A Narrowed Look Into Plant-Derived Testosterone 5α-Reductase Inhibitors for Androgenetic Alopecia

Year 2024, , 58 - 72, 06.07.2024

Nurten Abacı , İlkay Erdoğan Orhan

https://doi.org/10.38093/cupmap.1464497

Abstract

Androgenetic alopecia (AGA) is the most prevalent cause of hair loss in men and women, resulting from a combination of genetic susceptibility and androgen hormones. Increased activity of testosterone 5α-reductase in hair follicles leads to increased synthesis of dihydrotestosterone (DHT). DHT's destructive effect on hair follicles is one of the leading reasons for hair loss. Conventional pharmacotherapeutic treatments, e.g. finasteride and minoxidil, are frequently accompanied by adverse effects and may be ineffective for certain people. Recent years have seen a rise in research on plant-derived testosterone 5α-reductase enzyme inhibitors. These herbal substances produced by various plant extracts and natural ingredients show promise in terms of fewer side effects and improved tolerability. This mini review investigates herbal testosterone 5α-reductase inhibitors for treatment AGA.

Keywords

Androgenetic alopecia, testosterone, 5α-reductase, 5α-reductase inhibitors, herbal 5α-reductase inhibitors

Ethical Statement

none

Supporting Institution

none

Thanks

none

References

• 1. Adamowicz, R., Załęcki, P., Dukiel, A., & Nowicka, D. (2022). Association between androgenetic alopecia and psychosocial disease burden: A cross-sectional survey among Polish men. Dermatology Research and Practice, 2022. doi:10.1155/2022/1845044.
• 2. Al Najjar, O. A., Alkhars, M. A., Al Molhim, S. F., AlAjmi, M. S., Alhafith, A. A., Al Najjar, M. A., & Alajmi, M. S. (2023). The impact of androgenic alopecia on the quality of life of male individuals: A cross-sectional study. Cureus, 15(10). doi:10.7759/cureus.47760.
• 3. Alves, R. (2017). Androgenetic alopecia: a review and emerging treatments. Clinical Research in Dermatology, 4(04), 1-13. doi:10.15226/2378-1726/4/4/00164.
• 4. Alzaid, M. Y. M. (2023). Dutasteride for androgenetic alopecia. The Egyptian Journal of Hospital Medicine, 90(1), 1098-1101. doi:10.21608/EJHM.2023.280264.
• 5. Aukerman, E. L., & Jafferany, M. (2023). The psychological consequences of androgenetic alopecia: A systematic review. Journal of Cosmetic Dermatology, 22(1), 89-95. doi:10.1111/jocd.14983 .
• 6. Burns, T., Breathnach, S. M., Cox, N., & Griffiths, C. (2008). Rook's Textbook of Dermatology: John Wiley & Sons.
• 7. Chaiyana, W., Punyoyai, C., Somwongin, S., Leelapornpisid, P., Ingkaninan, K., Waranuch, N., & Schuster, R. (2017). Inhibition of 5α-reductase, IL-6 secretion, and oxidation process of Equisetum debile Roxb. ex vaucher extract as functional food and nutraceuticals ingredients. Nutrients, 9(10), 1105. doi:10.3390/nu9101105.
• 8. Chan, L., & Cook, D. K. (2018). Female pattern hair loss. Australian Journal of General Practice, 47(7), 459-464. doi:10.31128/AJGP-02-18-4498.
• 9. Chittur, S., Parr, B., & Marcovici, G. (2011). Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evidence-Based Complementary and Alternative Medicine, 2011. doi:10.1093/ecam/nep102.
