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Serum versus intratesticular testosterone: the roughly 100-fold gradient
One of the most important and most under-appreciated facts in male reproductive endocrinology is that the testosterone concentration inside the testis is vastly higher than the concentration measured in a blood test. Intratesticular testosterone (ITT) is on th
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- One of the most important and most under-appreciated facts in male reproductive endocrinology is that the testosterone concentration inside the testis is vastly higher than the concentration measured in a blood test. Intratesticular testosterone (ITT) is on the order of one to two orders of magnitude higher than serum testosterone, and this high local concentration is what normal spermatogenesis actually requires.[2] Sperm production is not driven by the testosterone your lab reports; it is driven by the far larger reservoir of testosterone bathing the seminiferous tubules.
- This single fact explains the central paradox of testosterone therapy. When a man takes exogenous testosterone, his serum testosterone rises — but that external testosterone suppresses the pituitary’s LH output through negative feedback, the Leydig cells stop being stimulated, and intratesticular testosterone collapses. Exogenous testosterone raises the number on the lab slip while starving the testis of the local androgen concentration sperm production depends on, which is why testosterone therapy is a well-documented, and preventable, cause of male infertility.[2] HCG’s clinical rationale flows directly from this gradient: by stimulating the Leydig cells directly, HCG keeps intratesticular testosterone up even when the pituitary has gone quiet.