Prostate cancer (PC) is the second most common cancer in men, involving the uncontrolled growth of cells in the small gland located beneath the bladder. Low testosterone, a condition known as hypogonadism, is characterized by abnormally diminished levels of the male sex hormone. The connection between these two conditions is often misunderstood, as the hormone that helps fuel prostate cancer growth is frequently the target of treatment, leading to an intentional state of low testosterone. Answering the question of whether the cancer itself causes this hormonal deficiency requires separating the underlying biology from the therapeutic interventions. The primary cause of low testosterone in men with prostate cancer is almost always the treatment administered to fight the malignancy.
The Role of Testosterone in Prostate Biology
Testosterone is an androgen, a class of hormones that supports male characteristics and stimulates the growth of prostate tissue, both normal and cancerous. The prostate gland converts circulating testosterone into a more potent androgen called dihydrotestosterone (DHT) via the enzyme 5-alpha reductase. This conversion creates a powerful local growth stimulant.
Both testosterone and DHT exert their effects by binding to specific proteins inside prostate cells known as androgen receptors. Once bound, the hormone-receptor complex travels to the cell nucleus, where it activates genes responsible for cell growth, division, and survival. This mechanism explains why prostate cancer cells remain dependent on androgens for their proliferation. Treating prostate cancer involves lowering androgen levels, effectively starving the cancer cells of their necessary fuel. Scientific models suggest that cancer cells only require a certain threshold level of androgen to be fully stimulated; removing it entirely halts the cancer’s progression.
Addressing the Core Question: Cancer Versus Treatment
Prostate cancer rarely causes a direct, primary decline in the body’s endogenous production of testosterone. A diagnosis of prostate cancer does not automatically mean a man will develop natural hypogonadism. The overwhelming majority of low testosterone cases in men with prostate cancer are iatrogenic, meaning they are a direct result of medical intervention.
Treatments are specifically designed to reduce testosterone to “castrate levels,” typically defined as a serum testosterone concentration below 50 nanograms per deciliter. This therapeutic goal is achieved through Androgen Deprivation Therapy (ADT), which is the cornerstone of treating advanced or recurrent disease. The resulting low testosterone is a symptom of successful treatment, not a symptom of the cancer itself.
Mechanisms of Treatment-Induced Testosterone Suppression
Androgen Deprivation Therapy employs several distinct methods to achieve castrate levels of testosterone, primarily by disrupting the communication axis between the brain and the testicles.
LHRH Agonists and Antagonists
The most common approach involves using luteinizing hormone-releasing hormone (LHRH) agonists, such as leuprolide or goserelin. These injectable medications initially cause a temporary surge in testosterone, known as a “flare,” before continuously overstimulating and desensitizing the pituitary gland’s receptors. The eventual result is a significant drop in the signal that tells the testicles to produce testosterone. A different class of drugs, LHRH antagonists, like degarelix, avoids this initial flare by immediately blocking the receptors on the pituitary gland. This results in a rapid and sustained drop in testosterone production. Both agonists and antagonists achieve the same therapeutic end: chemical castration, where testicular testosterone production ceases.
Other Androgen Suppression Agents
Other agents work downstream of production to suppress androgen action. Anti-androgens, such as bicalutamide or enzalutamide, work by physically blocking the androgen receptors on the cancer cells, preventing any remaining testosterone or DHT from binding and activating the cell growth signal. Furthermore, androgen synthesis inhibitors, like abiraterone, block the CYP17A1 enzyme, which is responsible for androgen production not only in the testicles but also in the adrenal glands and tumor tissue itself. In rare instances, surgical castration, or bilateral orchiectomy, is performed, which is the physical removal of the testicles, the main source of testosterone. This procedure achieves an immediate and permanent drop to castrate levels.
Managing Side Effects of Low Testosterone
The intended consequence of ADT is low testosterone, but this also leads to a range of uncomfortable and medically significant side effects. Common experiences include vasomotor symptoms, such as frequent and sudden hot flashes, and profound fatigue that often limits daily activities. These effects are directly linked to the absence of normal circulating androgen levels.
Low testosterone also has substantial metabolic consequences, including:
- Weight gain
- Increased body fat
- Higher risk of developing metabolic syndrome
- Higher risk of diabetes and cardiovascular issues
A serious long-term effect is the loss of bone mineral density, which can lead to osteoporosis and an increased risk of bone fractures. Patients are often advised to engage in regular resistance and aerobic exercise, along with dietary management, to mitigate muscle loss and metabolic changes. Specific interventions are often required to manage certain side effects, such as bisphosphonates or denosumab for bone health maintenance. Testosterone Replacement Therapy (TRT) is generally not administered during active ADT, as its purpose is to maintain a low-androgen environment to control the cancer. However, in select patients who have been successfully treated and remain cancer-free, cautious discussion about TRT may be considered in the survivorship setting to address persistent symptoms of hypogonadism.