Testosterone Replacement Therapy (TRT) is a common medical treatment used to manage the symptoms of low testosterone. This therapy introduces external testosterone to restore hormone levels and improve quality of life. However, a frequent concern for men starting TRT is the potential for testicular atrophy, or shrinkage of the testes. This physical change is a well-documented side effect resulting from how the body regulates its hormone production.
How TRT Causes Testicular Atrophy
The body maintains a careful balance of hormones through the Hypothalamic-Pituitary-Testicular Axis (HPTA). When testosterone levels are adequate, the hypothalamus and pituitary gland reduce their signaling to the testes. Introducing external testosterone through TRT signals the body that sufficient testosterone is already present.
This external signal causes the pituitary gland to significantly reduce the release of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). LH stimulates the testes’ Leydig cells to produce testosterone, while FSH supports the Sertoli cells for sperm production. With LH and FSH suppressed, the testes lose their primary signal for function, leading to disuse.
The testes are composed largely of sperm-producing tissue. When the signals to produce sperm and internal testosterone are absent, this tissue becomes less active. This lack of stimulation and reduced function causes the testes to decrease in size, a process called atrophy. The shrinkage is a predictable physiological response to HPTA suppression.
The Expected Physical Change
The degree of testicular shrinkage experienced on TRT varies, but some volume reduction is expected. This atrophy is measured as a decrease in testicular volume, often assessed using an orchidometer. Studies indicate that men on TRT typically see a volume decrease ranging from approximately 15% to 25% after several months of therapy.
The reduction can be more pronounced with higher dosages or prolonged therapy, though complete cessation of size is rare. Shrinkage usually begins within the first few weeks or months of starting TRT. The maximum effect is often observed within three to four months of continuous treatment, and the testes may also become noticeably softer.
The atrophy directly reflects the decrease in sperm production, as 80% of the testicular mass is comprised of seminiferous tubules where sperm is made. This effect is generally reversible; if TRT is discontinued, the HPTA axis can reactivate, and testicular size may return to its normal volume. However, recovery is not immediate and can take several months to a year or more for full restoration of size and function.
Options for Mitigation
Specific medical strategies are available to minimize or prevent testicular atrophy while on TRT by counteracting HPTA suppression. The most common and effective method involves the concurrent use of Human Chorionic Gonadotropin (hCG). hCG is a medication that closely mimics the action of Luteinizing Hormone (LH) in the body.
By acting as a stand-in for LH, hCG directly stimulates the Leydig cells, signaling them to continue producing internal testosterone. This stimulation helps maintain intratesticular testosterone levels, supporting testicular volume and function, including sperm production. Common dosing protocols involve administering 500 to 1,500 International Units (IU) subcutaneously two to three times per week alongside the TRT regimen.
Another strategy involves Selective Estrogen Receptor Modulators (SERMs), such as clomiphene citrate. SERMs block estrogen receptors primarily in the hypothalamus, tricking the brain into thinking estrogen levels are low. In response, the brain increases its output of LH and FSH, which stimulates the testes. Clomiphene citrate is sometimes used to help maintain testicular size, though its role is more complex when used alongside exogenous testosterone.
These mitigation treatments are designed to prevent the physical reduction in size by maintaining testicular activity despite external testosterone supply. The choice and dosage of the mitigation strategy are highly individualized, depending on patient goals, such as preserving current or future fertility. Regular monitoring of hormone levels and testicular size is important to ensure the combined therapy achieves the desired outcome.