Testosterone Replacement Therapy (TRT) involves administering external (exogenous) testosterone to treat symptoms of low natural hormone levels. While TRT is effective for improving energy, mood, and muscle mass, a common side effect is a decrease in the size of the testicles, known as testicular atrophy. This shrinkage is an expected physiological response, not a pathological complication. It occurs because the body detects the presence of external testosterone and adjusts its internal production accordingly. This article explains the biological mechanism behind this phenomenon and details strategies available to mitigate it.
The Hormonal Feedback Loop That Causes Shrinkage
The body regulates hormone levels through the Hypothalamic-Pituitary-Testicular Axis (HPTA). The hypothalamus releases Gonadotropin-Releasing Hormone (GnRH), signaling the pituitary gland to produce Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). These hormones, known as gonadotropins, travel to the testicles where they stimulate function.
When a man begins TRT, the exogenous testosterone raises the overall hormone level. The hypothalamus and pituitary gland sense this elevated level, interpreting it as a signal that the body has sufficient testosterone. They respond by reducing or stopping the release of GnRH, LH, and FSH through negative feedback inhibition. This shutdown directly causes testicular atrophy.
The testicles contain Leydig cells, which produce testosterone when stimulated by LH, and Sertoli cells, which support sperm production. Without the LH signal, Leydig cells become dormant and cease testosterone production. This lack of stimulation causes the physical reduction in size, sometimes resulting in an average decrease in testicular volume of about 17%. The atrophy occurs because the testicles are put on “rest” by the body’s regulatory system.
Implications for Sperm Production and Fertility
The suppression of the HPTA by TRT significantly impacts the testicles’ other function: sperm production. Follicle-Stimulating Hormone (FSH) is vital for initiating and maintaining spermatogenesis (sperm creation). Since TRT suppresses FSH release, the Sertoli cells within the testicles lose the necessary signal to produce mature sperm.
Exogenous testosterone, while improving general well-being, cannot replace the high concentration of testosterone needed inside the testicles for robust sperm development. The resulting drop in sperm count can be severe, often leading to azoospermia (no sperm present in the ejaculate) in up to 40% of patients. TRT is sometimes referred to as a form of “chemical contraception.”
This effect is a major consideration for men planning to conceive. While suppression is often reversible after stopping TRT, recovery is not guaranteed and can take several months or up to two years. Discussing fertility goals with a physician before starting therapy is important, as the transient infertility caused by TRT is a predictable side effect.
Countermeasures to Maintain Testicular Size and Function
Medical strategies exist to counteract HPTA suppression and maintain testicular size and function while on TRT. The most common and effective approach involves the concurrent use of Human Chorionic Gonadotropin (hCG), a hormone that closely mimics the action of Luteinizing Hormone (LH).
Administering hCG alongside testosterone artificially stimulates the Leydig cells, bypassing the suppressed LH signal. This encourages the testicles to continue producing intratesticular testosterone and maintain physical size. Low-dose hCG (500 to 1500 IU administered subcutaneously two to three times per week) is the standard protocol for preventing atrophy.
Adjunct Therapies for Fertility
Other adjunct therapies are used when fertility is the main concern. Selective Estrogen Receptor Modulators (SERMs), such as Clomiphene Citrate, block estrogen receptors in the brain, encouraging the pituitary to release its own LH and FSH. Maintaining the FSH signal through SERMs is necessary for men who wish to preserve sperm production during therapy.