This is old, but wanted to bring attention to any current users of the drug Zafirlukast. Thanks.
Hair Loss Treatment Method
INTRODUCTION
The significance of inflammation in acne pathogenesis is well described in the literature over the past several decades. In as much as it has been clinically proven that the inflammatory reaction associated with acne vulgaris and rosacea resolves in patients taking zafirlukast, which competitively antagonizes the cellular receptor for cysteinyl leukotrienes, the cyst LT 1 receptor 7 , there is still no adequate explanation as to why patients suffering from these dreaded diseases develop a state of remission while taking this drug. Having considered the research data presented thus far, several questions still remain. Considering the fact that acne vulgaris is androgen mediated, does zafirlukast exhibit antiandrogen activity, and if so, would this drug have any benefit in treating other diseases know to be mediated by antrogens? In an attempt to answers these questions, further study was undertaken to determine whether or not a biological marker exists that would explain our findings and if so would current and past scientific investigation support our conclusion.
DISCUSSION
STUDY
During the summer of 2000 an investigative study was initiated to determine the efficacy of zafirlukast in the treatment of androgenetic alopecia. A middle aged 40 year old blond haired caucasian male whom was actively undergoing genetically influenced alopecia was recruited and voluntarily enlisted into the study under informed consent. Prior to taking zafirlukast this patient had never received treatment for androgenetic alopecia and physical examination showed no evidence of pathological hair loss. Zafirlukast was initiated at a dose of 20 mg taken twice daily and within the first 6 weeks of zafirlukast treatment both the patient and his wife witnessed less ocurrence of hair loss and by the fourth month of treatment regrowth of hair in the area of temporat and vertex balding was observed. Serum ancillary studies obtained at the completion of his fourth month of zafirlukast therapy revealed a dihydrotestosterone level of 32 NG/DL (normal 25 to 75 NG/DL). Just two months earlier serum luteinizing hormone, total testosterone, androstenedione and dehydroepiandrosterone sulfate levels were determined to be normal. Having considered that dihydrotestosterone levels may have been suppressed to a low normal range, as pre treatment dihydrotestosterone serum determination had not been performed, the dose of zafirlukast was increased to 40 mg taken by mouth twice daily. Continuing this dose for a one month period of time, serum dihydrotestosterone levels were reanalized and determined to be 21 NG/DL (normal 25 to 75 NG/DL). Additionally, serum 3-alpha androstanediol glucuronide, estrone, androstenedione, total testosterone, prostate specific antigen, and progesterone levels were within normal limits at this time. The patient was then withdrawn from zafirlukast therapy and there were no specific complications or side effects during a one month abstinence from zafirlukast and serum dihydrotestosterone levels were redetermined and found to be 15 NG/DL (normal 25 to 75 NG/DL). This patient was then given the option to continue treatment with zafirlukast at a dose of 40 mg taken by mouth twice daily for the treatment of androgenic alopecia and decided to do so as he had witnessed the continued regrowth of hair and remission of hair loss while taking zafirlukast. There were never any side effects observed while he was taking zafirlukast. In an attempt to verify and cross reference these significant findings with a male patient. undergoing treatment with zafirlukast for acne vulgaris and a female patient whom enlisted into a study to determine the effects of zafirlukast on hereditary balding and whom had previous treatment failures with finasteride, blood serum analysis was performed to determine whether or not dihydrotestosterone suppression was also ocurring in these individuals as well. The results are as follows:
In a 19 year white male undergoing treatment for Grade IV cystic acne vulgaris with zafirlukast at 40 mg po bid (by mouth twice a day) for 4 weeks, preceded by 2 weeks of zafirlukast treatment at 30 mg bid, his serum dihydrotestosterone level was determined to be 16 NG/DL (normal was 25 to 75 NG/DL).
