Medical Restoration

Dutasteride is an oral synthetic 4-azasteroid, is a potent, selective, irreversible inhibitor of type 1 and type 2 -5alpha-reductase (5AR), the enzyme that converts testosterone to dihydrotestosterone (DHT) intracellularly.

Dutasteride has been approved by the US FDA for treatment of prostate enlargement in the elderly. Although dutasteride is not approved for the treatment of hair loss, hair transplant surgeons sometimes prescribe dutasteride “off-label” for treatment of male-pattern hair loss, if characteristics of an individual patient warrant such use of the drug. Dutasteride is approved by the Korean FDA treatment of hair loss.

Mode of action of dutasteride in patients of hair loss

Dutasteride inhibits both type 1 and type 2 5α-reductase and is approved at the 0.5-mg dose for treatment of symptomatic benign prostatic hyperplasia (BPH). It is about 3 times as potent as finasteride at inhibiting type 2 5α-reductase and more than 100 times as potent at inhibiting the type 1 5α-reductase enzyme.

Dutasteride caused scalp and serum dihydrotestosterone levels to decrease and testosterone levels to increase in a dose-dependent fashion. Whereas 5-mg finasteride decreases serum DHT by about 70%, dutasteride can decrease serum DHT by more than 90%.

Efficacy of dutasteride

In one of the studies conducted, dutasteride 0.5 mg was found to be significantly more effective than finasteride 1 mg in men aged 18–40 years with androgenetic alopecia as assessed by hair counts, subject self-assessment and blinded and non-blinded evaluation of global photographs.In another 24-week, double-blind, placebo controlled, dose-ranging study, dutasteride increased hair growth in a dose-dependent manner. Dutasteride, 0.5 mg and 2.5 mg significantly improved hair counts after 24 weeks as compared to finasteride, 5 mg.

The 2.5-mg dutasteride dose was consistently superior to 0.5-mg dutasteride in promoting scalp hair growth. The 2.5-mg dose was also better than the 0.5-mg dose at suppressing scalp DHT (79% vs. 51%), whereas it was only marginally better at suppressing serum DHT (96% vs. 92%). This difference in the dose-response of serum and scalp DHT to inhibition with dutasteride is likely to be due to the greater contribution of type 1 5α-reductase to scalp DHT concentrations.

Other studies have confirmed efficacy of oral dutasteride compared with placebo in men with androgenetic alopecia as well as in comparison with finasteride.

Adverse effect profile of dutasteride

The adverse effect profile of dutasteride is quite similar to finasteride with the difference being in the plasma half-life of the drugs. Pharmacologic data has revealed a half-life for dutasteride of >240 hours, as compared to finasteride, with a half-life of 6–8 hours. This long half-life was evident in the persistent suppression of DHT with the 0.5-mg and 2.5-mg doses after dutasteride treatment was stopped. Because of this long half-life, men being treated with dutasteride should not donate blood until at least 6 months past their last dose to prevent administration to a pregnant female transfusion recipient.

Important potential side effects of dutasteride in a minority of patients may include sexual dysfunction and depression.

The phase 2 studies comparing dutasteride and finasteride showed that they were well tolerated and there were no new safety concerns. The incidence of sexual side effects in another study published in 2017 showed that dutasteride and finasteride were relatively well-tolerated with comparable sexual side effects in both the groups which were consistent with previously reported data.The incidence of adverse effects is also shown not be effected with long term use of dutasteride.

The Phase III BPH (benign prostatic hypertrophy) trials for Dutasteride were conducted on 4300 male subjects between the ages of 47 and 94 years old, 90% of them being Caucasian. The average age was 66 years old and the participants received either a placebo or a 0.5mg daily dose of Dutasteride. 2158 men received the placebo and 2166 of the men received Dutasteride. A total of 267 subjects (6% of each treatment group) were withdrawn from the studies due to adverse experiences, usually associated with the reproductive system. Withdrawal due to adverse events considered by the investigators to have a reasonable possibility of being caused by the medication occurred in 3% of the subjects receiving Dutasteride and in 2% of the subjects receiving the placebo.

There were no significant differences in side effects, serious adverse events, or withdrawals due to adverse events among any of the treatment groups, including the placebo group.

Current role of dutasteride in hair loss management

Although hair restoration surgeons prescribe FDA-approved medications for off-label use, it is important to keep in mind that the FDA has not approved dutasteride for the treatment of male pattern hair loss (MPHL). Therefore, when used to treat androgenetic alopecia, the beneficial effects, short- and long-term side effects and proper dosing of the medication is not known and shuld be clearly discussed with the patient.

Dutasteride has been FDA approved for prostatic enlargement in a dose of 0.5mg. The recommended dose of Dutasteride for benign prostatic hypertrophy (BPH) is 1 capsule (0.5 mg) taken orally once a day. The capsules should be swallowed whole. Dutasteride may be administered with or without food. No dosage adjustment is necessary for subjects with renal impairment or for the elderly.

It is important to check the liver function before starting the medication as it is completely metabolized in the liver. Given the long half-life it should not be used in individuals with liver issues.