Roxanne Nelson, BSN, RN

June 02, 2017

CHICAGO — A substantial percentage of testicular cancer survivors have low testosterone levels, which in turn puts them at risk for a plethora of chronic health conditions, including hypertension, diabetes, erectile dysfunction, anxiety, and depression, according to findings from a large multicenter study.

For example, compared to survivors with normal testosterone levels, those with hypogonadism were about three times more likely to be taking medication for dyslipidemia (20% vs 6%; P < .001) and twice as likely to be treated for diabetes (6% vs 3%; P = .07).

They were also more likely to be undergoing treatment for hypertension (19% vs 11%; P = .01), anxiety or depression (15% vs 10%), and erectile dysfunction (20% vs 12%; P = .02).

"Testicular cancer occurs at a young age and is highly curable, and patients can expect to live for 40 years after their diagnosis, but there is a long-term risk for late complications from treatment," said lead study author Mohammad Issam Abu Zaid, MBBS, an assistant professor of medicine at the Indiana University School of Medicine in Indianapolis. He was presenting the findings here at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

"Clinical and genetic factors can increase the risk for hypogonadism, and providers should screen testicular cancer survivors for hypogonadism and treat those with symptoms," he said.

Late Events in Testicular Cancer Survivors

As previously reported by Medscape Medical News, survivors of testicular cancer face a worrisome risk of developing certain metabolic effects, such as hypertension, that are tied to platinum-based chemotherapy. Several European studies have shown that survivors have up to a sevenfold increased risk of developing cardiovascular disease.

Although it's been known for some time that low testosterone levels occur in a significant proportion of survivors of testicular cancer, the current study is one of the first to examine its relationship with long-term health complications in North American patients.

Research has also been limited, Dr Zaid noted, as far as taking into account genetic variations when evaluating the relationship between hypogonadism and adverse health outcomes. One European study, for example, reported that the prevalence of metabolic syndrome was higher among survivors of testicular cancer who were homozygous for a single-nucleotide polymorphism (SNP), rs523349 (V89L), in 5-α-reductase gene (SRD5A2). That study also found the prevalence of metabolic syndrome to be 67% in survivors with low testosterone levels who carried the variant genotype.

Clinical and Genetic Factors

In the current study, Dr Zaid and his colleagues evaluated the first 491 patients who are participants in the Platinum Study, which aims to be the largest study of survivors of testicular cancer worldwide. To date, more than 1600 survivors have been enrolled, and the study is still actively recruiting.

The focus of the findings that were presented was on the incidence of hypogonadism in this population, as well as predisposing factors.

All patients received chemotherapy and were younger than 55 years when they were diagnosed with cancer. The median age at clinical evaluation was 38 years.

The authors found that there were two SNPs in the sex-hormone-binding globulin (SHBG) locus, and survivors with two or more risk alleles for these 2 SNPs had a twofold increased risk for hypogonadism (odds ratio [OR] = 2.2; P = .12).

"This finding needs to be confirmed in larger studies, and we will do so in the next phase of the Platinum Study," said Dr Zaid.

Survivors with hypogonadism were also more likely to report adverse health outcomes. Roughly one third (35%) of those with hypogonadism reported having none or one adverse health outcome, compared to 49% with normal levels (P = .003).

Aside from the genetic profile, the authors identified other risk factors for developing hypogonadism. These included older age (OR = 1.4 per 10-year increase; P = .007) and a body mass index ≥25 kg/m2 (OR = 2.2; P = .003).

In contrast, vigorous physical activity appeared protective (OR = 0.6; P = .06). They type of chemotherapy regimen and socioeconomic factors did not appear to have any impact.

SHBG polymorphisms appear important in survivors of testicular cancer, but the study was underpowered to confirm an association, Dr Zaid commented.

"Our findings underscore the need for clinicians to assess testicular cancer for physical signs or symptoms of hypogonadism and to measure testosterone in those who do," he concluded.

Caution in Testosterone Testing

"This is an important study and sends a loud message to those us who take care of these patients," commented ASCO Expert Timothy D. Gilligan, MD. "We need to watch for it and ask our patients about symptoms."

He added that these are young men with many years of life ahead of them, and thus not treating hypogonadism could leave them with long-term associated health problems. "We hope this study will get the message out there more broadly, as I don't think many doctors are as aware of it as they might be."

However, Dr Gilligan cautioned that the fact that hypogonadism affects a significant number of patients does not mean that testing should be universal. Testosterone levels can vary widely in men, a fact that underscores the importance of recognizing symptoms.

"We should not be testing testosterone levels in all patients, but instead, looking for symptoms is the key," he said.

The study was funded by the National Institutes of Health. Dr Zaid has disclosed no relevant financial relationships. Several coauthors have relationships with industry, as noted in the abstract. Dr Gilligan has a relationship with Wellpoint.

2017 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract LBA10012, presented June 3, 2017.


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