Hormonal levels in patients with male Androgenetic Alopecia < 26 years of age

[bornthisway]

I'll be busy for a few more days but here's something more to add,
study size=270 / ages=14-58 / norwood 3 & 4, it was observed that higher levels of DHT in patients less than 26 years of age is an indicator of favorable response to 1mg finasteride. A 50% decrease in the younger group was noticed over the course of the year, notably at 6 months. After a year, PSA levels decreased more so in those greater than 26 years of age. They also state that no variations in sebum levels were observed from baseline to 6 months to a year. There was no noticeable decrease of DHT in those > 26 years reported.. I don't see why this was omitted since I can't imagine there not being a change. Did all younger patients have high DHT levels at the start? I'll try to see if I can find a copy of this somewhere later... from reading this it would seem there was nothing else significant to report. I'm curious how inflammation and higher DHT affected the younger group, as we have many poor/non-responders to finasteride or minoxidil in that age group and it's usually thought to be the greater sebum production and/or associated inflammation which would make an inhibitory environment for hair growth. Even though each individual in the entire group was in a similar phase of Androgenetic Alopecia (norwood 3 & 4).. this makes me imagine the role of DHT in hair loss may be less significant, especially if those best treated by finasteride have age and high DHT requirements.

Value of hormonal levels in patients with male androgenetic alopecia treated with finasteride: better response in patients under 26 years old.

British Journal of Dermatology. 2008 Mar 20

F.M. Camacho, M.J. García-Hernández, J.L. Fernández-Crehuet

Department of Dermatology, Hospital Universitario Virgen Macarena, Avda. Dr Fedriani s/n. 41071 Sevilla, Spain.

F.M. Camacho.
E-mail: camachodp_AT_medynet.com

Background: Finasteride is a 5alpha-reductase inhibitor that has proved to be an effective treatment for men with androgenetic alopecia.

Objectives: To investigate the hormonal influence of finasteride 1 mg daily on hormonal levels and hair growth in men of different ages and with different degrees of alopecia according to the Hamilton-Norwood scale.

Methods: Two hundred and seventy men aged 14-58 years with male androgenetic alopecia III-VI Hamilton-Norwood score (II-III Ebling score) were treated with finasteride 1 mg daily. Steroid hormone (free testosterone, 5alpha-dihydrotestosterone, dehydroepiandrosterone-sulphate, delta4-androstenedione, 17-hydroxyprogesterone), prostate-specific antigen (PSA) and sebum levels, and trichogram changes were determined at baseline, and at 6 and 12 months of treatment.

Results: According to significant hormonal statistical analysis, the patients were divided by age (up to or over 26 years). In the group of patients </= 26 years, higher levels of 5alpha-dihydrotestosterone were found at the beginning of the treatment, but there was a 50% decrease between the onset of treatment and month 12, particularly noticeable at 6 months (P < 0.05) of treatment, running parallel to an improvement of the alopecia and an increase of anagen hairs in the trichogram. At 1 year, PSA levels decreased 20%, particularly in patients > 26 years. No variations in sebum levels were observed.

Conclusions: High levels of 5alpha-dihydrotestosterone in patients </= 26 years at the beginning of treatment are a predictive factor of good response to treatment with finasteride 1 mg daily.

PMID: 18363752

 

[billythekid]

interesting report

i distinctly remember that when i started taking finasteride, my forehead / temples became really oily - and this is where i had the most hairloss

 

[bornthisway]

This study reminds me of a prior study where patients took finasteride and those who expressed increased IGF-I levels had positive response to treatment. Two other studies indicated IGF-I decline is linear in men with advancing age and one of them also indicates insulin resistance significantly decreases IGF-I bioavailability. Significantly lower IGF-I is also linked to metabolic syndrome.

Curiously... such a small concentration of topical RK can greatly increase dermal IGF-I and provide significant regrowth in a relatively small time frame (oral capsaicin/isoflavone were shown to significantly increase plasma levels of IGF-I in humans as well and provide regrowth).

To me it seems like increasing dermal IGF-I is of importance in Androgenetic Alopecia, and likely why those younger responded better to finasteride treatment than those older (increased expression of IGF-1 messenger RNA levels). Any number of factors with increasing age will decrease IGF-I. It seems increasing dermal IGF-I instead of plasma IGF-I [ which may be correlated with Androgenetic Alopecia.. the relation is poorly understood and not necessarily a causative factor, based on the oral capsaicin/isoflavone study I would imagine it's safe to think the link is elsewhere ] is key and perhaps the best approach to facilitate regrowth while still addressing the many inflammation related aspects. It's also interesting to note that IGF-I provides protection from UVB-induced apoptosis.

