Posts Tagged ‘Dihydrotestosterone DHT’

Study: Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group

Sunday, September 18th, 2011

 -:: This Abstract is posted here for posterity and archival purposes only ::-

J Am Acad Dermatol. 1998 Oct;39(4 Pt 1):578-89.
Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group.
Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, Price VH, Van Neste D, Roberts JL, Hordinsky M, Shapiro J, Binkowitz B, Gormley GJ.
Source

Department of Clinical Research, Merck Research Laboratories, Rahway, NJ 07065, USA.

Abstract
BACKGROUND:

Androgenetic alopecia (male pattern hair loss) is caused by androgen-dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II 5alpha-reductase, decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT.

OBJECTIVE:

Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss.

METHODS:

In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in blinded extension studies for a second year. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, and review of photographs by an expert panel.

RESULTS:

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Study: Treatment of Male Pattern Baldness with Botulinum Toxin: A Pilot Study

Sunday, September 18th, 2011

Comment by Ethan:

This study is important because it reminds us that T conversion to DHT occurs in low oxygen environments, that the muscles (or anything) that constricts blood flow also reduces the availability of Oxygen in the scalp and dermal papilla.  Thus, relaxing these muscles, via botox (something I would not recommend since botox is a toxin), other approaches to relax the muscles and/or increase circulation and Oxygen levels include: various types of scalp massages, acupuncture, diet and nutrition, reducing inflammation, relaxation exercises etc is helpful to men with hair loss resulting from a genetic sensitivity to DHT.

 

 -:: This Abstract is posted here for posterity and archival purposes only ::-

Treatment of Male Pattern Baldness with Botulinum Toxin: A Pilot Study

Freund, Brian J. D.D.S., M.D.; Schwartz, Marvin D.D.S., M.Sc.

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Plastic and Reconstructive Surgery . 126(5):246e-248e, November 2010.

doi: 10.1097/PRS.0b013e3181ef816d

Author Information

Crown Institute; Pickering, Ontario, Canada

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Trace elements content and hormonal profiles in women with androgenetic alopecia

Thursday, May 12th, 2011

J Trace Elem Med Biol. 2010 Dec 15.
Trace elements content and hormonal profiles in women with androgenetic alopecia.
Skalnaya MG, Tkachev VP.

Russian Society of Trace Elements in Medicine, Zemlyanoy Val str., 46, Moscow 105064, Russia; ANO “Centre for Biotic Medicine”, Zemlyanoy Val str., 46, Moscow 105064, Russia.

It is well-known that some trace element imbalances play a significant role in the pathomechanism of many forms of alopecia. Androgenetic alopecia, however, is a specific local sensitivity of hair follicle receptors to androgens.

In a clinical and laboratory study, 153 women with androgenetic alopecia (AGA) and 32 control women were examined. In AGA patients telogen hair and vellus hair (miniaturization, D<30μm) significantly differed in frontal and parietal hair comparison with occipital area (20±0.9% vs. 12±0.5% and 33±0.9% vs. 12±0.6% respectively).

In the AGA group levels of androstenedione and dihydrotestosterone were higher than in the control group. Hair elemental content, analyzed by ICP-MS, demonstrated a lowered Cu and Zn content in the frontal area in comparison to the occipital area. It is important to note, that the AGA patients with elevated levels of androstenedione and dihydrotestosterone presented an increased Cu content and decreased Mn, Se, Zn contents in the occipital area of scalp. The occipital level of Cu positively correlated with the concentration of free testosterone in the serum.

A negative correlation between the Zn content in the occipital area and the dehydroepiandrosterone level in the blood was found.

Unfortunately, a routine treatment course of AGA patients, including topical inhibitor of 5-alpha-reductase and minoxidil, had no effect on the Cu hair content in occipital and frontal areas.

However, there were positive changes in the morphological structure and other trace element contents. These data led us to hypothesize a key role of Cu metabolism disturbances in the AGA onset, development of AGA, and potential pharmaceutical targets for the treatment of AGA.

Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia

Monday, May 9th, 2011

Br J Dermatol. 2011 Mar 24. doi: 10.1111/j.1365-2133.2011.10335.x. [Epub ahead of print]

Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia.

Cobb JE, Wong NC, Yip LW, Martinick J, Bosnich R, Sinclair RD, Craig JM, Saffery R, Harrap SB, Ellis JA.

Department of Physiology, University of Melbourne, Victoria Australia 3010 Developmental Epigenetics, Murdoch Childrens Research Institute, Flemington Road, Parkville, Victoria Australia 3052 Department of Dermatology, St Vincent’s Hospital, Victoria Australia 3065 New Hair Clinic, 627 Chapel Street, South Yarra, Victoria Australia 3141 National Hair Institute, 104 Canterbury Road, Middle Park, Victoria Australia 3206 Environmental and Genetic Epidemiology

