Prostate cancer (PCa) is the second most common cancer in men. Its relationship with the primary male sex hormone, testosterone (T), is often misunderstood. Testosterone is an androgen that regulates male characteristics and plays a role in functions like muscle mass and bone density. While PCa growth is influenced by T, the tumor itself usually does not significantly change the body’s overall T levels. The most profound shifts in a patient’s hormone profile result from the intentional suppression of T used as cancer treatment.
Testosterone as a Driver of Prostate Cancer Growth
Most prostate cancer cells require androgens, such as testosterone and dihydrotestosterone (DHT), to survive and multiply. These hormones attach to the androgen receptor (AR) protein inside the cancer cells. When the androgen binds to the AR, the complex moves into the cell’s nucleus, activating genes that promote cell growth and division.
This biological dependency means testosterone acts as a growth promoter for existing prostate tumors. Testosterone does not initiate prostate cancer formation, but it accelerates the proliferation of cells already present. This dependency on androgen signaling is the fundamental principle guiding treatment strategies.
The relationship between circulating T levels and tumor growth is often described by the “saturation model.” This theory suggests that once T levels reach a certain threshold, the androgen receptors become saturated. Adding more testosterone beyond this point does not necessarily cause additional cancer growth. Men with very low testosterone levels, below this saturation point, may have a reduced risk of developing PCa, but if cancer does develop, it may be more aggressive.
Does the Tumor Itself Alter Testosterone Levels?
In the majority of cases, localized or early-stage prostate cancer does not cause a measurable change in a patient’s circulating testosterone levels. The cancer is typically confined to the prostate gland and does not interfere with the body’s primary hormone-producing organs, such as the testes. Consequently, a man’s serum testosterone level often remains within a normal range at the time of diagnosis.
Some studies have noted a correlation between lower baseline testosterone and more aggressive prostate cancer, such as those with a higher Gleason grade. This suggests the tumor is not actively elevating systemic T levels to fuel its growth.
In extremely advanced or metastatic disease, the overall burden of cancer and associated chronic illness may sometimes contribute to a general state of hypogonadism. However, these low T levels reflect a broader systemic decline rather than a direct action of the tumor on hormone regulation centers. Therapeutic intervention designed to suppress the hormone remains the overwhelming factor responsible for low T levels in PCa patients.
Androgen Deprivation Therapy and Its Goal
The strongest link between prostate cancer and low testosterone is Androgen Deprivation Therapy (ADT), also called hormone therapy. The goal of ADT is to reduce androgens to castrate levels, typically below 50 nanograms per deciliter. This profound reduction aims to “starve” androgen-dependent cancer cells of necessary growth signals.
Methods of Androgen Deprivation
One common method uses Luteinizing Hormone-Releasing Hormone (LHRH) agonists, such as leuprolide or goserelin. These synthetic hormones are administered via injection or implant. They initially cause a temporary surge in T production, known as a “flare,” before shutting down the signal for T production in the testes. LHRH antagonists, like degarelix, work by directly blocking pituitary receptors, achieving rapid T suppression without the initial flare.
Surgical castration, or orchiectomy, is another method involving the removal of the testicles, the body’s main source of testosterone. This procedure achieves an immediate and permanent reduction in testosterone levels equivalent to medical castration. Regardless of the method, suppressing testicular T causes most prostate cancer cells to stop proliferating or undergo programmed cell death.
Although the testes produce the majority of testosterone, other sites like the adrenal glands and cancer cells can produce small amounts of androgens. Newer-generation therapies, such as abiraterone, block the CYP17 enzyme, preventing androgen synthesis in these secondary sites. These advanced approaches ensure a more comprehensive blockade of all androgen signals, enhancing treatment effectiveness.
Addressing the Effects of Treatment-Induced Low Testosterone
The state of hypogonadism induced by ADT impacts a patient’s quality of life. The loss of testosterone often leads to hot flashes, decreased libido, and erectile dysfunction. These effects occur because testosterone regulates body temperature and sexual desire.
Metabolic and physical changes are also common. Patients often experience a loss of muscle mass and strength, coupled with an increase in body fat, particularly around the abdomen. This change in body composition can lead to fatigue and increase the risk of developing metabolic issues, including type 2 diabetes and cardiovascular disease.
Long-term ADT causes the gradual loss of bone mineral density, which can lead to osteopenia and osteoporosis, increasing the risk of bone fractures. Low testosterone can also affect mental health, contributing to mood changes, depression, and cognitive impairment. Management strategies to mitigate these effects include regular resistance and aerobic exercise, alongside dietary adjustments to manage weight and metabolic risk factors.