Testicular cancer (TC) is the most common solid malignancy found in men of reproductive age. The testes are responsible for producing sperm and the primary male hormone, testosterone. The relationship between a TC diagnosis and low testosterone, medically termed hypogonadism, is complex. It is influenced by the tumor’s characteristics, the removal of the affected testis, and any additional treatments required. Low testosterone can be a consequence of the disease itself or a side effect of curative treatments, meaning the risk is determined by a combination of factors.
How Testicular Cancer Directly Affects Testosterone
Testosterone is produced by cells within the testes called Leydig cells. Even before treatment begins, the growing tumor can impair or displace these cells within the affected testicle. Some patients show evidence of Leydig cell dysfunction before the cancerous testis is removed, particularly those with larger tumors or higher levels of the tumor marker human chorionic gonadotropin (hCG). This dysfunction indicates a reduced baseline production capacity, even in the unaffected testis. When present at diagnosis, this condition increases the likelihood of developing chronic low testosterone after treatment.
Low Testosterone After Surgical Removal
The standard initial treatment for testicular cancer is a radical inguinal orchiectomy, the surgical removal of the entire cancerous testis. Because one testis is removed, the remaining healthy testis must increase its hormone production to compensate for the loss. In most cases, the remaining testicle is functional and successfully increases its output to maintain testosterone levels within the normal range. The body achieves this compensation through the pituitary gland, which releases more luteinizing hormone (LH) to stimulate the remaining Leydig cells to work harder.
However, if the remaining testicle had a pre-existing subclinical dysfunction, it may be unable to produce enough testosterone. The resulting state is often called compensated hypogonadism, where the remaining testis is working at maximum capacity, indicated by high LH levels, yet testosterone levels remain low or borderline. The removal of both testicles, known as bilateral orchiectomy, is rare but results in an immediate and permanent decline in testosterone. These men require lifelong Testosterone Replacement Therapy (TRT) to avoid severe deficiency symptoms.
Hormone Impact of Chemotherapy and Radiation
Beyond surgery, subsequent treatments like chemotherapy and radiation therapy can introduce long-term hormonal risks to the remaining testicle. Testosterone-producing Leydig cells are generally more resistant to radiation than sperm-producing cells, but high-dose radiation exposure can still cause damage. Chemotherapy, particularly regimens using platinum-based drugs like cisplatin, causes late-onset Leydig cell dysfunction. These toxic effects can damage the Leydig cells in the remaining testicle, even years after treatment has concluded.
Studies show that the risk of developing low testosterone increases with the cumulative dose of chemotherapy received. Survivors who received the highest doses of cisplatin-based chemotherapy have a significantly elevated risk of long-term hypogonadism compared to those who only had surgery. This damage can lead to a gradual decline in the remaining testis’s ability to respond to the pituitary’s signaling, resulting in persistent low testosterone. Because of this potential for delayed effects, long-term monitoring of hormone levels is an important aspect of survivorship care.
Recognizing and Treating Low Testosterone
Chronic low testosterone can manifest through physical and psychological symptoms that significantly impact a man’s quality of life. Common signs include persistent fatigue, a noticeable decrease in libido, and changes in mood such as increased depression or irritability. Other physical symptoms may involve erectile dysfunction, a loss of muscle mass, or a reduction in bone density, which can increase the risk of fractures over time. These symptoms often overlap with the general lingering effects of cancer treatment, making specific hormonal testing necessary.
Diagnosis is confirmed through a blood test, ideally conducted in the morning when testosterone levels are naturally at their peak. A low total testosterone level, typically below a threshold like 8 to 10 nanomoles per liter, combined with persistent symptoms, warrants a diagnosis of hypogonadism. The standard treatment is Testosterone Replacement Therapy (TRT). TRT can be administered through several methods:
- Intramuscular injections.
- Transdermal gels or patches.
- Pellets implanted under the skin.
The goal of TRT is to restore testosterone levels to a normal physiologic range and alleviate symptoms. Starting TRT requires consultation with a doctor, often an endocrinologist or urologist, who determines the appropriate dosage and delivery method. Regular blood monitoring is necessary to ensure the hormone levels remain safe and effective long term.