In a 53 year old white female undergoing treatment with zafirlukast at 40 mg po bid for hereditary balding, her pretreatment dihydrotestosterone level was 5 NG/DL (normal 5 to 30 NG/DL); after 4 weeks of continuous treatment her dihydrotestosterone serum concentration was 4 NG/DL (normal 5 to 30 NG/DL) and at 6 weeks of continued treatment her serum dihydrotestosterone level was determined to be less than 3 NG/DL.
In both of these individuals not only was dihydrotestosterone suppression realized but a significant improvement in acne lesion remission and clearing in the male individual and regrowth of frontal hair in the female individual was documented. Both individuals continued medical treatment and management of their respective illnesses under informed consent never witnessing any side effects or adversities and are pleased with their outcomes thus far.
DISCUSSION
For many years medical researchers have studied the pathways of androgen metabolism and have recognized its undesirable consequences i.e., acne vulgaris, androgenetic alopecia, idiopathic hirsutism and benign prostatic hypertrophy, besides others. There now appears to be significant evidence to suggest that in some individuals the drug zafirlukast not only blocks the potent inflammatory reaction mediated by leukotrienes, but also possess antiandrogen activity as well.
In this study a dose and time dependent effect has been identified with the treatment of both acne vulgaris and common baldness in genetically susceptible men and women without physical or psychological compromise, or forfeit of quality of life. The use of zafirlukast in treating these dreaded diseases appears to be safe and effective at doses above those recommended for the treatment of asthma as shown in this study. Serum liver function studies monitored during this study remained in the normal range of value except in one patient with known Hepatitis C and abnormal pretreatment liver function studies; however, in all patients including the one patient with Hepatitis C, serum liver function studies improved with zafirlukast treatment possibly indicating a role in treating liver diseases in the future.
There are several biological mechanisms that could be implicated in explaining the results of this study including the following:
A) By inhibiting the action of 5-alpha reductase or 17 beta-hydroxysteroid dehydrogenase, the two principal pathways of testosterone metabolism in all growing hairs and skin cells 7 .
B) By inhibiting the formation or action of the metabolite of testosterone or androstenedione i.e. dihydrotestosterone, 5-alpha androstanediol, 5-alpha androstanedione, 5-alpha androsterone or estrone 7 .
C) By inhibiting the peripheral conversion of androstenedione to testosterone in the skin 7 .
D) By inhibiting adenyl cyclase due in fact to high dihydrotestosterone levels in the hair follicle (high dihydrotestosterone levels in genetically marked hair follicles initiate baldness by inhibiting adenyl cyclase) 7 .
E) By alteration of the androgen receptor protein in the peripheral target cells allowing them to concentrate androgens at the presumed site of action in the cell nucleus i.e., interception, antagonism, or inhibition of the highly specific antrogen receptor protein that binds with dihydrutestosterone and transports it to the cell nucleus 7 .
F) By blocking dihydrotestosterone at a given target site 7 .
G) By promoting the formation of progesterone 7 .
H) By promoting the formation of steroids all having structural resemblance to testosterone and thus competing with testosterone for the binding site on the enzyme 5-alpha reductase i.e., 4 androsten-3-one-17 beta-carboxylic acid, androstenedione and deoxycorticosterone 7 .
CONCLUSION
Zafirlukast is both safe and effective in the treatment and management of inflammatory and androgen mediated disorders for which dihydrotestosterone suppression and leukotriene antagonism is desired. Although more rapid and sustained effects are produced at elevated dosage levels, adequate disease resolution ocurrs at doses not associated with serum dihydrotestosterone suppression below the lower limits of normal relative to one's age or sex, suggesting that a dual mechanism of action exist for zafirlukast i.e., antileukotriene and antiantrogen effects. This new found idea and discovery will help strengthen our understanding of treating acne vulgaris, androgenic alopecia, female hereditary balding and other androgen or leukotriene mediated illnesses and in fact may change our way of thinking and approach to these significant illnesses whose symptoms and disease characteristics are ameliorated with the use of zafirlukast. Additional research and development of the drug zafirlukast is recommended at this time.
