Is Androgenetic Alopecia (AGA) Caused Only by the Effects of DHT ?

Despite the Myth, Androgenetic Alopecia is Not Simply a Story of DHT

Androgenetic alopecia is a type of hair loss that affects men and women. In males, this condition is also referred to as male balding or male pattern hair loss and eventually affects some 80 to 90 % of males. In females, the condition is referred to as female pattern hair loss or simply hair thinning and affects 40% of women by age 50. The purpose of this article is to deal with some misconceptions, wrong information, errors and myths that many people have about the role of DHT in the balding process. DHT is certainly important - but other factors must be considered too.

The Evolution of the DHT Theory of Male Balding

Some of the earliest observations about the role of hormones in male balding happened in the time of Aristotle back in 300 BC. Aristotle showed that castrated males (eunuchs) did not develop balding. JB Hamilton in 1942 did additional pioneering work to understand male balding. He showed that male hormones are relevant to the balding process. Specifically, he confirmed observations by Aristotle and others that males that were castrated before puberty did not go on to develop balding. Hamilton took this further and showed that if testosterone was given back to castrated males, the males proceeded to develop male balding. This showed that male balding was an “androgen-dependent” process.

Further key work in understanding male balding was done in the 1970s and ultimately published in the New England Journal of Medicine. These were studies that showed that male pseudohermaphrodite living in the Dominican Republic with a genetic deficiency known as 5 alpha reductase deficiency did not produce dihydrotestosterone (DHT) and did not develop male balding. These findings lead ultimately to the rational development of drugs such as finasteride and dutasteride which block 5 alpha reductase and lower DHT levels.

The Story of Male Pattern Balding has a DHT Chapter but Don't Forget to Read the Others

From 300 BC to the 1990’s, the story of male balding seemed pretty clear. Male hormones, particularly the infamous DHT, seemed to be what male balding was all about. Blocking DHT was what treatments were all about.

Many people incorrectly assume that male balding is just a DHT story. Many people incorrectly assume that this DHT chapter is the only chapter they need to read when trying to understand male balding. While it’s true that DHT has a whole lot to do with male balding - the correct way to state it is “male balding is due in part to the effects DHT on hair follicles that are genetically sensitive to this hormone.”

DHT not the only chapter in the balding story

DHT not the only chapter in the balding story. One only need to consider a few other treatments that are used for balding to very quickly realize that male balding must be much more complex than just a DHT story. Minoxidil (Rogaine), for example, has nothing to do with DHT - and yet it helps some people with male balding. Granted I agree that finasteride and dutasteride are much much better treatments than minoxidil - but if DHT was the only thing we need to think about when it comes to treating male balding then minoxidil would not be expected to have any sort of benefit. Well, it does. Low level laser therapy also has nothing to do with DHT hormone levels - and yet it helps some males with their male balding. Platelet rich plasma (PRP) also has very little to do with DHT- and yet it helps some males with their male balding.

Drug Companies are Investing Large Sums with the Knowledge that Male Balding is Far Far More than A Simply DHT Story.

At least 12 pharmaceutical companies are investing millions upon millions of dollars with the clear understanding that DHT is not the only chapter in the balding storybook. These companies are hoping to the first to market with brand new types of drugs - again drugs that have nothing really to do with DHT. A brief summary of the drugs is below.

If Male AGA is Far More than A Simply DHT Story, Female AGA is Far Far Far More than A DHT Story

If you have now come to realize that male balding is a bit more complex than simply a story about DHT, I’d like to point out that female androgenetic alopecia (i.e. female pattern hair loss) is even more complex. If you think for even a moment that you’re going to apply the same DHT story that you used in males to explain balding to the mechanisms operating in females with androgenetic alopecia, you’re going to come up short in terms of your ability to explain hair thinning in women.

Androgenetic alopecia in females is a far more complex story - and we still don’t know all of the mechanisms that govern how hairs thin in women. Of course, there is some aspects of the DHT story that relevant to female thinning. But finasteride and spironolactone and anti-androgens are far less consistently helpful in females than in males. Other treatments such as minoxidil and laser may be far more helpful in some women than in males. In other words, there are likely several different mechanisms that are contributory to androgenetic alopecia in females besides simply a DHT story. As further information for reflection to readers who still doubt this information, one must consider that some women with a genetic condition that completely makes them insensitive to the effects of androgens (called androgen insensitivity syndrome) can still develop androgenetic alopecia. Even women with low testosterone and low DHT levels can develop androgenetic alopecia. There are even some androgen deficient women who do not develop any balding whatsoever when you give them back supplemental androgens through various means of testosterone replacement therapy.

