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5-alpha reductase inhibitor

Indications: - treatment of benign prostatic hypertrophy (BPH) - may reduce prostate cancer mortality in men with prostate cancer [10] - androgenic alopecia [3] Contraindications: - women & children - prevention of prostate cancer [1] - no affect on mortality in men without prostate cancer [10] Adverse effects: 1) fetal abnormalities in male fetus a) absorbed through skin b) may be passed to pregnant woman through blood transfusion 2) impotence < 5% (transient) - sexual dysfunction may persist after discontinuation [6] 3) erectile dysfunction - no increase in risk [5] - common [7] 4) gynecomastia < 1% 5) depression [4] 6) not a risk factor for high-grade prostate cancer [6] - delayed diagnosis & increased mortality from prostate cancer [9] 7) increased risk for type 2 diabetes (RR= 1.3 vs tamsulosin) [8] Mechanism of action: - inhibition of testosterone 5-alpha reductase - shrinks androgen-sensitive prostate tissue - is not an androgen receptor antagonist

Interactions

drug adverse effects of 5-alpha reductase inhibitors

Related

3-oxo-5-alpha-steroid 4 dehydrogenase; steroid 5-alpha reductase; testosterone 5-alpha reductase androgen receptor antagonist; androgen receptor signaling inhibitor (ARSI)

Specific

dutasteride (Avodart) finasteride (Proscar, Propecia)

General

endocrine agent enzyme inhibitor

References

  1. Andriole GL et al Effect of Dutasteride on the Risk of Prostate Cancer New Eng J Med 2010 362:1192-1202 PMID: 20357281 - Walsh PC Chemoprevention of Prostate Cancer New Eng J Med 2010 362:1237 PMID: 20357287
  2. Robinson D et al Use of 5alpha-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study. BMJ 2013;346:f3406 PMID: 23778271 http://www.bmj.com/content/346/bmj.f3406?etoc=
  3. Deprecated Reference
  4. Welk B, McArthur E, Ordon M et al Association of Suicidality and Depression With 5alpha-Reductase Inhibitors. JAMA Intern Med. Published online March 20, 2017 PMID: 28319231 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2610105
  5. Hagberg KW, Divan HA, Persson R, Nickel JC, Jick SS. Risk of erectile dysfunction associated with use of 5-alpha reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink. BMJ 2016;354:i4823 PMID: 27659058 Free Article http://www.bmj.com/content/354/bmj.i4823
  6. Unger JM, Hershman DL, Till C et al. Using Medicare claims to examine long-term prostate cancer risk of finasteride in the Prostate Cancer Prevention Trial. J Natl Cancer Inst 2018 Nov; 110:1208-1215. PMID: 29534197 - Wallerstedt A, Strom P, Gronberg H, Nordstrom T, Eklund M. Risk of prostate cancer in men treated with 5alpha-reductase inhibitors - A large population-based prospective study. J Natl Cancer Inst 2018 Nov; 110:1216-1221 PMID: 29548030
  7. Medical Knowledge Self Assessment Program (MKSAP) 18, 19 American College of Physicians, Philadelphia 2018, 2022
  8. Wei L, Lai EC, Kao-Yang YH et al Incidence of type 2 diabetes mellitus in men receiving steroid 5alpha-reductase inhibitors: population based cohort study. BMJ 2019;365:l1204 PMID: 30971393 Free Article https://www.bmj.com/content/365/bmj.l1204 - Andrew R, Wei L, Walker B, MacDonald D Reducing the risk of type 2 diabetes in men with benign prostatic hyperplasia - old steroids, new tricks. thebmjopinion. April 10, 2019 https://blogs.bmj.com/bmj/2019/04/10/reducing-the-risk-of-type-2-diabetes-in-men-with-benign-prostatic-hyperplasia-old-steroids-new-tricks/
  9. Sarkar RR, Parsons JK, Bryant AK et al Association of Treatment With 5alpha-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer. JAMA Intern Med. 2019;179(6):812-819. PMID: 31058923 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2732119
  10. Bjornebo L et al. Association of 5-alpha-reductase inhibitors with prostate cancer mortality. JAMA Oncol 2022 Jul; 8:1019. PMID: 35587340 PMCID: PMC9121300 (available on 2023-05-19) https://jamanetwork.com/journals/jamaoncology/fullarticle/2792528