Possible explanation for failure with Propecia or Avodart.

[youngbaldie]

"The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia"


"In a small uncontrolled study of 9 patients with Androgenetic Alopecia, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride."


Division of Dermatology, The University of British Columbia, Vancouver Hospital, Canada.



"BACKGROUND: It is generally believed that dihydrotestosterone is one of the pivotal mediators of hair loss in androgenetic alopecia (Androgenetic Alopecia). Finasteride, which blocks the conversion of testosterone to dihydrotestosterone, has now become an integral part of the current treatment approaches for male Androgenetic Alopecia. Several lines of evidence support the notion that dermal papilla (DP) cells represent the androgen target within the hair follicle. The specific molecular regulators modulated by androgens within hair follicles in the balding scalp are unknown. OBJECTIVE: The purpose of this study was to identify and quantify changes in expression of specific molecular hair growth regulators in DP of men with Androgenetic Alopecia treated with finasteride and correlate these findings to clinical efficacy. METHODS: Biopsy specimens were collected from 9 male patients from both the balding area and nonbalding occipital area before and after 4 months of finasteride therapy. DP were microdissected and total RNA was extracted from an equal number of DP from each biopsy specimen. The expression of various cytokines, including insulin-like growth factor (IGF)-1, was determined by reverse transcription polymerase chain reaction. The signals were detected by autoradiography. All 9 patients were given finasteride for 1 year and evaluated for efficacy at month 12. Efficacy was graded on a 7-point scale on the basis of comparison with initial baseline photography. RESULTS: IGF-1 was up-regulated by finasteride treatment in 4 of 9 patients. Among the patients with increased IGF-1 expression, 3 of them showed moderate clinical improvement after 12 months of treatment and another patient remained unchanged. In contrast, 3 patients with decreased IGF-1 expression in the balding scalp showed clinical worsening after 12 months. The other 2 patients without noticeable change in IGF-1 expression showed either slight improvement or no change in their hair condition. CONCLUSION: In a small uncontrolled study of 9 patients with Androgenetic Alopecia, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride."

PMID: 12894070 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/sites/entre ... med_docsum

 

[LulzKiller]

Hmm, didn't think so.

 

[youngbaldie]

Well I am not to familiar with Insulin Growth Factor, but from what I gather from the study, I would assume that its possible that those with the more aggressive male pattern baldness have lower levels of this.

Perhaps, supplementation of IGF in combination with Finasteride or Dutasteride treatment might provide more satisfying results?

Honestly, I am not sure what to make of this very small study. I have seen others that seem to indicate IGF-1 is bad for balding.

High levels of IGF-1 are also associated with increased cancer risk. Infact, if you have ever had cancer, you should probably never take it as a supplement.

 

[Bryan]

Interesting, but could this also mean that increased expression of IGF-1 is just correlated with more aggressive male pattern baldness and has nothing to do with finasteride itself?

Yes, although you have it backwards. DECREASED expression of IGF-1 is correlated with male pattern baldness! :wink:

 

[docj077]

Interesting, but could this also mean that increased expression of IGF-1 is just correlated with more aggressive male pattern baldness and has nothing to do with finasteride itself?

Yes, although you have it backwards. DECREASED expression of IGF-1 is correlated with male pattern baldness! :wink:

Umm...I think that TruthSmoker had it right. Areas with baldness (especially vertex baldness) typically have higher levels of IGF-1.

 

[harold]

DHT upregulates IGF-1 in beard dermal papillae. This is a good thing for growing hair as opposed to the TGF-beta tht it upregulates in dp from balding scalp regions. What is there that says that IGF-1 is a negative in terms of hair growth?
hh

 

[powersam]

the important bit

IGF-1 was up-regulated by finasteride treatment in 4 of 9 patients. Among the patients with increased IGF-1 expression, 3 of them showed moderate clinical improvement after 12 months of treatment and another patient remained unchanged. In contrast, 3 patients with decreased IGF-1 expression in the balding scalp showed clinical worsening after 12 months. The other 2 patients without noticeable change in IGF-1 expression showed either slight improvement or no change in their hair condition. CONCLUSION: In a small uncontrolled study of 9 patients with Androgenetic Alopecia, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride.

