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 Ketoconazole for pattern baldness
 Antiandrogens for pattern baldness
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Ketoconazole was originally used as a treatment for skin diseases and fungal infections especially in immuno-comprised patients. Ketoconazole is a synthetic antifungal drug that is a derivative of an organic crystalline based Imidazole (whch inhibits histamine) which inhibits steroid biosynthesis and is an effective oral agent having a broad spectrum of anti-fungal activity. High doses of Ketoconazole also have the potential to lower androgens, leading to its use in the treatment of advanced prostate cancer.

Research studies were able to show that ketoconazole inhibits Cytochrome P450 dependant enzymes and this interferes with steroidogenesis in patients. When Ketoconazole interacts with Cytochrome P450 at the heme iron binding sites on cells that can be found in several organs like gonads and adrenals, it destroys the molecule containing iron (heme portion) of Cytochrome P450, inhibiting its action and effectively suppressing the androgen production of the testis and the adrenals.

So far, there have been no extensive clinical trials aiming to prove the efficiency of Ketoconazole apparent with the only anecdotal reports of the use of Ketoconazole in treating hirsutism but none in women with pattern hair loss. Ketoconazole inhibits synthesis of adrenal corticosteroids in the adrenal gland and gonads. A higher concentration of Ketoconazole is needed to affect Cytochrome P450-dependent enzymes in mammals compared with those in fungi. One study tested 39 subjects, 27 of which used 2% Ketoconazole shampoo exclusively 2–4 times a week for 21 weeks while the rest in the control group used an un-medicated shampoo. The group using the Ketoconazole shampoo showed increase in hair density, size and proportion of anagen hair follicles post treatment.

Authors of the study that documented the effects of Ketoconazole on 5a-reductase were asserting that pattern baldness has multi-factorial pathogenesis with an inflammatory reaction caused by a Malassezia fungal infection. They further claim that the effectivity of Ketoconazole lies in the beneficial effects it has on fungal scalp infections in genetically predisposed individuals. The study was concluded with Ketoconazole being restricted in its effects of reducing inflammation through anti-inflammatory properties and by clearing the adjacent fungal infection.

The study of Jaworsky et al, driven by the inflammatory aspect of pattern baldness, showed that the patients with pattern baldness exhibited T-cell infiltration of follicular stem cell epithelium. However, the reliability of this study is largely uncertain since the study only has 4 subjects, 3 among whom were men.

One theory believes that the role played by Ketoconazole in alopecia is the disruption of dihydrotestosterone (DHT) pathway rather than an anti-inflammatory effect. Overproduction of 5a-reductase and an over expression of androgen receptor are the two main reasons why pattern baldness develops in genetically susceptible individuals. Ketoconazole has been noted of causing 5a-reductase inhibition in studies on rats.

All studies on Ketoconazole suggest that it inhibits the production of DHT much like Finasteride. Ketoconazole inhibits the binding of 5a-reductase to sex hormone globulins in humans and the two-fold effect of Ketoconazole binding to human androgen receptors gives it an advantage over Finasteride. The authors believed that Ketoconazole blocks the pathway that leads to the characteristic miniaturization of hair follicles in pattern baldness through its inhibition of DHT and/or inhibiting the binding of DHT to AR.

Ketoconazole causes a reduction in the production of testosterones and other androgens by the adrenal gland and the reproductive organs of both male and female. Ketoconazole is formulated as tropical treatment, a tablet, and a shampoo and could be availed by prescription. Nizoral shampoo contains about 2% Ketoconazole and is prescribed for the treatments of scalp conditions and for pattern baldness in combination with other treatments. There are available 1% version in the over-the-counter although it may not be as effective compared to the 2% prescription strength.

When treating alopecia with Ketoconazole, it is not advised to take it orally as higher concentrations (usually higher than the safety limit) are required to be able to enforce binding. For treatment of pattern baldness, the only tissue that must be subjected with a higher concentration of Ketoconazole is the hair follicle, and direct application of Ketoconazole on the affected area in the form of shampoo is the best treatment option, thus avoiding systemic toxicity. So far, no research study has been made to analyze the systemic absorption or concentration of Ketoconazole when using 2% Ketoconazole shampoo.

There is therefore a need for further clinical analysis to evaluate and establish the effectiveness of Ketoconazole in the treatment of pattern baldness. These trials should also be geared to determine whether the Ketoconazole affects pattern baldness through its effect on inflammations or through its inhibition of the DHT pathway.

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