GnRH agonists are commonly used therapeutically to induce hypogonadism by overstimulating (and thus rendering insensitive) the pituitary to real endogenous GnRH. They commonly cause a 'flare' of excess hormone production before causing complete shutdown.

But I wonder, what if one only used them briefly, wouldn't these drugs be mighty useful for PCT?

No, because the problem is not lack of signaling at the GnRH receptor, nor lack of LH, its lack of response to LH at the leydig cells, due to changes in LH receptor expression/regulation and downstream signaling. This is why HCG low dose EOD on cycle and then a SERM post-cycle is the best way to avoid short and longterm disruption of endogenous hormone production/homeostatsis when using AAS.

This doesn't make sense...as I understand it, the testes atrophy due reduced LH signaling from the pituitary in response to increased AR activation by the AAS. If this were not the case, 'blinding' the pituitary with a SERM would not be effective at restoring function and the testes would be unresponsive to HCG...yes?

The testes should maintain their sensitivity to HCG if it's used throughout the cycle, as per his suggestion.

I've posed that same question about the SERM to you before, IIRC...

Yes you have and I can't recall how I earlier answered but I think it goes something like this. Even when we are "shut down" there is still some T being produced, perhaps if only from adrenal androgens and some of this is being aromatized into estrogen...so using a SERM at this juncture (or an AI) is like pushing a car out a snowbank...the power comes mostly from the car and once it gets going it can continue without your help but it needs a little shove to start off.

But its all about the pituitary as far as I can tell...this is where the go/nogo command to the testes originates based on what the body can tell of circulating androgen and estrogen levels.

What's remains unclear then is why a few puffs of nafarelin nasal spray for a day or two at the start of PCT wouldn't do a world of good.

I had the same question back in the day...

http://www.mindandmuscle.net/forum/index.p...121&hl=klee

seems to me that a shot of GnRH as PCT begins would have a similar effect as a high-dose shot of HCG, despite the dissimilar method. surge of your own testosterone (the former accomplished by stimulation of the pituitary, the latter by stimulation of the testes by what is effectively LH) that has the potential to shut you down if the excess T is sufficient (in both cases your pituitary would respond by reducing output)

unless i am misapprehending...

Would this amount really be of any physiological significance, though? I suppose the enzyme kinetics at low [S] would make this T:E ratio less than at high [test], although I really can't comment on the (theoretical) point where test levels might begin to saturate aromatase and overpower the initial 1st order rate.

I wish I had full text to determine how serious of a cycle these guys were doing, but it looks like at least moderate doses, and they were at ~147 ng/dl if my math is right, and up to ~420 after 9 weeks. So I don't know how much aromatization would occur at those levels, but it could be enough to have a decent effect I suppose. I'm surprised, I thought shutdown (especially after an aromatizable androgen) would be harder.



Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes.
Alèn M, Rahkila P, Reinilä M, Vihko R.

Department of Health Sciences, University of Jyväskylä, Finland.

Endocrine responses in seven power athletes were investigated during a 12 week strength training period, when the athletes were taking high doses of androgenic-anabolic steroids, and during the 13 weeks following drug withdrawal. During the use of steroids significant decreases (P less than 0.05 to 0.001) in the serum concentrations of thyroid stimulating hormone, thyroxine, triidothyronine, free thyroxine, and thyroid hormone-binding globulin (TBG) were found, whereas the value of triidothyronine uptake increased (P less than 0.001). In relation to the changes in the thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis. In five of the seven subjects, serum concentrations of growth hormone increased at some point of the study 5 to 60-fold. Because of the use of exogenous testosterone, serum testosterone concentration tended to increase. This increase was associated with a corresponding increase (P less than 0.001) in serum estradiol. Furthermore, there were major decreases in serum LH (P less than 0.01) and FSH (P less than 0.01) concentrations, and testicular testosterone production was therefore decreased. This was characterized by a very low serum testosterone concentration (5.1 +/- 1.8 nmol/l) 4 weeks following drug withdrawal. Cessation of drug use resulted in return of all the variables measured to the initial values, except for serum testosterone, which was at a low level (14.6 +/- 8.8 nmol/l) 9 weeks after drug withdrawal, indicating prolonged impairment of testicular endocrine function. No consistent changes were found in the eight control athletes.

PMID: 3661817 [PubMed - indexed for MEDLINE]


I wish I could find a comparison of LH surge due to just coming off cycle vs coming off + SERM.



I don't think it would do much good without HCG on cycle to prevent "testicular atrophy" (I know nightop is touchy with that term ). It would be like trying to push your "car in the snow" -- but with flat tires.



That's what I would expect. Same deal -- but neither seems like it could produce miraculous results unless you've preserved Leydig cell function.

I'm not familiar with this steroid, or if this amount is likely to have caused serious shutdown (doesn't look like it from the numbers), but figured this was relevant anyway.