 

[harold]

the important bit

Think the next sentence is just as important at least in terms of showing that IGF-1 seems to be a primary marker of response and not just another growth factor.

IGF-1 was up-regulated by finasteride treatment in 4 of 9 patients. Among the patients with increased IGF-1 expression, 3 of them showed moderate clinical improvement after 12 months of treatment and another patient remained unchanged. In contrast, 3 patients with decreased IGF-1 expression in the balding scalp showed clinical worsening after 12 months. The other 2 patients without noticeable change in IGF-1 expression showed either slight improvement or no change in their hair condition. CONCLUSION: In a small uncontrolled study of 9 patients with Androgenetic Alopecia, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride.

and the one after as well
in summary on finasteride:
IGF-1 goes up = moderate improvement to maintenance
IGF-1 goes down = hair lost
IGF1 stays same = slight improvement to maintenance
hh

 

[Beethoven]

Perhaps, supplementation of IGF in combination with Finasteride or Dutasteride treatment might provide more satisfying results?

Another (more immediately) benefit could be:
We see many posts of people saying something like: "I'm 8 months on finasteride, I think it doesn't help, how could I know? should I wait more time?"
In case this research will prove to be right, this could lead to a simple test, so people could know if finasteride is working for them after a month or two, and not waste many months and lose hair without knowing.

 

[Bryan]

Notwithstanding docj's skepticism about IGF-1, here's something I posted recently over on HLH:


IGF-1 is considered to be a substance which is beneficial to hair growth. Here's a brief passage from the excellent review article "Do Androgens Influence Hair Growth by Altering the Paracrine Factors Secreted by Dermal Papilla Cells?", Randall et al, Eur J Dermatol 2001; 11: 315-20.

"A range of growth factors and cytokines have been implicated in hair growth. Several of these have been shown to be produced by cultured dermal papilla cells...either by measurement of protein production by ELISA of conditioned media or by examining their expression of mRNA by RT-PCR. One of the most studied of these is insulin like growth factor-1, IGF-1, a potent mitogen which plays an important role in maintaining anagen in cultured human scalp follicles in vitro and which causes abnormal patterns of growth and differentiation of hair follicles when its effects are blocked in the IGF-1 receptor deficient knockout mouse. Itami and colleagues have identified the expression of mRNA for IGF-1 in beard dermal papilla cells and confirmed its importance by blocking the mitogenic effect of dermal papilla cells on co-cultured outer root sheath cells with an antibody to IGF-1."

 

[docj077]

Notwithstanding docj's skepticism about IGF-1, here's something I posted recently over on HLH:


IGF-1 is considered to be a substance which is beneficial to hair growth. Here's a brief passage from the excellent review article "Do Androgens Influence Hair Growth by Altering the Paracrine Factors Secreted by Dermal Papilla Cells?", Randall et al, Eur J Dermatol 2001; 11: 315-20.

"A range of growth factors and cytokines have been implicated in hair growth. Several of these have been shown to be produced by cultured dermal papilla cells...either by measurement of protein production by ELISA of conditioned media or by examining their expression of mRNA by RT-PCR. One of the most studied of these is insulin like growth factor-1, IGF-1, a potent mitogen which plays an important role in maintaining anagen in cultured human scalp follicles in vitro and which causes abnormal patterns of growth and differentiation of hair follicles when its effects are blocked in the IGF-1 receptor deficient knockout mouse. Itami and colleagues have identified the expression of mRNA for IGF-1 in beard dermal papilla cells and confirmed its importance by blocking the mitogenic effect of dermal papilla cells on co-cultured outer root sheath cells with an antibody to IGF-1."

