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antagonists, one of them being cetrorelix, another being Ozarelix. Debruyne et al

reported on a placebo-controlled, dose-ranging, phase II trial using cetrorelix,

subcutaneously administered, in men with LUTS and BPH in different dosages.

One hundred and forty patients were enrolled, and the study shows a remarkable

decrease in the symptom score (Fig 1 in the original article), compared with the

placebo group that is sustained throughout the observation period of the trial.

Commensurate with it, an improvement in peak urinary flow rate was observed,

whereas the reduction in testosterone was incomplete and only limited to the

first week of treatment. Similar findings have been reported at national and inter-

national meetings for other LHRH antagonists, such as Ozarelix and Teverelix.

These agents, when administered subcutaneously at week 0 and week 2, induce

a temporary and incomplete reduction in serum T but not to a castrate level. As

the testosterone returns back to baseline levels, it stands to reason that mecha-

nisms other than androgen ablation or temporary testosterone reduction must be

involved in the efficacy observed over prolonged periods of time with either one

of these agents. It will be interesting to see what basic research studies may

present, in terms of evidence for the presence of LHRH receptors in the prostate,

or for the activity of LHRH antagonists directly in the prostate upon inflammatory

changes and/or growth factors. The concept of ischemia being part of male

pelvic disorders is quite popular these days. Clearly, ischemia is at the heart

and soul of erectile dysfunction in men.

C. G. Roehrborn, MD

The Effect of 5a-Reductase Inhibition With Dutasteride and Finasteride onBone Mineral Density, Serum Lipoproteins, Hemoglobin, Prostate SpecificAntigen and Sexual Function in Healthy Young MenAmory JK, Anawalt BD, Matsumoto AM, et al (Veterans Affairs-Puget Sound

Health Care System, Univ of Washington, Seattle, WA; et al)

J Urol 179:2333-2338, 2008

Purpose.—Dutasteride and finasteride are 5a-reductase inhibitors thatdramatically decrease serum levels of dihydrotestosterone. Because andro-gens affect bone, lipids, hematopoiesis, prostate and sexual function, wedetermined the impact of 5a-reductase inhibitors on these end points.

Materials and Methods.—We conducted a randomized, double-blinded,placebo controlled trial of 99 men 18 to 55 years old randomly assigned toreceive 0.5 mg dutasteride (33), 5 mg finasteride (34) or placebo (32) dailyfor 1 year. Bone mineral density was measured at baseline, after 1 year oftreatment and 6 months after drug discontinuation. In addition, markersof bone turnover, fasting serum lipoprotein concentrations, hemoglobinand prostate specific antigen were measured at baseline, after 26 and 52weeks of treatment, and again 24 weeks after drug discontinuation. Sexualfunction was assessed at these points by a validated questionnaire.

Results.—Significant suppression of circulating dihydrotestosteronelevels with the administration of dutasteride or finasteride did not signifi-cantly affect bone mineral density or markers of bone metabolism.

Chapter 12–Benign Prostatic Hyperplasia / 89

Similarly serum lipoproteins and hemoglobin were unaffected. Serumprostate specific antigen and self-assessed sexual function decreasedslightly during treatment with both 5a-reductase inhibitors but returnedto baseline during followup.

Conclusions.—Profound suppression of circulating serum dihydrotes-tosterone induced by 5a-reductase inhibitors during 1 year does notadversely impact bone, serum lipoproteins or hemoglobin, and hasa minimal, reversible effect on serum prostate specific antigen and sexualfunction in normal men. Circulating dihydrotestosterone does not appearto have a clinically significant role in modulating bone mass, hematopoi-esis or lipid metabolism in normal men.

:

This is to my knowledge one of the very few if not the only randomized,

placebo-controlled direct comparator trial between dutasteride and finasteride

in a group of 99 men, of which one third received placebo for one year’s

time. The authors’ interest was not so much in terms of improvement in symp-

toms and flow rate and shrinkage of prostate gland but rather the impact on

bone mineral density, lipoproteins, hemoglobin, prostate specific antigen

(PSA), and sexual function in healthy young men. Specifically, to be enrolled

in this trial men had to be 18-55 years of age. The authors were clearly moti-

vated by the observation that androgen manipulation in elderly men with pros-

tate cancer had the most in bone mineral density, osteopenia, and osteoporosis

and, oftentimes, fractures. The study showed a significant suppression of DHT

with dutasteride and finasteride, as well as a significant decrease in serum PSA.

However, bone mineral density, serum lipoproteins, and hemoglobin were not

affected and thus the authors conclude that circulating DHT does not appear

to have a clinically significant role in either modulating bone mass influencing

hematopoiesis or lipid metabolism. This observation is of great importance as

these drugs are given, chronically, to elderly men at risk for osteoporosis and,

oftentimes, having comorbid conditions relative to lipid metabolism. The find-

ings clearly demonstrate the absence of any significant effect in the presence

of a most significant reduction of circulating DHT. An interesting analysis

was also performed regarding sexual function, and it is noteworthy that there

was no decrease in overall satisfaction with sexual activity during treatment

with either medication in this, admittedly, relatively young group of patients.

C. G. Roehrborn, MD

Surgical Treatment

Meta-analysis of holmium laser enucleation versus transurethral resectionof the prostate for symptomatic prostatic obstructionTan A, Liao C, Mo Z, et al (Guangxi Medical University, China)

Br J Surg 94:1201-1208, 2007

Background.—Holmium laser enucleation (HoLEP) is an alternative totransurethral resection (TURP) of the prostate for symptomatic prostaticobstruction.