Questions About Baldness-- FAQ

Peter H. Proctor pproctor at sam.neosoft.com
Thu Sep 21 11:03:20 EST 1995


In article <43qg20$sk7 at newsbf02.news.aol.com> spilchard at aol.com (S pilchard) writes:
>From: spilchard at aol.com (S pilchard)
>Subject: Questions About Baldness
>Date: 20 Sep 1995 21:44:32 -0400

>I'm looking for reliable information concerning baldness, thinning hair,
>and male pattern-baldness (I don't know any of the distinctions) and their
>purported causes.  I'm also interested in any information about
>preventing, arresting, or reversing receding hairlines, etc.  Perhaps, you
>have some information or you can refer me to some sources.

FAQ: Hair-loss and Balding

Part 1: Pathophysiology and some treatment agents

Pattern Balding:

Incidence in males roughly corresponds to age (i.e.,at age
35, about 35% of males have it ). Incidence in women half to
third this, at least before menopause.

*Inheritance complicated.  Possibly: "autosomal dominant with
mixed penetrance". Translation: you can inherit from mom or
dad and it expresses itself variably.

*What you inherit is susceptibility to male sex hormones.
multiple factors, including increased uptake, conversion to
more active forms, receptor sites may be involved.

*Four major androgens: Testosterone, DHT, DHEA, and
androstenedione.  DHT most potent-- but, DHEA from adrenals
important in women and possibly men. Likewise, androstene
dione in men.

Other factors in balding: immunological, damage to blood
vessel lining.

_Emerging Model for Pattern Balding_ (after Kligman, others )

     Hormones do something to hair follicle which causes it
to be read as "foreign body" by immune system, which then
mounts an attack. Main damage in balding is probably
immunologically-mediated.  Damage to lining of blood vessels,
which produces hair growth-stimulatory factors, makes this
worse.

A) Evidence for hormonal factors:

     Castration, lack of DHT-receptors/enzymes (testicular
feminization) , feminine status block progression. However,
women and castrated males have other sources of androgens and
can still experience pattern loss.  Even complete castration
( as in male to female sex change operations ) does not reverse
balding much.

Immunological factors

* Microscopically, Balding looks like organ rejection.
Cells of your immune system clustor around the follicle base.
BTW,  Immune system cells normally cluster around the
hair follicle.   They may have a role in the normal hair cyle.

* Organ rejection drugs ( e.g., cyclosporin ) reverse
balding a whole lot better than antiandrogens.  This gives a
rough indication of the relative importance of hormonal
verses immunological factors in maintaining the balding state.

* Antibodies to hair follicles present in blood.

B) Blood Vessel Lining evidence

*Minoxidil, other agents may imitate hair growth factors (
nitric oxide radical, etc. ) produced by vessel lining.
In diseases involving damage to vessel lining
(e.g.,atherosclerosis) production of these is decreased.
Such diseases are associated epidemiologically with severe
balding.  Also, decreases in circulation reported in balding
scalp may reflect local damage to vessel lining

II) Treatment of Pattern Loss

Aside: Forget looking in the medical literature for new
agents.  Because of the commercial potential, everyone
(including me) goes after patents.  Most drug companies want
to keep things secret as long as possible and so often don't
publish on a new drug until it's just about ready for
commercial release.

    BTW,  when developing any drug, the first place a PhD
pharmacologist ( the guys who really develop drugs ) looks is
in the patent literature.   Most physicians and nonpharmacologist
biomedical researchers do not know about about looking at
patents,  so you will rarely see them quoted.

    Even if a researcher is just interested in basic mechanisms,
this is a bad mistake.  For example,  several patents from multiple
sources indicate that superoxide dismutases stimulate hair growth.
Further, another patent from the Procter and Gamble Company
involves using an inhibitor of SODases ( DDTC ) to inhibit
hair growth.

    The implication is that superoxide radical ( an important
messenger in many other systems) is also a messenger
modulating hair growth.   There is not a hint of this in
the  "open"  biomedical literature.

    Besides,  at last count, over forty US and several
hundred foreign patents are issued in this area.
Probably most work at least some--few if any have been published.

Treatment Agents

A) Antiandrogens: E.g.: Proscar, Cyoctal, spironolactone.

