Bypass the HPTA

[DLMCBBB]

Swale,

What is the proposed mech of clomid? I have heard recently that it can bypass the HPTA, and work by direct glandular stimulation. Is there any validity in regards to those statements? I have not seen any studies supporting that claim. But I have heard stories of men "stating" that clomid helps restore testicular atrophy even when under the presence of androgens.

 

[SWALE]

Clomid blocks estrogen at the HP, and therefore elevates LH production. Its acti is integral to, rather than a "bypass" of the HPTA.

I know of no direct action at the testes.

 

[freedomfighter]

The only thing that I know of that affects the testes directly is HCG. The effect you mention is an old BBing urban legend. While you are on Clomid can not cause the HP to release LH.

Freedomfighter

 

[DLMCBBB]

The only thing that I know of that affects the testes directly is HCG. The effect you mention is an old BBing urban legend. While you are on Clomid can not cause the HP to release LH.

Freedomfighter

Freedomfighter,

When guys are noticing that within 12-48 hrs after ingestion of clomid during the presence of androgens, their "balls" come back, its hard not to appreciate. That tells me that it bypasses the HPTA. If the Hypo is already saturated, then how can the clomid dock at those sites?

If what swale says is true, that "Clomid blocks estrogen at the HP, and therefore elevates LH production". Then we should expect the same results with respect to bringing the boys back, with the sole use of arimidex (post cycle), yet we dont, why?

On a side note, from personal experience, hCG never prevented testicular atrophy during any treatment. Then again, we are all different, and know what works best for us. What are your thoughts.

 

[freedomfighter]

The reason the body shuts down production in the first place is it seeks to maintain homeostasis-a balancing act. When it detects an abnormaly high androgen level the HPTA will not secrete LH. Now HCG is a LH analogue, so it is very effective at preventing testicular atrophy even at very small doses. This is proven. I can speak from personal experience as well. I believe your friends may be experiencing a placebo effect.

Freedomfighter

 

[DLMCBBB]

freedomfighter,

Thanks for your reply, you may be right. Placebo affect, might be stretching it though. Here is a diagram I found on the net, "in women" where clomid has two pathways, one PRIMARY the (HP), and the other SECONDARY the (OVARY) itself.

http://medlib.med.utah.edu/kw/human_reprod/mml/hrinfert_14.html

What about my earlier comments on arimidex?

 

[freedomfighter]

Well clomiphene has estrogenic properties. It does bind with the ERs. I don't know what you mean about Ari. When I used it my recovery time was reduced as long as I used it during cycle. Estrogen supresses the HPTA more vigorously than Test. So If you didn't take Ari while on, Estrogen would still form and supress.

Freedomfighter

 

[SWALE]

Estrogenic binding at the HP (and elsewhere) is instantly competitive. Estrogen is constantly binding, and releasing, from the ER (estrogen receptor), by the concentration of same. The same is also true of other bioactive substances, such as drugs of the SERM class.

you alos have to remember that all receptors have a half-life. This limits the effects of "suicide" (covalent) binders to the ER, such as 16-alpha-hydroxyestrone).

Drugs of the SERM class (i.e. Clomid) indeed elevate LH production. That is why we use them to help "jump-start" the HP. I believe they restart the hypothalamic impulse generator, so it once again produces GnRH, whihc stimulates the pituitary to produce LH.

One way to come to understand this concept is to remember "if you don't use it, you lose it". Also think of then needing to "prime the pump."

 

[MANWHORE]

Swale,I've heard that even though Nolva and Clomid are concidered ANTI-Estrogens they act differently in different estrogen receptors. Clomid acts as an estrogen agonist in the HPTA and Nolva acts as an estrogen antagonist there which is why Clomid is better used when estrogen is under control post cycle(when Arimidex or other anti aromitase taken during cycle)and Nolva is best used when no Anti aromitase were used during and estrogen is out of control post. Nolva also acts as an estrogen agonist in the liver which is good for cholesterol. What do you think of that? thanks

 

[DLMCBBB]

Swale,

Overtime, does clomid loose its effectiveness with regards to sponsoring LH secretion? You said it "jump starts" so to speak of the HP impulse generator, doesnt that require intermitent every 90 minute bursts of GnRH to consistently increase LH and then testosterone? If you take the pharmokinetics of clomid, which I think has a half life of 5 days, how can we sponser or mimic 90 minute bursts, as it takes us 5 days to eliminate half of a given dosage? If it didnt work thousands of bb would not be using it, and you would not be prescribing it to your patients, but I was wondering over time if it loses its effectiveness. Sorry if im unclear in what I type, its hard to get across.

 

[SWALE]

Clomid acts as an estrogen agonist at the HP, which is why it induces LH production. But it is true that drugs of the Selective Estrogen Receptor Modulator (SERM) class act as estrogens (agonists) at some receptors, and block estrogen (antagonists) at others.

I am not sure of the actions of all SERM's at the liver.

Good point, D, naturally GnRH is produced in bursts. Perhaps the secret of why SERM's are effective is that they act at both the hypothalamus and the pituitary simultaneously.

I do not know if SERM's lose their effectiveness over time. I do not prescribe them for a long enough time to have seen this. Also, most use too much each day. Even 25mg per day of Clomid is a big dose. Dr. Shippen and I have independently found this to be true, as discussed in a private conversation a year ago.

 

[DLMCBBB]

Thanks swale for the reply.

From experience, I see tremendous results when the serum concentration of clomid is within the range of (95-178mg). I agree most use too much. For me, if the serum concentration increases a few hundred above (95-178) I get diminishing returns, and have to wait until blood conc levels go down. So maybe the guys that say they dont respond well to clomid therapy, simply use TOO MUCH.