Is it true that men with low serum free testosterone (T) often have normal sperm counts because local testosterone in the testes remains sufficient?

Relationship Between Low Serum Free Testosterone and Normal Sperm Counts

Yes, men with low serum free testosterone often have normal sperm counts because local testosterone in the testes remains sufficient for spermatogenesis, independent of circulating testosterone levels. 1

Testicular Testosterone Production and Spermatogenesis

• Spermatogenesis requires high local concentrations of testosterone within the testes, which can be maintained even when serum testosterone levels are low 2
• The testes have two distinct functions: spermatogenesis and testosterone production, which can be affected differently by various conditions 2
• Local testosterone production in the testes is primarily regulated by luteinizing hormone (LH) and can remain adequate for sperm production even when serum levels are low 3

Evidence from Clinical Studies

• A 2023 study found that among men with normal sperm concentration (≥15 million/mL), 44.1% had low serum testosterone (<300 ng/dL), demonstrating that normal spermatogenesis often occurs despite low circulating testosterone 1
• Research shows no significant difference in median testosterone levels between men with normal vs. abnormal sperm concentration (316 ng/dL for both groups), suggesting that serum testosterone is not strongly correlated with sperm production 1
• In male partners of infertile couples with total sperm count greater than 5 million, low total testosterone was not significantly associated with alterations in semen parameters including volume, count, motility, or morphology 4

Mechanisms Explaining This Phenomenon

• The blood-testis barrier creates a microenvironment where local testosterone concentrations can be 50-100 times higher than serum levels, allowing normal spermatogenesis despite low circulating testosterone 2
• In hypogonadotropic hypogonadism, hormone stimulation therapy can restore sperm production in up to 75% of men with nonobstructive azoospermia, demonstrating the testicular capacity to respond to appropriate hormonal signals even when baseline testosterone is low 2
• Intratesticular testosterone is primarily what matters for spermatogenesis, not serum testosterone levels 3

Clinical Implications

• Fertility evaluation should not rely solely on serum testosterone levels, as normal sperm parameters can exist despite low circulating testosterone 1
• For men with suspected testosterone deficiency, both free and total testosterone should be measured, as binding protein abnormalities can affect the relationship between total testosterone and the biologically active free fraction 3, 5
• When evaluating male infertility, follicle-stimulating hormone (FSH) may be a more reliable marker of spermatogenic function than testosterone, as elevated FSH is more strongly associated with impaired spermatogenesis 1

Important Caveats

• While normal sperm counts are possible with low serum testosterone, the quality of sperm and overall fertility potential may still be affected 4
• Long-term low testosterone has health implications beyond fertility, including increased risk for metabolic syndrome and cardiovascular disease, warranting consideration for treatment 3, 1
• Treatment of low testosterone with exogenous testosterone can paradoxically reduce sperm production through negative feedback on the hypothalamic-pituitary axis, an important consideration in men desiring fertility 6
• Alternative treatments that increase endogenous testosterone production (such as selective estrogen receptor modulators, aromatase inhibitors, or human chorionic gonadotropin) may be preferred for men with both low testosterone and fertility concerns 6