Why isn't there a larger effort to reverse and block the effects of androgens on skin?

Question

Puberty wreaks havoc on skin. There's no arguing against the mountains of empirical evidence. Acne and pimples are the most common complaint, followed by unwanted hair and armpit odors, all of which were previously absent. And this NIH academic article (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978100/) specifies that "Inhibition of androgen is known to promote skin wound healing" (see the abstract) - a topic with applications in both the military and regenerative medicine.

"Puberty did so much to improve my skin." - said no one ever.

Usually, androgens are to blame for these (in both men and women). With the massive number of problems, it's way past time for a serious health project to eliminate or neuter (pun intended) all androgen receptors in dermal (skin) cells. I have yet to find any article or scholarly research paper that names one advantageous effect that androgens have on skin - all of them are harmful.

Technology developments in recent years are a gold mine of solutions just waiting to be put into practice. Different cell types have different markers, and it's easy to envision adding an inhibitor to the gene that codes for androgen receptors such that a compound that only dermal cells produce regularly binds to the inhibitor and prevents dermal cells from growing androgen receptors.

While waiting for CRISPR/Cas9 to be ready, there are plenty of cell signaling based approaches. Medication that gets inside skin cells through endocytosis and prevents androgen receptors from "communicating" through blockage of enzyme cascades. Blocking 1 step in the cascade is enough to extinct the previously mentioned health problems.

An even more short-term and lower-tech stopgap would be a topical that soaks down into the skin and irreversibly damages/blocks androgen receptors. Apply on face and neck to prevent acne. Apply to armpits to stop hair growth and odors. Apply to wounds to promote healing. Regularly apply anywhere else to inhibit unwanted hair growth. Topical is built to denature/inactivate permanently in highly acidic conditions to prevent unwanted side effects on accidental ingestion.

The present availability of anti-androgen topicals is a joke. Most of them are prescription only. Almost all of them are specific to either men or women. None of these solutions are practical for wide-scale deployment in civilian life, first aid and emergency service, or the military.

Answer 1

Why, oh, why? Looking into the mirror was sometimes a waking nightmare.

This is partly an XY-Problem and secondly not a pessimists complaint but an overoptimistic expectation. So, let's re-analyse and maybe rephrase or reframe the objectives first.

• What are the real goals here?

  1. To be healthy
  2. To also look healthy, that is: looking good and beautiful.

• What are the goals as formulated in the question?
  Severely disrupting several systems of not yet fully understood complexity in an adolescent body; that is an ever changing system that just started the biggest remake changes in the course of maturing a body into adulthood. This in an attempt to achieve real goal No. 2 without regard to real goal No. 1.

Reasons for progress on this to be perceived as too slow

That "puberty wreaks havoc on the skin" is a correlation based on time. In puberty certain unpleasant skin disorders may manifest themselves. True. But this is not a monocausal explanation like in "puberty causes acne". And this is easily evident from the question itself:

That "[…][anti-androgen]5 […] are prescription only. Almost all of them are specific to either men or women." – Well, having "anti-sex-hormones" differentiated for the different sexes seems required. Men and and women have different levels of hormones. My guess here is that absolutely nobody wants zero androgens in his system. And considering the side-effects: Topical agents may have a systemic effects. If it gets into your skin to affect cells there, it is in your system, almost free to travel anywhere.

"Usually, androgens are to blame for these…" Meaning that with certain levels of androgens (you were never free of them, maybe they are useful?) a certain number of people are more prone to develop skin issues? That is one part of a probably true explanation.

Acne vulgaris that is “the end of my life forever” for one teen can be ignored by another. Acne rosacea can be embarrassing beyond belief and a huge social handicap, or a minor nuisance.⁽²⁾

Acne is not an illness like tuberculosis where you have one pathogen clearly causing a sharply definable set of symptoms. What is colloquially called acne is better described as a syndrome where many symtopms, many causes and many treatment options are available now and will become available in the future. As it's stated in the question "this is a goldmine". But one mine that is still a bit difficult to explore and extract the wealth from.

