expert panels agreed that dutasteride improved the front.
http://findarticles.com/p/articles/mi_m ... _n19171476
The authors report a phase II, multicenter, randomized, double-blinded, placebo-controlled study assessing the efficacy of dutasteride at 4 different doses compared to finasteride in the treatment of androgenetic alopecia. Inclusion criteria included men aged 21 to 45 years with mild to moderate male pattern hair loss (Hamilton-Norwood patterns IIIv, IV, or V). Exclusion criteria included prior use of 5[alpha]-reductase inhibitors, use of any alopecia medication within 6 months, use of androgenic or antiandrogenic drugs within 6 months, or any significant health problem. Patients were randomized to receive placebo, finasteride 5 mg daily, or dutasteride at 0.05, 0.1,0.5, or 2.5 mg daily for 24 weeks. The primary end-point was change in target area hair count by macrophoto-graphic assessment of a tattoo-marked site at 12 and 24 weeks. Secondary endpoints included blinded expert panel assessment of change from baseline, investigator ratings of change, patient global assessment of change in scalp hair, serum testosterone and dihydrotestosterone (DHT) levels, scalp testosterone and DHT levels, and adverse events.
A total of 416 patients were enrolled to receive placebo (n=64), dutasteride at 0.05 mg (n=71), 0.1 mg (n=72), 0.5mg (n=68), 2.5 mg (n=71), or finasteride 5 mg (n=70). There were no significant differences in the demographics or disease state of the treatment groups at baseline. Mean hair counts in all active treatment arms increased at both 12 and 24 weeks, while mean counts decreased in the placebo arm. In the active treatment groups, the mean improvement in hair counts from baseline was significantly different from placebo (P<.001). The mean change in hair count from baseline in the 2.5 mg dutasteride arm was greater than seen with finasteride (P=.009). Dutasteride 0.1 mg and finasteride resulted in similar mean change in hair counts, and dutasteride 0.5 mg showed slightly higher mean counts. Expert panel ratings and investigator ratings showed similar trends with week 24 improvements being greater than week 12 improvements in all treatment arms. By 24 weeks, dutasteride 0.1, 0.5, and 2.5 mg and finasteride performed better than placebo as measured by mean ratings of vertex and frontal hair photographs. Dutasteride 2.5 mg was superior to finasteride, while 0.1 and 0.5 mg dutasteride were comparable to finasteride by mean panel and investigator ratings. Expert panel assessments at 24 weeks saw improvement in hair growth in 48% of patients getting dutasteride 0.5 mg, 61% of patients getting 2.5mg and 45% of patients getting finasteride. All active treatment arms had higher mean patient self-assessment scores than placebo; however, only dutasteride 2.5 mg and finasteride were significantly better.
Laboratory examinations showed a dose-dependant suppression of serum and scalp DHT and compensatory increases in testosterone with dutasteride. At 24 weeks, dutasteride 0.5 and 2.5 mg suppressed greater than 90% of serum DHT, and 51% and 79% of scalp DHT, respectively. Finasteride suppressed 73% of serum DHT and 41% of scalp DHT. The amount of DHT suppression in the scalp or serum correlated well with clinical improvement in hair loss. There were no significant differences in adverse events or patient withdrawals due to adverse events between treatment groups. Only sexual function adverse events were itemized in the manuscript. Notably, 9 (13%) of patients taking dutasteride 2.5 mg reported decreased libido compared to 2 (3%) of the placebo group (2-tailed P=0.06 by Fisher's exact test). No differences were observed with respect to ejaculation disorders or impotence compared to placebo. All sexual adverse events were mild to moderate, and most resolved while the patients were still taking therapy.
Comment
Male pattern hair loss or androgenetic alopecia is a common but poorly understood disorder. The influence of androgens and the type 2 5[alpha]-reductase enzyme in the pathogenesis of this condition are now well established. (1) 5[alpha]-reductase converts testosterone to the more active DHT, and the type 2 isoform is expressed in androgen-responsive tissues such as the hair follicle. The type 1 isoform of 5[alpha]-reductase is widely expressed in many tissues.
