Anti-androgen question.

[decro435]

Why doesn't everybody get side effects from inhibiting DHT with an anti-androgen. The role of androgens in the body is clear , why would they be there if we don't need them? Isn't this extremely dangerous?

"Testes formation

During mammalian development, the gonads are at first capable of becoming either ovaries or testes.[1] In humans, starting at about week 4 the gonadal rudiments are present within the intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial sex cords develop within the forming testes and incorporate the germ cells as they migrate into the gonads. In males, certain Y chromosome genes, particularly SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads.

[edit] Androgen production

The mesoderm-derived epithelial cells of the sex cords in developing testes become the Sertoli cells which will function to support sperm cell formation. A minor population of non-epithelial cells appear between the tubules by week 8 of human fetal development. These are Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens.

[edit] Androgen effects

The androgens function as paracrine hormones required by the Sertoli cells in order to support sperm production. They are also required for masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the mesonephron, the Wolffian ducts, develop into the epididymis, vas deferens and seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells,MIH (Mullerian Inhibitory Hormone), which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for the normal movement of testes into the scrotum.

[edit] Early regulation

Before the production of the pituitary hormone LH by the embryo starting at about weeks 11-12, human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells and their production of androgens. Androgen action in target tissues often involves conversion of testosterone to 5?-dihydrotestosterone (DHT).

[edit] Spermatogenesis

During puberty, androgen, LH and FSH production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production.[2] Exogenous androgen supplements can be used as a male contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum.

[edit] Inhibition of fat deposition

Males typically have less adipose tissue than females. Recent results indicate that androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function.[3] Also, androgens, but not estrogens, increase beta adrenergic receptors while decreasing alpha adrenargic receptors- which results in increased levels of epinephrine/ norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/ norepinephrine then acting on lipolysis-inducing beta receptors.

[edit] Muscle mass

Males typically have more skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells and probably act in a coordinated manner to enhance muscle function by acting on several cell types in skeletal muscle tissue.[4] One type of cell that conveys hormone signals to generating muscle is the myoblast. Higher androgen levels lead to increased expression of androgen receptor. Fusion of myoblasts generates myotubes, in a process that is linked to androgen receptor levels.[5]

[edit] Brain

Circulating levels of androgens can influence human behavior because some neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human aggression[6] and libido."

I just don't get how we can go and inhibit an androgen without getting side effects. If nature didn't intend on it being there it wouldn't exist? Someone explain to me why we can do this?

I've got some serious side effects from the drug finasteride , my hormones have gone all out of sync. I feel sluggish and different , it's just about effecting everything in my body. How can other people handle this? Why do some people need more DHT then the other?

 

[Bryan]

Why doesn't everybody get side effects from inhibiting DHT with an anti-androgen. The role of androgens in the body is clear , why would they be there if we don't need them? Isn't this extremely dangerous?

Your post is confusing to me for two or three reasons. What do you mean by "inhibit DHT"? What do you mean by "inhibit DHT with an anti-androgen"? Did you mean to say "reduce the production of DHT with a 5a-reductase inhibitor"? And for your information, finasteride isn't an "antiandrogen" at all, it's a 5a-reductase inhibitor.

The general idea behind the use of finasteride by fully grown men is that although DHT is known to be essential for genital development in the growing embryo (the first half of your own post is devoted to that), it isn't thought to be essential for normal function AFTER that. Testosterone (not DHT) is considered to be the main androgen in the body by that point, even though DHT is the main androgen that's responsible for balding and probably prostate development.

So the main point I'm making here is that everybody _does_ get side effects from inhibiting the actions of androgens (including testosterone) with antiandrogens, which is exactly why antiandrogens aren't used in grown men, except for very serious diseases like prostate cancer. But 5a-reductase inhibitors like finasteride and dutasteride are something different, and are thought to be considerably safer and more benign than antiandrogens. Experience shows that they apparently _do_ cause problems in some men, but still to nowhere nearly the same degree as true antiandrogens like flutamide and cyproterone acetate.

 

[decro435]

Thanks for the information Byran.

The one question on my mind is why doe's the use of finasteride effect my erections and volume of ejaculate when it doesn't for others. I realise you might not have the answer to this question , but please respond if you know any more. Thanks.

 

[Nuli]

I would guess the weak erections come from the reduction of Nitric oxide that finasteride seemly gives.

 

[casperz]

And for your information, finasteride isn't an "antiandrogen" at all, it's a 5a-reductase inhibitor.

What is spironolactone Bryan?

 

[Bryan]

What is spironolactone Bryan?

It's definitely an antiandrogen.

As to whether or not it also has any 5a-reductase inhibiting properties, I've seen conflicting references: one study stating that it does, another stating that it doesn't. Since that's the only suggestion I've ever seen about it in that regard, my best guess is that if it _is_ able to inhibit 5a-reductase at all, it must be relatively weak.

 

[rcom440]

What is spironolactone Bryan?

It's definitely an antiandrogen.

As to whether or not it also has any 5a-reductase inhibiting properties, I've seen conflicting references: one study stating that it does, another stating that it doesn't. Since that's the only suggestion I've ever seen about it in that regard, my best guess is that if it _is_ able to inhibit 5a-reductase at all, it must be relatively weak.

What do you think Bryan, It is ok to use Nizoral, minoxidil 5% and spironolactone or it is overkill?
Where can we buy spironolactone at reasonable price?
I also added green tea to my regime ;]

 

[Mew]

And for your information, finasteride isn't an "antiandrogen" at all, it's a 5a-reductase inhibitor.

I wouldn't be so sure about that.

From FDA Propecia Clinical Trials:
http://www.fda.gov/cder/foi/nda/97/2078 ... PHARMR.PDF

Screenshot from page 5... more available if requested. Drug may act as a 5AR inhibitor but it certainly has anti-androgenic effects when it comes to inhibiting DHT, an androgen.

 

[Bryan]

Screenshot from page 5... more available if requested. Drug may act as a 5AR inhibitor but it certainly has anti-androgenic effects when it comes to inhibiting DHT, an androgen.

They're merely speaking rather colloquially when they say that finasteride is in the general antiandrogenic "category" of drugs, and it's just because it's able to reduce the net effect of androgens. But doctors and scientists have a precise definition for the term "antiandrogen": it's a substance which binds to the androgen receptor and inactivates it. Finasteride definitely doesn't do that.

For your information, there was actually an article in a medical journal a while back which suggested broadening the definition of the word "antiandrogen" to include 5a-reductase inhibitors, but nothing came of it.