I can confirm the correctness of the following article from at least 2
additional sources. In a nutshell, DHT and
progesterone are the good
hormones because they are opposing the growth promoting/oxidative
stress inducing properties of estrogen in men and women,
respectively. They have also pro-apoptotic properties which may help
killing precancerous cells (in addition to e.g. hair follicles in the
case of DHT). So all men praise you balding scalp and you will be
rewarded with cancer and BPH protection! A side note for chemists:
not by a pure coincidence the estrogen molecule carries the highest
number of double bonds (in an aromatic ring) like the PUFAs such as
arachidonic acid which act synergically with it to promote oxidative
stress. On the other hand the good DHT is nearly fully saturated
molecule. IMHO the double bonds are essential for the pro-growth
signaling in all biological systems.
DHT - Is It All Bad?
by Patrick Arnold
A considerable chunk of my work day is always spent answering people’s
questions about prohormones and steroids. Of course, one of the
biggest concerns people have is about estrogen and estrogen related
side effects. Right behind that however are questions about DHT. It
seems that people have the misconception that DHT is some evil
androgen by product that serves no purpose in the body but to make our
prostates blow up and our hair fall out.
The real situation is of course much more complex. DHT is one of those
good guy / bad guy hormones that is sorely misunderstood. For many
people, it is NOT something that you want to reduce or eliminate in
the body. For some others though, keeping DHT levels under control is
probably a prudent course of action. Knowing the facts about DHT will
help you decide just which group you belong to.
Testosterone is a prohormone?
The main androgen secreted by the testes is of course testosterone.
However, in most of the body, the androgenic signal is not carried
through by testosterone. In these tissues, which include the brain
(CNS), skin, genitals – practically everything but muscle – the active
androgen is actually DHT. Testosterone in this case simply acts as a
prohormone that is converted to the active androgen DHT by the action
of the enzyme 5alpha reductase (5-AR).
5-AR is concentrated heavily in practically every androgen dependent
area of the body except for skeletal muscle. This results in very
little testosterone actually getting through to these parts of the
body to bind to androgen receptors. Instead, it is quickly transformed
into DHT, which then interacts with receptors.
This transformation serves a very important biological function in
these tissues. You see, DHT is a much stronger androgen than
testosterone – it binds about 3-5 times more strongly to the androgen
receptor. If you took away 5-AR from these tissues and blocked the
formation of DHT, then you would see some dramatic changes in
physiology.
A good case in point is demonstrated in male pseudohermaphroditism due
to congenital 5-AR deficiency. This is a relatively rare disorder,
however it is actually quite common in the Dominican Republic. In this
disorder, males are born with little or no 5-AR enzyme. They have
ambiguous genitalia and are often raised as girls. When puberty
occurs, their testosterone levels elevate normally although their DHT
levels remain very low. Their musculature develops normally like that
of other adults, however, they end up with little or no pubic / body
hair and underdeveloped prostate and penis. Their libido and sexual
function is often disrupted also.
Testosterone is the active androgen in muscle
Skeletal muscle is unique from other androgen dependent tissues in the
body. It actually contains little or no 5-AR, so little or no DHT is
actually formed in the muscle. In addition to this, any DHT that is
formed, or that is already present in the blood and travels to the
muscle, is quickly deactivated by an enzyme called 3alpha-
hydroxysteroid reductase (3a-HSD).
So at least as far as muscle is concerned, testosterone is the primary
active androgen. This is not to say that administering exogenous DHT
is not without any anabolic effect. It actually does have some
anabolic activity in the muscle, albeit significantly weaker than that
of an equal amount of testosterone. This is due to its quick breakdown
by 3a-HSD into the weak metabolite 5alpha-androstan-3a,17b-diol. If
this enzyme were somehow blocked, it is likely that DHT would exhibit
very potent anabolic effects on muscle.
It is important to understand that even though testosterone is the
active androgen in muscle, and DHT exhibits relatively little direct
anabolic effects on muscle in men, DHT is still very important for the
full performance enhancement effects from testosterone. What I
specifically mean here are the effects of DHT on the central nervous
system, which lead to increased neurological efficiency (strength),
and increased resistance to psychological and physical stress - not to
mention optimal sexual function and libido.
I have heard several anecdotal reports of individuals who have stacked
testosterone with
proscar (a 5-AR inhibitor) and have noticed
significantly reduced performance enhancement effects. What’s going on
here? We know it couldn’t be due to the inhibition of the direct
anabolic activity of testosterone on muscle anabolism. Most likely it
is due to the reduction of androgenic effects in other parts of the
body that contribute to the ergogenic effects, specifically the CNS,
which is stimulated by androgens to increase neural output leading to
greater strength and greater recoverability. Another possibility is a
reduction in the production of androgen dependent liver growth factors
(such as IGF-1), since DHT is an important androgen in the liver.
Anti – Estrogen effects of DHT
One important function of DHT in the body that does not get much
discussion is its antagonism of estrogen. Some men that take Proscar
learn this the hard way – by developing a case of gynecomastia. By
reducing DHT’s protection against estrogen in the body, these men have
fallen victim to its most dreaded ramification – bitch tits!
