Causes of Elevated FSH and LH
Elevated FSH and LH levels indicate primary gonadal failure (hypergonadotropic hypogonadism) in most clinical contexts, where the pituitary increases gonadotropin production in response to inadequate sex hormone feedback from failing gonads.
Primary Gonadal Failure (Most Common)
In Females:
- Primary ovarian insufficiency/menopause - The ovaries fail to produce adequate estrogen, leading to loss of negative feedback and compensatory elevation of FSH and LH 1
- Polycystic ovary syndrome (PCOS) - Characterized by hypersecretion of LH with relative hypofunction of the FSH-granulosa cell axis, resulting in elevated LH:FSH ratio 1
- Premature ovarian failure - Early depletion of ovarian follicles before age 40, causing elevated gonadotropins 1
In Males:
- Primary testicular failure - Direct testicular damage from various causes leads to inadequate testosterone production and elevated compensatory LH and FSH 2
- Klinefelter syndrome - Chromosomal abnormality causing primary testicular failure with markedly elevated gonadotropins
- Testicular damage from radiation or chemotherapy - Radioactive iodine therapy produces dose-dependent impairment of spermatogenesis with FSH elevation up to 2 years, with permanent germ cell damage possible at high doses 2
Thyroid Dysfunction Effects
Hyperthyroidism:
In hyperthyroid patients, LH and FSH levels are typically elevated due to pituitary hypersensitivity to GnRH, not primary gonadal failure 3. The mechanism involves:
- Enhanced pituitary responsiveness - Chronic thyroid hormone excess makes pituitary gonadotrophs "hypersensitive" to GnRH, with LH and FSH responses significantly larger in thyrotoxic versus euthyroid states 3
- Elevated sex hormone-binding globulin (SHBG) - Hyperthyroidism increases SHBG concentrations, which binds testosterone and reduces free testosterone despite normal or elevated total testosterone 4, 2
- Increased LH and estradiol - Male hyperthyroid patients show significantly elevated LH (8.41±3.61 U/L) and estradiol (19.9±7.7 pmol/L) levels that normalize with antithyroid treatment 4
- Reversibility - These gonadotropin elevations resolve when euthyroidism is restored with antithyroid drug therapy 4, 3
Hypothyroidism:
- Hypogonadotropic hypogonadism - Primary hypothyroidism is associated with subnormal LH responses to GnRH and reduced free testosterone, which normalizes with thyroid hormone replacement 2
- Elevated FSH in children - Male children with primary hypothyroidism show elevated FSH associated with testicular enlargement without virilization 2
Immune Checkpoint Inhibitor Therapy
Hypophysitis from anti-CTLA4 therapy causes simultaneous low TSH, ACTH, and FSH/LH levels (not elevated), representing secondary hypogonadism rather than elevated gonadotropins 1. This is the opposite pattern from primary gonadal failure.
Clinical Pitfalls
- Do not confuse elevated gonadotropins in hyperthyroidism with primary gonadal failure - The mechanism is pituitary hypersensitivity, not gonadal dysfunction, and resolves with treatment of hyperthyroidism 3
- SHBG elevation in hyperthyroidism creates discordance between total and free testosterone levels - free testosterone is reduced despite normal/elevated total testosterone 4, 2
- Polycystic ovaries (33% of general population) differ from PCOS - Only PCOS shows the characteristic hormonal abnormalities including elevated LH 1