Conclusion

Is androgenetic alopecia simply due to the sensitivity of hair follicles to DHT? Well, it’s a good story, but it’s only part of the story. The DHT chapter is an important chapter to read in the story of male balding and female thinning, but be sure to read the remaining chapters of the story book. The DHT story is not the only story - and many pharmaceutical companies are banking on this concept.

What is the difference between Latisse and Lumigan?

Latisse vs Lumigan

Latisse and Lumigan have the same active ingredient but are not the same. Lumigan contains bimatoprost at a concentration of 0.01 % and is meant as an eye drop to be placed in the eye.  It is commonly used as a treatment for glaucoma.

Latisse contains bimatoprost at three times the concentration - at 0.03 % and comes with brushes designed for application to the upper eyelid margin.
 

Things to Consider when Latisse won't work

When Latisse Won't Work

Latisse is an FDA approved and Health Canada approved treatment for improving eyelash length, thickness and darkness in patients with eyelash hypotrichosis (not enough eyelashes). Latisse contains the ingredient bimatoprost.

Clinical studies have shown that Latisse is very effective for many user. Many notice changes as early as 4 weeks and 50 % have changes by the second month.  By 16 weeks, 80 % will have an improvement.

Latisse Non-Responders: When Latisse just doesn't work

Latisse is effective for many individuals. However, about 1 out of every 5 users is not going to find that the medication worked all that well for them.  A large proportion of the patients I see in my office come to see me wanting to know why Latisse did not work as good as the advertising stated it should.  Let's review some of the reasons for poor results.

1. The patient is simply in the "20 % group."

Latisse does not help everyone. By 16 weeks, 80 % will be pleased with the money they spent. 20 % won't. I tell my patients that someone has to be in the "80 % group" and someone has to be in the "20 % group." Not everyone responds to Latisse.

2. The bottle does not contain bimatoprost and so it is not Latisse.

Latisse is available through physician's offices (and some drug stores), but there are many other ways of obtaining Latisse and products that claim to be Latisse. I encourage readers to simply enter phrases such as "buy Latisse online" in their Google search engine to see the array of possibilities. Most of these sites will ultimately lead to a box of Latisse (containing the true ingredient bimatoprost) showing up at the door.  But not all.  Patients need to keep in mind the possibility of counterfeit products. It's rare but most certainly does happen.

3. The method of application is wrong.

One needs to apply Latisse nightly to the lower eyelid margin of the upper eyelid with the brushes provided. I can't tell you how many variations of this simple sentence there actually are. Like any drug, it needs to be used according to instructions.

4. The individual has a medical condition of the hair follicle.

It comes as a surprise to many individuals that there are well over 100 reasons for eyelash loss. Not all lash loss is simply due to "aging" or a "tainted bottle of mascara" that was used in the past or improper use of a heated eyelash curler. These certainly can cause temporary or even permanent lash loss. Rather a variety of inflammatory and autoimmune conditions are associated with eyelash loss. 

Eyelash Loss: What else?
 

A careful review of one's story (called the medical history) and up close examination of the eyelashes is needed to determine the cause. One must also examine the eyebrow and scalp hair at the same time as there is no other way to confidently come to the diagnosis.

Causes of eyelash loss include

1. Inflammatory and Autoimmune Conditions. Inflammation of the hair follicle can cause it to fall out. Alopecia areata, frontal fibrosing alopecia, Scleroderma/ en coupe de sabre and lupus are all potential causes.  A variety of true dermatological conditions can also cause lash loss including various eczemas, seborrheic dermatitis and psoriasis. In such cases it is scratching and rubbing that often leads to lash loss.

2. Trichotillomania. 3-5 % of the world will purposefully pull out one or more of their hair follicles somewhere on the body during their lifetime. When repeated, the diagnosis of trichotillomania needs to be considered. Plucking of the lashes is quite common and may even be one sided. 

3. Endocrine disorders. Isolated eyelash loss is uncommon in patients presenting with endocrine disorders. However, one needs to consider thyroid, parathyroid and pituitary disorders.

4. Infections. Infections with fungus, bacteria, viruses all have the potential to cause lash loss. Isolated lash loss is uncommon but can be seen with conditions such as leprosy and syphilis. 

5. Drugs. There are many drugs now implicated in lash loss ranging from cancer drugs to antidepressants (escitalopram) to diabetes medications (sitagliptin and metformin) to methylphenidate. Other drugs include blood thinners, cholesterol meds, propranolol, valproic acid. Even cocaine vapour can cause lash loss.

6.  Infiltrative Conditions. Eyelashes can fall out when cells enter the hair loss that normally don't reside there. Lymphomas are a good example. Eyelash loss can also occur with a variety of local tumors including basal cell carcinoma, squamous cell carcinomas, sebaceous carcinomas and many others.

