harold
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Hey dunno if this study has been brought up before but thought I would post the abstract and a few bits of interest from the full article. Though it is looking at treatment of BPH there are some interesting points in terms of the relationship between testosterone and sexual function while on the drug and treatment response that may be suggestive.
Relationship among Serum Testosterone, Sexual Function, and Response to Treatment in Men Receiving Dutasteride for Benign Prostatic Hyperplasia
Michael Marberger 1
Claus G. Roehrborn 2
Leonard S. Marks 3
Timothy Wilson 4
Roger S. Rittmaster 4
1 Department of Urology (M.M.), University of Vienna, A-1090 Vienna, Austria;
2 Department of Urology (C.G.R.), The University of Texas Southwestern Medical Center, Dallas, Texas 75390;
3 Department of Urology (L.S.M.), University of California, Los Angeles, School of Medicine and Urological Sciences Research Foundation, Los Angeles, California 90095;
4 and Departments of Biostatistics (T.W.) and Clinical Development and Medical Affairs (R.S.R.), GlaxoSmithKline, Research Triangle Park, North Carolina 27709
Abbreviations:
AUA-SI
American Urological Association-Symptom Index
BMI
body mass index
BPH
benign prostatic hyperplasia
BST
baseline serum testosterone
DHT
dihydrotestosterone
ED
erectile dysfunction
PSA
prostate-specific antigen
SFI
Sexual Function Inventory
Context: Although benign prostatic hyperplasia (BPH) is an androgen-dependent disorder, little is known regarding the influence of serum testosterone levels on sexual or prostate function or clinical response to dutasteride.
Objective: The objective of the study was to explore these relationships in a large cohort of men treated with dutasteride for BPH.
Design, Setting, Patients, and Outcome Measures: Among 4254 men with BPH participating in 2-yr placebo-controlled dutasteride trials, 27% had a pretreatment serum testosterone less than 300 ng/dl. These 1162 men were divided into seven groups based on their serum testosterone level (<150, 150–174, 175–199, 200–224, 225–249, 250–274, and 275–299 ng/dl) and compared with men with normal baseline serum testosterone (BST; ≥ 300 ng/dl). Questionnaires were used to assess sexual function, prostate-specific antigen (PSA), and prostate volume to assess androgenic stimulation of the prostate and the American Urological Association Symptom Index to assess clinical responses.
Results: Although lower BST was associated with increased sexual dysfunction, this increase was not seen until BST was less than 225 ng/dl. There was no decrease in baseline PSA and prostate volume at low BST levels. Dutasteride was effective at decreasing PSA and prostate volume and improving BPH symptoms at all BST levels.
Conclusions: In men with BPH, the frequency of sexual dysfunction increases at serum testosterone concentrations less than 225 ng/dl. However, PSA and prostate volume were similar at all testosterone levels, explaining why BPH can occur in men that would otherwise be considered hypogonadal. The fact that dutasteride is also effective in men with normal and low testosterone levels suggests that the high levels of 5α-reductase and dihydrotestosterone in the prostate allow the development and progression of prostatic hyperplasia, even at low circulating testosterone levels. ( J Clin Endocrinol Metab 91: 1323–1328, 2006)
Relationship between serum testosterone and sexual function
Lower levels of BST were associated with lower proportions of subjects who were sexually active ( P = 0.004) and a higher prevalence of ED ( P = 0.001) and lack of libido ( P = 0.001). However, these effects were not observed until the testosterone level was less than 200 ng/dl for reduced sexual activity and less than 225 ng/dl for ED and lack of libido ( Fig. 3, A–C ). The mean SFI score for men with a normal BST was 6.8, and lower levels of BST were associated with slightly lower baseline SFI scores ( P = 0.05) ( Table 1 ).
