Editing Functional: Pharmacological Management of LUTS (section)

==== 5α-reductase inhibitors ====

===== Mechanism of action =====

*'''<span style="color:#ff0000">5α-reductase converts testosterone to DHT</span>'''
** '''<span style="color:#ff0000">Type 1 5α-reductase is expressed primarily in the non-genital skin and liver, and to a lesser extent in the prostate, testis, and brain</span>'''
** '''<span style="color:#ff0000">Type 2 5α-reductase is expressed predominantly in the prostate epithelium and other genital tissues such as the epididymis, genitalia, seminal vesicle, testis, but also in liver, uterus, breast, hair follicles, and placenta</span>'''
** '''<span style="color:#ff0000">Finasteride inhibits type 2, dutasteride inhibits both type 1 and 2</span>'''

===== Landmark studies =====

*'''<span style="color:#ff00ff">Finasteride Study Group</span>'''
** 895 men with some symptoms of urinary obstruction, an enlarged prostate gland on digital rectal examination, and maximal urinary-flow rates of less than 15 ml per second (with a voided volume of 150 ml or more).
** Randomized to 3 arms: 1mg finasteride vs. 5mg finasteride vs. placebo once daily for 12 months
** Results
*** The mean serum dihydrotestosterone concentrations decreased significantly in the two finasteride-treated groups (P<0.001) during the first two weeks of treatment and did not change thereafter 
**** The decrease in serum dihydrotestosterone concentrations among the men who received 5 mg of finasteride daily was significantly greater than that among the men who received 1 mg of finasteride daily
*** In both finasteride-treated groups, serum testosterone concentrations increased approximately 8 to 10 percent after two weeks of treatment, and they remained increased thereafter.
**** Despite the increases, all values were within the normal range at all times.
*** Serum luteinizing hormone concentrations increased in all three groups during the first two months. However, the increases in both finasteride-treated groups were significantly higher than those in the placebo group
*** the men in both finasteride-treated groups had significant reductions in serum prostate-specific antigen for the comparison with the placebo group) at all times from month 3 through month 12 of treatment
**** The median decrease was 50 percent among the men who received 5 mg of finasteride and 48 percent among those who received 1 mg of finasteride.
*** Men treated with 5 mg of finasteride had a '''significant decrease in total symptom scores'''. The men treated with 1 mg of finasteride had no significant changes in the symptom scores.
*** During the 12 months of treatment, the '''maximal urinary-flow rates increased''' progressively in both finasteride-treated groups, but not in the group given placebo
*** During the first six months, the median size of the prostate decreased progressively in both finasteride-treated groups, after which it did not change significantly, and it was significantly smaller in both finasteride-treated groups than in the placebo group at all times. After 12 months of treatment, the '''prostate had shrunk by 19 percent from base line''' in the group given 5 mg of finasteride, by 18 percent in the group given 1 mg of finasteride, and by 3 percent in the group given placebo
** [https://pubmed.ncbi.nlm.nih.gov/1383816/ Gormley, Glenn J., et al."The effect of finasteride in men with benign prostatic hyperplasia." ''New England Journal of Medicine'' 327.17 (1992): 1185-1191.]

===== Adverse events =====

*'''Most common (4):'''
*# '''<span style="color:#ff0000">Reduced volume of ejaculate</span>''' (absolute risk difference 4%)
*# '''<span style="color:#ff0000">Erectile dysfunction</span>''' (4%)
*# '''<span style="color:#ff0000">Loss of libido</span>''' (3%)
*# '''<span style="color:#ff0000">Gynecomastia</span>''' (2%)

===== Other benefits of 5-ARIs (4): =====
# '''Improves sensitivity of PSA and DRE for prostate cancer detection'''
# '''Reduced risk of prostatitis'''
# '''Reduced risk of acute urinary retention'''
# '''Reduced risk of BPH-related surgical intervention'''