Hair Loss Study Abstract: Ketoconazole shampoo:
effect of long-term use in androgenic alopecia (genetic hair loss).
Authors: Pierard-Franchimont C. De Doncker P. Cauwenbergh G. Pierard GE.
Institution: Department of Dermatopathology, University of Liege, Belgium.
Title: Ketoconazole shampoo: effect of long-term use in androgenic alopecia.
Source: 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.
Nizoral 1% Study
The effects of chronic use of 1% ketoconazole or a 1% zinc pyrithione shampoo on the general health of hair and scalp.
G. Piérard 1and G. Cauwenbergh2
1. Dept Dermatopathology, University of Liège, Belgium; 2. Skin research Center, Johnson &Johnson , Skillman, N.J., USA
Hundred male volunteers with mild to moderate dandruff and somewhat oily scalp, have used, in a double-blind fashion, a 1% ketoconazole shampoo or a 1% zinc pyrithione shampoo. The test shampoos were applied 2 to 3 times weekly for a total period of 6 months. Several parameters that affect the general health of hair and scalp were assessed at start, and after 1, 3 and 6 months. These parameters included the percent of hairs in anagen phase, the diameter of the hairs, sebum excretion rate at the hairline, and the number of hairs shed in the 24-hour period prior to each assessment. At the end of the study, the participants were asked to complete a questionnaire regarding the cosmetic acceptability of the test shampoos.
Forty-four ketoconazole users and forty-three zinc pyrithione users completed the 6 month study period. Analysis of the different parameters shows that the hair diameter gradually increases with chronic ketoconazole use (+8.46%) over a 6 month period, whereas the diameter shows a trend to decrease with zinc pyrithione use over the same period (-2.28%). The sebum excretion rate is reduced with ketoconazole (-6.54%) while it increases with zinc pyrithione (+8.2%) over the same period of time. The number of hair shed over a 24-hour period is reduced by 16.46% with ketoconazole and 6.02% with zinc pyrithione after 6 months. Finally, the percentage hairs in anagen phase increased by 6.4% and 8.4% respectively during the study time. Except for the percentage of hairs in anagen, which showed no difference between the two groups, all other parameters were significantly different in favor of the ketoconazole shampoo.
Both shampoos have been shown to be good anti-dandruff ingredients. Assessment of parameters than can affect the health of hair and scalp, suggests that both ingredients show distinct differences in the way they affect the scalp; indicating that ketoconazole increases hair diameter and reduces scalp oil, whereas zinc pyrithione seems to yield opposite effects. This suggests that, besides their effect on the lipophilic yeast Malassezia spp, ketoconazole and zinc pyrithione act though quite different mechanisms. An overall analysis of hair diameter changes as a function of changes in sebum excretion rate suggests that a reduction in scalp oiliness seems to result in an increased hair diameter. This suggests that, in people with oily hair, regular use of ketoconazole shampoo may result in overall hair fullness.
Nizoral 1% Effects
Research studies show that Ketoconazole can interfere with steroidogenesis in patients and rat in vitro systems by inhibiting Cytochrome P450 dependant enzymes. The interaction of Ketoconazole with Cytochrome P450 at the heme iron site in several organs, including gonads and adrenals, may result in destruction of the heme portion (molecule containing iron) of Cytochrome P450, thereby inhibiting Cytochrome P-450 and effectively suppresses testicular and adrenal androgen production.
Therefore in the adrenal gland and gonads, Ketoconazole inhibits synthesis of adrenal corticosteroids. However, much higher concentrations are necessary to affect Cytochrome P450-dependent enzymes in mammals compared with those in fungi. Extensive clinical trials to prove the efficacy of Ketoconazole have not been carried out. In fact, there are only anecdotal reports of Ketoconazole use in hirsutism, but none in women with pattern hair loss. In one particular study, 27 subjects used 2% Ketoconazole shampoo exclusively 2–4 times a week for 21 weeks. The remaining 12 in the control group used an un-medicated shampoo. The group using the Ketoconazole shampoo showed results of an increase in hair density, size and proportion of anagen hair follicles post treatment.
