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Low testosterone levels prevalent among testicular cancer survivors
CHICAGO – Nearly 40% of testicular cancer survivors had low testosterone levels, known as hypogonadism, according to a study presented at the ASCO Annual Meeting.
Further, survivors with low testosterone levels appeared more likely to have a range of chronic health problems, including high blood pressure, diabetes, erectile dysfunction, night sweats, fatigue, anxiety or depression.
“Testicular cancer is the most common cancer among young men, but 95% of all testicular cancer patients are cured of their disease thanks to cisplatin-based chemotherapy that was first discovered in 1974,” Mohammad Issam Abu Zaid, MBBS, assistant professor of medicine at Indiana University School of Medicine, said during a press conference. “Today, testicular cancer survivors can expect to live for more than 40 years from the time of their diagnosis. However, they are at risk for other health problems that may be related to their cancer treatments, including complications from chemotherapy.”
Men with testicular cancer can present with low testosterone at the time of diagnosis, or can experience a decrease in testosterone as a side effect of surgery or chemotherapy.
Researchers evaluated the relationship between low testosterone and long-term health complications in 491 North American men enrolled in The Platinum Study, which enrolled more than 1,600 survivors of testicular cancer.
All patients received diagnoses at age younger than 55 years and all underwent chemotherapy. Median age at clinical evaluation was 38 years (range, 19-68).
Researchers defined hypogonadism as serum testosterone at or less than 3 ng/mL or the use of testosterone replacement therapy.
At evaluation, 38.5% of patients had a low testosterone level or received testosterone replacement therapy. Older age (OR per 10-year increase = 1.4; P = .007) and higher BMI (25 or more, OR = 2.2; P = .003) appeared associated with lower testosterone.
Researchers also found a genetic abnormality in the sex hormone binding globulin gene that appears to predispose some men to low testosterone, but noted the finding needs to be confirmed in larger studies.
Survivors participating in vigorous physical activity appeared to have higher levels of testosterone, although this did not reach statistical significance (OR = 0.6).
Compared with survivors who had normal testosterone, a greater proportion of those with low testosterone took medicine for high cholesterol (20% vs. 6%), high blood pressure (19% vs. 11%), erectile dysfunction (20% vs. 12%), diabetes (6% vs. 3%), or anxiety or depression (15% vs. 10%).
“There will always be potential for complications from curative platinum chemotherapy,” Abu Zaid said. “Mitigating approaches include weight control, exercise and monitoring blood pressure and cholesterol levels. Recognizing and treating symptomatic hypogonadism can improve quality of life and reduce adverse outcomes.”
Increasing testosterone levels can help prevent some of the adverse effects associated with chemotherapy in young men treated for testicular cancer, but accurately assessing those levels is challenging, according to Abu Zaid.
“It’s a very muddy field that is not clearly defined,” he said. “Every study uses a different definition for what they consider a low testosterone level. If it is as low as 2 or 3, you probably will treat more patients than necessary. You do not want to treat somebody who does not have symptoms. I would hypothesize that testosterone replenishment would actually help young men. However, in elderly men studies show that increased testosterone levels can carry an increase in cardiac disease. It’s a completely different population.” – by Chuck Gormley
Reference:
Abu Zaid, et al. Abstract LBA10012. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosures: The NCI funded this study. Abu Zaid reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ financial disclosures.
Perspective
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In some respects, we did not recognize how prevalent hypogonadism is in testicular cancer survivors. The magnitude of low levels of testosterone in testicular cancer survivors was not realized until this study. Today, there is greater focus on survivorship in testicular cancer survivors, and this study highlights one more area we must pay attention to.
We had known there is a higher risk for heart disease in testicular cancer survivors who received chemotherapy. These findings provide us with another metric we should follow and suggest we should intervene by providing testosterone replacement.
One of the realities is that the range of normal testosterone levels is broad — between 220 and 800. Most men have a level in the 400 to 500 range. If it is at 200 and the patient is tired, it may be beneficial in referring the patient to an endocrinologist for evaluation
This study also is practice changing for internal medicine physicians, as many of these patients are referred back to their internists for continued care and are not followed by an oncologist.
Perspective
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This sends a loud message to those of us who take care of patients with testicular cancer who we need to watch for hypogonadism. We should conduct blood tests to test testosterone and other hormone levels in patients for whom we are worried might have hypogonadism. These are young patients with many years of life; often, many may have decades of suffering if hypogonadism goes undetected. I have seen a surprising number of patients who have had symptoms of hypogonadism, and I hope this study gets that message out there more broadly. Those of us who see a lot of this have been trying to teach fellows to watch for it already, but I do not think it is widely understood among oncologists who take care of these patients. Even if the number of patients affected is lower than 38%, that is still a high number of patients.
We need to be cautious and not think this means we should test testosterone levels in all patients, which is a risky thing to do. The definition of normal testosterone is very fuzzy. There is a wide range of normal, meaning what is normal for me may not be normal for another man. That’s why looking for symptoms is what guides this work.
From an endocrinology level, it is well documented that if you take a man and lower his testosterone level, he develops insulin resistance almost immediately. In terms of hypogonadism, too low testosterone is bad, but too high is also bad. The problem is we have a hard time establishing exactly what normal is. It is important that symptoms dictate testing. We are trying to get men to the right level, but giving them too much hurts them, and if they have too little it hurts them. We want to get them to a normal zone, but that is easier said than done.