7.  Nutritional Issues. Poor diets and specific deficiencies can all cause lash loss. This ranges from severe illness with marasmus, to deficiencies of protein, zinc and iron.

8. Congenital and genetic conditions. Many many genetic syndromes are associated with less than normal eyelash density. Well over 50 conditions fall in this category from KID syndrome, Rothmund Thompson syndrome, Incontinentia Pigmenti, Keratosis follicularis spinulosa decalvans, Progeria, Bloom syndrome, Menke's syndrome, Monilethrix to Trichothiodystrophy. Many many others are on this list as well.

Conclusion

There are many causes of eyelash loss. Not every cause of eyelash loss responds to Latisse.

 

Bimatoprost for Androgenetic Alopecia: An intensely researched area

Bimatoprost for Male Balding

Bimatoprost is a prostaglandin F2 alpha analogue that stimulates hair growth. Bimatoprost at 0.03 % is a well known eyelash growth stimulatory compound and marketed under the name Latisse. 

Bimatoprost has been studied for use in androgenetic alopecia. At low concentrations, it is not particularly effective. Allergan is currently studying higher concentrations (1 and 3%). Data released by Allergan and available to the public online suggest that these higher concentrations may be beneficial in treating hair loss. This is an exciting area to watch out for in the near future.

The graph shows how bimatoprost compares to minoxidil in these Allergan led studies. In their preliminary results, higher concentrations of bimatoprost was similarly or even slightly more effective that minoxidil (the gold standard FDA approved topical treatment for androgenetic alopecia).

Thermal Stability of Latisse

Heat Stability of Latisse

I've recently had an large number of questions relating to whether or not Latisse is still safe to use if it has been left in a car for brief periods during elevated temperatures.  Should the Lattise be thrown out? Is it safe to use?

What this question is really asking is what do we know about the stability of Latisse at different temperatures? The stability of a drug as a function of temperature is known as the "thermal stability." Studies to date would suggest that Latisse has remarkable "thermal stability" - at least up to 50 degrees Clecius.

A 2011 study by Johnson and colleagues looked at how the concentration of Latisse (and other prostaglandins) changed when exposed to elevated temperatures including 37 C and 50 C for 3, 6, 9,15 or 30 days. By carefully assaying the concentration of Latisse at each time point the researchers found that there was no change in the concentration of Latisse over time at any of these temperatures. 

Is Latisse safe in my hot car?

To answer this specific question, we really need to know how hot the Latisse was in the car. Of course if the Latissereaches temperatures well above 50 C we enter a grey area and don't fully know the answer based on all studies to date. However Latisse can withstand quite a bit of heat due to its remarkable thermable stability. It is likely to be unaffected to any significant degree following a short period of time at elevated temperature.

Reference 

Thermal stability of bimatoprost, latanoprost, and travoprost under simulated daily use.

Johnson TV, et al. J Ocul Pharmacol Ther. 2011.

Latisse and eye color changes

Can bimatoprost (Latisse) change eye color?

Bimatoprost (Latisse) is a popular product for growing longer lashes. Users of the product are likely very familiar with the fact that the drug was originally used for glaucoma to lower eye pressures. 

The actual drug stimulates pigmentation in the iris because of  the ability of bimatoprost to  increase in pigment granulates in melanocytes. This side effect is mostly observed when individuals put the bimatoprost drops right into the eyes (as is done for those using the medication for glaucoma).

Pigmentation of the iris is not typically observed with those used bimatoprost for the eyelids or eyebrows. However, pigmentation of the surrounding skin can be observed.

Bimatoprost (Latisse) for treating alopecia areata: New study

New study supports use of bimatoprost for alopecia areata 

Bimaprost is FDA approved for treating glaucoma. It's also FDA approved for treating thin eyelashes in those with sparse eyelashes, and in this case is known popularly as Latisse. The use of bimatoprost in treating alopecia areata has only recently been investigated. Studies have suggested a role in treating eyelash loss in those with alopecia areata. 

Bimatoprost in Treating Scalp Loss

A new study, published in Paediatric Dermatology, supports the use of bimatoprost in treating scalp hair loss in patients with alopecia areata. The authors described a 9 year old girl with alopecia areata who had been treated with steroid injections, topical steroids and minoxidil. Despite these treatments, she did not experience regrowth. A decision was made to initiate treatment with bimatoprost solution one drop twice daily on the patches of hair loss. 

Within one month the patient experienced the first signs of regrowth and by 7 months the patient had regrown her hair and was able to stop the bimatoprost. 

Reference

Li and Antaya. Successful Treatment of Pediatric Alopecia Areata of the Scalp Using Topical Bimatoprost. Pediatr Dermatol. 2016