Long-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease

Idan, Amanda; Griffiths, Kalinda; Harwood, D. Tim; Seibel, Markus J.; Turner, Leo; Conway, Ann J.; Handelsman, David J.

doi:10.7326/0003-4819-153-10-201011160-00004

Cited by 81 publications

(71 citation statements)

References 61 publications

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“…Subsequent studies have corroborated these findings and have linked estradiol deficiency to more rapid rates of bone loss in older men (7,8). Additionally, treatment with dihydrotestosterone, a nonaromatizable androgen that reduces estradiol levels, and aromatase inhibitors provoke substantial bone mineral density loss in men (9,10). Furthermore, there is a stronger inverse association between estrogen level and fractures in older men than testosterone (11,12).…”

Section: Introductionsupporting

confidence: 53%

Battle of the sex steroids in the male skeleton: and the winner is…

Weber¹

2016

Journal of Clinical Investigation

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Section: Introductionsupporting

confidence: 53%

Battle of the sex steroids in the male skeleton: and the winner is…

Weber¹

2016

Journal of Clinical Investigation

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“…In this regard, we met our expected non-completion rate of 20% at 6 mo, whereas the 12-mo noncompletion rate in our study (i.e., 33%) was slightly higher than anticipated. Importantly, noncompletion was similar among all groups ( 2 P value ϭ 0.48, indicating no differences) and was comparable to the noncompletion rates of 27-29% in other long-term testosterone studies (4,11,26). Additionally, our non-completion rate was not exceedingly high, given that once-weekly visits to the hospital were required for 52 consecutive weeks and that we observed a significant main effect for testosterone in each of our primary and secondary outcomes and a significant interaction for prostate volume (the only primary outcome powered on 12-mo data), as hypothesized.…”

Section: E438 Testosterone and Finasteride In Older Menmentioning

confidence: 66%

Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial

Borst

Yarrow

Conover

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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SC, Cannady DF 2nd, Shuster JJ. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial. Am J Physiol Endocrinol Metab 306: E433-E442, 2014. First published December 10, 2013; doi:10.1152/ajpendo.00592.2013.-Testosterone acts directly at androgen receptors and also exerts potent actions following 5␣-reduction to dihydrotestosterone (DHT). Finasteride (type II 5␣-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged Ն60 yr with a serum testosterone concentration of Յ300 ng/dl or bioavailable testosterone Յ70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 ϫ 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8 -14% (P ϭ 0.015 to Ͻ0.001), fat-free mass 4.04 kg (P ϭ 0.032), lumbar spine bone mineral density (BMD) 4.19% (P Ͻ 0.001), and total hip BMD 1.96% (P ϭ 0.024) while reducing total body fat Ϫ3.87 kg (P Ͻ 0.001) and trunk fat Ϫ1.88 kg (P ϭ 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P Ͻ 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm 3 (P ϭ 0.0051), an effect that was completely prevented by finasteride (P ϭ 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue. testosterone; hypogonadal; prostate enlargement SOME STUDIES OF TESTOSTERONE TREATMENT in older, hypogonadal men report substantial increases in muscle strength and bone mineral density (BMD) (12, 21), whereas others report only modest improvements (31, 41). Studies documenting substantial effects typically employed intramuscular (im) doses of Ն100 mg/wk im injection of long-acting testosterone esters (12, 21). In contrast, lower doses of testosterone that result from transdermal patch or gel administration produce only modest myotrophic effects (31, 32, 41). Meta-analysis data indicate that im testosterone produces a 4% increase in lumbar spine BMD, while transdermal testosterone has no effect (39). Unfortunately, higher doses of testosterone also increase the risk of adverse events, including three that have been confirmed by meta-analysis: polycythemia, a small reduction in HDL-cholesterol, and increased inci...

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“…In a 4-week RCT of DHT vs placebo in 31 men, despite robust increases in circulating DHT in the DHT-treated group, there was again no difference in intraprostatic DHT or testosterone concentrations, epithelial cell proliferation or AR-regulated gene expression (Page et al 2011). In addition, a larger RCT of DHT therapy of 2 year duration in 114 healthy men showed no effect on prostate volume (measured by ultrasonography) or PSA levels (Idan et al 2010).…”

Section: Effects Of Sex Steroids On Pcamentioning

confidence: 95%

Androgens, diabetes and prostate cancer

Grossmann¹,

Wittert²

2012

Endocrine-Related Cancer

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Metabolic disorders such as diabetes, obesity and the metabolic syndrome have been shown to modulate prostate cancer (PCa) risk and aggressiveness in population-based and experimental studies. While associations between these conditions are modest and complex, two consistent findings have emerged. First, there is observational evidence that obesity and associated insulin excess are linked to increased PCa aggressiveness and worse outcomes. Secondly and somewhat paradoxically, long-standing diabetes may be protective against PCa development. This apparent paradox may be due to the fact that long-standing diabetes is associated with insulin depletion and decreased IGF1 signalling. Men with obesity or diabetes have moderate reductions in their androgen levels. The interconnectedness of metabolic and androgen status complicates the dissection of the individual roles of these factors in PCa development and progression. Metabolic factors and androgens may promote prostate carcinogenesis via multiple mechanisms including inflammation, adipokine action, fatty acid metabolism and IGF signalling. Moreover, androgen deprivation, given to men with PCa, has adverse metabolic consequences that need to be taken into account when estimating the risk benefit ratio of this therapy. In this review, we will discuss the current epidemiological and mechanistic evidence regarding the interactions between metabolic conditions, sex steroids and PCa risk and management.

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Long-Term Effects of Dihydrotestosterone Treatment on Prostate Growth in Healthy, Middle-Aged Men Without Prostate Disease

Abstract: BHR Pharma.

Cited by 81 publications

References 61 publications

Battle of the sex steroids in the male skeleton: and the winner is…

Battle of the sex steroids in the male skeleton: and the winner is…

Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial

Androgens, diabetes and prostate cancer

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