Ketoconazole is an anti-androgen drug sometimes used to treat hirsutism
Information on hirsutism and hair removal treatments
Ketoconazole for Hirsutism
Ketoconazole is a synthetic imidazole derivative, which has been used to treat steroidigenesis in precocious puberty, prostatic cancer and Dashing’s syndrome. It has also been used to treat hirsutism.
Recently a study was undertaken to observe the effects of small doses of ketoconazole on 42 women suffering from hirsutism and acne. Of these 42 women, who had an average age of 23 years, 36 had hirsutism, 17 had acne in moderate or severe form, 6 had acne without hirsutism and 11 had both acne and hirsutism.
After obtaining their informed consent, the women were given 200mg. of ketoconozole twice a day. A six-month therapy was planned starting on the fifth day of the menstrual cycle. The procedures followed were all according to the Helsinki declaration.
For hair growth evaluation, 12 out of the 36 hirsute patients were shaved in a prefixed area of the right thigh. After 30 days, at least 20 hairs were cut with a curved scissor from that area. This area was shaved again and ketoconazole treatment started. After 90, 60 and 30 days of therapy, hairs were removed and the area re-shaved. Hair length and diameter was measured by an IBAS image analyzer and the hair growth rate calculated. Of the 42 subjects, 14 went through the entire 6-month therapy, the others having dropped out for various reasons.
Hirsutism had improved in the above-mentioned 14 subjects. While no significant effects were seen in 22 subjects who did not go through the entire therapy, 7 out of these 22 hirsute subjects showed improvement of hirsutism and slower hair growth rate on subjective appraisal. Mean daily rate of hair growth fell progressively from around 0.258 mm to 0.184 mm The mean diameter fell from around 0.123 mm to 0.110 mm. Nine subjects had a significant reduction in their mean hair length and the daily rate of hair growth after 90 days. Alongside these reductions, there was a fall in androgen levels, though no statistically significant correlation was found.
There were major side effects in 23 patients during the first 60 days of treatment. Six patients suffered loss of scalp hair, which became significantly worse in 5 cases. Eight patients complained of nausea and 4 had headaches. There was dryness of skin and desquamation in 6 cases and asthenia and itching in 3 cases each. One patient had acute hepatitis after 30 days of treatment and another had toxic erythema in the legs.
There were no changes in blood glucose. The cholestrol level decreased but the HDL cholesterol remained unchanged.
Twenty four patients had regular ovulatory cycles, 13 had polymenorrhoeic anovulatory cycles and 11 had no menstrual changes. Menstrual changes were more frequent during the first months of treatment after which basal menstrual conditions were resumed. According to one author, ovary is the primary target of ketoconazole.
Conclusions from the study
Normalization of androgen levels was associated with improvement of hirsutism but only 38 subjects showed satisfactory results. To obtain clinically evident results of hirsutism, a long period of therapy is required. This is evident from the fact that those patients who underwent the entire 6-month ketoconazole therapy showed significant improvement of hirsutism. The IBAS image analyzer was found to be a very accurate instrument for measuring objectively hair dimensions and rate of growth.
Almost 40% of patients failed to show any marked improvement of hirsutism, though their early exit from therapy might have affected the subjective assessment. This study and another one showed generally poor acceptability of ketoconazole with tolerance level rarely exceeding 6 months of treatment. Besides the side effects mentioned earlier, some authors have also reported modification of some biochemical liver parameters. Such observations suggest that ketoconazole should be used with caution.
While hirsutism does improve with falling androgen levels, the length of treatment needed results in several side effects and complications. Therefore, given the need for long term treatment and the fact that there is a relapse of hirsutism on withdrawal of androgen suppressing drugs, it was suggested that ketoconazole should be given as an adjunct to the more widely used anti-androgenic drugs.
Ketoconazole may be given when steroids cannot be administered. The drug can also be prescribed for a brief period to prevent acute relapse of hirsutism in adolescents, since it has less suppressive effects on the ovarian cycle than steroids.
Even though ketoconazole prescribed for hirsutism does lower androgen levels, only selected patients are eligible as the long term treatment required causes many side effects and complications. Therefore at all times, careful and detailed monitoring throughout the treatment is essential.