In the search for various treatments for hair loss, sometimes we discover treatments that were visible in plain sight for years but were not used for the purpose of hair thinning prevention.
One of these is ketoconazole – a medicine used to treat fungal infections for decades but only recently saw a spike in interest for its potential in hair loss treatment. Let’s talk a bit about this ingredient, its role in alopecia, and where we see it coming into use to treat hair loss.
What is ketoconazole?
Ketoconazole is an imidazole derivative and is primarily used as an antifungal agent since it inhibits fungal cell wall formation. It is often present in various anti-dandruff and anti-hair loss shampoos or in creams and lotions to treat tinea infections and seborrheic dermatitis.
It also exerts anti-inflammatory activity by blocking the mediators that cause the inflammation. Besides, it also blocks testosterone hormone synthesis.
Ketoconazole’s role in the treatment of hair loss
Ketoconazole works in androgenetic alopecia by two primary mechanisms:
1. Reducing inflammation and microorganism growth:
One of the hypotheses of what causes androgenetic alopecia revolves around mild inflammation around the hair follicles in the balding area. Seborrhea or oily scalp is a common finding in people with male pattern hair loss, which causes the growth of lipophilic (oil-loving) microbes like the fungus Malassezia furfur.
The inflammation is triggered by these microbes present around the hair follicle. Androgenetic alopecia is further worsened by the acute phases of other inflammatory skin and scalp diseases like seborrheic dermatitis, psoriasis, etc.
Ketoconazole works as an anti-inflammatory and antimicrobial agent, especially against lipophilic microbes like Malassezia and Staphylococcus, to restore the normal ecosystem of the hair follicle and thus, reducing hair loss. Ketoconazole’s anti-inflammatory action is almost comparable to a mild steroid.
2. As an anti-androgen:
Androgen (testosterone, which eventually gets converted to dihydrotestosterone by the enzyme 5-alpha-reductase) and its binding to androgen receptors on hair follicles are the most important factors which cause androgenetic alopecia.
People predisposed to androgenetic alopecia or pattern hair loss usually have increased 5-alpha reductase production and increased expression of receptors that bind to androgen.
The most effective therapy for androgenetic alopecia is oral/ topical finasteride, which reduces DHT levels but doesn’t prevent it from binding to the receptors. In high doses, oral ketoconazole is known to have anti-androgen effects.
Ketoconazole can potentially inhibit DHT production and its binding to hormone receptors. Therefore, it is believed that external use will also show anti-androgen effects and will be effective in hormonal hair loss, especially to boost the action of existing treatments like finasteride, causing the complete blockage of DHT.
Effective forms of ketoconazole for hair loss:
Oral ketoconazole has not been investigated for its effectiveness against hair loss. Various topical application methods, on the other hand, have been studied for its usefulness in reducing the androgenetic alopecia and promoting hair growth:
The primary and most practical way to integrate ketoconazole in an anti-hair loss routine is using a 2% ketoconazole shampoo commonly available in drug stores and pharmacies as an anti-dandruff or anti-seborrheic dermatitis solution.
It is important to leave the shampoo on for 3-5 minutes after application to facilitate decent penetration of ketoconazole in the hair follicles.
In very mild hair loss, it can be used alone or combined with minoxidil and/or finasteride for moderate and severe patterned hair loss.
A small study with 39 subjects comparing 2% ketoconazole shampoo with unmedicated shampoo, 2-4 times a week, over 21 months showed that the ketoconazole group had an increased mean hair diameter as opposed to the non-medicated shampoo, which showed a decrease in hair diameter over this duration.
A small subset of the ketoconazole shampoo group (4 subjects) was then compared for its effects against minoxidil 2% after six months. A mean increase in hair diameter of 7% was seen in both the groups (which is important since hormonal hair loss is associated with the miniaturization of hair follicles), and a greater increase in hair density was seen in the ketoconazole group as compared to 2% minoxidil group.
The ketoconazole group also showed an increase in the anagen (growth phase) hair follicle. It also demonstrated a decrease in the mean sebaceous gland area, which, in contrast, was shown to be increased in the minoxidil group.
It is to be noted that the subjects that were selected for the study did not have any dandruff and seborrheic dermatitis.
Although the study may be too small to conclusively state that ketoconazole shampoo is better than minoxidil in androgenetic alopecia, it could be said that 2% ketoconazole shampoo does help in improving pattern hair loss.
Another study with 100 patients comparing various regimens in androgenetic alopecia showed that a combination of 2% ketoconazole shampoo thrice weekly and oral finasteride is superior to oral finasteride alone, as well as topical minoxidil alone in reducing the hair fall and promotion of hair growth.
The results obtained through combined ketoconazole shampoo and finasteride were almost comparable to a combination of oral finasteride and topical minoxidil.
There is another study conducted on 150 men with telogen effluvium (stress or deficiency induced hair loss) and hormonal hair loss. The subjects were assigned to three groups receiving either 1% ketoconazole, 1% piroctone olamine, or 1% zinc pyrithione shampoos.
Hair shedding decreased in all groups, but the ketoconazole group showed the highest reduction in hair loss. Besides, hair diameter also increased in the ketoconazole group, whereas it decreased in the zinc pyrithione group.
Interestingly, this effect was more prominent in the telogen effluvium group than the androgenetic alopecia group.
Ketoconazole leave-in formulation:
Ketoconazole leave-in formulations have been shown to stimulate hair growth in mice by converting hair follicles from the telogen (shedding) phase to anagen (growth) phase. Another study on mice showed that Ketoconazole leave-in solution increases the mean diameter and number of hair follicles as early as 21 days after use.
However, there is no reliable documented evidence of the efficacy of a leave-in formulation of ketoconazole in humans.
A very small study with six patients treated with 2% ketoconazole daily showed improvement in 3 of them after several months of use, with hair loss recurring after stopping the treatment in one of them. The study, however, is small, inconsistent, and qualitatively inadequate.
Side effects and limitations
Even though ketoconazole may be touted as a relatively safe therapy option, the following must be kept in mind before starting its use:
Topical minoxidil and finasteride are the only FDA-approved treatments for androgenetic hair loss. They come with their share of limitations (since not all patients respond adequately), side effects, and controversies. Thus, the search for safer and effective long-term therapy continues- as a booster to existing therapy or as an alternative.
The exact mechanism behind ketoconazole’s anti-air loss action is unclear: is it hormonal, anti-inflammatory, or both?
Even though there are no large-scale studies or evidence for ketoconazole’s role in androgenetic alopecia, ketoconazole 2% shampoo seems like a promising and low-risk adjunct to therapy for androgenetic alopecia.