Category Archives: Dihydrotestosterone (DHT)

Androgen Receptors, 5α-reductase, Dihydrotestosterone (DHT)

Destroying Androgen Receptors on the Scalp

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Recently, a reader and hair loss sufferer named “James K” sent me a very interesting e-mail pertaining to destroying androgen receptors. I have pasted most of his e-mail content towards the bottom of this post. Note that the androgen receptor is also known as NR3C4. Other options include looking into androgen receptor antagonists or androgen receptor silencing.

Destroying Androgen Receptors to Stop Hair Loss

Scientists know that male pattern hair loss (androgenetic alopecia) is caused by two factors that both need to be true:

  1. The presence of high levels of dihydrotestosterone (DHT — a derivative of testosterone) in the bloodstream and scalp. Note that 5-alpha reductase enzyme activity is what converts testosterone to dihydrotestosterone.
  2. The presence of a high level of androgen receptors on the scalp. Balding is a direct result of DHT binding to these receptors and then miniaturizing hair follicles. Many people can have high levels of DHT, but lack the androgen receptor (AR) gene. In those cases, they will not go bald. Finasteride drastically reduces DHT from binding to 5α-receptors, resulting in increased hair growth for many people.

Follicle sensitivity to the damaging effects of androgens varies by person. The number of androgen receptors on a scalp’s dermal papilla cells also varies from individual to individual. Research seems to suggest that genetic predisposition to AGA is polygenic in nature and there is no individual gene that is responsible for male or female pattern hair loss. Note that some sources seem to term “androgen receptors” as “DHT receptors”.

On a related note, eunuchs who are castrated never suffer from male pattern baldness. Their DHT levels are negligible for their whole lives. Also of interest is the androgen insensitivity syndrome intersex condition. I bet some blog readers wish they had such a problem.

Going back to “James K”, his main question pertained to why scientists have not done more research into destroying the androgen receptors on the scalp?

Or somehow destroying the androgen receptor gene? While we await CRISPR based gene modification, other techniques such as NdAgo have so far been a bust or overhyped.

How to Destroy Androgen Receptors?

I will quote “James K” in this section:

“I think that a cure would be to destroy these androgen receptors on the scalp, thereby making their sensitivity to androgens irrelevant. Androgen receptors are heat-liable and can be destroyed by trypsin.

Trypsin is possibly safe for topical application, but has the side effects of pain and burning. From a study on rats, trypsin causes hair cells to die and regrow slower, as it changed their gene expression.

Perhaps a safer/weaker version of this can be developed for hair loss? What do you think?”

My Thoughts

I am surprised that there is not much more research on this available online. Is it possible to destroy androgen receptors on the scalp without killing the actual hair follicles? Or is this nonsensical, with the only future solution being a genetic one? i.e., deactivating the AR gene responsible for hair loss?

Update: Someone sent me a link to research on silencing the androgen receptor.

Dutasteride, Avodart, Dihydrotestosterone (DHT), Marty Sawaya, Type I 5α-reductase, Type II 5α-reductase, Type III 5α-reductase

Dutasteride: Will it be Approved for Hair Loss Soon?

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Dutasteride Capsule.
Dutasteride Capsule.

Update: In 2015, Dutasteride was approved in Japan to treat hair loss. Moreover it was approved as a hair loss treatment in South Korea even earlier in around 2010. No wonder that some of the main studies involving Dutasteride and hair growth in men are coming from those two countries.

I think there is a decent chance that the same will happen in the US and EU in the future.

Dutasteride Approved for BPH

Dutasteride (brand name Avodart) was approved in the US in 2002 to treat benign prostate hyperplasia (BPH — aka prostate enlargement in men). Around that time, Dr. Marty Sawaya became the most discussed and popular person on hair loss forums due to her stunning conclusions about the excellent results she had witnessed on people who used the drug to combat hair loss. These results were significantly superior to Finasteride. Dr. Sawaya even appeared on The Bald Truth radio show and gave a number of interviews to hair loss related websites in the early 2000s.

It seemed like hair loss was essentially going to be cured via a medication. Besides stopping hair loss, Dutasteride also seemed to grow back hair that was thought to have become permanently vellus and miniaturized. A real miracle drug that inhibited almost all dihydrotestosterone (DHT) in the body, as well as all three isoforms of 5α-reductase: Type I 5α-reductase, Type II 5α-reductase and Type III 5α-reductase (Finasteride only inhibits Type II and Type III).

Dr. Sawaya’s most famous patient was was Dr. Monahan, and his interview on Hairsite is very good. Unfortunately, Dutasteride’s manufacturer GlaxoSmithKline never seriously attempted to get final Phase III FDA approval for its use as a hair loss medication. Dr. Sawaya mentioned that the main reason behind that decision was due to the fact that based on annual sales of Propecia (Finasteride) and Rogaine (Minoxidil), it was unlikely that Dutasteride would ever become a blockbuster drug with sales of over $500 million.

Approval for Hair Loss

However, recently, Glaxo has become serious about pursuing the final approval process. Here is an interesting recent thread to follow on Reddit regarding Glaxo’s pursuing phase III FDA approval for treating hair loss with Dutasteride.

Dutasteride 0.5mg/day clinical trial for final FDA approval — started in April 2013 and is expected to be completed in October 2014

Dutasteride trial from 2010-2012

Unfortunately, barring a few exceptions, most hair loss forum members who have been using Dutasteride over the past decade do not seem to have seen and major new hair growth based on anecdotal evidence. It is nevertheless likely that on average, the reported results on the forums have been superior to those attained from Finasteride. Just as the various studies have predicted.

Countless people have witnessed a cessation in hair loss after getting on Dutasteride. Once Dutasteride (Avodart) is approved as a hair loss drug, there will hopefully be many more forum members taking the drug, and we will therefore have far more data points to compare results relative to Finasteride.

Will Dr. Sawaya be proved correct after all in her optimism regarding Dutasteride being a miracle drug? Will we finally see a third non-surgical FDA approved hair loss treatment option after Finasteride and Minoxidil?