Author : Nandi12 (R.I.P.)
Summary : The questions here were posed to me by an editor of another online magazine, but as I have been unable to contact him in some time I decided to post my responses here. Please feel free to take issue with anything (or everything) you disagree with!
Q: What are some of the reasons Deca has been touted as one of if not the most suppresive adrogen?
A: Deca’s reputation as being highly suppressive to the Hypothalamic-Pituitary-Testicular Axis (HPTA) is probably deserved, but trenbolone may be even more suppressive. Unfortunately there is not much research to rely on here so we are forced to speculate to some degree. There are several reasons that could explain Deca’s ability to shut down the HPTA relatively strongly. First, the decanoate ester is very long lived. By this I mean because of its hydrophobicity (insolubility in water or plasma) it has a tendency to diffuse very slowly out of the injection site into the plasma where the ester is removed from the nandrolone molecule. I like to refer people to the study by Minto et al to see this depicted graphically in Fig 1.
http://jpet.aspetjournals.org/cgi/content/full/281/1/93
As Fig.1 shows, it takes over a month for nandrolone plasma levels to return to zero after a single injection of Deca. Figure 3 in the same study shows that plasma levels of endogenous testosterone levels are a virtual mirror image of plasma nandrolone levels, with testosterone taking a month to return to baseline. And bear in mind this is after just one injection of Deca.
The second reason Deca may be so suppressive is that besides being an androgen, it also has progestigenic properties, meaning it binds to the human progesterone receptor at relatively low concentrations where it acts as an agonist (1). As an example of the relative binding affinities of androgens to the progesterone receptor (PR), if progesterone itself is given an arbitrary relative binding affinity (RBA) of 100, testosterone's RBA is 1.1; DHT's is 0.9; nandrolone's RBA is 20; trenbolone's is 60 (2). So we see that nandrolone binds to the PR with about 20% of the strength of progesterone. The significance of this to our discussion is that progesterone, as well as synthetic progestins can act on the HPTA to reduce luteinizing hormone (LH) production (3). Most of our readers are aware that LH secreted from the pituitary is what drives testicular testosterone production. So by acting as a progesterone receptor agonist, nandrolone is contributing to the suppression of the HPTA. This is in addition to the ability of androgens in general to suppress pituitary LH production by interfering with the Gonadatropin Releasing Hormone (GnRH) signal sent from the hypothalamus to the pituitary, which drives LH secretion.
The abovementioned ability of Deca and other androgens to suppress natural testosterone production by acting to disrupt GnRH signaling is the third reason Deca is quite suppressive. The presence of androgen receptors in the GnRH secreting neurons has been demonstrated in a number of studies (see 4,5 for example) and it is believed that androgens act directly on these receptors to disrupt GnRH pulse signaling. As most readers are aware, nandrolone binds to the AR with a greater affinity than does testosterone, so this may be another factor in nandrolone being more suppressive than other steroids. However, as (4) points out, DHT could possibly be the active androgen in the hypothalamus. If this is the case, one might expect testosterone, via its conversion to DHT, to be more suppressive at the hypothalamic level. This clearly requires more research.
Deca also aromatizes to some degree, and since estrogens are quite suppressive, this certainly could contribute to Deca’s ability to shut a person down compared to nonaromatizing steroids. On the other hand, testosterone aromatizes quite readily and the resulting elevated estrogen levels contribute significantly to HPTA suppression. Moreover, by suppressing testosterone production, which is a superior substrate for aromatase, Deca has been shown to either lower estrogen levels or leave them unchanged. So aromatization is the least likely mechanism for Deca’s HPTA suppression.
In a recent issue of Mind & Muscle I described in an article entitled “Understanding Androgen Actions” how different androgens and anabolic steroids, after binding to the androgen receptor, preferentially bind to different genes:
http://www.avantlabs.com/page.php?p...&issueID=13
Quoting from the article,
“[There is] evidence for the existence of distinct steroid specific target gene transcription profiles following AR activation (3). In other words, the structures of androgen responsive genes vary in such a way that some genes are more readily activated by certain androgens than by others. The set of genes readily switched on by a given androgen determines the net physiological effect of that androgen.”
This is most likely the best explanation for the suppressive nature of Deca: due perhaps simply to the shape or charge distribution of the molecule, after binding to the androgen receptor (AR), the Deca/AR complex preferentially binds to genes that regulate LH and/or GnRH production, the net result being a decrease in the production of either or both of those hormones.
Q: What is the most effective method using clomid to recuperate post cycle?
A: Everyone seems to have his or her pet dosing regimen here. What I typically suggest is something like Clomid 300mg per day for the first 2 or 3 days, then 10days of 100mg and than ten days of 50mg. No doubt many people will take issue with this schedule, and if someone has a dosing regimen that seems to work for them, they should stick to it.
In my opinion the dosing schedule is not so important as is the need to accompany the Clomid with HCG either on a regular basis during the cycle, or towards the end of the cycle and extending into the post cycle recovery period, or simply at the end of the cycle. For example, a lot of guys at cuttingedgemuscle (CEM) are running 1000 IU/day of hCG for 10 days post cycle with either Clomid or Nolvadex. Again, opinions vary as to the most effective protocol and unfortunately we have little if any science to fall back on. After using Clomid and HCG primarily as post cycle ancillaries, I’m now still using Clomid in the traditional way after a cycle, but employing weekly injections of HCG throughout the cycle to (hopefully) reduce testicular atrophy. As most readers know, HCG acts like LH, stimulating the testicular Leydig cells. Probably more than anything else, testicular atrophy is what prolongs recovery. Studies have shown that post cycle, the pituitary recovers much more quickly than do the testes. In fact, after the pituitary has recovered several weeks post cycle, pituitary LH secretion becomes supraphysiological, presumably as the body tries to stimulate the still atrophied testes (6). If we can reduce the atrophy by keeping the testes “primed” with HCG recovery should be quicker.
