Survivors of Testicular Cancer At Risk Due to Low Testosterone Levels

Mohammad Issam Abu Zaid, MBBS

Chronic health issues, including high blood pressure, diabetes, erectile dysfunction, anxiety, or depression were noted in nearly 40% of testicular cancer survivors with low testosterone levels compared with survivors who had normal levels of testosterone, according to findings from a study that were released at the 2017 ASCO Annual Meeting.

The risk of hypogonadism (HG), defined as serum testosterone ≤ 3.0 ng/mL or the use of testosterone replacement therapy, can be exacerbated by older age, genetic factors, and being overweight or obese, the study showed.

Investigators said the study illustrates the need to understand the long-term health risks faced by survivors of testicular cancer, the most common cancer in young men. The cancer has a 5-year survival rate of 95%, and survivors may experience chronic health problems for an extended period of time.

“Because testicular cancer occurs at a young age and is highly curable, many survivors may live upwards of 5 decades,” said lead study author Mohammad Issam Abu Zaid, MBBS, an assistant professor of medicine at the Indiana University School of Medicine in Indianapolis, Indiana, in a statement. He also discussed the results in a presscast on Friday.

Patients with testicular cancer can have HG at the time of their diagnosis, or it can develop during their disease and treatment. Men who did not have testicular cancer also experience low testosterone and are at risk for developing these conditions, typically when they are 60 years or older; however, the difference is that patients with testicular cancer are quite young when they are diagnosed.

The goal of the study was to identify clinical and genetic factors that may help treating oncologists predict which survivors are at an increased risk for developing HG. The analysis comes from the first 491 survivors enrolled in the ongoing Platinum Study, which aims to be the largest North American study of testicular cancer survivors, with over 1600 survivors already enrolled.

To be eligible for this study, survivors must have been younger than 55 years at the time of their diagnosis and have been treated with platinum-based chemotherapy after 1990. The participants underwent physical examinations and genetic analyses, had their testosterone levels measured, and completed questionnaires concerning comorbidities, medications, and health behaviors.

“Some of these health problems have been previously linked to low testosterone levels among men in the general population and in a few studies of testicular cancer survivors, but this study is one of the most comprehensive to date—we are looking at 15 different health conditions,” said Abu Zaid. For their long-term health, testicular cancer survivors with low testosterone were more likely to take medication for high cholesterol, high blood pressure, erectile dysfunction, and anxiety or depression.

Of the 491 survivors considered for the chronic health analysis, the average age was 38 years, and 38% had a low testosterone level or were on testosterone replacement therapy. Age was determined to be a risk factor for developing HG; as survivors who were 18 to 39 years had a 29.7% risk for developing HG, those who were 40 to 49 years had a 45.3% risk, and those 50 years or older had a 56.1% risk.

In terms of how weight contributes to the risk of developing HG, survivors designated as normal weight had a 25.8% risk, survivors who were overweight had a risk of 41.9%, and those who were obese had a 44.3% risk for HG.

The investigators also found a genetic abnormality in that the sex-hormone-binding globulin (SHBG) gene seems to predispose some men to having low testosterone, although it was noted that this would need confirmation in a larger study. For patients who had no risk alleles on the SHBG gene, their risk for HG was 28.6%, those with 1 risk allele had a risk of 36.1%, and those with 2 or more risk alleles had a risk of 41.2%.

Survivors who engaged in regular exercise and maintained a normal weight tended to have higher levels of testosterone, and so Abu Zaid encouraged survivors to strive for a healthy weight and lifestyle. No correlation was found for the type of chemotherapy regimen or for socioeconomic factors.

Abu Zaid noted there would be an increase in quality of life for survivors with more vigilance from their treating physicians. “Our findings underscore the need for clinicians to assess testicular cancer survivors for physical signs or symptoms of HG and to measure testosterone levels in those who do,” he said.

The matter is complicated by a lack of standardization and recommendations for testing patients and survivors for HG. “It is not clearly defined; every study uses a different definition for what they consider a low testosterone level,” commented Abu Zaid. This leads to the risk of overtreating as well as not catching low testosterone, since the same testosterone level can mean different things to different clinicians. Overtreatment could even lead to additional cardiac risk factors, according to Abu Zaid.

As the next steps for this research, the investigators plan to follow this group of survivors in the Platinum Study and expand the analysis to the entire study cohort, including further examining their testosterone levels. They also plan to enroll a group of survivors who were cured with surgery only, in order to determine the effects of surgery versus chemotherapy on the development of adverse events.

Reference:

Abu Zaid MI, Menendez AG, El-Charif O, et al: The Platinum Study Group. Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: a multi-center study of North American testicular cancer survivors (TCS).J Clin Oncol.2017;35 (suppl; LBA10012).