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5α-Reductase inhibitor

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5α-Reductase inhibitors (or 5-alpha-reductase inhibitors) are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic (or androgenetic) alopecia. These drugs decrease the levels of available 5α-reductase prior to testosterone's binding with the enzyme, thus reducing levels of dihydrotestosterone that derives from such a bond.

Clinical use

Indications

5α-Reductase inhibitors are clinically used in the treatment of conditions that are exacerbated by dihydrotestosterone. To be specific, these indications may include:[1]

"Five-α reductase inhibitors (5-ARIs) reduce the incidence of prostate cancer in both general and higher-risk populations and are currently under study for tertiary prevention in active surveillance and biochemical recurrence patients.. . .Currently, there is neither clinical evidence to support the use of 5-ARIs for tertiary prevention in active surveillance or biochemical recurrence populations"[2] "Prostate cancer (pca) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (pcpt) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak."[3]

Adverse drug reactions

In general, adverse drug reactions (ADRs) experienced with 5α-reductase inhibitors are dose-dependent. Common ADRs include impotence, decreased libido, and decreased ejaculate volume. Rare ADRs include breast tenderness and enlargement, and allergic reaction.[1]

Pharmacology

The enzyme 5α-reductase is involved in the conversion of testosterone to the active form dihydrotestosterone by reducing the Δ4,5 double-bond. In benign prostatic hyperplasia, dihydrotestosterone acts as a potent cellular androgen and promotes prostate growth; therefore, inhibiting the enzyme reduces the excessive prostate growth. In alopecia, male-pattern baldness is one of the effects of androgenic receptor activation. Thus, reducing the levels of dihydrotestosterone reduces alopecia.

Results of an enzyme assay conducted with an extract of Ganoderma lucidum (Reishi) and the enzyme 5-alpha reductase.[4][vague]

Examples

Certain pesticides are able to disturb the sex steroid hormone system and to act as antiandrogens.[5]

Herbs

Many chemical compounds in nature are able to inhibit 5α-reductase, such as those found in the Reishi mushroom Ganoderma lucidum.[4][6][7] Ganoderic acid[8] or organoderol B may be the active compounds.[9]

Short chain fatty acids such as those found in coconut and many palm fruits have also been found to inhibit 5α-reductase.[10]

Other herbs include:

Not all of these plants have not been tested in human clinical trials, so effectiveness in humans for the treatment of BPH and related conditions has not been clinically proven. The best evidence exists for good extracts of Saw Palmetto (quality of extracts is variable). (Three more human, clinical trials are in progress)

