Effect of Testosterone Replacement Therapy on Prostate Tissue in Men With Late-Onset Hypogonadism

Marks, Leonard S.; Mazer, Norman A.; Mostaghel, Elahe A.; Hess, David L.; Dorey, Frederick J.; Epstein, Jonathan I.; Veltri, Robert W.; Makarov, Danil V.; Partin, Alan W.; Bostwick, David G.; Macairan, Maria Luz; Nelson, Peter S.

doi:10.1001/jama.296.19.2351

Cited by 368 publications

(261 citation statements)

References 64 publications

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“…[21][22][23] Moreover, among men on androgen depravation therapy for prostate cancer, studies have demonstrated that as men progress from castrate levels (likely unsaturated androgen receptors) toward more physiologic testosterone concentrations, a positive correlation between PSA and serum testosterone is identified. [22][23][24] Additional evidence supporting the androgen receptor saturation hypothesis was recently been provided by Marks et al (2006) 6 who, in landmark randomized, double-blind, placebo-controlled trial analyzed prostate tissue concentrations of the principal androgens of the prostate (testosterone and dihydrotestosterone) following 6 months of parenteral TRT in hypogonadal patients. Despite significant increases in serum testosterone concentrations to normal physiologic levels, researchers identified no significant changes in serum PSA, prostate tissue testosterone and dihydrotestosterone concentrations, or prostate cancer biomarkers and gene expression within the prostate tissue itself.…”

Section: Discussionmentioning

confidence: 98%

“…[1][2][3] More contemporary clinical trials have shown little, if consistent evidence of a carcinogenic influence or the tendency to 'unmask' subclinical prostate cancer when TRT is prescribed to otherwise healthy hypogonadal men. [4][5][6] On the basis of lingering concerns and uncertainly, coupled with the fact that the prostate is known to be a androgensensitive organ, most evidence-based clinical guidelines recommend close surveillance of the prostate with prostate-specific antigen (PSA) and digital rectal examination among men treated with TRT. 7,8 Recognizing that PSA remains the most sensitive screening test available for the early detection of prostate cancer, 9,10 a better understanding of the relationship between serum testosterone and PSA levels among men receiving TRT is essential.…”

Section: Introductionmentioning

confidence: 99%

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Correlation between simultaneous PSA and serum testosterone concentrations among eugonadal, untreated hypogonadal and hypogonadal men receiving testosterone replacement therapy

et al. 2008

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The primary objective of this study was to correlate simultaneous measures of prostate-specific antigen (PSA) and serum testosterone among large samples of eugonadal, untreated hypogonadal and hypogonadal men treated with testosterone replacement therapy (TRT). From 2001 to 2007, laboratory records were reviewed to identify men who underwent simultaneous measurement of PSA and serum testosterone levels. The data were stratified based on three groups of men: group 1 consisted of eugonadal men (T4300 ng per 100 ml) evaluated for BPH, reproductive failure or sexual dysfunction; group 2 consisted of untreated hypogonadal men (To300 ng per 100 ml); and group 3 comprised symptomatic hypogonadal men receiving TRT. Correlations were found between PSA (total and free fractions) and total serum testosterone levels among the three groups. Group 1: eugonadal men (n ¼ 385 patients), mean PSA and serum testosterone were 1.60 ng ml À1 and 484 ng 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r ¼ À0.01, P ¼ 0.8). Group 2: untreated hypogonadal men (n ¼ 229 patients), mean PSA and serum testosterone were 1.49 ng ml À1 and 269 ng per 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r ¼ 0.03, P ¼ 0.6). Group 3: hypogonadal men on TRT (n ¼ 229 patients and 994 individual samples analyzed) mean PSA and serum testosterone were 1.50 ng ml À1 and 555 ng per 100 ml, respectively. There was no significant correlation between PSA and serum testosterone levels (r ¼ À0.005, P ¼ 0.9). Mean total serum testosterone levels were increased significantly (Po0.001) following treatment. Mean PSA levels did not increase in a statistically or clinically significant manner following TRT (mean PSA increase from baseline 0.05 ng ml À1 , P ¼ 0.6). In conclusion, TRT does not appear to significantly influence serum PSA expression and no significant correlation was identified between PSA and serum testosterone among eugonadal, untreated hypogonadal and hypogonadal men receiving TRT.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Correlation between simultaneous PSA and serum testosterone concentrations among eugonadal, untreated hypogonadal and hypogonadal men receiving testosterone replacement therapy

et al. 2008

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“…131,132 Although endogenous testosterone concentrations are not associated with incidence of prostate cancer, 133 there is also some residual concern over the risk of developing or diagnosing prostate cancer following long-term treatment with testosterone, even though short-term therapy is probably safe in this regard. 131,132,134 Testosterone therapy can be offered to hypogonadal men who meet accepted criteria for the diagnosis of androgen deficiency, with monitoring for efficacy and safety during treatment. 120,130,[135][136][137][138][139] Use of accurate, reliable and validated testosterone assays is important.…”

Section: Testosterone Cardiovascular Risk and Mortality In Aging Menmentioning

confidence: 99%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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“…By contrast, a variety of studies, using various designs and testosterone formulations, over periods ranging from several months to 15 years, in men with a wide range of ages, have not revealed an increased risk of prostate cancer [139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154]. A meta-analysis found that testosterone treatment in older men compared to placebo was not associated with a significantly higher risk of detection of prostate cancer [131], although the frequency of prostate biopsies was much higher in the testosterone-treated group than in the placebo group [131].…”

Section: Lower Urinary Tract Symptoms and Prostate Diseasementioning

confidence: 98%

Androgens and male aging: current evidence of safety and efficacy

Gooren¹

2010

Asian J Androl

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Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.

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Effect of Testosterone Replacement Therapy on Prostate Tissue in Men With Late-Onset Hypogonadism

Cited by 368 publications

References 64 publications

Correlation between simultaneous PSA and serum testosterone concentrations among eugonadal, untreated hypogonadal and hypogonadal men receiving testosterone replacement therapy

Correlation between simultaneous PSA and serum testosterone concentrations among eugonadal, untreated hypogonadal and hypogonadal men receiving testosterone replacement therapy

Are declining testosterone levels a major risk factor for ill-health in aging men?

Androgens and male aging: current evidence of safety and efficacy

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