Ketoconazole shampoo for hair loss

What ketoconazole shampoo is

Ketoconazole belongs to the imidazole antifungals, active ingredients against fungi. As a 2 percent shampoo or solution it is approved in Germany for seborrheic dermatitis of the scalp and for pityriasis versicolor, without prescription but only in pharmacies. As a tablet, it now plays a role only in Cushing’s syndrome.

In hair loss research, the shampoo has appeared since the late 1990s: as an inexpensive add-on to minoxidil and finasteride, with a different point of attack. What is rated here is the state of knowledge. It is enough for a plausible hypothesis and some encouraging small studies, not for robust proof of efficacy.

How it works

In fungi, ketoconazole inhibits the formation of ergosterol, a building block of the cell membrane. On the scalp, this affects the Malassezia yeasts that are involved in dandruff and seborrheic dermatitis. The hypothesis for hair loss: inflammation around the hair follicles triggered by these yeasts could aggravate hereditary hair loss, and ketoconazole also has an anti-inflammatory effect.

An antiandrogenic effect is also frequently mentioned. What is established is that ketoconazole inhibits enzymes of steroid synthesis in the adrenal gland within the body; that is why it is approved as a tablet for Cushing’s syndrome. For the shampoo, such an effect on the scalp has not been shown. According to the prescribing information, ketoconazole is not measurable in the blood after application to the scalp, whereas it is after application to the whole body.

What the studies show

Piérard-Franchimont 1998: the comparison with minoxidil

The research group compared 2 percent ketoconazole shampoo with a shampoo without active ingredient, each with or without 2 percent minoxidil. Hair density, hair thickness and the proportion of growing hairs improved to a similar extent under ketoconazole and under minoxidil, and the amount of sebum on the scalp decreased under ketoconazole. The authors interpreted this as an indication of a role for Malassezia yeasts and themselves called for larger controlled studies.

Piérard-Franchimont 2002: three anti-dandruff shampoos

150 men with hair loss and dandruff were randomly assigned to one of three shampoos with 1 percent ketoconazole, piroctone olamine or zinc pyrithione, over six months. All three quickly eliminated itching and dandruff. Hair density at the vertex remained unchanged, but hair loss during washing decreased, under ketoconazole by 17.3 percent. The hair shafts became 5.4 percent thicker under ketoconazole and 7.7 percent thicker under piroctone olamine. There was no group without active ingredient.

Khandpur 2002: ketoconazole as an add-on to finasteride

In an open-label randomized study with 100 men, dermatologists compared finasteride, minoxidil, both together, and finasteride plus ketoconazole shampoo over one year. Finasteride with minoxidil performed best, followed by finasteride with ketoconazole, then finasteride alone. All finasteride groups were significantly ahead of minoxidil alone. The ketoconazole group, however, had only 10 men, and assessment was based on ratings and photos, not blinded.

Fields 2020: the review

A systematic review included seven papers, five in humans with a total of 318 participants and two in mice. The human studies report thicker hair shafts, one study a higher hair index made up of growth proportion and hair thickness, plus improvements in photo assessment and self-assessment. The authors see ketoconazole as a promising add-on or alternative and consider randomized controlled trials necessary.

Where the data stop

• No placebo-controlled trial. For hereditary hair loss, ketoconazole shampoo has never been tested in a blinded study with a shampoo without active ingredient as the control.
• Hair density. In the largest study, the hair became thicker and less fell out, but the number of hairs did not increase. Whether ketoconazole makes new hair grow or mainly improves dandruff and inflammation is open.
• People without dandruff. Many participants also had dandruff or seborrheic dermatitis. Whether the shampoo also helps against hereditary hair loss on a healthy scalp has hardly been studied.
• Antiandrogenic effect. It is often mentioned, but has not been shown for application to the scalp; ketoconazole is not measurable in the blood afterwards.

Status, approval and legal

In Germany, ketoconazole is prescription-only, except for external use. Shampoo and solution at 2 percent are therefore available without prescription, but only in pharmacies. They are approved for seborrheic dermatitis and pityriasis versicolor, not for hair loss.

The EU suspended ketoconazole tablets for fungal infections in 2013 because of the risk of liver damage. In doing so, the EMA explicitly stated that creams, ointments and shampoos can continue to be used, because only very little active ingredient enters the body. Since 2014, ketoconazole tablets have been approved only for endogenous Cushing’s syndrome. Ketoconazole is not banned in sport.

Safety

The shampoo is well studied and considered well tolerated. The prescribing information lists skin irritation, burning, itching, dryness, acne, contact dermatitis and hypersensitivity reactions. Contact with the eyes should be avoided.

Notable for the topic of hair loss: the prescribing information itself lists hair loss, abnormal hair texture and hair discoloration among the possible side effects. Seborrheic dermatitis is often accompanied by hair loss; in rare cases this has also been observed with the shampoo. After long treatment with corticosteroid preparations, the prescribing information recommends a gradual transition to avoid a relapse.

Sources

• Piérard-Franchimont C et al., Dermatology 1998 – ketoconazole shampoo in androgenetic alopecia, comparison with minoxidil
• Piérard-Franchimont C et al., Int J Cosmet Sci 2002 – three anti-dandruff shampoos in 150 men with hair loss
• Khandpur S et al., J Dermatol 2002 – finasteride, minoxidil and ketoconazole alone and combined, open-label randomized study with 100 men
• Jiang J et al., J Dermatol 2005 – ketoconazole promotes hair growth in mice
• Fields JR et al., Dermatol Ther 2020 – topical ketoconazole in androgenetic alopecia, systematic review
• Prescribing information Ketozolin 2% shampoo (as of February 2021) – indications, side effects, pharmacokinetics
• Prescribing information Terzolin 2% solution (STADA) – indications, safety from 22 studies
• German Ordinance on Prescription-Only Medicines (AMVV), Annex 1 – ketoconazole, except for external use
• EMA 2013 – suspension of oral ketoconazole medicines because of liver damage, topical products not affected
• EMA – Ketoconazole Esteve (formerly Ketoconazole HRA) for Cushing’s syndrome, European public assessment report