Hormone sensitive metastatic prostate cancer is treated with androgen deprivation therapy, typically with gonadotropin releasing hormone analogues, which essentially turn off the pituitary release of luteinizing hormone through sustained stimulation (as opposed to pulsatile release, which is physiological). This results in chemical castration.
The issue assumes relevance when you consider the practice of testosterone replacement therapy (TRT). In recent years, TRT has become popular among primary care physicians, as a sort of panacea for fatigue, lassitude and muscle wasting, particularly in elderly subjects. The FDA recently mandated that preparations for TRT explicitly carry a warning against a higher risk of myocardial infarction and stroke in users. Nevertheless, a subset of subjects with low serum testosterone genuinely benefit from TRT, particularly when associated with diminished libido, or loss of morning or nocturnal erection despite being otherwise healthy, a condition known as adult onset hypogonadism. Such subjects have low total and free serum testosterone and normal LH levels.
When such subjects are elderly, as they often are, it is logical to ask whether such TRT increases the risk of causing hormone sensitive cancers in the future. In fact, TRT can increase the likelihood of developing breast cancer in those who have another risk factor such as BRCA1 or 2 or Cowden's syndrome. However, such cancers are very uncommon. A much more relevant concern is whether TRT stores up a future risk of prostate cancer.
In a disease which, when metastasised, is treated with surgical, or more commonly, chemical castration, it therefore came as a surprise to learn from RCTs that firstly, low testosterone levels were associated with a higher risk of prostate cancer. Secondly, subjects with adult onset hypogonadism had more advanced prostate cancer at diagnosis by stage, grade and volume. Thirdly, TRT was not associated with a higher risk of prostate cancer in any RCT.
Reference
Mayo Clinic Proceedings, Vol. 91, Issue 7, p908–926
The issue assumes relevance when you consider the practice of testosterone replacement therapy (TRT). In recent years, TRT has become popular among primary care physicians, as a sort of panacea for fatigue, lassitude and muscle wasting, particularly in elderly subjects. The FDA recently mandated that preparations for TRT explicitly carry a warning against a higher risk of myocardial infarction and stroke in users. Nevertheless, a subset of subjects with low serum testosterone genuinely benefit from TRT, particularly when associated with diminished libido, or loss of morning or nocturnal erection despite being otherwise healthy, a condition known as adult onset hypogonadism. Such subjects have low total and free serum testosterone and normal LH levels.
When such subjects are elderly, as they often are, it is logical to ask whether such TRT increases the risk of causing hormone sensitive cancers in the future. In fact, TRT can increase the likelihood of developing breast cancer in those who have another risk factor such as BRCA1 or 2 or Cowden's syndrome. However, such cancers are very uncommon. A much more relevant concern is whether TRT stores up a future risk of prostate cancer.
In a disease which, when metastasised, is treated with surgical, or more commonly, chemical castration, it therefore came as a surprise to learn from RCTs that firstly, low testosterone levels were associated with a higher risk of prostate cancer. Secondly, subjects with adult onset hypogonadism had more advanced prostate cancer at diagnosis by stage, grade and volume. Thirdly, TRT was not associated with a higher risk of prostate cancer in any RCT.
Reference
Mayo Clinic Proceedings, Vol. 91, Issue 7, p908–926
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