Relationship between serum testosterone and therapeutic response to dutasteride treatment
Among men with a normal testosterone level, the mean change in SFI in response to dutasteride was a reduction of 1.0 vs. a reduction of 0.3 points for placebo, at month 12. Subjects with lower BST within both treatment groups showed larger decreases in mean SFI from baseline ( P < 0.05) ( Fig. 4 ). The mean change in prostate volume at month 24 was a decrease of 25.2% for those treated with dutasteride, compared with an increase of 1.6% for placebo in those with normal BST. Slightly larger differences were noted between placebo- and dutasteride-treated subjects with lower BST ( P < 0.05) ( Fig. 5 ). The mean change in PSA at month 24 in dutasteride-treated subjects was a decrease of 52.0%, compared with an increase of 15% in those treated with placebo, in those with normal BST. Overall, percentage change in PSA at month 24 was similar across BST categories in the placebo group but slightly higher reductions in PSA for lower levels of BST were observed in the dutasteride group ( P = 0.007). There was no correlation between baseline AUA-SI and BST (data not shown). Among men with normal BST, the mean change in AUA-SI at month 24 in response to dutasteride treatment was a decrease of 4.5 U, compared with a decrease of 2.3 U in men receiving placebo. Dutasteride was equally effective at improving AUA-SI at all BST levels ( Fig. 6 ).
It is clear that many men with normal serum testosterone have sexual dysfunction and that many men with low serum testosterone do not.
Hence, one role of 5α-reductase in the prostate may be to allow the prostate to function normally and undergo age-related growth, even in the presence of low circulating testosterone levels. As a consequence, despite the increasing prevalence of low serum testosterone levels among aging men, BPH is common. Furthermore, the beneficial effects of dutasteride on BPH could therefore be expected, even in men with low testosterone levels.
The 52 men with the lowest BST levels of less than 150 ng/dl behaved differently from the rest of the study population: they were slightly older; had larger prostates and a greater increase in prostate volume over time with placebo; and had higher BMI, greater incidence of ED, altered libido, lower SFI, and greater decrease in sexual function over time with placebo. These findings could be a manifestation of obesity-associated metabolic syndrome and are worthy of further examination in other data sets.
INteresting that those who had borderline low testosterone at the beginning of the trial seemed to take a larger hit in sexual function on dutasteride than others. Those same men also seemeed to have a better treatment response than men with higher testosterone levels.
hh
Relationship among Serum Testosterone, Sexual Function, and Response to Treatment in Men Receiving Dutasteride for Benign Prostatic Hyperplasia
Michael Marberger 1
Claus G. Roehrborn 2
Leonard S. Marks 3
Timothy Wilson 4
Roger S. Rittmaster 4
1 Department of Urology (M.M.), University of Vienna, A-1090 Vienna, Austria;
2 Department of Urology (C.G.R.), The University of Texas Southwestern Medical Center, Dallas, Texas 75390;
3 Department of Urology (L.S.M.), University of California, Los Angeles, School of Medicine and Urological Sciences Research Foundation, Los Angeles, California 90095;
4 and Departments of Biostatistics (T.W.) and Clinical Development and Medical Affairs (R.S.R.), GlaxoSmithKline, Research Triangle Park, North Carolina 27709
Abbreviations:
AUA-SI
American Urological Association-Symptom Index
BMI
body mass index
BPH
benign prostatic hyperplasia
BST
baseline serum testosterone
DHT
dihydrotestosterone
ED
erectile dysfunction
PSA
prostate-specific antigen
SFI
Sexual Function Inventory
Context: Although benign prostatic hyperplasia (BPH) is an androgen-dependent disorder, little is known regarding the influence of serum testosterone levels on sexual or prostate function or clinical response to dutasteride.
Objective: The objective of the study was to explore these relationships in a large cohort of men treated with dutasteride for BPH.
Design, Setting, Patients, and Outcome Measures: Among 4254 men with BPH participating in 2-yr placebo-controlled dutasteride trials, 27% had a pretreatment serum testosterone less than 300 ng/dl. These 1162 men were divided into seven groups based on their serum testosterone level (<150, 150–174, 175–199, 200–224, 225–249, 250–274, and 275–299 ng/dl) and compared with men with normal baseline serum testosterone (BST; ≥ 300 ng/dl). Questionnaires were used to assess sexual function, prostate-specific antigen (PSA), and prostate volume to assess androgenic stimulation of the prostate and the American Urological Association Symptom Index to assess clinical responses.
