Abstract
An international expert consensus conference regarding testosterone deficiency (TD) (also known as hypogonadism) and its treatment was held on 1 October 2015, in Prague, Czech Republic. The impetus for this meeting was to address several key scientific issues that have been misunderstood or distorted during the recent intense media attention to this topic. Eighteen experts from 11 countries participated, from the disciplines of urology, endocrinology, andrology, diabetology, and basic science research. The goal was to identify scientific concepts for which there was broad agreement. It was noted that recent public controversies regarding testosterone therapy have been anchored by two retrospective studies reporting increased cardiovascular (CV) risks. Both these studies contained major flaws, and are contradicted by a large body of evidence suggesting CV benefits with testosterone therapy. Other topics discussed included the negative impact of TD on male health; the questionable validity of restrictions on treatment based on age-specific cut-offs, presence of identified underlying conditions, or application of rigid biochemical thresholds; and the lack of evidence regarding prostate cancer risks. Final consensus statements (resolutions) are under development. It is hoped these will serve as a scientific foundation for further discussion, and will thereby reduce misinformation regarding TD and its treatment.
An international expert consensus conference on testosterone deficiency and its treatment was held on 1 October 2015, in Prague, Czech Republic, to address several of the key issues in the field, many of which have become highly controversial. The purpose of this consensus conference was to provide clear guidance to clinicians and the public based on review of the underlying science.
The meeting was organized by the International Society for the Study of the Aging Male, and the Institute of Pharmaceutical Sciences, King’s College London. The chairman was Professor Abraham Morgentaler (USA) and the vice-chairman was Professor Michael Zitzmann (Germany). Participants included 18 experts from 11 countries on four continents. This conference brought together international experts in various disciplines related to testosterone deficiency (TD), including endocrinology, andrology, urology, diabetology and basic science research. Representatives from regulatory agencies from the USA and the European Union were invited to attend: a representative from the European Medicines Agency did attend. The conference was held without participation or financial support from any pharmaceutical company.
The impetus for this meeting arose from the considerable controversy in the field of TD and testosterone therapy (T therapy) that has developed over the last 2 years. That controversy was precipitated by a number of events, including reactions to the rise in testosterone prescriptions [Citation1], two reports of increased cardiovascular (CV) risks [Citation2,Citation3] and regulatory actions to limit the use of T therapy [Citation4]. To experienced scientists and clinicians within the field, the strong negative public response to these reports and actions was not justified by the evidence. In particular, both studies reporting increased CV risk contained major flaws that prevented any conclusion of increased risk, and were contradicted by a substantial body of literature suggesting possible benefits of T therapy for CV risks [Citation5]. Yet, the false impression of increased CV risk has adversely impacted patient care, physician practices and scientific discourse.
Assertions regarding increased CV risk with T therapy have anchored a number of critical commentaries regarding TD and its treatment. These include: the decline in testosterone should be regarded as normal aging; the symptoms are not important enough to merit treatment; this is a false condition created by the pharmaceutical industry; the benefits of treatment are unproven; only very few men merit treatment based on rare conditions such as pituitary tumors or absent testicles; it should not be used in men older than 65 years; testosterone causes prostate cancer; testosterone increases the risk of CV disease and death.
The misinformation and distortions created by these various comments have created considerable confusion and uncertainty for the public and for clinicians. This international expert consensus conference was organized specifically to respond to this lack of clarity by establishing elemental evidence-based concepts as touchstones for academic, clinical and public discussions on this important issue.
One of the initial topics discussed was terminology. The panel discussed and agreed to use the term TD in place of the older term hypogonadism or late-onset hypogonadism and adopted the term T therapy in place of testosterone replacement therapy. The use of T therapy implies the medical use of testosterone treatment for men with the clinical condition of TD.
Key topics discussed included:
the negative impact of TD on male health;
the global impact of TD;
the validity of age-specific restrictions on the use of T therapy in older men;
whether treatment should be restricted only to men with identified underlying etiologies;
validity of concerns regarding prostate cancer and CV risks;
the application of rigid biochemical thresholds for the diagnosis of TD and
future research to investigate possible cardiometabolic benefits of T therapy in men with TD.
The expert panel limited its discussion to the medical use of T therapy for men with TD, and did not address the abuse of steroids by athletes and those that pursue body-enhancement.
The proceedings of this conference and the final resolutions will be reported at a later date with a more detailed discussion and references.
Declaration of interest
There are no conflicts of interest to declare for Anthony Fox, Michael Zitzmann, or AM Traish. Dr. Morgentaler has the following conflicts to declare: Consulting, scientific advisory boards, research grants, or lecture honoraria from AbbVie, Antares, Bayer, Clarus, Eli Lilly, Endo, Pfizer.
References
- Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med 2013;173:1465–6
- Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013;310:1829–32
- Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 2014;9:e85805
- Nguyen CP, Hirsch MS, Moeny D, et al. Testosterone and “age-related hypogonadism” – FDA concerns. N Engl J Med 2015;373:689–91
- Morgentaler A, Miner MM, Caliber M, et al. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc 2015;90:224–51