Testosterone deficiency – data available from RHYME study in 2013

April 2011

The natural history of testosterone deficiency in men and outcomes associated with testosterone therapy: a multi-national patient registry. RC Rosen, AB Araujo, AB O'Donnell, JB McKinlay. New England Research Institutes, Watertown, MA, USA.

Despite testosterone (T) therapy being used to treat testosterone deficiency for approximately 70 years, no large scale, long term study has fully addressed the natural history of testosterone deficiency or the long term safety of testosterone treatment.1

In May 2009 it was announced that a Registry of Hypogonadism in Men (RHYME) would be established to maintain a multi-national (European) data-set of around 1,000 patients (aged 18 and over), drawn from some 20 clinical sites, diagnosed with late-onset hypogonadism (HG), hypogonadism secondary to medical illness, and classical hypogonadism (eg, Klinefelter's syndrome).1,2 Men registered on RHYME are not required to undergo T treatment for diagnosed HG.

The primary goal of RHYME is to examine the association between testosterone therapy and prostate health (eg, rate of positive prostate biopsies (primary endpoint), incidence of prostate cancer and Benign Prostatic Hyperplasia) of men with HG that some believe is put at risk by testosterone therapy. Other goals include the assessment of HG symptoms and general health outcomes in men with HG treated with T, as well as their clinical course compared to those men with HG who are not treated.

The Registry will draw on observational studies at baseline, three months, and then yearly intervals (for a minimum of two years). Data collected will include a full medical history, a physical examination, blood sampling, and patient questionnaires.

What is known

Studies have reported that prevalence estimates of low testosterone range between 20-30 percent in men over the age of 60.3-7 Studies also suggest that hypogonadism in men is often under-diagnosed and under-treated because the symptoms can be easily attributed to aging or other medical causes.

The effects of hypogonadism can have a significant impact on quality of life and cause men to experience diminished sexual desire and erection quality/frequency, changes in mood and decreased cognitive function, decreased lean body mass and muscle volume/strength, increased visceral fat, and decreased bone mineral density.

Lack of knowledge about androgen effects in normal health and aging, concerns about safety and potential adverse effects of T treatment, as well as a lack of familiarity with current treatment options have been cited frequently as important barriers to effective management of the disorder. Scientific concerns have been raised regarding the long-term benefits and risks of testosterone therapy.8, 9

What this study will add

Researchers expect the data will confirm and extend the information about the safety of testosterone therapy, serve as a resource for ancillary studies of genetic or other biomarkers for testosterone deficiency in men, and provide a network of investigators and patients for future cost-efficient clinical trials. The primary endpoint for the study is the rate of positive prostate biopsy, with other measures of prostate health (eg, Benign Prostatic Hyperplasia) and sexual function (eg, Erectile Dysfunction) being studied as secondary endpoints.

Final study results are expected in 2013. By 7th January 2011, 612 patients had been recruited onto the Registry at 23 sites.


  • The natural history of testosterone deficiency in men and outcomes associated with testosterone therapy: a multi-national patient registry. RC Rosen, AB Araujo, AB O'Donnell, JB McKinlay. New England Research Institutes, Watertown, MA, USA. Return to content
  • https://clinicaltrials.gov/ct2/show/study/NCT00858650. Accessed May 2022. Return to content
  • Vermeulen A, Rubens R, Verdonck L. Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab. Apr 1972;34(4):730−735 Return to content
  • Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. Feb 2002;87(2):589−598. Return to content
  • Morley JE, Kaiser FE, Perry HM, 3rd, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. Apr 1997;46(4):410−413. Return to content
  • Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum Biol. Dec 1981;53(4):499−511. Return to content
  • Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. Oct 2005;26(6):833−876. Return to content
  • Liverman CT, Blazer DG, eds. Testosterone and aging: Clinical research directions.Washington D.C.: The National Academies Press; 2004. Return to content
  • Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. Jun 2006;91(6):1995−2010. Return to content