Understanding TRT Through Education and Negative Feedback Mechanisms
At our clinic, we encourage education as shared responsibilities of TRT between your provider and yourself will help achieve the best outcomes and address issues before they arise.
Negative feedback is an important concept to understand, as TRT involves negative feedback consequences which explain the possible adverse effects.
Negative Feedback Mechanism
In TRT, negative feedback primarily affects the hypothalamic-pituitary-gonadal (HPG) axis, influencing both Sertoli and Leydig cells in the testes. The process works as follows:
When testosterone is administered externally, it increases the overall levels of circulating testosterone in the body.
The hypothalamus senses these elevated testosterone levels and reduces its secretion of Gonadotropin-releasing hormone (GnRH). This decrease in GnRH is a direct response to maintain hormonal balance and prevent excessive testosterone levels.
With less GnRH being produced, the pituitary gland subsequently lowers its secretion of Luteinising hormone (LH) and Follicle-stimulating hormone (FSH).
Leydig cells, which are responsible for producing testosterone in the testes, receive less stimulation from LH due to its reduced levels. Consequently, these cells decrease their natural production of testosterone.
Sertoli cells, which support sperm production and are stimulated by FSH, also receive less stimulation due to decreased FSH levels. This reduction can lead to diminished spermatogenesis and potential impacts on fertility.
Clinical Implications
The suppression of natural testosterone production and decreased spermatogenesis through this negative feedback loop are critical considerations in TRT. This mechanism can lead to several clinical issues including:
Reduced Fertility - Due to lower stimulation of Sertoli cells and reduced spermatogenesis.
Testicular Atrophy - Prolonged lack of LH and FSH stimulation can lead to shrinkage of testicular tissue.
Long-Term HPG Axis Suppression - Chronic use of exogenous testosterone can lead to prolonged suppression of the axis, potentially making recovery of natural testosterone production difficult if TRT is discontinued.
To manage these effects, it’s essential to monitor regularly through blood tests and semen analysis if fertility is a concern. Adjusting the dose of administered testosterone, or integrating other treatments like human chorionic gonadotrophin (hCG) or selective oestrogen receptor modulators (SERMs), may help mitigate some of the suppressive effects on the HPG axis and support more natural hormonal function.