• 10. Cho, C. H., Bae, J. S., & Kim, Y. U. (2010). 5α-Reductase inhibitory components as antiandrogens from herbal medicine. Journal of Acupuncture and Meridian Studies, 3(2), 116-118. doi:10.1016/S2005-2901(10)60021-0.
• 11. Choi, G. S., Sim, W. Y., Kang, H., Huh, C. H., Lee, Y. W., Shantakumar, S., & Cheng, W. Y. (2022). Long-term effectiveness and safety of dutasteride versus finasteride in patients with male androgenic alopecia in South Korea: A multicentre chart review study. Annals of Dermatology, 34(5), 349. doi:10.5021/ad.22.027.
• 12. Choi, H. M., Jung, Y., Park, J., Kim, H. L., Youn, D. H., Kang, J., & Lee, S. G. (2016). Cinnamomi cortex (Cinnamomum verum) suppresses testosterone-induced benign prostatic hyperplasia by regulating 5α-reductase. Scientific Reports, 6(1), 31906. doi:10.1038/srep31906.
• 13. Chumlea, W. C., Rhodes, T., Girman, C. J., Johnson-Levonas, A., Lilly, F. R., Wu, R., & Guo, S. S. (2004). Family history and risk of hair loss. Dermatology, 209(1), 33-39. doi:10.1159/000078584.
• 14. Cwynar, A., Olszewska-Słonina, D., & Czajkowski, R. (2020). The impact of oxidative stress in the androgenic alopecia in women. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 37(1), 119-120. doi:10.5114/ada.2019.81685.
• 15. Dallob, A., Sadick, N., Unger, W., Lipert, S., Geissler, L., Gregoire, S., & Tanaka, W. (1994). The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. The Journal of Clinical Endocrinology & Metabolism, 79(3), 703-706. doi:10.1210/jcem.79.3.8077349.
• 16. De Lacharrière, O., Deloche, C., Misciali, C., Piraccini, B. M., Vincenzi, C., Bastien, P., & Tosti, A. (2001). Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Archives of Dermatology, 137(5), 641-646.
• 17. Devjani, S., Ezemma, O., Kelley, K. J., Stratton, E., & Senna, M. (2023). Androgenetic alopecia: Therapy update. Drugs, 83(8), 701-715. doi:10.1007/s40265-023-01880-x.
• 18. Dhanotia, R., Chauhan, N. S., Saraf, D. K., & Dixit, V. K. (2011). Effect of Citrullus colocynthis Schrad fruits on testosterone-induced alopecia. Natural Product Research, 25(15), 1432-1443. doi:10.1080/14786410802632820.
• 19. Ellis, J. A., Sinclair, R., & Harrap, S. B. (2002). Androgenetic alopecia: pathogenesis and potential for therapy. Expert Reviews in Molecular Medicine, 4(22), 1-11.
• 20. Feldman, P. R., Gentile, P., Piwko, C., Motswaledi, H. M., Gorun, S., Pesachov, J., & Feldman, O. J. (2023). Hair regrowth treatment efficacy and resistance in androgenetic alopecia: A systematic review and continuous Bayesian network meta-analysis. Frontiers in Medicine, 9, 3800. doi:10.3389/fmed.2022.998623.
• 21. Fischer, T. W., Hipler, U., & Elsner, P. (2007). Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. International Journal of Dermatology, 46(1), 27-35. doi:10.1111/j.1365-4632.2007.03119.x.
• 22. Fus-Mazurkiewicz, L., Nowiński, M., Sak, J., Mazurkiewicz, W., & Król, D. (2024). Review of current knowledge and management of androgenetic alopecia. Polish Journal of Applied Sciences, 9(3), 32-35. doi:10.34668/PJAS.2023.9.3.05.
• 23. Guerrero, A. R., & Ch, M. K. (2011). Alopecias. Revista Médica Clínica Las Condes, 22(6), 775-783.
• 24. Hamilton, J. B. (1951). Patterned loss of hair in man: types and incidence. Annals of the New York Academy of Sciences, 53(3), 708-728. doi:10.1111/j.1749-6632.1951.tb31971.x.
