[B]ArticleShould we even use Clomid? If so are Anti-E's really enough in PCT?[/B] [B]
Should we even use Clomid? Are Anti-E's really enough in PCT? While doing some reading on my first cycle of:
500mg weekTest E,
10mg Novla ed throught
Clomid PCT Graduated down
I found some informative articles written on why we should not use Clomid PCT and why we should be adding HCG in a post cycle plan. They are as follows:
Clomid, Nolvadex and Testosterone Stimulation
By William Llewellyn
Editors Note: I am extremely pleased to have Bill Llewellyn contributing an article for us this week. For those who are unaware, he is the author of Anabolics 2000 and Anabolics 2002 and is one of the bodybuilding world's foremost experts on androgens and anabolics. He is also the President of Molecular Nutrition, one of the most innovative companies in this business. Along with Avant Labs and ErgoPharm, Molecular Nutrition is one of the few companies dedicated to putting forth only those products backed by legitimate research, rather than excessive hype and other such B.S. Two products, in particular, that deserve to be more well-known are Viritase, a potent anti-estrogen, and Boldione, a boldenone precursor. To find out more about these, and the rest of their products, I reccomend that you head over to their website -- but only after you have finsished reading big Mf'r and spent all of your money on our products, of course :)
Now, on to the article:
Introduction
I have received a lot of heat lately about my preference for Nolvadex over Clomid, which I hold for all purposes of use (in the bodybuilding world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting drug, and as a testosterone-stimulating compound. Most people use Nolvadex to combat gynecomastia over Clomid anyway, so that is an easy sell. And for cholesterol, well, most bodybuilders unfortunately pay little attention to this important issue, so by way of disinterest, another easy opinion to discuss. But when it comes to using Nolvadex for increasing endogenous testosterone release, bodybuilders just do not want to hear it. They only seem to want Clomid. I can only guess that this is based on a long rooted misunderstanding of the actions of the two drugs. In this article I would therefore like to discuss the specifics for these two agents, and explain clearly the usefulness of Nolvadex for the specific purpose of increasing testosterone production.
Clomid and Nolvadex
I am not sure how Clomid and Nolvadex became so separated in the minds of bodybuilders. They certainly should not be. Clomid and Nolvadex are both anti-estrogens belonging to the same group of triphenylethylene compounds. They are structurally related and specifically classified as selective estrogen receptor modulators (SERMs) with mixed agonistic and antagonistic properties. This means that in certain tissues they can block the effects of estrogen, by altering the binding capacity of the receptor, while in others they can act as actual estrogens, activating the receptor. In men, both of these drugs act as anti-estrogens in their capacity to oppose the negative feedback of estrogens on the hypothalamus and stimulate the heightened release of GnRH (Gonadotropin Releasing Hormone). LH output by the pituitary will be increased as a result, which in turn can increase the level of testosterone by the testes. Both drugs do this, but for some reason bodybuilders persist in thinking that Clomid is the only drug good at stimulating testosterone. What you will find with a little investigation however is that not only is Nolvadex useful for the same purpose, it should actually be the preferred agent of the two.
Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using Nolvadex instead of Clomid for increasing testosterone levels (1). Here, researchers looked the effects of Nolvadex and Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant. What was found, just in the early parts of the study, was quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum testosterone levels to 142% of baseline, which was on par with the effect of 150mg of Clomid daily for the same duration (the testosterone increase was slightly, but not significantly, better for Clomid). We must remember though that this is the effect of three 50mg tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the Nolvadex side.
Pituitary Sensitivity to GnRH
But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The tests showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.
The Estrogen Clomid
The above discrepancies are likely explained by differences in the estrogenic nature of the two compounds. The researchers' clearly support this theory when commenting in their paper, "The difference in response might be attributable to the weak intrinsic estrogenic effect of Clomid, which in this study manifested itself by an increase in transcortin and testosterone/estradiol-binding globulin [SHBG] levels; this increase was not observed after tamoxifen treatment". In reviewing other theories later in the paper, such as interference by increased androgen or estrogen levels, they persist in noting that increases in these hormones were similar with both drug treatments, and state that," …a role of the intrinsic estrogenic activity of Clomid which is practically absent in Tamoxifen seems the most probable explanation".
