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topical finasteride
- Thread starter neurotic
- Start date
b1ewsw32
New member
From what I have read mostly from various doctors(quacks) I hear that it isn't as effective as the oral version.neurotic said:
People were also curious as to why Merck didn't make it topical after it received approval for the MPB indications.
Now I here that Merck is working on it...Business ploy?..in the sense of first hooking everyone on the 1mg oral, then when sales aren't climbing and people are complaining about systemic effects..then introduce the topical. Some speculate anouncing their intention on developing a topical, will protect their baby as it will allow them longer patent times to avoid replication from generic companies.
I heard that the vehicle you use is important and that isopropyl alcohol wouldn't be as effective as a water-miscible vehicle like dermovan cream. You could always try this method.
I'm going to try to get you the whole abstract of this article from my local health science library, as I feel it could shed some valuable info. and answer some of our questions, as there is no way I'm going to pay $30 U.S.
See if you can dig it up as well....http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=10927075&dopt=Abstract
B32
neurotic said:
I think it was a joke. IM mean inter-muscular...ie...by injection.
Mini Viper
New member
as posted by doublebicep
IM means intra-muscular not 'inter'
IM means intra-muscular not 'inter'
Mini Viper said:as posted by doublebicep
IM means intra-muscular not 'inter'
Yes, I know. The point it that it means in your muscle.
b1ewsw32
New member
Well I finally received my HP PSC, so I will be able to scan and submit full-tect documents much easier.
Lack of effect of topical finasteride suggests an endocrine role for dihydrotestosterone
Androgen-dependent hair growth is influenced by dihydrotestosterone (DHT) at the hair follicle. The DHT
production from testosterone is regulated by the enzyme 5a-reductase, which exists as two isoforms, type I and type 2. Type I 5a-reductase is nearly ubiquitous, being present in tissues such as liver, skin, and adipose, whereas type 2 5a-reductase has a limited distribution, in adult genital skin, prostate, seminal vesicles, and epididymis. The presence of type 2 5a-reductase in the hair follicle is still debated. Use of flnasteride (primarily a type 2 5a-reductase inhibitor) is clinically effective in treating hirsutism. Finasteride may inhibit type 2 5a-reductase in the liver, resulting in lower circulating levels of DHT and less generalized exposure of hair follicles to androgen stimulation. Finasteride may decrease hair growth by local inhibition of type 2 or possibly type I 5a-reductase at the level of the hair follicle.
Nine premenopausal women (surgically sterilized) with lower abdominal hirsutism randomly received daily, blinded application of a topical 0.25% finasteride solution (n = 2), a 0.5% finasteride solution (n = 3), or a placebo solution (n = 4) for 6 months. All women retained their ovaries and were not receiving treatment for hirsutism. This study was approved by the Institutional Review Committee of the Greenville Hospital System.
Preparation of solutions included 240 tablets of 5 mg of finasteride dissolved in 480 mL of ethanol (0.25%), 480 tablets for the 0.5% solution, and lactose for the placebo solution. Tablets were pulverized, dissolved in 100% ethanol, and filtered through a 12-step process to remove excipient material. One milliliter of solution was applied daily to a 10 X lO-cm shaved area between the umbilicus and pubic hair triangle.
Outcomes between the 0.25% and 0.5% finasteride groups showed no difference; thus, results were combined into one treatment group. Photography, comparing hair density of visit I to visit 6 using Fisher's exact test, by six neutral observers showed no difference with time or between groups. Mean hair diameter, measured monthly by microscopy, showed no overall difference between finasteride and placebo (64.5 +/- 17.8 um vs. 66.3 +/- 17.3 um, P=.344, analysis of variance [ANOVA]) with a power of 84% to determine a 9.4-um difference. Serum, collected at baseline, 3 months, and 6 months, was assayed in a single batch for testosterone and dihydrotestosterone. In Figure I, circulating testosterone levels significantly increased from baseline to 3 months in both finasteride (30 +/- 7.9 vs. 37.2 +/- 8.6 ng/dL) and placebo (44.5 +/- 10.1 vs. 58.8 +/- 9.9 ng/dL), but there was no difference between baseline and 6 months for finasteride (30 +/- 7.9 vs. 28.6 +/- 4.5 ng/dL), or placebo (44.5 +/- 10.1 vs. 34.3 +/- 7.4 ng/dL), or at any time between groups (power 88% to determine a 7 ng/dL change). Dihydrotestosterone levels were not different between groups or with time (power 82% to determine a 14 pg/mL change). Despite lack of objective changes, on questioning, all patients in the finasteride group perceived a decrease with time in hair growth, whereas in the placebo group 50% perceived a decrease, 25% an increase, and 25% no change. All subjects reported that they would use a product like this if available.