Results: Although lower BST was associated with increased sexual dysfunction, this increase was not seen until BST was less than 225 ng/dl. There was no decrease in baseline PSA and prostate volume at low BST levels. Dutasteride was effective at decreasing PSA and prostate volume and improving BPH symptoms at all BST levels.
Conclusions: In men with BPH, the frequency of sexual dysfunction increases at serum testosterone concentrations less than 225 ng/dl. However, PSA and prostate volume were similar at all testosterone levels, explaining why BPH can occur in men that would otherwise be considered hypogonadal. The fact that dutasteride is also effective in men with normal and low testosterone levels suggests that the high levels of 5α-reductase and dihydrotestosterone in the prostate allow the development and progression of prostatic hyperplasia, even at low circulating testosterone levels. ( J Clin Endocrinol Metab 91: 1323–1328, 2006)
Relationship between serum testosterone and sexual function
Lower levels of BST were associated with lower proportions of subjects who were sexually active ( P = 0.004) and a higher prevalence of ED ( P = 0.001) and lack of libido ( P = 0.001). However, these effects were not observed until the testosterone level was less than 200 ng/dl for reduced sexual activity and less than 225 ng/dl for ED and lack of libido ( Fig. 3, A–C ). The mean SFI score for men with a normal BST was 6.8, and lower levels of BST were associated with slightly lower baseline SFI scores ( P = 0.05) ( Table 1 ).
Relationship between serum testosterone and therapeutic response to dutasteride treatment
Among men with a normal testosterone level, the mean change in SFI in response to dutasteride was a reduction of 1.0 vs. a reduction of 0.3 points for placebo, at month 12. Subjects with lower BST within both treatment groups showed larger decreases in mean SFI from baseline ( P < 0.05) ( Fig. 4 ). The mean change in prostate volume at month 24 was a decrease of 25.2% for those treated with dutasteride, compared with an increase of 1.6% for placebo in those with normal BST. Slightly larger differences were noted between placebo- and dutasteride-treated subjects with lower BST ( P < 0.05) ( Fig. 5 ). The mean change in PSA at month 24 in dutasteride-treated subjects was a decrease of 52.0%, compared with an increase of 15% in those treated with placebo, in those with normal BST. Overall, percentage change in PSA at month 24 was similar across BST categories in the placebo group but slightly higher reductions in PSA for lower levels of BST were observed in the dutasteride group ( P = 0.007). There was no correlation between baseline AUA-SI and BST (data not shown). Among men with normal BST, the mean change in AUA-SI at month 24 in response to dutasteride treatment was a decrease of 4.5 U, compared with a decrease of 2.3 U in men receiving placebo. Dutasteride was equally effective at improving AUA-SI at all BST levels ( Fig. 6 ).
It is clear that many men with normal serum testosterone have sexual dysfunction and that many men with low serum testosterone do not.
Hence, one role of 5α-reductase in the prostate may be to allow the prostate to function normally and undergo age-related growth, even in the presence of low circulating testosterone levels. As a consequence, despite the increasing prevalence of low serum testosterone levels among aging men, BPH is common. Furthermore, the beneficial effects of dutasteride on BPH could therefore be expected, even in men with low testosterone levels.
The 52 men with the lowest BST levels of less than 150 ng/dl behaved differently from the rest of the study population: they were slightly older; had larger prostates and a greater increase in prostate volume over time with placebo; and had higher BMI, greater incidence of ED, altered libido, lower SFI, and greater decrease in sexual function over time with placebo. These findings could be a manifestation of obesity-associated metabolic syndrome and are worthy of further examination in other data sets.
INteresting that those who had borderline low testosterone at the beginning of the trial seemed to take a larger hit in sexual function on dutasteride than others. Those same men also seemeed to have a better treatment response than men with higher testosterone levels.
hh