Re: Testosterone deficiency

“I keep six honest serving men (They taught me all I knew)”
—Rudyard Kipling

The article by Dr Bebb[1] is based on a survey that, left unchallenged, may lead to overservicing and cost in­creases for our already overburdened medical care system, while its translation in the Vancouver Sun as “Nearly half of men over 45 affected by tes­tosterone deficiency”[2] may cause un­necessary anxieties. The article is based on the Hypogonadism in Men (HIM) study[3] and gives a misleading impression of the prevalence of hypo­gonadism in the general population. 

To minimize bias and ensure clinical relevance of any publication, we must ask six questions: 
1. Who published it? 
2. In what group of subjects was the study done?
3. Where was the study done? 
4. How was it done? 
5. Is it statistically significant?
6. Is it clinically important? 

The answer to “who?” is Thomas Mulligan and four co-authors.[3] Mulligan acknowledged having received funding from and having acted as a consultant for Solvay Pharmaceuticals, Inc., the manufacturer of AndroGel, a transdermal testosterone preparation. One of his co-authors (CM) was an employee of Solvay and the remaining three co-authors (MF, QZ, and AS) were employees of Covance Periapproval Services, Inc., which “conducted the study on behalf of Solvay Pharmaceuticals, Inc.” 

At this point we may be excused if we stop reading as there is significant potential for bias and we are unlikely to gain evidence from the article that we might usefully apply in practice. If we, nevertheless, do press on and ask in what group (sample) and where the study was done we find “2162 men… aged = 45 years visiting primary care practices in the United States… re­gardless of the reason for their visit,” a group of subjects not representative of the population targeted by Bebb in his article. 

Reading on we find that the answer to how hypogonadism was diagnosed is defined as a total testosterone (TT) value of 300 ng/dl (10 nmol/L) in “a blood sample between… 8 a.m. and noon,” a time interval that misses the peak testosterone values reported to occur in many men before 8 a.m.[3,4

The only question of statistical significance that can reasonably be ask­ed of this survey is how does it compare to the results of an observational cohort study in a population-based random sample of men in the Massachusetts Male Aging Study (MMAS)[4] conducted in 2004. It re­ported a prevalence rate of 6% using a cutoff for TT of 400 ng/dl (13.3 nmol/L). Had it used the same cut-off value as in the Mulligan survey the prevalence would have been lower yet, estimated at approximately 1 in 20, not “Nearly half of men age 45…” 

As to clinical importance, not only does the article give a misleading impression of the prevalence of hypogonadism even when low testosterone levels are found, one has to ask whether replacement is indicated, as gradually declining testosterone levels may be part of the normal aging process. As a point of interest the cost of AndroGel is between $5.30 and $12 per day in Canada, depending on the dose used.
—Gerald Tevaarwerk, MD


1. Bebb R. Testosterone deficiency: Practical guidelines for diagnosis and treatment. BCMJ 2011;53:474-479.
2. Fayerman P. Nearly half of men over age 45 affected by testosterone deficiency. The Vancouver Sun. 3 November 2011. Accessed 23 December 2011. www
3. Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: The HIM study. Int J Clin Pract 2006;60:762-769.
4. Araujo AB, O’Donnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: Estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2004;89:5920-5926.

Gerald J.M. Tevaarwerk, MD, FRCPC. Re: Testosterone deficiency. BCMJ, Vol. 54, No. 1, January, February, 2012, Page(s) 13-14 - Letters.

Above is the information needed to cite this article in your paper or presentation. The International Committee of Medical Journal Editors (ICMJE) recommends the following citation style, which is the now nearly universally accepted citation style for scientific papers:
Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected patients. N Engl J Med. 2002;347:284-7.

About the ICMJE and citation styles

The ICMJE is small group of editors of general medical journals who first met informally in Vancouver, British Columbia, in 1978 to establish guidelines for the format of manuscripts submitted to their journals. The group became known as the Vancouver Group. Its requirements for manuscripts, including formats for bibliographic references developed by the U.S. National Library of Medicine (NLM), were first published in 1979. The Vancouver Group expanded and evolved into the International Committee of Medical Journal Editors (ICMJE), which meets annually. The ICMJE created the Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals to help authors and editors create and distribute accurate, clear, easily accessible reports of biomedical studies.

An alternate version of ICMJE style is to additionally list the month an issue number, but since most journals use continuous pagination, the shorter form provides sufficient information to locate the reference. The NLM now lists all authors.

BCMJ standard citation style is a slight modification of the ICMJE/NLM style, as follows:

  • Only the first three authors are listed, followed by "et al."
  • There is no period after the journal name.
  • Page numbers are not abbreviated.

For more information on the ICMJE Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals, visit

BCMJ Guidelines for Authors

Leave a Reply