Although these two are related anti-estrogens, they appear to act very differently at different sites of action. Nolvadex seems to be strongly anti-estrogenic at both the hypothalamus and pituitary, which is in contrast to Clomid, which although a strong anti-estrogen at the hypothalamus, seems to exhibit weak estrogenic activity at the pituitary. To find further support for this we can look at an in-vitro animal study published in the American Journal of Physiology in February 1981 (2). This paper looks at the effects of Clomid and Nolvadex on the GnRH stimulated release of LH from cultured rat pituitary cells. In this paper, it was noted that incubating cells with Clomid had a direct estrogenic effect on cultured pituitary cell sensitivity, exerting a weaker but still significant effect compared to estradiol. Nolvadex on the other hand did not have any significant effect on LH response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.
Conclusion
To summarize the above research succinctly, Nolvadex is the more purely anti-estrogenic of the two drugs, at least where the HPTA (Hypothalamic-Pituitary-Testicular Axis) is concerned. This fact enables Nolvadex to offer the male bodybuilder certain advantages over Clomid. This is especially true at times when we are looking to restore a balanced HPTA, and would not want to desensitize the pituitary to GnRH. This could perhaps slow recovery to some extent, as the pituitary would require higher amounts of hypothalamic GnRH in the presence of Clomid in order to get the same level of LH stimulation.
Nolvadex also seems preferred from long-term use, for those who find anti-estrogens effective enough at raising testosterone levels to warrant using as anabolics. Here Nolvadex would seem to provide a better and more stable increase in testosterone levels, and likely will offer a similar or greater effect than Clomid for considerably less money. The potential rise in SHBG levels with Clomid, supported by other research (3), is also cause for concern, as this might work to allow for comparably less free active testosterone compared to Nolvadex as well. Ultimately both drugs are effective anti-estrogens for the prevention of gyno and elevation of endogenous testosterone, however the above research provides enough evidence for me to choose Nolvadex every time.
In next month's follow-up article I will be discussing the role anti-estrogens play in post-cycle testosterone recovery. Most specifically, I will be detailing what a proper post-cycle ancillary drug program looks like, and explain why anti-estrogens alone are not effective during this window of time.
References:
1. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen, Comhaire. Fertil and Steril 29 (1978) 320-7
2. Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro. Adashi EY, Hsueh AJ, Bambino TH, Yen SS. Am J Physiol 1981 Feb;240(2):E125-30
3. The effect of clomiphene citrate on sex hormone binding globulin in normospermic and oligozoospermic men. Adamopoulos, Kapolla et al. Int J Androl 4 (1981) 639-45
AND THE SECOND ARTICLE:
Understanding Post Cycle “T” Recovery
by William Llewellyn
O.K. You have been on an awesome 4-month cycle of Sustanon and Dianabol. You’ve gained a massive 20 lbs, and are extremely pleased with your results. You can’t stop looking in the mirror. But there is a problem now starting to eat away at you. You are going to run out of steroids very soon (you know you need a break anyway), and your testicles are the size of raisins. Your body is producing less testosterone than a 9-year-old girl, and you are scrambling to figure out what to do to avoid a nasty post-cycle crash that could potentially strip away some of your hard-earned muscle. The opinions on how to restore endogenous testosterone production post-cycle seem to be different everywhere you look. What option is best? Without an understanding of exactly what is going on in your body, and why certain compounds help to correct the situation, choosing the right post-cycle program can be quite confusing. In this article I would therefore like to discuss the role of anti-estrogens and HCG during this delicate window of time, while detailing an effective strategy for their use.