Hair Loss Treatment Method
INTRODUCTION
The significance of inflammation in acne pathogenesis is well described in the literature over the past several decades. In as much as it has been clinically proven that the inflammatory reaction associated with acne vulgaris and rosacea resolves in patients taking zafirlukast, which competitively antagonizes the cellular receptor for cysteinyl leukotrienes, the cyst LT 1 receptor 7 , there is still no adequate explanation as to why patients suffering from these dreaded diseases develop a state of remission while taking this drug. Having considered the research data presented thus far, several questions still remain. Considering the fact that acne vulgaris is androgen mediated, does zafirlukast exhibit antiandrogen activity, and if so, would this drug have any benefit in treating other diseases know to be mediated by antrogens? In an attempt to answers these questions, further study was undertaken to determine whether or not a biological marker exists that would explain our findings and if so would current and past scientific investigation support our conclusion.
DISCUSSION
STUDY
During the summer of 2000 an investigative study was initiated to determine the efficacy of zafirlukast in the treatment of androgenetic alopecia. A middle aged 40 year old blond haired caucasian male whom was actively undergoing genetically influenced alopecia was recruited and voluntarily enlisted into the study under informed consent. Prior to taking zafirlukast this patient had never received treatment for androgenetic alopecia and physical examination showed no evidence of pathological hair loss. Zafirlukast was initiated at a dose of 20 mg taken twice daily and within the first 6 weeks of zafirlukast treatment both the patient and his wife witnessed less ocurrence of hair loss and by the fourth month of treatment regrowth of hair in the area of temporat and vertex balding was observed. Serum ancillary studies obtained at the completion of his fourth month of zafirlukast therapy revealed a dihydrotestosterone level of 32 NG/DL (normal 25 to 75 NG/DL). Just two months earlier serum luteinizing hormone, total testosterone, androstenedione and dehydroepiandrosterone sulfate levels were determined to be normal. Having considered that dihydrotestosterone levels may have been suppressed to a low normal range, as pre treatment dihydrotestosterone serum determination had not been performed, the dose of zafirlukast was increased to 40 mg taken by mouth twice daily. Continuing this dose for a one month period of time, serum dihydrotestosterone levels were reanalized and determined to be 21 NG/DL (normal 25 to 75 NG/DL). Additionally, serum 3-alpha androstanediol glucuronide, estrone, androstenedione, total testosterone, prostate specific antigen, and progesterone levels were within normal limits at this time. The patient was then withdrawn from zafirlukast therapy and there were no specific complications or side effects during a one month abstinence from zafirlukast and serum dihydrotestosterone levels were redetermined and found to be 15 NG/DL (normal 25 to 75 NG/DL). This patient was then given the option to continue treatment with zafirlukast at a dose of 40 mg taken by mouth twice daily for the treatment of androgenic alopecia and decided to do so as he had witnessed the continued regrowth of hair and remission of hair loss while taking zafirlukast. There were never any side effects observed while he was taking zafirlukast. In an attempt to verify and cross reference these significant findings with a male patient. undergoing treatment with zafirlukast for acne vulgaris and a female patient whom enlisted into a study to determine the effects of zafirlukast on hereditary balding and whom had previous treatment failures with finasteride, blood serum analysis was performed to determine whether or not dihydrotestosterone suppression was also ocurring in these individuals as well. The results are as follows:
In a 19 year white male undergoing treatment for Grade IV cystic acne vulgaris with zafirlukast at 40 mg po bid (by mouth twice a day) for 4 weeks, preceded by 2 weeks of zafirlukast treatment at 30 mg bid, his serum dihydrotestosterone level was determined to be 16 NG/DL (normal was 25 to 75 NG/DL).