Finasteride (Merck & Co., Inc., Whitehouse Station, NJ) is an inhibitor of type 2 5[alpha]-reductase and is approved as Propecia (1 mg) for the treatment of male pattern hair loss. It is also approved as Proscar (5mg) for benign prostatic hyperplasia. Dutasteride is a potent inhibitor of both isoforms of 5[alpha]-reductase. (2) Avodart (dutasteride 0.5 mg, GlaxoSmithKline, Brentford, Middlesex, UK) is approved for the treatment of benign prostatic hyperplasia. In this phase II trial, the authors investigate the efficacy and safety of dutasteride at different doses in the treatment of androgenetic alopecia. They find that dutasteride suppresses DHT and improves clinical hair loss in a dose-dependent fashion. In men 21 to 45 years old over a 24-week period, dutasteride 0.1 or 0.5 mg daily is comparable to finasteride 5 mg daily, and dutasteride 2.5 mg is superior to finasteride. It is unclear if the increased efficacy of dutasteride is a function of more potent type 2 5[alpha]-reductase inhibition or its additional function as an inhibitor of type 1 5[alpha]-reductase. It is also unclear how the 2 drugs will compare with long-term use, as the maximal effects of finasteride on hair loss take place after 24 weeks of treatment. Neither drug is capable of completely reversing hair loss.
Side effect profiles for dutasteride in the treatment of benign prostatic hyperplasia are similar to those reported for finasteride with low levels of impotence, reduced libido, ejaculation disorders, and gynecomastia reported. Doses of dutasteride above 0.5 mg have not been extensively tested for safety. In this study, dutasteride 2.5 mg demonstrated the highest efficacy. At the same time, 13% of patients taking this does experienced decreased libido. Larger trials are needed to assess the safety of dutasteride at doses above 0.5 mg daily. This is especially true as dutasteride has an elimination half-life of 4 to 5 weeks. This fact was reflected in the long delay for serum DHT to return to the normal range after discontinuing dutasteride 2.5 mg (2.4-14 months). In addition to sexual adverse events, there are other concerns with 5[alpha]-reductase inhibitors including drug-drug interactions, inability to donate blood until the drug is cleared, and prostate effects. As both finasteride and dutasteride reduce PSA levels and reduce prostate size, their use can potentially hinder the detection of prostate cancer. This may be why finasteride was found to be effective in reducing prostate cancer rates while simultaneously being associated with the detection of higher-grade tumors. (3) A more recent concern is the suggestion that depression may also be associated with use of finastride. (4,5)
http://findarticles.com/p/articles/mi_m ... _n19171476
The authors report a phase II, multicenter, randomized, double-blinded, placebo-controlled study assessing the efficacy of dutasteride at 4 different doses compared to finasteride in the treatment of androgenetic alopecia. Inclusion criteria included men aged 21 to 45 years with mild to moderate male pattern hair loss (Hamilton-Norwood patterns IIIv, IV, or V). Exclusion criteria included prior use of 5[alpha]-reductase inhibitors, use of any alopecia medication within 6 months, use of androgenic or antiandrogenic drugs within 6 months, or any significant health problem. Patients were randomized to receive placebo, finasteride 5 mg daily, or dutasteride at 0.05, 0.1,0.5, or 2.5 mg daily for 24 weeks. The primary end-point was change in target area hair count by macrophoto-graphic assessment of a tattoo-marked site at 12 and 24 weeks. Secondary endpoints included blinded expert panel assessment of change from baseline, investigator ratings of change, patient global assessment of change in scalp hair, serum testosterone and dihydrotestosterone (DHT) levels, scalp testosterone and DHT levels, and adverse events.
A total of 416 patients were enrolled to receive placebo (n=64), dutasteride at 0.05 mg (n=71), 0.1 mg (n=72), 0.5mg (n=68), 2.5 mg (n=71), or finasteride 5 mg (n=70). There were no significant differences in the demographics or disease state of the treatment groups at baseline. Mean hair counts in all active treatment arms increased at both 12 and 24 weeks, while mean counts decreased in the placebo arm. In the active treatment groups, the mean improvement in hair counts from baseline was significantly different from placebo (P<.001). The mean change in hair count from baseline in the 2.5 mg dutasteride arm was greater than seen with finasteride (P=.009). Dutasteride 0.1 mg and finasteride resulted in similar mean change in hair counts, and dutasteride 0.5 mg showed slightly higher mean counts. Expert panel ratings and investigator ratings showed similar trends with week 24 improvements being greater than week 12 improvements in all treatment arms. By 24 weeks, dutasteride 0.1, 0.5, and 2.5 mg and finasteride performed better than placebo as measured by mean ratings of vertex and frontal hair photographs. Dutasteride 2.5 mg was superior to finasteride, while 0.1 and 0.5 mg dutasteride were comparable to finasteride by mean panel and investigator ratings. Expert panel assessments at 24 weeks saw improvement in hair growth in 48% of patients getting dutasteride 0.5 mg, 61% of patients getting 2.5mg and 45% of patients getting finasteride. All active treatment arms had higher mean patient self-assessment scores than placebo; however, only dutasteride 2.5 mg and finasteride were significantly better.