In order to compare and clarify the underlying hormonal basis, a study was conducted in 12 young women (ages 14-33) and 12 young men (ages 18-30) with AGA (Sawaya and Price, 1997). Androgen receptor, type I and type II 5x-reductase, and cytochrome p-450 aromatase, were measured in hair follicles from scalp biopsies of these young subjects. Both young women and young men had higher levels of type I and type II 5x-reductase and androgen receptors in frontal hair follicles compared to occipital hair follicles; however, the levels in women were approximately half the levels in men (Sawaya and Price, 1997). At the same time, young women had much higher levels of cytochrome p-450 aromatase in frontal follicles than men who had minimal aromatase, and women had even higher aromatase levels in occipital follicles. The differences in aromatase, which is capable of converting testosterone to estradiol, are particularly notable. The findings of this study suggest that the milder expression of AGA in women may in part be the result of lower levels of 5x-reductase and androgen receptors in frontal follicles of women compared to levels in men; additionally, higher levels of aromatase in women may result in increased local formation of estradiol from testosterone, and less formation of 5x-reductase products such as DHT.

Dermal Papilla Androgen Sensitivity, Androgen Receptors & Methylation

Thursday, December 30th, 2010

Due to the understanding of male pattern baldness as Androgenic Alopecia (i.e. as an androgen-dependent process), many studies have focused on androgen metabolism (AM) in the body and how androgens effect hair.  Studies have shown that “all dermal papilla cells from androgen-sensitive sites contain low capacity, high affinity androgen receptors.” [18]

The dermal papilla (DP), at the base of the hair follicle, has androgen receptors (AR’s) that androgens from the blood bind to. In androgen-sensitive follicles, the androgens are synthesized and diffused over small distances; this induces changes in neighboring cells (like keratinocytes cells) in what is known as “paracrine interactions”. The diffusible proteins are called paracrine factors. [18]

When beard and scalp cells were incubated in androgens, androgens stimulated the cells’ ability to triggered mitosis (cell division) in beard cells but not in scalp cells. The interesting outcome here was that incubation with androgens had the exact opposite effect on scalp cells; these (scalp) cells’ mitogenic capacity was inhibited. [18]

Androgen-sensitive follicles are not simply targeted and affected by androgens; they are actually involved in androgen metabolism (AM) and can convert androgens using steroid-producing (steroidogenic) enzymes, also known as intrafollicular steroidogenic enzymes. [25]

A 2004 study shed more light on specific processes that shorten the hair cycle (that occur within the DP). According to the study, the three processes are as follows: “(1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network.” [6]

The research seems to indicate AM activity at the DP of the hair follicle, amongst other interactions is not fully understood yet. Some of the known intrafollicular steroidogenic enzymes found in the DP are: Steroid Sulfatase (STS), 17beta-hydroxysteroid dehydrogenases (17b-HSD), 3beta-hydroxysteroid dehydrogenases (3b-HSD)  and type 1 and 2 5alpha-reductase (type 1 and type 2 5alpha-R). Type 2 5-alpha-reductase has been the target of a number of studies that showed it to accelerate the conversion of free testosterone into DHT. [10] [11] [12] [24] [25] [28] [31]

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Free Testosterone

Thursday, December 30th, 2010

The levels of free testosterone (free T) and the type 2 5alpha-reductase enzyme in serum has been the target of research; there seems to exist a strong coloration between the levels of available free testosterone in serum of the human body and baldness. [21] [23]

A 1997 study found that “several strong associations also were found between hormone levels and hair patterning.” This study found that “men with vertex and frontal baldness had higher levels of free T”. [2]

It is also known that both 5alpha-reductase enzymes types 1 and 2 convert testosterone (T) to dihydrotestosterone (DHT) as mentioned earlier, [4] particularly type 2.

Should the Term “Androgenic Alopecia” Be Used? (Research History)

Wednesday, December 29th, 2010

About 60 years ago Hamilton made an important observation when he noticed that castrated men did not have AGA. He concluded that hair growth on the scalp was androgen-dependent.

Despite androgens causing hair loss in many men, androgens are actually crucial as they are responsible for the development of puberty; they also aid in, if not cause, male maturation, growth of muscles and the appearance of other sexual characteristics in young humans. [25]

Androgens, such as testosterone (T) and dihydrotestosterone (DHT), have been identified by researchers to be the main regulators of hair growth. Androgens contribute to the changing of vellus (tiny, un-pigmented) hairs into terminal (thicker) hair follicles. [18]

Paradoxically, androgens are also are often thought of as the main culprit behind male pattern baldness.

Androgens in the scalp of adults with androgen-dependent hair follicles seem to have two undesirable effects. The first being that they shorten the anagen phase (long growth phase). [6]

A study published in November 2002 further explained that the follicles experience a “transformation from long growth (anagen) and short rest (telogen) cycles, to long rest and short growth cycles.”  [3]

The second effect always accompanies the first and maybe the manifestation of it. This effect is manifested as the gradual changing of (thick) terminal hair follicles to (thinner) vellus hair (due to the reduction of the cellular hair matrix volume). This change in thickness has been referred to as a “progressive miniaturisation of the follicle.”[3] [5] [18] [23]

In summary, androgens shorten the long growth cycle (anagen phase) and cause follicles to enter into the resting cycle (telogen phase) faster and remain in that phase longer; this results in finer and finer hair. This process  is what we’ve identified as, or termed, AGA.

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