Scientific References:
Ketoconazole as an adjunct to finasteride (Propecia) in the treatment of androgenetic alopecia in men .
Hugo Perez California College of Podiatric Medicine, 371 Columbus Avenue, San Francisco, CA 94133, USA Medical Hypotheses, Volume 62, Issue 1, Pages 112-115
Dihydrotestosterone (DHT) binding to androgen receptors (AR) in hair follicles is commonly accepted as the first step leading to the miniaturizing of follicles associated with androgenetic alopecia (AGA). Testosterone is converted to DHT by the enzyme 5α-reductase. Finasateride a 5α-reducase inhibitor blocks the production of DHT and is currently used to treat AGA. The inhibition is not complete but a reduction of DHT systemically and in the scalp is accomplished. Ketoconazole has been clinically shown to be effective in the treatment of AGA. In this paper, evidence is presented to support the hypothesis that ketoconazole 2% shampoo has a local disruption of the DHT pathway. It is proposed that using ketoconazole 2% shampoo as an adjunct to finasteride treatment could lead to a more complete inhibition of DHT and thus better treat AGA.
Reversal of androgenetic alopecia by topical ketoconazole: Relevance of anti-androgenic activity.
Shigeki Inui, Satoshi Itami, Journal of Dermatological Science - January 2007 (Vol. 45, Issue 1, Pages 66-68, DOI: 10.1016/j.jdermsci.2006.08.011)
Ketoconazole (KCZ), an imidazole anti-fungal agent, is known to be effective for the treatment of seborrheic dermatitis and dandruff. In addition, 2% KCZ shampoo was found to improve hair density and the size and proportion of anagen follicles in androgenetic alopecia (AGA) and, in combination with finasteride, to have an additive effect for AGA. Six Japanese males from 23 to 51 years old were enrolled in this study with their written informed consent. They presented with grade II vertex to IVa AGA according to the Hamilton–Norwood classification. The subjects applied topical 2% KCZ lotion (Nizoral®) almost every day during or immediately after hair washing with their own unmedicated shampoos. When they revisited our clinic every several months, clinical pictures were obtained to determine the efficacy of the treatment. Two of the men, one 23 years old with grade II vertex and the other 25 years old with Va AGA, showed remarkable hair regrowth after 6 and 10 months, respectively. The 23-year-old male stopped using KCZ and 3 months later hair loss recurrence on the vertex was noted. When he started using KCZ again during shampooing, hairs on the vertex grew again after 3 months. These findings constitute evidence of the clinical efficacy of KCZ for AGA. A 41-year-old male showed a slight increase in vertex hair growth after 1 year. Other three of the men, 31, 38 and 51 years old did not show significant improvement.
Ketoconazole shampoo: effect of long-term use in androgenic alopecia (genetic hair loss). Pierard-Franchimont C. De Doncker P. Cauwenbergh G. Pierard GE. Department of Dermatopathology, University of Liege, Belgium.Dermatology. 196(4):474-7, 1998.
BACKGROUND: The pathogenesis of androgenic alopecia is not fully understood. A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly.
OBJECTIVE: The aim of our study was to determine if ketoconazole (KCZ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia.
METHOD: The effect of 2% KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2% minoxidil therapy. RESULTS: Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens. The sebum casual level appeared to be decreased by KCZ. CONCLUSION: Comparative data suggest that there may be a significant action of KCZ upon the course of androgenic alopecia and that Malassezia spp. may play a role in the inflammatory reaction. The clinical significance of the results awaits further controlled study in a larger group of subjects.
Minoxidil is a vasodilator and was exclusively used as an oral drug (Loniten®) to treat high blood pressure. It was, however, discovered to have the interesting side-effect of hair growth and reversing baldness, and in the 1980s, Upjohn Corporation produced a topical solution that contained 2% minoxidil to be used to treat baldness and hair loss, under the brand name Rogaine® in the United States, and Rogaine® outside the United States. Treatments usually include a 5% concentration solutions that are designed for men, whereas the 2% concentration solutions are designed for women. It is unknown how the drug stimulates hair growth. In 2007 a novel, foam-based formulation of 5% Minoxidil was shown to be an effective treatment of androgenetic alopecia without the usual side-effects of the topical solution. Minoxidil is a “potassium channel agonist.” It contains the chemical structure of nitric oxide (NO), a blood vessel dilator, and may be a nitric oxide agonist. This may explain Minoxidil’s ability to stimulate hair growth and treat hair loss. The patent on Minoxidil expired on February 13, 1996.
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