     Poorly-effective alone.  Mainly useful as adjuvants to
other therapy where they 1) make it work better 2) Help
prevent tolerance.  Every few years, a new antiandrogen will
be presented as the ultimate "solution for balding". This has
yet to work out.  E.g., clinical trials with cyoctal,
arguably the most potent topical antiandrogen, were
terminated because of lack of effectiveness.

    We'll see about proscar ( the weakest one ).  Early reports
suggest it works about as well as topical spironolactone or cyoctal
( e.g., about half of patients show a 10% or greater number of
hairs on their heads after a year on treatment ).   Because
Proscar is already FDA-approved for prostate enlargement,
Merck will have an easier time getting FDA opproval for it.

    BTW, I have prime patents in this area ( for growth stimulators
plus antiandrogens ).   In fact, because of the publication of our
patents, the combination of a hair growth stimulator plus and
antiandrogen is now " obvious " and thus unpatentable.   I
sure wish antiandrogens worked better.

    Possible explaination: Male hormones only initiate balding.
Further, whatever hormones do seems to be mostly irreversible.
The main damage to the hair follicle seems to be done by other
factors, especially immunological.

B) Direct Hair Growth Stimulators

There are two main kinds:

1) Agents like minoxidil.   These mimic the transmitter
substance nitric oxide, which tells hair to grow and not fall out.

2) SODases and related agents.  These destroy the tramsmitter
substance superoxide, which tells hair to stop growing
and fall out.

Examples

Nitroxides: Minoxidil, nicorandil, NANO, etc.

     Some of these are blood vessel dialating hair-growth
stimulators. OTOH, most dialating agents don't stimulate hair
growth, nor do all these agents dialate blood vessels.
So, vessel dilatation is not _directly_ related to
hair growth stimulation.

     Possible explaination: Nitrovasodialators mimic natural
substance mediating _both_ dialation and hair growth.  Best
candidate: nitric oxide ( aka, EDRF ), a ubiquitous
transmitter which has identical effects to minoxidil on blood
vessels.

Superoxide Dismutase Mimetics.

    These include Iamin, " trichomin" (Procyte corporation),
Copper-Binding Peptide (Procter and Gamble),  TEMPOL,
others (In the late 70's, we found that SODase prevents
stress loss in experimental animals ).   Another copper-binding
peptide SODase hair-growth stimulator made from soy protein
was just patented.  Other radical scavengers also effective
( e.g., various US and foreign patents-- including some to us.)

     BTW, the US patent office just awarded me the prime
patent for SODases in hair loss.

     Further, this technology is so mature that the Procter
and Gamble corporation has a US patent on a SODase inhibitor
( Diethyldithiocarbamate ) to PREVENT hair growth.

     SODases destroy superoxide free radical: Superoxide
reacts with nitric oxide ( the putative "natural" minoxidil )
to produce other toxic free radical products.  OTOH, in many
systems, superoxide is a messenger substance in its own right.
In such systems, it ofter opposes the action of nitric oxide.
So, SODases may work by increasing nitric oxide levels or
more directly.

     Alternately, such agents may interfere with
the immunological component in hair growth.  Active oxygen
species are the most important mediators of cell-mediated
immunity.   BTW,  a mild infiltrate of immune cells
develops around the normal follicle as the hair cycle progresses.
This may be the source of the superoxide that tells hair to
stop growing.

     Significantly,  nitric oxide and superoxide have
opposing "yin-yang" effects on a number of bodily systems.
Examples include blood-vessel dialatation ( nitric oxide
dialates, superoxide constricts ), blood clotting, etc.

      These paired agents may be the most ubiquitous
transmitter substances around.   You can explain a lot by
assuming that nitric oxide is the transmitter that initiates
and maintains hair growth, while superoxide both inhibits
hair growth and causes hair to transition from the growth
phase to the loss phase.
__________________________________________________________

     I am an MD,PHD pharmacologist who practices dermatology
and does hair-loss research.  Repost, but please leave the
credit.

BTW: Please address general questions to the newsgroup so that
I don't have to keep answering the same ones over and over.


Peter H. Proctor, MD,PhD
Suite 1616, 4126 SW Freeway
Houston, TX 77027
(713) 960-1616
pproctor at sam.neosoft.com

Shameless Plug: Send your surface mail address and
we'll tell you about our program for treating hair loss.
Sorry, our stuff is not in electronic form yet.


c 1995 Peter H. Proctor






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