Lastly, it's possible overstimulating IGF-I receptors could cause IGF-I resistance or insensitivity (if greater IGF-I plasma levels can be associated with Androgenetic Alopecia in the long run). So, increasing plasma IGF-I levels may not be the best way to go about it. Increasing dermal IGF-I seems like the best solution, and to avoid overstimulation by varying the frequency.

 

[tino]

To me it seems like increasing dermal IGF-I is of importance in Androgenetic Alopecia, and likely why those younger responded better to finasteride treatment than those older (increased expression of IGF-1 messenger RNA levels).

Good post....i totally agree with you in all ranks here.I also think that the younger responder, respond better because of age dependent higher igf-1.And i think that the higher DHT inhibitis the igf-1 in young ones.Take away the DHT increases the dermal IGF-1.

DHT can inhibit Growth hormone production....see here.

http://jcem.endojournals.org/cgi/reprint/76/4/996


Tino

 

[bornthisway]

To me it seems like increasing dermal IGF-I is of importance in Androgenetic Alopecia, and likely why those younger responded better to finasteride treatment than those older (increased expression of IGF-1 messenger RNA levels).

Good post....i totally agree with you in all ranks here.I also think that the younger responder, respond better because of age dependent higher igf-1.And i think that the higher DHT inhibitis the igf-1 in young ones.Take away the DHT increases the dermal IGF-1.

DHT can inhibit Growth hormone production....see here.

http://jcem.endojournals.org/cgi/reprint/76/4/996


Tino

Thanks Tino.

Something else I was thinking.. ROS drives the expression of TGF-beta1 in dermal papilla, by decreasing ROS we decrease the inhibitory growth expression of TGF-beta1. Also by reducing TGF-beta1, the likeliness for mast cells to accumulate should decrease (increased mast cells are linked to dermal fibrosis). ROS also acts on the IGF-I receptor, where ROS is required for proper IGF-I receptor functionality.. though high concentrations of ROS causes IGF-I receptor insensitivity, so reducing ROS will increase IGF-I receptor sensitivity. So in essence, reducing ROS will decrease affinity for mast cell accumulation and TGF-beta1 expression in dermal papilla (inhibitory growth factor), and ensure proper IGF-I receptor functionality. This approach would address major contributory factors in Androgenetic Alopecia.

Related studies:

Role of reactive oxygen species (ROS) on androgen-inducible TGF-beta1 regulation of dermal papilla cells.

Hyeon Gyeong Yoo, Yong Jung Kang, Se Rah Lee, Hyun Keol Pyo, Oh Sang Kwon, Kyu Han Kim, Hee Chul Eun, Kwang Hyun Cho,

Department of Dermatology, Seoul National University, College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital and Institute of Dermatological Science, Seoul National University, Seoul, Korea

Little is known about the roles of androgen on the regulation of redox state in the dermal papilla cells, a cellular process known to profoundly increase with aging. The androgen receptor (AR) has been reported to modulate TGF-beta1/Smad signaling and to be overexpressed in androgen-dependent scalp area of the patients with androgenetic alopecia. The rat vibrissae dermal papilla cell line (DP-6) overexpressed with AR was investigated to evaluate the role of ROS on androgen-induced increase of TGF-beta1 secretion. The AR stably-transfected DP-6 cells were incubated with R1881 or dihydrotestosterone (DHT). Flow cytometry and laser scanning confocal microscopy were undergone to measure ROS production and ELISA assay to evaluate TGF-beta1 secretion after androgen treatment. TGF-beta1 promoter activity assay was also performed whether to be influenced by pretreatment of ROS scavengers. Androgen markedly increased ROS generation and the androgen-inducible ROS augmented TGF-beta1 secretion from dermal papilla cells. Treatment with ROS scavenger or several species of inhibitors decreased ROS production and TGF-beta1 expression. Luciferase reporter assays showed suppression of TGF-beta1 promoter signaling by ROS scavengers. In conclusion, our study shows for the first time that androgen-induced TGF-beta1 accumulation in dermal papilla cells would be mediated by ROS production and prevented by antioxidants or ROS inhibitors.

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Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells.

Arch Dermatol Res. 2008 Mar;300(3):147-52. Epub 2008 Feb 20.

Won CH, Kwon OS, Kim YK, Kang YJ, Kim BJ, Choi CW, Eun HC, Cho KH.

Department of Dermatology, Seoul National University College of Medicine, Yongon-Dong 28, Chongno-Gu, Seoul, 110-744, Republic of Korea.