Laboratory examinations showed a dose-dependant suppression of serum and scalp DHT and compensatory increases in testosterone with dutasteride. At 24 weeks, dutasteride 0.5 and 2.5 mg suppressed greater than 90% of serum DHT, and 51% and 79% of scalp DHT, respectively. Finasteride suppressed 73% of serum DHT and 41% of scalp DHT. The amount of DHT suppression in the scalp or serum correlated well with clinical improvement in hair loss. There were no significant differences in adverse events or patient withdrawals due to adverse events between treatment groups. Only sexual function adverse events were itemized in the manuscript. Notably, 9 (13%) of patients taking dutasteride 2.5 mg reported decreased libido compared to 2 (3%) of the placebo group (2-tailed P=0.06 by Fisher's exact test). No differences were observed with respect to ejaculation disorders or impotence compared to placebo. All sexual adverse events were mild to moderate, and most resolved while the patients were still taking therapy.
Comment
Male pattern hair loss or androgenetic alopecia is a common but poorly understood disorder. The influence of androgens and the type 2 5[alpha]-reductase enzyme in the pathogenesis of this condition are now well established. (1) 5[alpha]-reductase converts testosterone to the more active DHT, and the type 2 isoform is expressed in androgen-responsive tissues such as the hair follicle. The type 1 isoform of 5[alpha]-reductase is widely expressed in many tissues.
Finasteride (Merck & Co., Inc., Whitehouse Station, NJ) is an inhibitor of type 2 5[alpha]-reductase and is approved as Propecia (1 mg) for the treatment of male pattern hair loss. It is also approved as Proscar (5mg) for benign prostatic hyperplasia. Dutasteride is a potent inhibitor of both isoforms of 5[alpha]-reductase. (2) Avodart (dutasteride 0.5 mg, GlaxoSmithKline, Brentford, Middlesex, UK) is approved for the treatment of benign prostatic hyperplasia. In this phase II trial, the authors investigate the efficacy and safety of dutasteride at different doses in the treatment of androgenetic alopecia. They find that dutasteride suppresses DHT and improves clinical hair loss in a dose-dependent fashion. In men 21 to 45 years old over a 24-week period, dutasteride 0.1 or 0.5 mg daily is comparable to finasteride 5 mg daily, and dutasteride 2.5 mg is superior to finasteride. It is unclear if the increased efficacy of dutasteride is a function of more potent type 2 5[alpha]-reductase inhibition or its additional function as an inhibitor of type 1 5[alpha]-reductase. It is also unclear how the 2 drugs will compare with long-term use, as the maximal effects of finasteride on hair loss take place after 24 weeks of treatment. Neither drug is capable of completely reversing hair loss.
Side effect profiles for dutasteride in the treatment of benign prostatic hyperplasia are similar to those reported for finasteride with low levels of impotence, reduced libido, ejaculation disorders, and gynecomastia reported. Doses of dutasteride above 0.5 mg have not been extensively tested for safety. In this study, dutasteride 2.5 mg demonstrated the highest efficacy. At the same time, 13% of patients taking this does experienced decreased libido. Larger trials are needed to assess the safety of dutasteride at doses above 0.5 mg daily. This is especially true as dutasteride has an elimination half-life of 4 to 5 weeks. This fact was reflected in the long delay for serum DHT to return to the normal range after discontinuing dutasteride 2.5 mg (2.4-14 months). In addition to sexual adverse events, there are other concerns with 5[alpha]-reductase inhibitors including drug-drug interactions, inability to donate blood until the drug is cleared, and prostate effects. As both finasteride and dutasteride reduce PSA levels and reduce prostate size, their use can potentially hinder the detection of prostate cancer. This may be why finasteride was found to be effective in reducing prostate cancer rates while simultaneously being associated with the detection of higher-grade tumors. (3) A more recent concern is the suggestion that depression may also be associated with use of finastride. (4,5)
