Finasteride, 1 mg (Propecia), Is the Optimal Dose for the Treatment of Men With Male Pattern Hair Loss

In the Commentary "Study of the Food and Drug Administration Files on Propecia: Dosages, Side Effects, and Recommendations" published in the March 1999 issue of the ARCHIVES, Frankel¹ challenges the decision by the Food and Drug Administration to approve finasteride, 1 mg (Propecia; Merck & Co Inc, Whitehouse Station, NJ), for the treatment of men with male pattern hair loss. Frankel argues that the dose of Propecia is "far higher than the level measured as necessary for inhibition of the conversion of testosterone to DHT [dihydrotestosterone]," based on serum and scalp DHT levels we measured in balding men treated with finasteride for 6 weeks.^{2 - 3}

While the scalp DHT study was designed to demonstrate the biochemical efficacy of the drug at the target tissue over a broad dose range, that study was followed by a 6-month clinical dose-ranging study to fully characterize the dose-response relationship of finasteride in men with male pattern hair loss, using clinically relevant end points. In the clinical dose-response study, the 1-mg dose demonstrated significantly better efficacy compared with the 0.2-mg dose based on hair counts (P=.04, 1 mg vs 0.2 mg at month 3) and by an expert panel review of standardized clinical photographs (P=.02, 1 mg vs 0.2 mg at month 6).^{2 ,4} At month 6, the expert panel rated improvements in hair growth in 52% of patients receiving the 1-mg dose, compared with only 38% of patients who received 0.2 mg.⁴ Consistent trends in the data up to 12 months in a blinded extension to the dose-response study supported the superiority of the 1-mg dose.^{2 ,4} Also in agreement with the superior efficacy of the 1-mg dose, serum DHT was suppressed more with the 1-mg dose than with the 0.2-mg dose (median±SE percent decrease, −68.5%±1.4% vs −61.2%±1.7%, respectively, at month 6; P=.002, 1 mg vs 0.2 mg).⁴ Frankel concluded incorrectly that the difference in clinical efficacy at month 6 between the 1-mg and 0.2-mg dose groups was not significant because their values "overlapped statistically at the 95% confidence level."¹ This is a common mistake that has long been highlighted in both the statistical⁵ and nonstatistical^{6 - 7} literature. Frankel goes further and recommends that men with male pattern hair loss take the lower (0.2-mg) dose of finasteride, a dose that is suboptimal and is neither approved nor available to patients.

In contrast with the other concerns raised by Frankel, the safety profile of finasteride is well understood and is based on extensive, long-term clinical trial data and marketed experience with finasteride, 5 mg (Proscar; Merck & Co Inc), since 1992, as well as over 5 years of clinical trial experience with Propecia. The product label for Propecia identifies the low incidence of adverse events reported by a few men taking the drug in controlled clinical trials, and long-term data demonstrate that there is no increase in adverse events with continuing therapy.⁸ The data on semen parameters show that median ejaculate volume decreased by 0.3 mL (−10.9%; 95% confidence interval, −18.9% to 4.3%) in Propecia-treated subjects, but there was also a decrease of 0.2 mL (−7.8%; 95% confidence interval, –25.5% to 3.9%) in placebo-treated subjects^{8 - 9} and a between-treatment group difference of only 0.03 mL (1%; 90% confidence interval, –10.4% to 13.1%; P=.92).⁹ No significant difference between treatment groups was observed for any other semen parameter.⁹ These controlled clinical trial data, as well as extensive preclinical studies in multiple animal species and clinical observations in men with genetic type 2 5α-reductase deficiency, support the conclusion that there is no effect on male fertility with Propecia. Lastly, the product label for Propecia instructs physicians how to adjust the measured serum prostate-specific antigen level in men taking Propecia to compensate for the effect of finasteride.⁸ This simple adjustment has been demonstrated to preserve the sensitivity and specificity of the test in the detection of prostate cancer.¹⁰

Frankel stated that he was unable to find additional information in the medical literature, based on a MEDLINE search of the term Propecia. This is likely because the brand name of a drug is not generally used in scientific publications. A search of the term finasteride would have revealed several articles of interest, including the results of the multicenter phase 3 pivotal trials with finasteride, 1 mg, in 1553 men¹¹ as well as an independent, comprehensive review of finasteride in the treatment of men with male pattern hair loss.¹² Regardless, the documents obtained by Frankel under the Freedom of Information Act² provide ample evidence, based on efficacy and safety, to support the selection of the 1-mg dose of finasteride for the treatment of men with male pattern hair loss.