Effect of an anabolic steroid (metandienon) on plasma LH-FSH, and testosterone and on the response to intravenous administration of LRH.
Holma P, Adlercreutz H.

Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as the response of LH and FSH to the intravenous administration of 100 mug of luteinizing hormone releasing hormone (LRH) were measured in 16 well-trained athletes (mean age 30 years) before and after 2 months of daily oral intake of 15 mg of metandienon, and anabolic steroid (Anabolin, 17 alpha-methyl-17beta-hydroxy-1,4-androstadien-3-one, Medica, Finland). All athletes continued to train regularly, just as they had done for several years. During administration of metandienon the mean plasma testosterone level fell 69%, from 29.4 +/- 11.6 nmol/1 to 9.1 +/- 7.5 nmol/1. The mean plasma levels of LH and FSH also fell significantly (P less than 0.001 and P less than 0.01, respectively), both about 50%. Because LH and FSH levels were low after administration of the steroid the maximum stimulation values after LRH administration were also lower than pre-treatment values although the mean increments did not differ significantly before and after administration of the anabolic steroid. However, after treatment, the FSH response curve had a biphasic pattern in most subjects, with peaks at 10 to 20 and 50 to 60 min after the iv injection of LRH. Administration of LRH after the treatment period had no effect on FSH secretion in two subjects and no effect on LH secretion in one. Our results show that administration of an anabolic steroid causes a pronounced lowering of plasma levels of testosterone, LH and FSH but causes no gross alteration in the response of LH secretion to stimulation by LRH. The reason for the biphasic response pattern of FSH to LRH administration in most subjects is not known.

PMID: 793272 [PubMed - indexed for MEDLINE]

During cycle, negative feedback at the hypothalamus and pituitary decrease GnRH and LH release (technically the nature of the effect is AAS and individual/context specific, but in general there is a decrease in the frequency and/or amplitude of the pulses of both hormones). So, less LH signaling at the testes means less endogenous androgen production, i.e. 'shutdown'. Upon cessation of AAS use, GnRH and LH release returns to normal fairly quickly, but if the AAS-use period has been long enough, the testes have by-then altered response to the LH, making 'recovery' a slow process.

If you take HCG during cycle, you will still have decreased GnRH and LH release, but the HCG acts as LH in the testes, maintaining endogenous hormone production and responsiveness of the testes. This way, once you stop the cycle, you quickly taper the HCG and begin use of a SERM, so that GnRH and LH release returns to normal as fast as possible, and your testes don't skip a beat. Even better would be to start the SERM at a low/moderate dose while on cycle with the HCG, so that the main negative feedback is AR-mediated, which is less pronounced then ER-mediated. That way, you still have some degree of GnRH and LH release along with HCG signaling at the testes, so that at the end of the cycle, you just stop the HCG.

Now, that is the right way to use AAS, and virtually nobody does it. Lets now consider your question about using a GnRH agonist post-cycle. If you ran a normal AAS cycle without a SERM or HCG on-cycle, and then post cycle you used a GnRH receptor agonist/mimetic (which is what I assume you mean by GnRH agonist), this will not help the recovery, because LH is already returning to normal quickly but the testes have very low response to it. So, using a GnRH receptor agonist post-cycle is not ideal or really beneficial.

Now, the next scenario, which is not what you were asking, but actually could be beneficial, is to use a GnRH receptor agonist during cycle along with a SERM (but no HCG), so that your LH release remains somewhat near-normal, keeping testicular response and function somewhat normal, so that at the end of the cycle, you stop everything but the SERM, and then endogenous GnRH will quickly return to normal and nothing skips a beat. This is entirely speculation though, as there are a lot of variables that are too complicated to go into here, which could confound such a situation.

Furthermore, the old canonical HPTA mechanisms/theory is actually not very accurate. There are entirely independent regulatory and signaling mechanisms involved at multiple levels, that have very little cross-talk with the normal GnRH/LH/testes pathways that people are so familiar with.

I ought to just make this part of my sig. -- the best way to run an AAS cycle is as follows (excluding general-health related ancillaries/supplements):

Moderate dose testosterone
3-6 weeks duration
low dose HCG EOD or EOOD
low/moderate dose SERM

Upon cessation of the testosterone, quickly taper or just stop HCG use, and increase the SERM dose a little, while eating hypercaloric diet, then after a few weeks taper the SERM, with a steroidal AI on-hand for any estrogen-related rebound issues. Tah-dah.

That makes much more sense and I find your hypothesis for on-cycle use interesting. The big advantage I see of these over HCG is that they can be administered via nasal spray rather than injection.

VERY good point. Aside from the general lack of awareness of HCG, the injectible-requirement is prohibitive for many people, and if the GnRH receptor agonists work as presumed, using one with a SERM on cycle, and then only the SERM post-cycle, would be a viable alternative to HCG use on-cycle. My question would be one of dosing of the GnRH receptor agonist -- this would have to be carefully titrated, as you don't want to go much higher than the normal physiological range of GnRH signaling.