The term “endogenous” refers to something produced and secreted within the body, while “exogenous” refers to something introduced from an external source.
“Endogenous testosterone” refers to the testosterone that the body produces and secretes on its own in the Leydig cells of the testes.
On the other hand, “exogenous testosterone” is administered into the body through various methods such as transdermal application, injection, or oral intake.
In this article, we will cover the production of endogenous testosterone, its related dynamics, the problem of testosterone deficiency, and its treatment methods.
Specifically, we will examine the risks, causes, and common treatments for testosterone deficiency, as well as long-term testosterone replacement therapy (TRT).
A Brief Explanation of Endogenous Testosterone
We have already explained how endogenous or exogenous testosterone functions in the human body.
Endogenous testosterone, produced in the Leydig cells of the testes, is part of a large network called the HPTA (Hypothalamic-Pituitary-Testicular Axis), where various hormones transmit signals to stimulate testosterone production.
Endogenous testosterone production is the main outcome, and the hormones involved in the operation of the HPTA play a vital role in facilitating this production.
Understanding this process is essential for comprehending testosterone secretion, causes of deficiency, treatment methods, PCT (Post Cycle Therapy), and the intricacies of the endocrine system.
The diagram shown above is a depiction of the HPTA.
The HPTA is an interconnected system that regulates the secretion of endogenous testosterone.
This system operates based on a genetically determined maximum testosterone level, which can be influenced by various factors such as age, diet, body composition, and lifestyle.
The HPTA detects and regulates excessive or deficient testosterone levels through a negative feedback mechanism.
When excess testosterone is detected, the body reduces its endogenous production; conversely, when levels are deficient, testosterone production is stimulated.
This process involves the hypothalamus releasing GnRH, which then stimulates LH and FSH, prompting the testes to produce testosterone.
The function of the HPTA can be suppressed by excess testosterone or estrogen.
An excess of these hormones signals the hypothalamus to stop producing signaling hormones, which ultimately decreases testosterone production.
This process can take several months until normal hormonal balance is restored.
Signs, Symptoms, and Risks of Testosterone Deficiency
In the past couple of years, awareness of testosterone deficiency and its associated risks has surged.
This is less a result of increased diagnoses and more a reflection of men becoming more aware of this condition, with andropause and hypogonadism being classified as the primary causes.
Andropause is the age-related decline in testosterone, while hypogonadism is a condition characterized by inadequate testosterone production from the testes.
Andropause is a form of hypogonadism caused by the Leydig cells in the testes becoming less sensitive to LH due to aging, which results in decreased testosterone production.
Symptoms of testosterone deficiency include sexual dysfunction, fatigue, loss of muscle mass, increased body fat, and mood swings, which can lead to health risks such as anemia, osteoporosis, diabetes, cardiovascular disease, and depression.
TRT (Testosterone Replacement Therapy) is especially beneficial for treating sarcopenia and is recommended for men with low testosterone levels.
Although andropause is sometimes still not recognized as a condition requiring treatment, it is gaining wider acceptance in the United States, Europe, and Asia.
To diagnose testosterone deficiency, it is crucial to rule out other potential causes and confirm the diagnosis with blood tests before starting treatment.
TRT should be considered a lifelong therapy, and its long-term safety has been well-established.
Common Treatments for Testosterone Deficiency
While treatments for testosterone deficiency can vary, they generally fall into two main categories.
1. Testosterone Replacement Therapy (TRT)
2. Attempting HPTA recovery using testosterone-stimulating compounds
1. Testosterone Replacement Therapy (TRT)
Testosterone Replacement Therapy (TRT) is the most common treatment for testosterone deficiency, primarily involving the administration of exogenous testosterone to maintain normal physiological levels.
While TRT is generally the first line of treatment, it is advisable to first attempt to restore endogenous testosterone production and HPTA function before committing to replacement therapy.
TRT is typically administered as a weekly 100mg injection of Testosterone Cypionate or Enanthate, although transdermal gels like AndroGel are also an option.
During treatment, it is essential to periodically monitor levels of testosterone, SHBG, estrogen, thyroid function, liver enzymes, cholesterol, and PSA through blood work.
To prevent testicular atrophy, a common side effect of TRT, it is crucial to periodically use HCG (Human Chorionic Gonadotropin).
HCG helps prevent testicular atrophy by stimulating the testes to produce testosterone.
A common protocol involves administering 500-1000 IU of HCG at 12-week intervals.
2. Attempting HPTA Recovery with Testosterone-Stimulating Compounds
Although this is a lesser-known and less frequently attempted treatment, it should be considered more often before committing a patient to lifelong TRT with exogenous testosterone.
However, many TRT patients experience andropause due to the aging of their Leydig cells, rather than from insufficient LH secretion from the pituitary gland.
In such cases, the only viable method to treat the testosterone deficiency is through the use of exogenous testosterone.
For example, a patient with suppressed LH and FSH production following anabolic steroid use may attempt to restore HPTA function with testosterone-stimulating compounds.
However, it’s possible this approach may not restore endogenous production to a level that is self-sustaining for life without further external support.
Therefore, an attempt is made to restore HPTA function using a combination therapy of Aromatase Inhibitors (AIs), Selective Estrogen Receptor Modulators (SERMs), and HCG. If this fails, TRT is then implemented.
SERMs, in particular, increase LH and FSH through their antagonistic action on estrogen receptors, which in turn stimulates the testes to produce more testosterone.
