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There is no doubt that androgens are intimately involved in male pattern baldness. Famous castrati in the time of Handel and Teleman not only retained strong soprano voices, but were assured of a lifetime of beautiful locks. Castration after the onset of puberty arrests the progression of human alopecia (1). On the other hand, the administration of therapeutic doses of testosterone to hypogonadal adult males results in the loss of scalp hair (whereas there is no noticeable change in the scalp hair of normal men). The active androgen in the balding scalp appears to be dihydrotestosterone, which is produced from testosterone through the activity of the 5-alpha-reductase enzyme (2). Biopsies and biochemical analyses corroborate the elevated 5-alpha-reductase levels in the frontal scalp of balding men and the lack of hair loss in human males with 5-alpha-reductase deficiencies.(3) In fact, the levels of 5-alpha-reductase is usually 4 times higher in balding areas than the occiput. Recently, two isoenzymes of 5-alpha-reductase have been identified in human tissue. The type 1 isoenzyme is found in scalp skin, whereas 5-alpha-reductase of type 2 is the predominant form in the prostate (4). Propecia, also known as 1 mg. finasteride, is a potent inhibitor of human 5-alpha-reductase, yet devoid of antiandrogen activity (5) itself, so the circulating levels of testosterone are not affected and these agents have not been reported to cause sexual problems in human males. Finasteride, manufactured and marketed by Merck Pharmaceutical as Proscar, has been shown to be effective in the treatment of benign prostatic hyperplasia. At the therapeutic dose of 5 mg/day, finasteride lowers serum dihydrotestosterone levels in men by 65-80% compared to baseline levels and decreases intraprostatic levels of dihydrotestosterone by 85% compared to placebo (6). Proscar has been approved for use in treatment of BPH since 1994. Since the pathogenesis of balding in the stumptail macaque monkey and human appears to be similar and partially reversible in both species by long term use of topical minoxidil solutions, clinical trials were performed in 1991 in these primates to evaluate the hair growth effects of oral administration of finasteride alone and in combination with topical minoxidil (7). The results showed that the combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Furthermore, folliculograms of scalp biopsy tissue showed a higher frequency of late anagen follicles in subjects treated with 5% minoxidil than in those administered a 2% concentration (7). At the 1995 American Association of Dermatology Meeting in New Orleans, results from a one year, double-blind, randomized, placebo-controlled study with finasteride in the treatment of male pattern baldness were presented. Men taking oral finasteride (5 mg/day) had significantly increased hair counts and significantly improved clinical change from baseline as assessed by multiple parameters including patient self evaluation. There were few drug related side effects reported, with similar numbers in both finasteride and placebo groups. At the same meeting, results from a dose-range-finding study were presented, evaluating finasteride at doses of 0.01, 0.05, 0.2, 1 and 5 mg/day. A six week trial measured concentrations of scalp skin and serum dihydrotestosterone. Surprisingly, other than the group taking 0.01 mg/day, no significant differences between the doses were seen. However, significant differences were documented between the groups that received finasteride (excluding those receiving 0.01 mg/day) and the group that received placebo. It was determined that a low dose of oral finasteride will be used for further studies in the treatment of male pattern baldness. At the annual meeting of the American Academy of Dermatology during March, 1997 in San Francisco, the Phase III clinical trials were presented for Propecia, 1 mg. finasteride. The tests evaluated 1,553 men with male pattern baldness in placebo controlled studies for one year. According to Keith Kaufman, M.D., director of clinical research at Merck & Co., Inc., there was a 107-hair improvement in men taking Propecia (1mg finasteride) compared to those receiving placebo. Scalp hair growth was measured by counting hairs in a 1 inch diameter circle of active hair loss at the vertex. The increased hair growth achieved with 1mg finasteride was evaluated by the patients as well as by clinical investigators and by review of patient photographs by a panel of dermatologists with expertise in hair loss. By all parameters, treatment with oral daily 1mg doses of finasteride demonstrated improved hair growth. Overall improvement was seen as early as three months with continued improvement over the 12 month trial. The 1mg daily oral doses of finasteride were generally well tolerated as side effects were uncommon. Safety was evaluated in more than 3200 men through clinical and laboratory monitoring. Ironically, discontinuation of therapy in Phase III trials due to adverse experience occurred in a higher percentage in the men on placebo (2.1%) than in the men treated with Propecia (1.7%). Less than 2% of men experienced decreased libido. Less than 1.5% of men had difficulty achieving an erection. And, less than 1% of men complained of a decrease in the amount of semen. According to Dr. Kaufman, these side effects resolved in men who discontinued therapy with Propecia and, in fact, in many who continued therapy with Propecia. Analysis of the results suggests that side effects, all related to sexual function, may be more psychosomatic than actual. The concentration of dihydrotestosterone in the scalp is decreased by approximately 60% in patients taking 1mg of finasteride daily. Since finasteride inhibits a key factor responsible for miniaturization of scalp hair follicles, this allows for a reversal of the balding process. Subsequent reports from Merck & Co., Inc. demonstrate that daily doses of 1mg finasteride is also effective at halting hair loss. Evaluation at the end of a one year study showed that only 14% of patients on Propecia lost hair, as opposed to 58% of patients on placebo. More recent results proved that finasteride is also successful in reversing frontal hair loss, although slightly less effectively than at the vertex. This additional information is very encouraging to many patients who are disappointed in the limited ability of minoxidil to stimulate frontal hair growth.
Merck & Co., Inc. submitted a new drug application for Propecia (1mg finasteride tablets) to the U.S. Food and Drug Administration on December 19, 1996. (1)Hamilton JB. Male hormone stimulation is prerequisite and incitant in common baldness. Am J Anat. 71:451-80, 1942 (2)Ebling FJG. Hair follicles and associated glands as androgen targets. Clin Endocrinol Metab. 15:319-39, 1986 (3)Bingham KD, Shaw DA. The metabolism of testosterone by human male scalp skin. J Endocrinol. 57:111-21, 1973 (4)Jenkins, Anderson S, Imperato-McGinley J, Wilson JD, Russell DW. Genetic and pharmacological evidence for more than one human steroid 5-alpha-reductase. J Clin Invest. 89:293-300, 1992 (5)Stoner E. The clinical development of a 5-alpha-reductase inhibitor, finasteride. J Steroid Biochem Mol Biol. 37:375-378, 1990 (6)Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med. 327:1185-1191, 1992 (7)Diabi AR, Mulholland MJ, Shull KL, Kubicek MF, Johnson GA, Schostarez HJ, Brunden MN and Buhl AE. Hair Growth Effects of Oral Administration of finasteride, a steroid 5-alpha-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque. J Clin Endocrinol Metab. 74:345-350, 1992 INSTRUCTIONS FOR USE:
Propecia will not work faster or better if you take it more than once a day.
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