• 25. Hirata, N., Tokunaga, M., Naruto, S., Iinuma, M., & Matsuda, H. (2007). Testosterone 5α-reductase inhibitory active constituents of Piper nigrum leaf. Biological and Pharmaceutical Bulletin, 30(12), 2402-2405. doi:10.1248/bpb.30.2402.
• 26. Hong, G. L., Park, S. R., Jung, D. Y., Karunasagara, S., Lee, K. P., Koh, E. J., & Jung, J. Y. (2020). The therapeutic effects of Stauntonia hexaphylla in benign prostate hyperplasia are mediated by the regulation of androgen receptors and 5α-reductase type 2. Journal of Ethnopharmacology, 250, 112446. doi:10.1016/j.jep.2019.112446
• 27. Hsu, J., & Anthony, W. (1971). Impairment of cystine-35S incorporation into skin protein by zinc-deficient rats. The Journal of Nutrition, 101(4), 445-452. doi:10.1093/jn/101.4.445.
• 28. Inui, S., Fukuzato, Y., Nakajima, T., Yoshikawa, K., & Itami, S. (2003). Identification of androgen-inducible TGF-β1 derived from dermal papilla cells as a key mediator in androgenetic alopecia. Paper presented at the Journal of Investigative Dermatology Symposium Proceedings.
• 29. Jenkins, B. J., & Powell, B. C. (1994). Differential expression of genes encoding a cysteine-rich keratin family in the hair cuticle. Journal of Investigative Dermatology, 103(3), 310-317. doi:10.1111/1523-1747.ep12394770.
• 30. Kaliyadan, F. (2022). Androgenetic alopecia–Medical management. Clinical Dermatology Review, 6(2), 75-79. doi:10.4103/cdr.cdr2721.
• 31. Karaca, N., & Akpolat, N. D. (2019). A comparative study between topical 5% minoxidil and topical “Redensyl, Capixyl, and Procapil” combination in men with androgenetic alopecia. Journal of Cosmetology & Trichology, 150370987. doi:10.4172/2471-9323.1000140.
• 32. Karunasagara, S., Hong, G. L., Jung, D. Y., Kim, K. H., Cho, K., & Jung, J. Y. (2020). Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α-reductase type 2 and induced cell apoptosis. Public Library of Science One, 15(8), e0236879. doi:10.1371/journal.pone.0236879.
• 33. Katharina, W., Wolf‐Bernhard, S., & Christoph, L. (2004). Diseases on hair follicles leading to hair loss part I: nonscarring alopecias. SKINmed: Dermatology for the Clinician, 3(4), 209-214. doi:10.1111/j.1540-9740.2004.02326.x.
• 34. Kaya Erdogan, H., Bulur, I., Kocaturk, E., Yildiz, B., Saracoglu, Z. N., & Alatas, O. (2017). The role of oxidative stress in early‐onset androgenetic alopecia. Journal of Cosmetic Dermatology, 16(4), 527-530.
• 35. Koseki, J., Matsumoto, T., Matsubara, Y., Tsuchiya, K., Mizuhara, Y., Sekiguchi, K., & Hattori, T. (2015). Inhibition of rat 5α-reductase activity and testosterone-induced sebum synthesis in hamster sebocytes by an extract of Quercus acutissima cortex. Evidence-Based Complementary and Alternative Medicine, 2015. doi:10.1155/2015/853846.
• 36. Kumar, N., Rungseevijitprapa, W., Narkkhong, N.A., Suttajit, M., & Chaiyasut, C. (2012). 5α-Reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment. Journal of Ethnopharmacology, 139(3), 765-771. doi:10.1016/j.jep.2011.12.010.
• 37. Küster, W., & Happle, R. (1984). The inheritance of common baldness: Two B or not two B? Journal of the American Academy of Dermatology, 11(5), 921-926. doi:10.1016/s0190-9622(84)80498-3. 38. Lee, C. J., Chen, L. G., Chang, T. L., Ke, W. M., Lo, Y. F., & Wang, C. C. (2011). The correlation between skin-care effects and phytochemical contents in Lamiaceae plants. Food Chemistry, 124(3), 833-841. doi:10.1016/j.foodchem.2010.07.003.