The Axis
The Hypothalamic-Pituitary-Testicular Axis, or HPTA for short, is the thermostat for your body’s natural production of testosterone. Too much testosterone and the furnace will shut off. Not enough, and the heat is turned up, to put it very simply. For the purposes of our discussion here we can look at this regulating process as having three levels. At the top is the hypothalamic region of the brain, which releases the hormone GnRH (Gonadotropin-Releasing Hormone) when it senses a need for more testosterone. GnRH sends a signal to the second level of the axis, the pituitary, which releases Luteinizing Hormone in response. LH for short, this hormone stimulates the testes (level three) to secrete testosterone. The same sex steroids (testosterone, estrogen) that are produced serve to counter-balance things, by providing negative feedback signals (primarily to the hypothalamus and pituitary) to lower the secretion of testosterone when too much of this hormone is sensed. Synthetic steroids, of course, suppress testosterone the same way. This quick background of the testosterone-regulating axis is necessary to furthering our discussion, as we need to first look at the underlying mechanisms involved before we can understand why natural recovery of the HPTA post-cycle is a slow process. Only then can we implement an ancillary drug program to effectively deal with it.
Testicular Desensitization
Although steroids suppress testosterone production primarily by lowering the level of gonadotropic hormones discussed above, the big roadblock to a restored HPTA after we come off the drugs is surprisingly not the level of LH itself. This problem is made clearly evident in a study published in Acta Endocrinologica back in 1975(1). Here blood parameters, including testosterone and LH levels, were monitored in male subjects whom were given testosterone enanthate injections of 250mg weekly for 21 weeks. Subjects remained under investigation for an additional 18 weeks after the drug was discontinued. At the start of the study, LH levels became suppressed in direct relation to the rise in testosterone, which is to be expected. Things looked very different, however, once the steroids had been withdrawn (see Figure I). LH levels went on the rise quickly (by the 3rd week), while testosterone barely budged for quite some time. In fact, on average it was more than 10 weeks before any noticeable movement started. This lack of correlation makes clear that the problem in getting androgen levels restored is not the level of LH, but in fact testicular atrophy and desensitization to this hormone. After a period of inactivation the testes have apparently lost mass (atrophied), making them unable to perform the workload required by heightened levels of LH.
Post-Cycle LH Levels
Post Cycle Testosterone Levels
Figure I. LH and Testosterone measurements starting 1 week after the last injection of 250mg of testosterone enanthate (pretreated measures were 5 mU/ml and 4.5 ng/ml respectively). Note that between weeks 1 and 5, as testosterone levels are declining due to the cessation of exogenous androgen administration, LH levels are already rebounding. From weeks 5 to 10 testosterone levels are at or very near baseline, to spite the substantial LH levels by this point. No significant increase in testosterone is noted until after the 10-week mark.
The Role of Anti-estrogens
It is important to understand that anti-estrogens alone do not do much to restore endogenous testosterone release after a cycle. Normally they only foster LH by blocking the negative feedback of estrogens, and we now see that LH rebounds quickly without help anyway. Plus, post cycle there is not an elevated level of estrogen for anti-estrogens to block, as testosterone (now suppressed) is a major substrate used for the synthesis of estrogens in men. Serum estrogen levels will actually be lower here as a result, not higher. Any estrogen rebound that occurs post-cycle likewise happens concurrently with a rebound in testosterone levels, not prior to it (note there is an imbalance in the ratio post cycle, but this is another topic altogether). We are seeing no mechanism in which anti-estrogenic drugs can really help here. We can see why this fact would not be difficult to overlook, however. The medical literature is filled with references showing anti-estrogenic drugs like Clomid and Nolvadex to increase LH and testosterone levels, and in normal situations these drugs do indeed increase endogenous androgen production by blocking the negative feedback of estrogens. Combine this with the fact that just as many studies can be found to show that steroid use lowers LH levels when suppressing testosterone, and we can see how easy it would be to jump to the conclusion that post-cycle we need to focus on restoring LH. We would miss the true problem of testicular desensitization unless we were really looking into the actual recovery rates of the hormones involved. When we do, we immediately see little value in using anti-estrogenic drugs.
