Update on Dutasteride

This blog entry was written by Bernard P. Nusbaum, MD, and posted with his permission.

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Finasteride, which is the generic name for Propecia, has been approved for the treatment of Male Pattern Hair Loss since 1998. Finasteride works by inhibiting the enzyme ,5 alpha reductase type II, that forms DHT. There has been a lot of interest by both patients and physicians in dutasteride, which is a drug that inhibits both type I and type II 5 alpha reductase enzyme.Dutasteride is three times more potent than finasteride inhibiting the type II enzyme and 100 times more potent than finasteride inhibiting the type I form of the DHT producing enzyme. Dutasteride is not approved by the FDA for the treatment of Male Pattern Hair Loss and is approved at a dose of 0.5 mg a day for the treatment of prostate enlargement. While both the type I and type II enzymes are found in the hair follicle, there is a recent study which shows that type I is present in the human brain.The function of this enzyme in the brain is still unclear.

The most extensive study of dutasteride in the treatment of male pattern hair loss was published by Olsen and others in the Journal of the American Academy of Dermatology in December of 2006. This was a randomized, placebo-controlled study of 416 men for a 24 week treatment period. The study evaluated various doses of dutasteride versus 5 mg of finasteride versus placebo. At the time of the study the 1 mg finasteride dose (Propecia) was not commercially available, but the comparison is valid since the effects on hair growth of 5 mg. 1 mg. of finasteride are equal.

The results of the study were as follows: Hair counts in the vertex showed that only dutasteride at a dose of 2.5 mg a day (which is five times the dose approved for prostate enlargement) was better than finasteride at 12 and 24 weeks. When an expert panel evaluated photographs before and after treatment, the 2.5 mg dose was better than finasteride at 12 weeks and both the 0.5 and 2.5 mg doses were better than finasteride at 24 weeks — in other words, dutasteride at a 2.5 mg daily dose worked faster than 0.5 mg .

Scalp DHT suppression, which is felt to be correlated to a drug’s effectiveness, was measured and showed that finasteride decreased scalp DHT by 32%, dutasteride 0.5 mg by 51% and dutasteride 2.5 mg showed 79% suppression. DHT concentration in the blood was decreased 73% by finasteride, 92% by dutasteride 0.5mg. and 96% by dutasteride 2.5 mg . The speed by which drugs are eliminated from the body are measured by a value which is called “half-life”. The half-life of finasteride is six to eight hours whereas for dutasteride it is four to five weeks, which means that when one stops taking dutasteride, it will take several months before the drug is out of the system. When blood DHT was measured in these patients 12 weeks after stopping the medication, the finasteride treated patients had a normal DHT level while the dutasteride 0.5 still showed a 10% decrease and the dutasteride 2.5 mg treated patients still had significantly lowered DHT levels.

Sexual side effects were determined and, although there were no statistically significant differences between placebo, finasteride and dutasteride, it is noteworthy that in the patients treated with 2.5 mg dutasteride daily, 13% complained of decreased libido. As has been the experience with finasteride, half of these patients experienced resolution of their side effects despite continuing to take the medication. The other 50% had to stop the treatment in order for side effects to subside.

Side effects of dutasteride which have been reported in the treatment of prostatic enlargement are 1) breast tenderness and enlargement, and 2) reduced sperm counts. In a separate study of 28 patients treated with dutasteride 0.5 mg daily there was a significant decrease in sperm count at 26 weeks of treatment. That study states that it is difficult to determine the significance of these sperm count abnormalities and that the reports vary as to what sperm counts are required for fertility. It is quite concerning that two of the 28 patients in the study had a greater than 90% decrease in sperm count while taking the medication and 24 weeks after stopping the drug, they still had a 70% reduction in sperm count. Although the study did not give figures on the percentage of patients that developed sperm count abnormalities, this side effect, in my opinion, is worrisome especially since we commonly treat young men for male pattern hair loss. It should be noted that finasteride 1 mg (Propecia) was shown in a separate study to have no effect on sperm count.

In conclusion, dutasteride improved hair growth in male pattern hair loss more rapidly and to a greater degree than finasteride at a dose of 2.5 mg per day which is five times the dose approved for prostate enlargement. Dutasteride is approved by the FDA for the treatment of prostatic enlargement at a dose of 0.5 mg per day and there is insufficient safety data on higher doses. Dutasteride is NOT approved by the FDA for the treatment of Male Pattern Hair Loss and patients should be informed about the benefits versus the possible adverse effects. Finasteride 1 mg (Propecia) has been shown to stop the progression of male pattern baldness in 90% of the patients treated with the drug. It has an excellent safety profile with only 2% of patients experiencing decreased sex drive and no reports of sperm count abnormalities.

We are currently awaiting the results of a phase III study being conducted in Korea to evaluate dutasteride 0.5 mg daily in the treatment of male pattern hair loss.