• 39. Liu, D., Xu, Q., Meng, X., Liu, X., & Liu, J. (2024). Status of research on the development and regeneration of hair follicles. International Journal of Medical Sciences, 21(1), 80. doi:10.7150/ijms.88508.
• 40. Loing, E., Lachance, R., Ollier, V., & Hocquaux, M. (2013). A new strategy to modulate alopecia using a combination of two specific and unique ingredients. Journal of Cosmetic Science, 64(1), 45-58.
• 41. Lolli, F., Pallotti, F., Rossi, A., Fortuna, M. C., Caro, G., Lenzi, A., & Lombardo, F. (2017). Androgenetic alopecia: a review. Endocrine, 57, 9-17. doi:10.1007/s12020-017-1280-y.
• 42. Ludwig, E. (1977). Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. British Journal of Dermatology, 97(3), 247-254. doi:10.1111/j.1365-2133.1977.tb15179.x.
• 43. Lyakhovitsky, A., Tzanani, I., Gilboa, S., Segal, O., Galili, E., Baum, S., & Barzilai, A. (2023). Changing spectrum of hair and scalp disorders over the last decade in a tertiary medical centre. Journal of the European Academy of Dermatology and Venereology, 37(1), 184-193. doi:10.1111/jdv.18570.
• 44. Madaan, A., Verma, R., Singh, A. T., & Jaggi, M. (2018). Review of hair follicle dermal papilla cells as in vitro screening model for hair growth. International journal of Cosmetic Science, 40(5), 429-450. doi:10.1111/ics.12489.
• 45. Murata, K., Noguchi, K., Kondo, M., Onishi, M., Watanabe, N., Okamura, K., & Matsuda, H. (2012). Inhibitory activities of Puerariae Flos against testosterone 5α-reductase and its hair growth promotion activities. Journal of Natural Medicines, 66, 158-165. doi:10.1007/s11418-011-0570-6.
• 46. Murata, K., Noguchi, K., Kondo, M., Onishi, M., Watanabe, N., Okamura, K., & Matsuda, H. (2013). Promotion of hair growth by Rosmarinus officinalis leaf extract. Phytotherapy Research, 27(2), 212-217.
• 47. Murata, K., Takeshita, F., Samukawa, K., Tani, T., & Matsuda, H. (2012). Effects of ginseng rhizome and ginsenoside Ro on testosterone 5α‐reductase and hair re‐growth in testosterone‐treated mice. Phytotherapy Research, 26(1), 48-53. doi:10.1002/ptr.3511.
• 48. Nahata, A., & Dixit, V. (2014). Evaluation of 5α‐reductase inhibitory activity of certain herbs useful as antiandrogens. Andrologia, 46(6), 592-601. doi:10.1111/and.12115.
• 49. Nestor, M. S., Ablon, G., Gade, A., Han, H., & Fischer, D. L. (2021). Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics. Journal of Cosmetic Dermatology, 20(12), 3759-3781. doi:10.1111/jocd.14537.
• 50. Norwood, O. T. (1975). Male pattern baldness: classification and incidence. Southern Medical Journal, 68(11), 1359-1365. doi:10.1097/00007611-197511000-00009.
• 51. Ntshingila, S., Oputu, O., Arowolo, A. T., & Khumalo, N. P. (2023). Androgenetic alopecia: An update. The Journal of the American Academy of Dermatology, 13, 150-158. doi:10.1016/j.jdin.2023.07.005.
• 52. Osborn, D. (1916). Inheritance of baldness: various patterns due to heredity and sometimes present at birth—a sex-limited character—dominant in man—women not bald unless they inherit tendency from both parents. Journal of Heredity, 7(8), 347-355. doi:10.1093/oxfordjournals.jhered.a110746.