References

  1. ^ a b Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2
  2. ^ Silberstein J.L., Parsons J.K. "Prostate cancer prevention: Concepts and clinical recommendations" Prostate Cancer and Prostatic Diseases 2010 13:4 (300-306)
  3. ^ Trottier G., Lawrentschuk N., Fleshner N.E. "Prevention strategies in prostate cancer" Current Oncology 2010 17:SUPPL. 2 (s4-s10)
  4. ^ a b Liu J, Kurashiki K, Shimizu K, Kondo R (2006). "5alpha-reductase inhibitory effect of triterpenoids isolated from Ganoderma lucidum". Biol. Pharm. Bull. 29 (2): 392–5. doi:10.1248/bpb.29.392. PMID 16462054. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Lo, S; King, I; Alléra, A; Klingmüller, D (2007). "Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells". Toxicology in vitro : an international journal published in association with BIBRA. 21 (3): 502–8. doi:10.1016/j.tiv.2006.10.016. PMID 17218080.
  6. ^ Liu, J; Tamura, S; Kurashiki, K; Shimizu, K; Noda, K; Konishi, F; Kumamoto, S; Kondo, R (2009). "Anti-androgen effects of extracts and compounds from Ganoderma lucidum". Chemistry & biodiversity. 6 (2): 231–43. doi:10.1002/cbdv.200800019. PMID 19235153.
  7. ^ Noguchi, M; Kakuma, T; Tomiyasu, K; Yamada, A; Itoh, K; Konishi, F; Kumamoto, S; Shimizu, K; Kondo, R (2008). "Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms". Asian journal of andrology. 10 (5): 777–85. doi:10.1111/j.1745-7262.2008.00361.x. PMID 18097505.
  8. ^ Liu, J; Shiono, J; Shimizu, K; Kukita, A; Kukita, T; Kondo, R (2009). "Ganoderic acid DM: anti-androgenic osteoclastogenesis inhibitor". Bioorganic & medicinal chemistry letters. 19 (8): 2154–7. doi:10.1016/j.bmcl.2009.02.119. PMID 19289282.
  9. ^ Liu, J; Shimizu, K; Konishi, F; Kumamoto, S; Kondo, R (2007). "The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum". Bioorganic & medicinal chemistry. 15 (14): 4966–72. doi:10.1016/j.bmc.2007.04.036. PMID 17499997.
  10. ^ Liu, J; Shimizu, K; Kondo, R (2009). "Anti-androgenic activity of fatty acids". Chemistry & biodiversity. 6 (4): 503–12. doi:10.1002/cbdv.200800125. PMID 19353546.
  11. ^ Plants for a Future: Angelica koreana
  12. ^ Seo, EK; Kim, KH; Kim, MK; Cho, MH; Choi, E; Kim, K; Mar, W (2002). "Inhibitors of 5alpha -reductase type I in LNCaP cells from the roots of Angelica koreana". Planta medica. 68 (2): 162–3. doi:10.1055/s-2002-20258. PMID 11859469.
  13. ^ Li, YH; Yang, YF; Li, K; Jin, LL; Yang, NY; Kong, DY (2009). "5 alpha-reductase and aromatase inhibitory constituents from Brassica rapa L. pollen". Chemical & pharmaceutical bulletin. 57 (4): 401–4. PMID 19336936.
  14. ^ Pandit S. Chauhan NS. Dixit VK."Effect of Cuscuta reflexa Roxb on androgen-induced alopecia." Journal of Cosmetic Dermatology. 7(3):199-204, 2008 Sep.
  15. ^ Flora of China: Euphorbia jolkinii
  16. ^ Park, SH; Kim, JA; Hua, XG (2005). "Isolation of 5α-reductase inhibitors from Euphorbia jolkinii". Korean Journal of Pharmacognosy. 36 (1): 9–16.
  17. ^ Cho, CH; Bae, JS; Kim, YU (2010). "5alpha-reductase inhibitory components as antiandrogens from herbal medicine". Journal of acupuncture and meridian studies. 3 (2): 116–8. doi:10.1016/S2005-2901(10)60021-0. PMID 20633525.
  18. ^ Hirata, N; Tokunaga, M; Naruto, S; Iinuma, M; Matsuda, H (2007). "Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf". Biological & pharmaceutical bulletin. 30 (12): 2402–5. PMID 18057734.
  19. ^ Edgar AD. Levin R. Constantinou CE. Denis L. "A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS.Neurourology & Urodynamics. 26(4):458-63; discussion 464, 2007" [Review]
  20. ^ Raynaud, JP; Cousse, H; Martin, PM (2002). "Inhibition of type 1 and type 2 5alpha-reductase activity by free fatty acids, active ingredients of Permixon". The Journal of steroid biochemistry and molecular biology. 82 (2–3): 233–9. PMID 12477490.
  21. ^ Pais, P (2010). "Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II". Advances in therapy. 27 (8): 555–63. doi:10.1007/s12325-010-0041-6. PMID 20623347.
  22. ^ Abe, M; Ito, Y; Oyunzul, L; Oki-Fujino, T; Yamada, S (2009). "Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract". Biological & pharmaceutical bulletin. 32 (4): 646–50. PMID 19336899.
  23. ^ Roh, SS; Park, MK; Kim, YU (2010). "Abietic acid from Resina Pini of Pinus species as a testosterone 5α-reductase inhibitor". Journal of Health Science. 56 (4): 451–455. doi:10.1248/jhs.56.451.
  24. ^ Roh, SS; Kim, CD; Lee, MH; Hwang, SL; Rang, MJ; Yoon, YK (2002). "The hair growth promoting effect of Sophora flavescens extract and its molecular regulation". Journal of dermatological science. 30 (1): 43–9. PMID 12354419.
  25. ^ Park, WS; Son, ED; Nam, GW; Kim, SH; Noh, MS; Lee, BG; Jang, IS; Kim, SE; Lee, JJ (2003). "Torilin from Torilis japonica, as a new inhibitor of testosterone 5 alpha-reductase". Planta medica. 69 (5): 459–61. doi:10.1055/s-2003-39717. PMID 12802730.
  26. ^ Park, WS; Lee, CH; Lee, BG; Chang, IS (2003). "The extract of Thujae occidentalis semen inhibited 5alpha-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse". Journal of dermatological science. 31 (2): 91–8. PMID 12670719.
  27. ^ Matsuda H., Yamazaki M., Naruto S., Asanuma Y., Kubo M. "Anti-androgenic and hair growth promoting activities of Lygodii Spora (spore of Lygodium japonicum) I. Active constituents inhibiting testosterone 5α-reductase " Biological and Pharmaceutical Bulletin 2002 25:5 (622-626)
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