HCG
So we now see, contrary to the dominating opinion of the times, that anti-estrogens alone will do little to raise testosterone levels in the early weeks of the post-cycle window. This leaves us to focus on a very different level of the HPTA in order to hasten recovery: the testes. For this we will need the injectable drug HCG. If you are not familiar with it, HCG, or Human Chorionic Gonadotropin, is a prescription fertility agent that mimics the bodies own natural LH. Although the testes are equally desensitized to this drug as LH (they both work through the same mechanism), we are administering it as a measured drug and are therefore not constrained by the limits of our own LH production. We similarly can use HCG to provide a bolus dose of LH (of our choosing), which works only to augment the recovering LH levels we already have in the body. In essence we are looking to shock them with an overwhelmingly high level of LH activity, coming from both endogenous and exogenous sources. We want it to reach a level far above what our body, even when supported by anti-estrogens, could possibly do on its own. The result can be a rapid restoration of original testicular mass and functioning, which would allow normal levels of testosterone to be output much sooner than without such an ancillary program. What we are looking at now is HCG actually being the pivotal post-cycle drug, while anti-estrogens are relegated to a supportive role at best.
Finalizing the Program
An ideal post-cycle recovery program will focus on two things really. The first is hitting the testes hard with HCG. It is important, however, not to overuse this drug. Taken for too long, or at too high a dosage, the LH receptor will actually become desensitized to LH(2) , which may further exacerbate our post-cycle problem instead of helping it (this is why I am not in favor of regular HCG use on-cycle). My experience with HCG has led me to feel comfortable using it for a course of three weeks, at a dosage of maybe 5000-7500IU weekly. Often the last week I limit the dose to 2,500IU, unless the cycle has been particularly long or potent. This is timed so at least half of the total administered drug dosage will be given when there is still exogenous steroid in the body. On our graph above this would be at about the 3-week mark after the last injection of testosterone. This will give the testes some time to get back into shape before the baseline is actually hit with T levels. Secondly, Anti-estrogens are used to play a supportive role at the same time, so 20mg of Nolvadex or 50-100mg of Clomid would typically be added (my last article for Mind and Muscle discusses the comparative differences with these two agents). This is to combat the suppressive effects of estrogen as testosterone levels start to go back up, as well as potential side effects (HCG has been shown to increase testicular aromatase activity as well (3)). Although in the first couple of weeks the anti-estrogen does little, it may indeed be helpful when testosterone levels actually start to get back up near normal. To further stimulate the HPTA, and support continuingly high LH levels, the anti-estrogen remains to be used for 2 to 3 weeks after the HCG therapy has been stopped. A sample program, as it would be instituted in our sample post-cycle window, is provided below.
Sample Post-cycle Plan:
Week
Amount
Week 3:
5000IU HCG total + 20mg Nolvadex daily
Week 4:
5000IU HCG total + 20mg Nolvadex daily
Week 5:
2500IU HCG total + 20mg Nolvadex daily
Week 6:
20mg Nolvadex daily
Week 7:
20mg Nolvadex daily
Week 8:
20mg Nolvadex daily
In Closing
I hope this article provided a well-needed new look at the mechanisms involved in post-cycle testosterone recovery. Indeed I believe it should debunk a commonly held belief these days, as we seen now that those advocating the sole use of Clomid post cycle are sorely missing the mark. The problem goes much deeper than just getting LH levels back. In fact, we see that LH doesn’t even need much help kicking back into gear, and a drug like Clomid will do very little to help this anyway in the absence of significant estrogen levels anyway. HCG is a drug with undeniable usefulness during the post-cycle window, and many bodybuilders have been much too quick to abandon it. It is truly fundamental to an effective recovery program, and would not consider any dose or combination of anti-estrogens or aromatase inhibitors capable of doing the job without it.
References:
1. Effect of long-term testosterone oenanthate administration on male reproductive function: Clinical evaluation, serum FSH, LH, Testosterone and seminal fluid analysis in normal men. J. Mauss, G. Borsch et al. Acta Endocrinol 78 (1975) 373-84
2. Desensitization to gonadotropins in cultured Leydig tumor cells involves loss of gonadotropin receptors and decreased capacity for steroidogenesis. Freeman DA, Ascoli M Proc Natl Acad Sci U S A 1981 Oct;78(10):6309-13
3. Acute stimulation of aromatization in Leydig Cells by Human Chorionic Gonadotropin In-vitro. Proc Natl Acad Sci USA 76:4460-3,1079
The articles can be found at:
http://www.mindandmuscle.net/magazine/i6clomid.html
and
http://magazine.mindandmuscle.net/
Does anyone have any comments, I know that I've been told my cycle is fine, but is it really?
