On 2015 Apr 27, David Keller commented:

How much conflict of interest is acceptable for an author arguing for a controversial treatment?

The authors of the review paper “Testosterone and Cardiovascular Risk” [1] argue for the safety and therapeutic benefits of treating aging men with supplemental testosterone (which they call "T"), claiming health-enhancement beyond the simple correction of any T deficiency which may be present. Unfortunately, there is a lack of data from randomized, controlled trials to prove the safety or efficacy of widespread T supplementation for aging men. The authors use the existing observational data to argue that the benefits of routine testosterone treatments will far outweigh the faint signals of cardiovascular harm which have been detected. Their implied message is that aging men should not be denied the benefits of testosterone supplementation while we await the definitive large, randomized study confirming the observed associations of “T” with positive health outcomes.

Their arguments are reminiscent of those favoring routine post-menopausal estrogen replacement, prior to the Women's Health Initiative's disappointing results. Is it possible that the decline of sex hormone levels with age in both men and women is a natural process that should not be tampered with? Apparently not, according to the many pharmaceutical companies which market testosterone products, listed in the “Competing Interests” section of this paper.

For example, Auxilium, a pharmaceutical company specializing in trans-dermal testosterone products, paid doctors over $1.5 million last year [3]. The fifth-listed author of this paper received $82,445.33 in speaker’s fees, mostly for the Auxilium testosterone product Testim [4], at times giving talks at the rate of almost one per week. It is hard to imagine that any physician could remain unbiased by such payments. If he were to express doubts about the level of evidence supporting the safety or efficacy of administering testosterone for general health enhancement, he would risk losing risk a substantial chunk of income. Other authors of this paper accepted similar payments, including the lead author [2].

The degree of financial conflict of these authors causes me to question the pro-testosterone message of this paper. The pharmaceutical manufacturers could have funded a definitive randomized, controlled trial of testosterone with the money they have paid in speaker’s fees for “T” proponents to rehash observational data. Epidemiologists caution us that observational data may be used to generate hypotheses, but not to prove them; such data cannot establish the safety or efficacy of any intervention.

That is why reasonably cautious physicians should not prescribe testosterone to aging men for general health enhancement until a randomized, controlled trial proves the safety and benefits of doing so.

References

1: Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone Therapy and Cardiovascular Risk: Advances and Controversies. Mayo Clin Proc. 2014 Nov 1. Review. PubMed PMID: 25636998.

2: Open Payments CMS Website, searched for “Morgantaler” on 3/1/2015 https://openpaymentsdata.cms.gov/

3: Open Payments CMS Website, searched for “Auxilium” on 3/1/2015 https://openpaymentsdata.cms.gov/

4: Open Payments CMS Website, searched for “Mohit Khera” on 3/1/2015 https://openpaymentsdata.cms.gov/

On 2015 Apr 27, David Keller commented:

How much conflict of interest is acceptable for an author arguing for a controversial treatment?

The authors of the review paper “Testosterone and Cardiovascular Risk” [1] argue for the safety and therapeutic benefits of treating aging men with supplemental testosterone (which they call "T"), claiming health-enhancement beyond the simple correction of any T deficiency which may be present. Unfortunately, there is a lack of data from randomized, controlled trials to prove the safety or efficacy of widespread T supplementation for aging men. The authors use the existing observational data to argue that the benefits of routine testosterone treatments will far outweigh the faint signals of cardiovascular harm which have been detected. Their implied message is that aging men should not be denied the benefits of testosterone supplementation while we await the definitive large, randomized study confirming the observed associations of “T” with positive health outcomes.

Their arguments are reminiscent of those favoring routine post-menopausal estrogen replacement, prior to the Women's Health Initiative's disappointing results. Is it possible that the decline of sex hormone levels with age in both men and women is a natural process that should not be tampered with? Apparently not, according to the many pharmaceutical companies which market testosterone products, listed in the “Competing Interests” section of this paper.

For example, Auxilium, a pharmaceutical company specializing in trans-dermal testosterone products, paid doctors over $1.5 million last year [3]. The fifth-listed author of this paper received $82,445.33 in speaker’s fees, mostly for the Auxilium testosterone product Testim [4], at times giving talks at the rate of almost one per week. It is hard to imagine that any physician could remain unbiased by such payments. If he were to express doubts about the level of evidence supporting the safety or efficacy of administering testosterone for general health enhancement, he would risk losing risk a substantial chunk of income. Other authors of this paper accepted similar payments, including the lead author [2].

The degree of financial conflict of these authors causes me to question the pro-testosterone message of this paper. The pharmaceutical manufacturers could have funded a definitive randomized, controlled trial of testosterone with the money they have paid in speaker’s fees for “T” proponents to rehash observational data. Epidemiologists caution us that observational data may be used to generate hypotheses, but not to prove them; such data cannot establish the safety or efficacy of any intervention.

That is why reasonably cautious physicians should not prescribe testosterone to aging men for general health enhancement until a randomized, controlled trial proves the safety and benefits of doing so.

References

1: Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone Therapy and Cardiovascular Risk: Advances and Controversies. Mayo Clin Proc. 2014 Nov 1. Review. PubMed PMID: 25636998.

2: Open Payments CMS Website, searched for “Morgantaler” on 3/1/2015 https://openpaymentsdata.cms.gov/

3: Open Payments CMS Website, searched for “Auxilium” on 3/1/2015 https://openpaymentsdata.cms.gov/

4: Open Payments CMS Website, searched for “Mohit Khera” on 3/1/2015 https://openpaymentsdata.cms.gov/