Can hyperthyroidism (including iatrogenic or medication-induced) cause an elevation in Follicle-Stimulating Hormone (FSH) levels in men?

Hyperthyroidism and FSH Elevation in Men: Evidence-Based Analysis

Yes, hyperthyroidism (including iatrogenic/medication-induced) causes elevation in FSH and LH levels in men, along with increased testosterone, SHBG, and estradiol—all of which are reversible with treatment. 1, 2, 3

Documented Hormonal Changes in Hyperthyroid Men

Gonadotropin Elevation

• FSH levels are significantly elevated in men with hyperthyroidism, though the increase may be less pronounced than LH elevation 1, 3
• LH secretion is consistently increased in all hyperthyroid patients, with preserved pulsatile characteristics (frequency and peak shape remain normal) 3
• The gonadotropin elevation occurs without impairment of the hypothalamic-pituitary-gonadal axis function itself—rather, it represents a compensatory response 3

Sex Steroid and Binding Protein Changes

• Total testosterone levels are significantly elevated in hyperthyroid men (mean 29.9±9.5 nmol/L before treatment), but this represents a paradoxical state 2, 3
• SHBG concentrations are markedly increased (mean 146±111 nmol/L before treatment), which is the primary driver of elevated total testosterone 1, 2, 3
• Free testosterone is actually decreased (mean 0.24±0.08 nmol/L before treatment), indicating relative primary gonadal insufficiency despite elevated total testosterone 2, 3
• Estradiol levels are significantly elevated (mean 19.9±7.7 pmol/L before treatment), contributing to gynecomastia commonly seen in hyperthyroid men 1, 2, 3

Mechanism of Pituitary Dysregulation

• Men with hyperthyroidism exhibit hyperresponsiveness of LH to GnRH administration but subnormal responses to hCG, indicating altered pituitary-gonadal communication 1
• The copulsatility between LH and FSH, and between LH and prolactin, is more pronounced in hyperthyroid patients than controls, suggesting enhanced hypothalamic-pituitary coordination 3
• Prolactin levels are not consistently elevated except in cases of longstanding severe primary hypothyroidism, but decline following thyroid hormone normalization 1

Reversibility with Treatment

Timeline of Hormonal Normalization

• Thyroid hormone levels (FT3, FT4) gradually decrease to normal with antithyroid drug treatment, with TSH gradually increasing 2
• LH and estradiol levels progressively decrease throughout treatment (statistically significant at all time points, P<0.001) 2
• FSH decreases but less dramatically, with changes not always reaching statistical significance 2
• SHBG and total testosterone levels decrease significantly, while free testosterone, free testosterone percentage, bioavailable testosterone, and free androgen index all gradually increase and stabilize (all P<0.001) 2
• Complete normalization typically occurs within 5 months of achieving euthyroid status 2, 4

Post-Treatment Hormone Profiles

• After successful treatment, FSH, LH, testosterone, and estradiol levels show no significant difference from healthy controls (P>0.05) 4
• The ratio of free testosterone to LH (FT/LH) gradually increases during treatment, indicating improved gonadal responsiveness (P<0.001) 2

Special Consideration: Radioactive Iodine Effects

Iatrogenic Gonadal Dysfunction

• Radioactive iodine therapy (RAI) for thyroid cancer produces dose-dependent impairment of spermatogenesis with FSH elevation lasting up to approximately 2 years 1
• RAI commonly increases serum FSH and LH concentrations while reducing inhibin B levels without initially affecting testosterone 1
• Permanent testicular germ cell damage may occur with high-dose RAI, though most cases show recovery of both germinal and Leydig cell function by 18 months post-therapy 1

Clinical Implications

Diagnostic Pitfalls

• Elevated FSH in the context of hyperthyroidism should not be misinterpreted as primary testicular failure—check thyroid function (TSH, free T4) in any man presenting with elevated gonadotropins 1, 3
• The Free Androgen Index is significantly decreased in hyperthyroid males despite elevated total testosterone, reflecting the true androgenic state 3
• SHBG elevation is a key mediator of the hormonal changes, as thyroid hormone directly affects SHBG synthesis 5, 1

Management Approach

• Treatment of the underlying hyperthyroidism is the definitive therapy for associated gonadotropin and sex hormone abnormalities 2, 4
• No specific intervention for the elevated FSH/LH is required beyond achieving euthyroid status 2, 4
• Monitor for recovery of free testosterone levels as SHBG normalizes during treatment 2