• 53. Patel, S., Nag, M. K., Sharma, V., Chauhan, N. S., & Dixit, V. (2014). A comparative in vivo and in vitro evaluation of hair growth potential of extracts and an isolate from petroleum ether extract of Cuscuta reflexa Roxb. Beni-Suef University Journal of Basic and Applied Sciences, 3(3), 165-171. doi:10.1016/j.bjbas.2014.10.002.
• 54. Piraccini, B., & Alessandrini, A. (2014). Androgenetic alopecia. Italian Journal of Dermatology and Venereology, 149(1), 15-24.
• 55. Prie, B., Iosif, L., Tivig, I., Stoian, I., & Giurcaneanu, C. (2016). Oxidative stress in androgenetic alopecia. Journal of Medicine and Life, 9(1), 79.
• 56. Rossi, A., Anzalone, A., Fortuna, M. C., Caro, G., Garelli, V., Pranteda, G., & Carlesimo, M. (2016). Multi‐therapies in androgenetic alopecia: Review and clinical experiences. Dermatologic Therapy, 29(6), 424-432. doi:10.1111/dth.12390.
• 57. Semalty, M., Semalty, A., Joshi, G. P., & Rawat, M. S. M. (2011). Hair growth and rejuvenation: an overview. Journal of Dermatological Treatment, 22(3), 123-132. doi:10.3109/09546630903578574.
• 58. Sperling, L. (2008). Alopecias In: Bolognia JL, Jorrizzo JL, Rapini RP, Dermatology. In: New York, NY: Mosby.
• 59. Trilisnawati, D., Diba, S., Kurniawati, Y., Nugroho, S. A., Rusmawardiana, R., & Pamudji, R. (2021). Update treatment of male androgenetic alopecia. International Journal of Dermatology and Venereology, 33, 63-71. doi:10.20473/bikk.V33.1.2021.63-71.
• 60. Trüeb, R. M. (2009). Oxidative stress in ageing of hair. International Journal of Trichology, 1(1), 6-14. doi:10.4103/0974-7753.51923.
• 61. Tusubira, D., Aja, P. M., Munezero, J., Ssedyabane, F., Namale, N., Ifie, J. E., & Okoboi, J. (2023). Safety profile of colocasia esculenta tuber extracts in benign prostate hyperplasia. BMC Complementary Medicine and Therapies, 23(1), 187. doi:10.1186/s12906-023-04018-4
• 62. Upadhyay, S., Ghosh, A. K., & Singh, V. (2012). Hair growth promotant activity of petroleum ether root extract of Glycyrrhiza glabra L. (Fabaceae) in female rats. Tropical Journal of Pharmaceutical Research, 11(5), 753-758. doi:10.4314/TJPR.V11I5.8.
• 63. Xiao, F. L., Yang, S., Liu, J. B., He, P. P., Yang, J., Cui, Y., & Zhang, X. J. (2006). The epidemiology of childhood alopecia areata in China: A study of 226 patients. Pediatric Dermatology, 23(1), 13-18. doi:10.1111/j.1525-1470.2006.00161.x.
• 64. Yorulmaz, A. (2016). Androgenetik alopesi. Çağdaş Tıp Dergisi, 6(3), 248-254. doi:10.16899/ctd.45565.
• 65. Zhang, B., Zhang, R. W.., Yin, X. Q., Lao, Z. Z., Zhang, Z., Wu, Q. G., & Li, G. (2016). Inhibitory activities of some traditional Chinese herbs against testosterone 5α-reductase and effects of Cacumen platycladi on hair re-growth in testosterone-treated mice. Journal of Ethnopharmacology, 177, 1-9. doi:10.1016/j.jep.2015.11.012.
• 66. Winner, K., Polycarp, O., Ifeoma, I., & Chinedum, E. (2016). Effect of fractions of kolaviron on some indices of benign prostatic hyperplasia in rats: identification of the constituents of the bioactive fraction using GC-MS. Royal Society of Chemistry Advance, 6(97), 94352-94360. doi:10.1039/C6RA18266F