In a 53 year old white female undergoing treatment with zafirlukast at 40 mg po bid for hereditary balding, her pretreatment dihydrotestosterone level was 5 NG/DL (normal 5 to 30 NG/DL); after 4 weeks of continuous treatment her dihydrotestosterone serum concentration was 4 NG/DL (normal 5 to 30 NG/DL) and at 6 weeks of continued treatment her serum dihydrotestosterone level was determined to be less than 3 NG/DL.
In both of these individuals not only was dihydrotestosterone suppression realized but a significant improvement in acne lesion remission and clearing in the male individual and regrowth of frontal hair in the female individual was documented. Both individuals continued medical treatment and management of their respective illnesses under informed consent never witnessing any side effects or adversities and are pleased with their outcomes thus far.
DISCUSSION
For many years medical researchers have studied the pathways of androgen metabolism and have recognized its undesirable consequences i.e., acne vulgaris, androgenetic alopecia, idiopathic hirsutism and benign prostatic hypertrophy, besides others. There now appears to be significant evidence to suggest that in some individuals the drug zafirlukast not only blocks the potent inflammatory reaction mediated by leukotrienes, but also possess antiandrogen activity as well.
In this study a dose and time dependent effect has been identified with the treatment of both acne vulgaris and common baldness in genetically susceptible men and women without physical or psychological compromise, or forfeit of quality of life. The use of zafirlukast in treating these dreaded diseases appears to be safe and effective at doses above those recommended for the treatment of asthma as shown in this study. Serum liver function studies monitored during this study remained in the normal range of value except in one patient with known Hepatitis C and abnormal pretreatment liver function studies; however, in all patients including the one patient with Hepatitis C, serum liver function studies improved with zafirlukast treatment possibly indicating a role in treating liver diseases in the future.
There are several biological mechanisms that could be implicated in explaining the results of this study including the following:
A) By inhibiting the action of 5-alpha reductase or 17 beta-hydroxysteroid dehydrogenase, the two principal pathways of testosterone metabolism in all growing hairs and skin cells 7 .
B) By inhibiting the formation or action of the metabolite of testosterone or androstenedione i.e. dihydrotestosterone, 5-alpha androstanediol, 5-alpha androstanedione, 5-alpha androsterone or estrone 7 .
C) By inhibiting the peripheral conversion of androstenedione to testosterone in the skin 7 .
D) By inhibiting adenyl cyclase due in fact to high dihydrotestosterone levels in the hair follicle (high dihydrotestosterone levels in genetically marked hair follicles initiate baldness by inhibiting adenyl cyclase) 7 .
E) By alteration of the androgen receptor protein in the peripheral target cells allowing them to concentrate androgens at the presumed site of action in the cell nucleus i.e., interception, antagonism, or inhibition of the highly specific antrogen receptor protein that binds with dihydrutestosterone and transports it to the cell nucleus 7 .
F) By blocking dihydrotestosterone at a given target site 7 .
G) By promoting the formation of progesterone 7 .
H) By promoting the formation of steroids all having structural resemblance to testosterone and thus competing with testosterone for the binding site on the enzyme 5-alpha reductase i.e., 4 androsten-3-one-17 beta-carboxylic acid, androstenedione and deoxycorticosterone 7 .
CONCLUSION
Zafirlukast is both safe and effective in the treatment and management of inflammatory and androgen mediated disorders for which dihydrotestosterone suppression and leukotriene antagonism is desired. Although more rapid and sustained effects are produced at elevated dosage levels, adequate disease resolution ocurrs at doses not associated with serum dihydrotestosterone suppression below the lower limits of normal relative to one's age or sex, suggesting that a dual mechanism of action exist for zafirlukast i.e., antileukotriene and antiantrogen effects. This new found idea and discovery will help strengthen our understanding of treating acne vulgaris, androgenic alopecia, female hereditary balding and other androgen or leukotriene mediated illnesses and in fact may change our way of thinking and approach to these significant illnesses whose symptoms and disease characteristics are ameliorated with the use of zafirlukast. Additional research and development of the drug zafirlukast is recommended at this time.
