5-alpha-reductase inhibitor
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]
Adverse drug reactions
In general, adverse drug reactions (ADRs) experienced with 5α-reductase inhibitors are dose-dependent. Common ADRs include impotence, decreased libido, decreased ejaculate volume, depression, and anxiety. Rare ADRs include breast tenderness and enlargement (gynecomastia), and allergic reaction.[1][2]
The FDA has notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).[3]
Pharmacology
The enzyme 5α-reductase is involved in the conversion of testosterone to the active form dihydrotestosterone (DHT) 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.
Examples
- Pharmaceuticals
- Research chemicals
Zinc,[5] azelaic acid,[5] β-sitosterol,[6] certain unsaturated aliphatic fatty acids such as gamma-linolenic acid, alpha-linolenic acid, linoleic acid, and oleic acid,[7] and a variety of polyphenols[8] have been found to inhibit 5α-reductase activity to varying degrees.
Certain pesticides are able to disturb the sex steroid hormone system and to act as antiandrogens.[9]
Herbs
Many chemical compounds in nature are able to inhibit 5α-reductase, such as those found in the Reishi mushroom Ganoderma lucidum.[4][10][11] Ganoderic acid[12] or organoderol B may be the active compounds.[13]
Medium chain fatty acids such as those found in coconut and the kernel of many palm fruits have also been found to inhibit 5α-reductase.[14]
Other herbs include:
None of these plants have been tested in human clinical trials and their potential for the treatment of BPH and related conditions is unknown.
References
- ^ a b Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2
- ^ Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A (2006). "Finasteride induced depression: a prospective study". BMC Clinical Pharmacology 6: 7. doi:10.1186/1472-6904-6-7. PMC 1622749. PMID 17026771. http://www.biomedcentral.com/1472-6904/6/7.
- ^ http://www.drugs.com/fda/5-alpha-reductase-inhibitors-5-aris-label-change-increased-risk-prostate-cancer-12977.html
- ^ a b Liu J, Kurashiki K, Shimizu K, Kondo R (February 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.
- ^ a b Stamatiadis D, Bulteau-Portois MC, Mowszowicz I (November 1988). "Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid". The British Journal of Dermatology 119 (5): 627–32. doi:10.1111/j.1365-2133.1988.tb03474.x. PMID 3207614.
- ^ Cabeza M, Bratoeff E, Heuze I, Ramírez E, Sánchez M, Flores E (2003). "Effect of beta-sitosterol as inhibitor of 5 alpha-reductase in hamster prostate". Proceedings of the Western Pharmacology Society 46: 153–5. PMID 14699915.
- ^ Liang T, Liao S (July 1992). "Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids". The Biochemical Journal 285 ( Pt 2): 557–62. PMID 1637346.
- ^ Hiipakka RA, Zhang HZ, Dai W, Dai Q, Liao S (March 2002). "Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols". Biochemical Pharmacology 63 (6): 1165–76.
- ^ 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.
- ^ 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.
- ^ Noguchi, M; Kakuma, T; Tomiyasu, K; Yamada, A; Itoh, K; Konishi, F; Kumamoto, S; Shimizu, K et al. (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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Plants for a Future: Angelica koreana
- ^ 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.
- ^ Oku H. Ishiguro K.,"Cyclooxygenase-2 inhibitory 1,4-naphthoquinones from Impatiens balsamina L.", Biological & Pharmaceutical Bulletin. 25(5):658-60, 2002 May
- ^ 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.
- ^ 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.
- ^ Flora of China: Euphorbia jolkinii
- ^ Park, SH; Kim, JA; Hua, XG (2005). "Isolation of 5α-reductase inhibitors from Euphorbia jolkinii". Korean Journal of Pharmacognosy 36 (1): 9–16.
- ^ Fujita R. Liu J. Shimizu K. Konishi F. Noda K. Kumamoto S. Ueda C. Tajiri H. Kaneko S. Suimi Y. Kondo R."Anti-androgenic activities of Ganoderma lucidum.", Journal of Ethnopharmacology. 102(1):107-12, 2005 Oct 31.
- ^ 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.
- ^ 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.
- ^ 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]
- ^ 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. doi:10.1016/S0960-0760(02)00187-5. PMID 12477490.
- ^ 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.
- ^ 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. doi:10.1248/bpb.32.646. PMID 19336899.
- ^ 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.
- ^ 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.
- ^ Park, WS; Son, ED; Nam, GW; Kim, SH; Noh, MS; Lee, BG; Jang, IS; Kim, SE et al. (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.
- ^ 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.
- ^ 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)