A relationship has been suggested between mast cells (MCs) and male pattern hair loss (MPHL), because of histological evidence of perifollicular fibrosis and increased mast cell numbers. Two paired punch biopsies were taken from balding vertexes and non-balding occipital promontory areas of ten patients with MPHL (Ludwig-Hamilton IIIv to IV) and from five normal subjects aged from 20 to 35 years. Masson trichrome and Victoria blue staining were performed to observe collagen frameworks and elastic fiber structures. Numbers of immunoreactive MCs stained with anti-tryptase or anti-chymase antibody were counted. It was found that collagen bundles were significantly increased in balding vertexes than in non-balding occiput scalp skin. A near 4-fold increase in elastic fibers was observed in both vertex and occiput scalp skins with MPHL versus controls. Total numbers of MCs (tryptase-positive) in site-matched scalp samples were about 2-fold higher in MPHL subjects than in normal controls. Percentage elastic fiber (%) was found to be relatively well-correlated with tryptase and chymase-positive MCs. These findings suggest that accumulated MCs might be responsible for increased elastic fiber synthesis in MPHL, and indicate that future investigations are warranted.

PMID: 18286292

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Thanks to harold for posting this.

Transforming growth factor-beta 1 mediates mast cell chemotaxis

BL Gruber, MJ Marchese and RR Kew
Department of Medicine, State University of New York, Stony Brook 11794.

It remains unknown which factor(s) control mast cell recruitment in chronic immune reactions. Although TGF-beta has been shown to function as a potent chemotactic factor for monocytes, fibroblasts, and neutrophils, its effect on mast cells has not been previously determined. In this study, TGF-beta 1 was shown to cause directed migration of cultured mouse mast cells at femtomolar concentrations, with a maximal chemotactic response observed at 25 fM. Moreover, chemotaxis to TGF-beta was also seen using freshly isolated rat peritoneal mast cells. Addition of neutralizing Ab to TGF-beta abrogated its chemotactic activity for both freshly isolated rat peritoneal mast cells and cultured mouse mast cells, whereas an irrelevant species-matched control Ab had no effect. Checkerboard analysis confirmed the mast cell chemotactic activity after exposure to concentration gradients of TGF-beta. Mast cells were observed to undergo rapid and extensive shape changes on exposure to TGF-beta, assuming a polarized morphology in preparation for migration. Other known mast cell chemoattractants including laminin, c-kit ligand, and IL-3 were found to be considerably less potent on a molar basis in inducing directed migration. Affinity cross-linking studies identified TGF-beta binding proteins with M(r) at 70 and 288 kDa, consistent with types I and III TGF-beta receptors on the mast cells. In summary, TGF- beta is the most potent chemoattractant described for mast cells and conceivably relevant, because pathologic processes mediated by TGF-beta are often associated with mast cell accumulation.

 

[tino]

Something else I was thinking.. ROS drives the expression of TGF-beta1 in dermal papilla, by decreasing ROS we decrease the inhibitory growth expression of TGF-beta1. Also by reducing TGF-beta1, the likeliness for mast cells to accumulate should decrease (increased mast cells are linked to dermal fibrosis). ROS also acts on the IGF-I receptor, where ROS is required for proper IGF-I receptor functionality.. though high concentrations of ROS causes IGF-I receptor insensitivity, so reducing ROS will increase IGF-I receptor sensitivity. So in essence, reducing ROS will decrease affinity for mast cell accumulation and TGF-beta1 expression in dermal papilla (inhibitory growth factor), and ensure proper IGF-I receptor functionality. This approach would address major contributory factors in Androgenetic Alopecia.

Yes that s right.The oxidative stress caused by an Androgen/Estrogen imbalance(AR modulated) in the line of male pattern baldness, decreases the igf-1 and insulin receptor sensivity.....it inhibits growth in every line.It attacks the angiogenesis too.That s why i recommend Acetylcysteine in higher doses.NAC makes the insulin receptor work propper....respectively it increases his sensivity over ROS inhibition.One way of his working principal is.....it delivers glutathione to the cells,and this inhibits TGF-ß,respectively his actions too.I think we need antioxidant treatment additiv at any rate.Not only androgenes control Tgf-beta Expression over ROS.....Aldosteron,the mineralocorticoid receptor and Angiotensin do it too.Premature Aged hair follicles in the line of male pattern baldness do react negativ on every other stressor.

Its better to take more antioxidants and also ALCAR together.Only stabilize the complete antioxidative network will work suitable additiv to finasteride or Avodart and Rogaine.


http://ajplung.physiology.org/cgi/conte ... 286/1/L121

Thanks for the other references......is this ...

Role of reactive oxygen species (ROS) on androgen-inducible TGF-beta1 regulation of dermal papilla cells.


published in a journal by now?I would like to read a full work.....very intersting investigation.


Tino