How does DHT protect against estrogen? There are at least three ways
that this likely occurs. First of all, DHT directly inhibits estrogens
activity on tissues. It either does this by acting as a competitive
antagonist to the estrogen receptor or by decreasing estrogen-induced
RNA transcription at a point subsequent to estrogen receptor binding.
Second of all, DHT and its metabolites have been shown to directly
block the production of estrogens from androgens by inhibiting the
activity of the aromatase enzyme. The studies done in breast tissue
showed that DHT, androsterone, and 5alpha-androstandione are potent
inhibitors of the formation of estrone from androstenedione. 5alpha-
androstandione was shown to be the most potent, while androsterone was
the least.
Lastly, DHT acts on the hypothalamus / pituitary to decrease the
secretion of gonadotropins. By decreasing the secretion of
gonadotropins you decrease the production of the raw materials for
estrogen production – testosterone and androstenedione (DHT itself
cannot aromatize into estrogens). This property of DHT comes into
particular utility when it is administered exogenously, and this is to
be discussed in further detail in the next section.
DHT, estrogen, and the prostate
When it comes to sex hormones, few things are as misunderstood by the
general consumer as the relationship of the prostate to DHT. The
inaccurate and overly simplistic attitude that DHT is responsible for
prostate hypertrophy, and even prostate cancer predominates amongst
most people.
The real situation is, of course, much more complex. One must
understand that there are marked differences between healthy prostate
growth (developmental growth), prostate growth due to BPH, and
cancerous prostate growth.
The first period of prostate growth, deemed developmental growth, is
connected to puberty and the testicular secretion of androgens. This
takes the prostate from its prepubertal dormancy to the normal sized,
healthy, and functional prostate gland of an adult. During the early
and mid adult years the prostate stays at this stage, despite the
constant high levels of androgens in the body. However, if androgens
are blocked in the body then the adult prostate will shrink in size.
This can occur by castration, or even by blockade of 5-AR (recall that
DHT is the active androgen in the prostate).
Later in life, there is often a second stage of growth. This growth is
deemed benign prostate hypertrophy (BPH) and this growth occurs in a
wholly different hormonal environment than that of developmental
growth. Evidence is mounting that the existence of a high estrogen /
androgen ratio – a condition common in older men – is highly
correlated to the development of BPH.
Experimental studies have shown the inability of androgens with
saturated A rings (DHT related) to induce an initial condition of
prostate hypertrophy. These compounds are non-aromatizable.
Aromatizable androgens on the other hand, such as testosterone or
androstenedione can induce hyperplasic modifications of the prostate
of monkeys, but these effects are reversed by the addition of an
aromatase inhibitor.
So apparently, estrogen is a causative factor in BPH or, probably more
accurately, estrogen in the presence of a minimum, permissive amount
of androgen.
None of this may come as news to many of you, but I bet that very few
of you know that DHT can actually be used to treat BPH!! How can it do
that? It basically does this by replacing the testosterone in the
body, which then has the effect of reducing the amount of estrogen in
the body. As I started to explain before, DHT is a strong androgen
that will signal the pituitary to decrease the production of
gonadotropins. The decrease in gonadotropins will then cause less
testosterone to be produced which will in turn cause the estrogen
levels to drop. The resulting change in the hormonal milieu (high DHT,
low estrogen) then apparently results in a regression of BPH.
The clinical application of this theory is discussed in US patent
5,648,350 "Dihydrotestosterone for use in androgenotherapy". The
following illustrates the results:
"In 27 subjects in which the plasma DHT level was controlled, so as to
modulate the administered doses, said levels have been increased to
2.5 to 6 ng/ml. There resulted a decrease in gonadotrophy as well as
in the plasma levels of testosterone which exceeded at least 1.5 ng/ml
(from 0.5 to 1.4 according to the case); as to the
estradiol plasma
levels, these decreased by 50%.
Among this group of subjects, the volume of the prostate diminished
significantly, as was evaluated by ultrasound and by PSA (Prostate
Specific Antigen). The mean volume of the prostates was from 31.09.+-.
16.31 grams before treatment and from 26.34.+-.12.72 grams after
treatment, for a mean reduction of 15.4%, the treatment having a mean
duration of 1.8 years with DHT (P=0.01)."
This kind of flies in the face of the traditional thinking concerning
BPH now doesn’t it?
Conclusion
People have a natural tendency to classify things as either good or
bad, with no gray areas. DHT (like estrogen) has recently been on
everyone’s bad list, and is often considered to be a hormone that
serves no function in the body except to cause harm. As you can see,
this view is far from the truth. In my opinion, the widespread use of
5-AR inhibitors such as Proscar as a prophylactic agent for people
that really don’t need it should be reconsidered. So give DHT a break.
SOURCE:
http://www.mesomorphosis.com/articles/arnold/dht.htm
Also recommended reading about estrogen and PUFAs on the Ray Peat
site:
http://raypeat.com/articles/
Taka
DHT debunked 