reproductive function: in females, it stimulates ovarian follicle development and maturation leading to ovulation, while in males, it acts on Sertoli cells to support spermatogenesis and sperm production. 1, 2

Core Physiological Functions

In Females

• FSH drives folliculogenesis by stimulating granulosa cells in the ovary to promote the growth and maturation of ovarian follicles from early stages through to the formation of a large pre-ovulatory follicle capable of ovulation 2
• Essential for ovulation: FSH-dependent follicle maturation enables the follicle to respond to the mid-cycle LH surge, resulting in ovulation and corpus luteum formation 2
• Critical for fertility: Female mice lacking FSH are completely infertile due to a block in folliculogenesis before antral follicle formation, demonstrating FSH's non-redundant role in female reproduction 3

In Males

• Supports spermatogenesis: FSH acts on Sertoli cells in the testes to facilitate sperm production and maturation, though it is not absolutely required for male fertility 1, 3
• Promotes germ cell proliferation: FSH increases undifferentiated spermatogonia proliferation and plays a role in the self-renewal of germinative cells 1
• Maintains testicular function: Despite FSH's supportive role, male mice deficient in FSH remain fertile, though they have smaller testes, indicating FSH is important but not essential for male reproduction 3

Mechanism of Action

Receptor Binding and Signaling

• FSH is a heterodimeric hormone consisting of an alpha subunit (shared with LH, TSH, and hCG) and a hormone-specific beta subunit; biological activity requires the intact heterodimer 4, 1
• FSH receptors (FSHR) are located primarily on granulosa cells in the ovary and Sertoli cells in the testis, with recent identification in testicular stem cells and some extra-gonadal tissues 1
• Signal transduction: FSH binding activates adenylate cyclase, causing cAMP accumulation and stimulation of protein kinase A (PKA) pathways 4
• High-affinity binding: The FSH receptor's leucine-rich repeat (LRR) region forms an elongated tube-like structure where FSH binds in a "hand clasp" fashion with exceptionally high buried-charge density at the interface 4

Clinical Relevance

Diagnostic Applications

• Marker of gonadal function: Elevated FSH levels (>7.6 IU/L in males) indicate primary testicular or ovarian dysfunction, while low FSH suggests hypothalamic or pituitary disorders 4, 5
• Assessment of ovarian reserve: FSH levels help evaluate reproductive potential in women, with elevated levels indicating diminished ovarian reserve 4
• Evaluation of amenorrhea: FSH measurement distinguishes between primary ovarian failure (elevated FSH) and hypothalamic amenorrhea (low FSH) in women with absent menstruation 4

Therapeutic Uses

• Ovarian stimulation: FSH preparations (urinary or recombinant) are widely used in assisted reproductive technologies to stimulate multiple follicle development for IVF/ICSI 2
• Male infertility treatment: FSH analogues may improve sperm concentration, pregnancy rates, and live birth rates in men with idiopathic infertility, though benefits are limited compared to assisted reproductive technologies 4, 6
• Hypogonadotropic hypogonadism: In men with deficient LH and FSH secretion, treatment with hCG followed by FSH analogues can successfully initiate spermatogenesis 4

Important Clinical Pitfalls

Interpretation Caveats

• FSH levels alone cannot predict fertility: Up to 50% of men with non-obstructive azoospermia and elevated FSH still have retrievable sperm for assisted reproduction 5, 7
• FSH variability: Levels fluctuate due to pulsatile secretion patterns; repeat measurements are necessary to confirm abnormal values and eliminate laboratory error 7
• Context matters: Men with maturation arrest can have normal FSH and testicular volume despite severe spermatogenic dysfunction 7

Treatment Considerations

• Never use testosterone in men desiring fertility: Exogenous testosterone suppresses FSH and LH secretion through negative feedback, potentially causing azoospermia 4, 7
• Limited benefit of empiric FSH therapy: In men with normal pituitary function and idiopathic infertility, FSH treatment benefits are restricted to a subgroup of responders who cannot be identified before treatment 6
• Assisted reproduction is more effective: For couples with fertility challenges, IVF/ICSI offers superior pregnancy rates compared to empiric hormonal therapy with FSH, SERMs, or aromatase inhibitors 4, 7