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6.24.7.2.2 5a-Reductase inhibitors

5a-Reductase converts testosterone to DHT, and inhibition of this enzyme reduces the high levels of DHTevident in BPH. Two 5a-reductase inhibitors are recommended by guidelines (finasteride and dutasteride) (see Figure 15 for structures). Finasteride is a selective inhibitor of type 2 5a-reductase isoenzyme, which has been shown to decrease plasma DHT by 60-70% and prostatic DHT by 85%. In comparison, dutasteride inhibits both isoenzymes and decreases DHT concentrations by more than 90%.46 Data from placebo-controlled trials shows that both agents decrease prostate volume ( — 18% reduction for finasteride versus — 26% reduction for dutasteride), decrease IPSS ( — 3.3 versus — 4.5, respectively), and improve urine flow rate.47

6.24.7.2.3 Side effects

^-Adrenoceptor antagonists can be differentiated, to a certain extent, by their side effect profiles. At the maximal doses used in the clinic, with regard to cardiovascular adverse events, doxazosin and terazosin have higher dizziness rates (0-20%, corrected for placebo) than alfuzosin and tamsulosin (0-8%, corrected for placebo). Only a few direct comparative studies exist, which show that alfuzosin 2.5 mg once daily significantly decreases both diastolic and systolic blood pressure compared with tamsulosin 0.4 mg once daily. In addition, abnormal ejaculation, including retrograde ejaculation and reduced ejaculate volume, have been associated with one of these agents, tamsulosin, where the incidence of abnormal ejaculation has been shown to range from 4 to 30%.48 One hypothesis is that blockade of a1A- and a1D-adrenoceptors in the bladder neck, seminal vesicles, and vas deferens might induce these effects, and greater bladder neck closure and seminal vesicle contraction, which has been observed with tamsulosin, may account for these differences. However, the unusually high degree of sexual dysfunction observed with tamsulosin may involve interactions with receptor subtypes other than a1.48

Figure 15 5a-Reductase inhibitors.

5a-Reductase inhibitors have also been associated with sexual dysfunction side effects; findings from a large-scale trial known as the Medical Therapy Of Prostatic Symptoms (MTOPS) study showed that finasteride was significantly associated with decreased libido, erectile dysfunction, and ejaculatory disorders in comparison with placebo and

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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