What causes elevated Follicle-Stimulating Hormone (FSH) levels in men and how are they managed?

What Causes Elevated FSH in Men and How to Manage It

Elevated FSH in men results from primary testicular dysfunction (most commonly), compensated testicular stress, natural biological variation, or—rarely—laboratory artifact, and management depends entirely on whether fertility is a concern and whether reversible factors are present.

Primary Causes of Elevated FSH

Primary Testicular Dysfunction

• Non-obstructive azoospermia is the most clinically significant cause, characterized by FSH >7.6 IU/L, testicular atrophy, and failure of spermatogenesis within the testes 1
• Genetic abnormalities are established causes, including:
  • Klinefelter syndrome and other karyotype abnormalities 1
  • Y-chromosome microdeletions (AZFa, AZFb, AZFc regions) 1
• Exogenous testosterone use suppresses spermatogenesis and causes compensatory FSH elevation after discontinuation 1
• Prior testicular injury (orchitis, trauma) can result in compensated testicular disease where FSH remains chronically elevated to maintain normal or near-normal sperm production 2

Reversible Testicular Stress

• Varicocele creates a warmer testicular environment that temporarily reduces spermatogenic efficiency 3
• Acute illness including fever, viral infections (COVID, influenza, mumps) transiently suppress testicular function 3
• Metabolic dysfunction including obesity, diabetes, insulin resistance, and thyroid imbalance 3
• Nutritional deficiencies (vitamin D, zinc) 3
• Medications including certain drugs that interfere with the hypothalamic-pituitary-gonadal axis 3
• Lifestyle factors such as chronic stress, poor sleep, extreme exercise, smoking, and environmental toxins (lead, cadmium, occupational exposures) 1, 3

Compensated Testicular Function

• Some men maintain normal fertility despite FSH levels of 9-12 IU/L, representing biological variation where the pituitary compensates for slightly less efficient testicular function 1, 4
• FSH levels show natural variation among healthy men, with some maintaining levels in the 10-12 IU/L range throughout life with normal fertility and testosterone 4
• Two men with previous orchitis and one with testicular atrophy maintained normal sperm counts and fertility despite chronically elevated FSH, demonstrating that FSH may be a more sensitive marker of testicular disease than semen analysis alone 2

Age-Related Changes

• FSH gradually increases with age (especially after 35-40 years) as part of natural hormonal drift, though to a much smaller degree than in women 5

Laboratory Artifacts (Rare)

• Heterophilic antibodies against mouse proteins can cause falsely elevated TSH in some assays—a similar phenomenon could theoretically affect FSH 5
• Macro-FSH (FSH-immunoglobulin complexes) can cause spuriously elevated FSH levels 6

Diagnostic Approach: The Critical Algorithm

Step 1: Confirm True Elevation and Assess Context

• Obtain at least two semen analyses (2-3 months apart, after 2-7 days abstinence) to correlate FSH with actual reproductive function 3, 4
• Measure complete hormonal panel: testosterone, LH, and prolactin alongside FSH to evaluate the entire hypothalamic-pituitary-gonadal axis 1, 3
• Avoid testing during acute illness or metabolic stress, as transient conditions artificially elevate FSH and suppress the HPG axis 3

Step 2: Physical Examination Priorities

• Testicular volume and consistency: atrophy suggests primary testicular failure 1
• Presence of varicocele 3
• Body mass index (BMI) and waist circumference, as metabolic parameters directly impact the HPG axis 3

Step 3: Interpret FSH in Context

FSH >7.6 IU/L with abnormal semen parameters:

• Strongly suggests non-obstructive azoospermia or severe testicular dysfunction 1
• Proceed immediately with genetic testing: karyotype analysis and Y-chromosome microdeletion testing 1, 3
• Risk of abnormal semen quality is 5- to 13-fold higher compared to men with FSH <2.8 IU/L 7

FSH 4.5-7.6 IU/L:

• Associated with abnormal sperm morphology and concentration in infertile populations 7
• Warrants semen analysis and evaluation for reversible factors 7

FSH 9-12 IU/L with normal semen parameters:

• May represent compensated testicular function or biological variation 1, 4
• Address reversible factors first before concluding this is the patient's baseline 3

Step 4: Address Reversible Factors Before Definitive Diagnosis

• Weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism and normalize gonadotropins 3
• Physical activity shows similar benefits, with results correlating to exercise duration and weight loss 3
• Treat underlying conditions: thyroid disorders, diabetes, nutritional deficiencies 3
• Remove interfering substances: check for drugs that interfere with testosterone production or HPG axis function 3
• Repeat hormonal testing after 3-6 months of metabolic optimization—FSH often normalizes from 9-12 IU/L to 7-9 IU/L once reversible factors resolve 3

Management Based on Fertility Goals

For Men Seeking Current or Future Fertility

Critical Pitfall to Avoid:

• NEVER prescribe testosterone therapy—it will further suppress spermatogenesis through negative feedback on the hypothalamus and pituitary 3, 4

Treatment Options:

• FSH analogue treatment (recombinant FSH or human menopausal gonadotropin) may improve sperm concentration, pregnancy rate, and live birth rate in men with idiopathic infertility and FSH <8 IU/L 3
  • One case report demonstrated successful treatment of isolated FSH deficiency with 150 units hMG three times weekly, increasing sperm concentration from 2.5×10⁶/mL to 264×10⁶/mL over 3 months, resulting in natural conception 8
• Aromatase inhibitors may decrease estrogen production and improve spermatogenesis 1
• Selective estrogen receptor modulators (SERMs) or hCG may be used for low testosterone with elevated FSH, though benefits are limited compared to assisted reproductive technology 3
• Microsurgical testicular sperm extraction (TESE) offers the best chance of retrieving sperm for assisted reproductive technology in non-obstructive azoospermia—up to 50% success rate despite elevated FSH 1, 3
• Fertility preservation counseling if parameters remain suboptimal after optimization 3

For Men NOT Seeking Fertility

Asymptomatic men with FSH 10-12 IU/L and normal testosterone:

• Reassurance that this can represent normal biological variation 4
• Routine monitoring of testosterone levels to ensure continued normal gonadal function 4

Symptomatic hypogonadism with elevated FSH:

• Testosterone replacement therapy is appropriate only when fertility is not a concern 3

Important Caveats and Pitfalls

FSH Alone Cannot Predict Fertility

• Up to 50% of men with non-obstructive azoospermia may have retrievable sperm despite elevated FSH 1, 3
• Men with maturation arrest can have normal FSH and testicular volume despite severe spermatogenic dysfunction 1, 4
• FSH is negatively correlated with spermatogonia numbers, but this correlation is not absolute 1, 4

Genetic Testing is Essential When Indicated

• Complete AZFa and AZFb deletions result in almost zero likelihood of sperm retrieval 1
• Do not delay genetic testing if azoospermia or severe oligospermia (<5 million/mL) is found with FSH >7.6 IU/L—this guides prognosis and treatment options 3

Timing Matters

• Do not make definitive diagnoses during acute illness, metabolic stress, or before addressing obesity and lifestyle factors 3
• Borderline FSH levels (9-12 IU/L) often normalize to 7-9 IU/L once reversible factors are addressed 3