Although the effects of Ketoconazole on 5 alpha - reductase had been documented earlier, the authors of the study asserted that androgenetic alopecia has a multi-factorial pathogenesis with an inflammatory reaction caused by a Malassezia fungal infection, and claimed that the Ketoconazole shampoo was probably effective due to its beneficial effect on fungal scalp infections in genetically predisposed individuals. It was concluded that Ketoconazole was therapeutic by reducing inflammation through its anti-inflammatory properties and by clearing the adjacent fungal infection.
Exploration of the inflammatory aspect of androgenetic alopecia was largely based on the results of a biopsy study by Jaworsky et al., showing that androgenetic alopecia patients had signs of T-cell infiltration of follicular stem cell epithelium. However, the veracity of the conclusions drawn from the Jaworsky study is uncertain as the study included 4 subjects and only 3 of them were men.
However, another school of thought believes that the clinical efficacy of Ketoconazole shampoo in the treatment of androgenetic alopecia is primarily a function of dihydrotestosterone (DHT) pathway disruption rather than an anti-inflammatory effect. The development of androgenetic alopecia in genetically susceptible individuals has been linked to an overproduction of 5 -reductase and an over expression of androgen receptor, and in rat studies, Ketoconazole has been seen to cause 5 -reductase inhibition. Additionally, in humans Ketoconazole has also been shown to inhibit the binding of 5 -reductase to sex hormone globulins. All these clinical studies therefore suggest that Ketoconazole may inhibit the production of DHT just like Finasteride. In fact, the effect of Ketoconazole may be two fold, as it has been shown additionally to bind to human androgen receptor, having a distinct advantage over Finasteride. Therefore these authors believe that Ketoconazole inhibits the pathway that leads to the characteristic miniaturization of hair follicles in androgenetic alopecia by inhibiting DHT and/or inhibiting the binding of DHT to AR.
Nizoral 1% Study Shows Benefits for Androgenetic Alopecia
March 04, 2001 - American Academy of Dermatology Meeting - Washington DC - Scientists working for McNeil, makers of Nizoral anti-dandruff shampoo, presented the findings of a study done on 1% Nizoral shampoo which has good news for hair loss sufferers. It has long been known that 2% prescription Nizoral has beneficial effects on Androgenic Alopecia (male pattern baldness). It however has been unclear whether the same benefits can be obtained by using the non-prescription 1% version.
In the study presented (see below), one hundred male volunteers with mild to moderate dandruff and somewhat oily scalp, were using, in a double-blind fashion, either a 1% Nizoral shampoo or a 1% zinc pyrithione shampoo, 2-3 times a week for 6 months.
Analysis of the different parameters set up in the study shows that the hair diameter gradually increased with Nizoral use (+8.46%) over a 6 month period, whereas the diameter showed a trend to decrease with zinc pyrithione use over the same period (-2.28%). The sebum excretion rate was reduced with Nizoral (-6.54%) while it increased with zinc pyrithione (+8.2%) over the same period of time. The number of hair shed over a 24-hour period was reduced by 16.46% with Nizoral and 6.02% with zinc pyrithione after 6 months. Finally, the percentage hairs in anagen phase increased by 6.4% and 8.4% respectively during the study time.
The results are similar to a previous study done on 2% prescription strength Nizoral where it was shown that use of 2% Nizoral yielded a 7% average increase in hair shaft diameter similar to what was achieved by the control group using 2% Minoxidil and a non-medicated shampoo.
So for any hair loss sufferer, this research clearly indicates that using 1% or 2% Nizoral 2-3 times per week, will have positive effects on hair growth as well as controlling dandruff. It is still unclear at this time whether it's the anti-fungal properties or the anti-androgenic properties of Ketokonazole (active ingredient in Nizoral) thats responsible for the hair thickening effects, however because of the decrease in sebum rates as well, it is the authors opinion that the results are due to the anti-androgenic properties of Ketokonazole.