Acne is an extremely complex disease with elements of pathogenesis involving defects in epidermal keratinization, androgen secretion, sebaceous function, bacterial growth, inflammation, and immunity. In the past 30 years, much has been worked out, and we now have a fairly detailed understanding of the events that result in an acne pimple, although there is also much left to be discovered.⁽¹⁾

Among the so-called causes for acne there are really just a number of factors identified as contributing to the state of unpleasantness. Colloquially: Hormonal imbalances, oily skin, bacterial infections and:

Genetics, Diet, Hormones, Stress, Comedones (plugs in pores),[…]⁽²⁾

Or in another systematic:

Genetics, Androgens, Inflammation, Neuropeptides, Bacteria, The Acne Biofilm, Evidence Supporting a Link Between Acne and Nutrition, Smoking, Antimicrobial Peptides in Acne, Acne and Antimicrobial Lipids, Natural and Artificial Suntanning, Acne and Environmental Pollution (Chloracne), Myths and Beliefs of Acne Pathogenesis: Diet, Smoking, Hygiene, […] Drug-Induced Acne, Body-Builder Acne, Acne Cosmetica… ⁽³⁾

This multitude of causes, often found in countless variations or combinations, means that to arrive at "The Acne Gel" with just an anti-androgen in it is bound to fail.

Only if a condition is really classified as a androgen- or androgen-receptor disorder is there any reason to act upon this alone. Androgens are not "bad". Simply blocking, or yet destroying, the complete signalling pathway for that may yield quite unpleasant results.

Both estrogens and androgens play important parts in skin and hair physiology, […]Further studies with androgen-dependent skin are required to determine whether estrogen receptor β has a regulatory role on androgen receptor expression in the hair follicle in parallel with its role in other androgen-dependent tissues.

Androgens affect several functions of the human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing.

"Just removing this one bad guy" is just not an option. Or just imagine human skin without collagen, you would fall apart to see this:

Collagen, the major macromolecular component of skin, is responsible for maintaining the structural integrity of the tissue as well as for providing important functional characteristics, such as pliability and thickness. We have been studying the structure and regulation of collagen in mouse mutations affecting the skin. In the course of these studies, we found that there are significant differences in collagen content between the skin of wild-type male and female mice, which become evident at puberty. Furthermore, male mice with an X-linked mutation in the androgen receptor gene (formerly called testicular feminization and abbreviated as ArTfm) showed decreased levels of collagen, indicating that the androgen receptor pathway contributes to the observed differences. These findings demonstrate that there are striking differences in the collagen content of skin between male and female mice, and provide a biochemical explanation for these differences.

(An important side note should be allowed in reaction to the comment below: the odour dependent an androgens that is manufactured in the skin is what attracts the ladies (well to a certain extent, or likeminded identities), "the stink" found often in the same place is mainly manufactured by the bacteria on the skin feeding on accumulated waste there. )

Conclusion

"Irreversibly damaging" anything looks like a good idea? Most of those suffering from acne in their youth stop suffering from acne in adulthood. Starting to manipulatie anyones genes without first getting a much better understanding of all the complexities of these processes –in general– seems very pre-mature.

While I am by no means an expert in guessing the path of the future, I am convinced that there are better ways to treat acne now and even better treatments – without crispering genes – will become available. If a condition within this spectrum of unpleasantness is identified with certainty to be influenced positively by androgen receptor sensitivity modification then a treatment doing just that (but temporarily) will come quickly.

Understanding the complex relationships that form the background for these three diseases is essential in order to provide the “deliverable”⁽³⁾

Of course, only funding research into overly specific directions, like genetic modification or topical anti-androgens, may have detrimental effects in the long run. Please consider this the next time you have to vote on anything.

References

_{1 Guy F. Webster, Anthony V. Rawlings (2007):"Acne and its Therapy", Informa Healthcare: New York.}

_{2 F. William Danby (2015): "Acne: causes and practical management", Wiley: Chichester, Oxford.}

_{3 Christos C. Zouboulis Andreas D. Katsambas, Albert M. Kligman (2014): "Pathogenesis and Treatment of Acne and Rosacea", Springer: Heidelberg, New York, Dordrecht, London.}