Bryan, I don't question that IGF-1 is good for hair...under very particular conditions. Unfortunately, increased IGF-1 in the scalp is cause for concern. Increased IGF-1 is associated with a good 5AR inhibitor response and it's also associated with vertex baldness. The increase is likely happening through two different mechanisms. One is DHT mediated while the other is quite likely estrogen mediated.

 

[CCS]

so if estrogen is good, should I grind up a birth control pill and put it in alcohol and put that on my head?

 

[Bryan]

Bryan, I don't question that IGF-1 is good for hair...under very particular conditions. Unfortunately, increased IGF-1 in the scalp is cause for concern.

I suspect that there may be more to it than just that, since those studies you cited for me had to do with serum levels of IGF-1. In other words, some scalps may be balding not BECAUSE they possibly have higher levels of IGF-1 (via the bloodstream), but IN SPITE of it.

 

[Bryan]

Increased IGF-1 is associated with a good 5AR inhibitor response and it's also associated with vertex baldness. The increase is likely happening through two different mechanisms. One is DHT mediated while the other is quite likely estrogen mediated.

I'll also add here that I was puzzled by your previous suggestion that DHT would stimulate the production of IGF-1 in scalp hair follicles. SCALP follicles?? I would expect that in body hair follicles, but not scalp follicles.

 

[Bryan]

so if estrogen is good, should I grind up a birth control pill and put it in alcohol and put that on my head?

Unfortunately, there's a strong risk of systemic absorption from topically-applied estrogen. Kligman demonstrated that in a study from many years ago. Of course, it's ok to use the nearly inert 17a-estradiol, which has also shown to be of some benefit for hair, but apparently by a different mechanism than 17b-estradiol.

 

[ryan272]

can i ask you guys which website you recommend for finastride 5mg?

 

[Whyatt]

heh...should I countinue to fight IGF-1 in my scalp or should I promote it? :?

 

[docj077]

Increased IGF-1 is associated with a good 5AR inhibitor response and it's also associated with vertex baldness. The increase is likely happening through two different mechanisms. One is DHT mediated while the other is quite likely estrogen mediated.

I'll also add here that I was puzzled by your previous suggestion that DHT would stimulate the production of IGF-1 in scalp hair follicles. SCALP follicles?? I would expect that in body hair follicles, but not scalp follicles.

Can I ask why? It would seem to me that the androgen response should be the same with regards to androgens increasing IGF-1 at any given hair follicle. In fact, I'd expect it to be elevated more than body hair and less than beard hair. So, somewhere right in the middle.

 

[Bryan]

Oh heavens, I certainly don't have any PROOF that androgens downregulate IGF-1 in scalp hair follicles and upregulate it in body hair follicles, but doesn't it at the very least seem like a distinct possibility that IGF-1 is another of the factors that get altered differentially between those two classes of follicle? Randall et al certainly seem to imply as much in that study I quoted above, and further powerful circumstantial evidence is provided by that other small study that associates success with finasteride at least partly to the degree that IGF-1 increases in scalp hair follicles. I hate to sound like our friend Stephen Foote, but I think if William of Okham were a betting man, he'd put his money on IGF-1 as joining TGF-beta as one of those critical factors. There are probably others, too.

 

[Bryan]

Bryan, I don't question that IGF-1 is good for hair...under very particular conditions. Unfortunately, increased IGF-1 in the scalp is cause for concern.

I suspect that there may be more to it than just that, since those studies you cited for me had to do with serum levels of IGF-1. In other words, some scalps may be balding not BECAUSE they possibly have higher levels of IGF-1 (via the bloodstream), but IN SPITE of it.

I'll also add that I see an analogous situation here between IGF-1 and estrogen, in that some people have long tried to argue that because there's a statistical correlation between increasing estrogen levels in ageing men and increasing obesity, prostate, and hairloss problems, therefore the estrogen must be directly contributing to hairloss. But my position is that just like with serum IGF-1, hairloss worsens DESPITE the increasing estrogen, not BECAUSE of it.