What does it mean if my Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels are high?

High FSH and LH Levels: Clinical Significance

Elevated FSH and LH levels indicate primary gonadal failure (hypergonadotropic hypogonadism), where the pituitary gland increases gonadotropin production in response to inadequate sex hormone feedback from failing gonads.

In Women

Primary Ovarian Insufficiency/Failure

• High FSH (>35 IU/L) and LH (>11 IU/L) with low estradiol indicate primary ovarian failure, where the ovaries no longer respond adequately to pituitary stimulation 1
• FSH levels are negatively correlated with ovarian follicle reserve; elevated FSH reflects diminished follicular function 1
• This pattern is definitively seen in:
  • Premature ovarian failure (POF) in women under age 40 1
  • Menopause (natural or induced) 1
  • Post-chemotherapy or radiation-induced ovarian damage 1

Age-Related Changes

• FSH begins rising as early as age 29-30 years in regularly cycling women, reflecting progressive follicular depletion 2, 3
• This increase becomes more pronounced after age 43, with LH elevation following around age 35-36 2
• During perimenopause, FSH and LH can fluctuate dramatically, with transient postmenopausal-range elevations occurring alongside high estrogen levels 4
• Postmenopausal biochemical parameters (high FSH/LH) do not guarantee permanent postmenopausal status, as ovulatory cycles can occur within 16 weeks of apparent menopause 4

Polycystic Ovary Syndrome (PCOS)

• An LH/FSH ratio >2 is characteristic of PCOS, with elevated LH but relatively normal or low FSH 1
• This differs from primary ovarian failure where both hormones are elevated 1

In Men

Primary Testicular Failure

• Elevated FSH and LH with low testosterone indicate primary testicular dysfunction (hypergonadotropic hypogonadism) 1
• FSH levels are negatively correlated with spermatogonia numbers and reflect spermatogenic capacity 1
• Common causes include:
  • Klinefelter syndrome (most common chromosomal cause) 1
  • Chemotherapy or radiation-induced testicular damage 1
  • Y-chromosome microdeletions (AZF deletions) 1

Clinical Interpretation Caveats

• FSH does not accurately predict sperm retrieval success in azoospermic men, as those with maturation arrest can have normal FSH and testicular volume 1
• Men with FSH >7.5 IU/L have 5-13 fold higher risk of abnormal semen parameters compared to those with FSH <2.8 IU/L 5
• Even FSH levels >4.5 IU/L are associated with abnormal sperm morphology and concentration, suggesting the traditional "normal" range may be too broad 5

Diagnostic Workup

Essential Testing

• Measure FSH, LH, and sex hormones (estradiol in women, testosterone in men) simultaneously to distinguish primary from secondary hypogonadism 1
• In women with amenorrhea: FSH >35 IU/L on two occasions at least one month apart confirms primary ovarian insufficiency 1
• In men with infertility: FSH measurement is part of basic hormonal workup, especially with sperm concentration <5 million/ml or azoospermia 1

Additional Considerations

• FSH is unreliable for determining menopausal status in women on tamoxifen or after chemotherapy 1
• Serial measurements may be needed in perimenopausal women due to hormonal fluctuations 4
• Karyotype testing is indicated for men with azoospermia or severe oligospermia (<5 million/ml) when FSH is elevated 1
• Anti-Müllerian hormone (AMH) provides additional information about ovarian reserve in women and may predict sperm retrieval success in men 1

Clinical Implications

For Fertility

• High FSH/LH indicates significantly reduced fertility potential in both sexes 1
• In women, this pattern suggests poor ovarian reserve and reduced response to fertility treatments 1
• In men with non-obstructive azoospermia and elevated FSH, testicular sperm extraction may still retrieve sperm in 20-50% of Klinefelter syndrome cases 1

Long-Term Health

• Male infertility with hypogonadism carries increased cardiometabolic risk, including metabolic syndrome and cardiovascular disease 1
• Women with premature ovarian failure require estrogen replacement to prevent bone loss and other sequelae of hypoestrogenism 1