Finasteride is a selective, but not an absolute inhibitor of type 2 Sa-reductase. The concentration of finasteride necessary to 'inhibit 50% of type 2 Sa-reductase activity (ICso) is 4.2 nM, whereas the ICso of finasteride for type I Sa-reductase is 670 nM (I). Thus, there are three possible methods whereby finasteride may affect androgen-dependent hair growth. First, finasteride may primarily affect liver type 2 Sa-reductase, thus decreasing circulating DHT levels and the amount of DHT reaching the hair follicle. In this case, DHT would primarily act as an endocrine factor. Second, presuming type 2 Sa-reductase is located in hair follicles, finasteride may decrease type 2 activity at the level of the dermal papillae. In this case, DHT would act primarily as a paracrine-autocrine factor. Third, finasteride may partially inhibit type I Sa-reductase and decrease the production of DHT at the level of the hair follicle. Of course, the action of finasteride may also
involve a combination of these methods. The lack of effect of topical finasteride suggests that oral finasteride works by decreasing circulating DHT levels.
Finasteride is structurally similar to testosterone and DHT and is freely soluble in chloroform and alcohol. The potential for percutaneous absorption of finasteride exists on the basis of its steroid structure (2), resulting in a Food and Drug Administration warning that pregnant women should not even handle broken tablets. Our study suggests that topical application of finasteride does not result in significant systemic absorption. Despite daily application of 2.5-5 mg of topical finasteride, there was no increase in circulating testosterone or decrease in DHT levels over 6 months. This observation would have been strengthened by the ability to verify finasteride levels in the solution or in the circulation.
This study also illustrates the necessity of a placebo in hirsutism trials. The increase in testosterone levels at 3 months could have been thought indicative of a treatment effect if the placebo group had not shown a similar increase. This increase may have been due to chance or due to the alcohol base but was not caused by the finasteride treatment.
This study had adequate power (>80%) to determine a change in testosterone of 23% and a change in DHT of 16%. These differences are comparable with changes seen in oral finasteride studies with increases in testosterone of 14%-50% (3) and decreases in DHT of 11 %-76% (4). Thus, this study has adequate power to detect a difference in testosterone and DHT levels that have been commonly found in oral finasteride studies.
In summary, a 0.25%-0.5% finasteride solution was not effective in decreasing abdominal hirsutism, nor did it result in significant changes in circulating testosterone or dihydrotestosterone levels.
B32
Lack of effect of topical finasteride suggests an endocrine role for dihydrotestosterone
Androgen-dependent hair growth is influenced by dihydrotestosterone (DHT) at the hair follicle. The DHT
production from testosterone is regulated by the enzyme 5a-reductase, which exists as two isoforms, type I and type 2. Type I 5a-reductase is nearly ubiquitous, being present in tissues such as liver, skin, and adipose, whereas type 2 5a-reductase has a limited distribution, in adult genital skin, prostate, seminal vesicles, and epididymis. The presence of type 2 5a-reductase in the hair follicle is still debated. Use of flnasteride (primarily a type 2 5a-reductase inhibitor) is clinically effective in treating hirsutism. Finasteride may inhibit type 2 5a-reductase in the liver, resulting in lower circulating levels of DHT and less generalized exposure of hair follicles to androgen stimulation. Finasteride may decrease hair growth by local inhibition of type 2 or possibly type I 5a-reductase at the level of the hair follicle.
Nine premenopausal women (surgically sterilized) with lower abdominal hirsutism randomly received daily, blinded application of a topical 0.25% finasteride solution (n = 2), a 0.5% finasteride solution (n = 3), or a placebo solution (n = 4) for 6 months. All women retained their ovaries and were not receiving treatment for hirsutism. This study was approved by the Institutional Review Committee of the Greenville Hospital System.
Preparation of solutions included 240 tablets of 5 mg of finasteride dissolved in 480 mL of ethanol (0.25%), 480 tablets for the 0.5% solution, and lactose for the placebo solution. Tablets were pulverized, dissolved in 100% ethanol, and filtered through a 12-step process to remove excipient material. One milliliter of solution was applied daily to a 10 X lO-cm shaved area between the umbilicus and pubic hair triangle.
Outcomes between the 0.25% and 0.5% finasteride groups showed no difference; thus, results were combined into one treatment group. Photography, comparing hair density of visit I to visit 6 using Fisher's exact test, by six neutral observers showed no difference with time or between groups. Mean hair diameter, measured monthly by microscopy, showed no overall difference between finasteride and placebo (64.5 +/- 17.8 um vs. 66.3 +/- 17.3 um, P=.344, analysis of variance [ANOVA]) with a power of 84% to determine a 9.4-um difference. Serum, collected at baseline, 3 months, and 6 months, was assayed in a single batch for testosterone and dihydrotestosterone. In Figure I, circulating testosterone levels significantly increased from baseline to 3 months in both finasteride (30 +/- 7.9 vs. 37.2 +/- 8.6 ng/dL) and placebo (44.5 +/- 10.1 vs. 58.8 +/- 9.9 ng/dL), but there was no difference between baseline and 6 months for finasteride (30 +/- 7.9 vs. 28.6 +/- 4.5 ng/dL), or placebo (44.5 +/- 10.1 vs. 34.3 +/- 7.4 ng/dL), or at any time between groups (power 88% to determine a 7 ng/dL change). Dihydrotestosterone levels were not different between groups or with time (power 82% to determine a 14 pg/mL change). Despite lack of objective changes, on questioning, all patients in the finasteride group perceived a decrease with time in hair growth, whereas in the placebo group 50% perceived a decrease, 25% an increase, and 25% no change. All subjects reported that they would use a product like this if available.
Finasteride is a selective, but not an absolute inhibitor of type 2 Sa-reductase. The concentration of finasteride necessary to 'inhibit 50% of type 2 Sa-reductase activity (ICso) is 4.2 nM, whereas the ICso of finasteride for type I Sa-reductase is 670 nM (I). Thus, there are three possible methods whereby finasteride may affect androgen-dependent hair growth. First, finasteride may primarily affect liver type 2 Sa-reductase, thus decreasing circulating DHT levels and the amount of DHT reaching the hair follicle. In this case, DHT would primarily act as an endocrine factor. Second, presuming type 2 Sa-reductase is located in hair follicles, finasteride may decrease type 2 activity at the level of the dermal papillae. In this case, DHT would act primarily as a paracrine-autocrine factor. Third, finasteride may partially inhibit type I Sa-reductase and decrease the production of DHT at the level of the hair follicle. Of course, the action of finasteride may also
involve a combination of these methods. The lack of effect of topical finasteride suggests that oral finasteride works by decreasing circulating DHT levels.
Finasteride is structurally similar to testosterone and DHT and is freely soluble in chloroform and alcohol. The potential for percutaneous absorption of finasteride exists on the basis of its steroid structure (2), resulting in a Food and Drug Administration warning that pregnant women should not even handle broken tablets. Our study suggests that topical application of finasteride does not result in significant systemic absorption. Despite daily application of 2.5-5 mg of topical finasteride, there was no increase in circulating testosterone or decrease in DHT levels over 6 months. This observation would have been strengthened by the ability to verify finasteride levels in the solution or in the circulation.
This study also illustrates the necessity of a placebo in hirsutism trials. The increase in testosterone levels at 3 months could have been thought indicative of a treatment effect if the placebo group had not shown a similar increase. This increase may have been due to chance or due to the alcohol base but was not caused by the finasteride treatment.
This study had adequate power (>80%) to determine a change in testosterone of 23% and a change in DHT of 16%. These differences are comparable with changes seen in oral finasteride studies with increases in testosterone of 14%-50% (3) and decreases in DHT of 11 %-76% (4). Thus, this study has adequate power to detect a difference in testosterone and DHT levels that have been commonly found in oral finasteride studies.
In summary, a 0.25%-0.5% finasteride solution was not effective in decreasing abdominal hirsutism, nor did it result in significant changes in circulating testosterone or dihydrotestosterone levels.
B32
Last edited:
Whew, long report. In summary it says?