Getting back on topic, there is another reason I believe Clomid is important post cycle. This is strictly my theory and I admit I have no proof to back it up. I have noticed though from a number of studies, as well as from blood work posted by members, that Sex Hormone Binding Globulin (SHBG) remains low for many weeks (16 in some studies) after a cycle. SHBG levels control total test levels. Low SHBG means low total testosterone. Clomid acts as an estrogen in that it elevates SHBG. When clomid is used post cycle, the body will sense that testosterone is low relative to SHBG, and boost test production. (Technically what I believe will happen is that the elevated SHBG will lower free test levels by binding up more free test, blocking any suppressive effect of this test at the hypothalamic level. Lower free test also means lower aromatization into highly suppressive estrogen. Both effects should speed recovery.)
Q: Why has Testosterone long been suggested as a base for a cycle and the "safest" drug to use?
A: Let me address the second part of your question first. There are several things we need to look at when we talk about the safety of a drug. One topic I see discussed more and more often on my board and others is the effect of AAS on a person’s cholesterol profile. Maybe we’re all getting a little older and are more concerned about cardiovascular health. There is a wealth of data showing that oral 17 alpha alkylated steroids (Winstrol is often cited as a particularly bad culprit) are more effective at lowering HDL cholesterol, the good cholesterol, than are other injectable steroids. According to one study, it took 600 mg per week of testosterone enanthate administration before there was a statistically significant drop in HDL (7). On the other hand, as little as 6 mg/day of Winstrol can lower HDL by 33% (8). What about testosterone versus other injectables, like nandrolone? Unfortunately there is a lack of data on the effects of high doses of nandrolone on cholesterol. What studies that are out there typically use 100 to 200 mg per week. The results of these studies are variable. Some done in subjects with compromised health, such as HIV or dialysis patients, show a trend of decreasing HDL. Other studies in healthy individuals show little if any effect on cholesterol (9). So testosterone may or may not be special compared to other injectables as far as cholesterol goes. I think we can conclude though that testosterone is safer than orals.
Liver toxicity is probably the second most discussed health issue. Again, most bodybuilders know that oral AAS tend to raise liver enzyme values at much lower doses than do injectable steroids. We run into the same problem here comparing testosterone to other injectables as we did when addressing cholesterol. There is a lack of research on high doses of drugs other than test.
As far as using testosterone as a base for a cycle, I’m not convinced it is any better than other injectables like Deca or Equipoise. And let’s not forget our female readers for whom test might be a poor choice for a base because of its relative androgenicity. If a person chose to use something other than test around which to build their cycle, I would recommend throwing in some test however, if for no other reason than to help maintain libido. The advocates of building a cycle around test usually cite its ability to elevate DHT levels, which probably helps fuel aggression and allows for more intense training sessions, and its aromatization to estrogen, which elevates liver derived IGF-1.
I would counter these arguments by the observation that many bodybuilders make excellent gains while using test with an antiestrogen and/or finasteride, which blocks DHT production. Researchers are beginning to realize that the local production of IGF-1 within skeletal muscle by androgens is probably more important for muscle growth than is hepatically derived IGF-1, and other steroids, like Deca, are capable of inducing this local IGF-1 production (10). On the other hand, people certainly make terrific gains from test, so from an empirical standpoint, it is an excellent choice for a base around which to build a cycle. As an advocate of the KISS principle, I confess to being perplexed by the number of different drugs some bodybuilders use in a cycle. If someone asked me what would be my choice for a “favorite cycle”, I would say test and tren, or EQ and tren. Nothing else is needed, in my opinion. We’ll get some critical feedback from readers on this point, I’m sure. I do see a definite trend among members at CEM of less use of orals out of concerns for health. I think that is a positive movement.
Q: The D-Bol bridge theory claims that at the suggested dose of 10 mg each morning the HTPA will not be suppressed. Is there any truth to this?
A: None whatsoever that I have ever seen. I would say to the people making this claim that the burden is on them to present some evidence that bridging does NOT suppress the HPTA. There is ample evidence that very low doses of Dianabol and Anavar, two drugs often cited as being good for bridging, significantly suppress the HPTA. Advocates of bridging counter this fact with the claim that while that may be true, the studies where the HPTA was suppressed do not specify at which time of the day the drugs were taken. The claim made by bridging advocates is that LH and testosterone levels are highest in the morning, and if one were to take say 10 mg of dbol so that plasma dbol levels peaked at the same time plasma test levels peaked, the body would somehow fail to notice the extra plasma androgen and hence there would be no suppression. There is just no evidence the body works this way.
There are other points to consider as well. The observation that testosterone peaks in the AM is true in the majority of young people, but not in all. And as we age, this AM peak is blunted and the pattern becomes one of a series of rather uniform peaks throughout the 24-hour period. (In fairness to bridging advocates some very recently published data are at odds with this previously widespread reported loss in the diurnal fluctuations in testosterone with aging [11].) There is tremendous individual variation in in the timing of these peaks and troughs. We also talked above about how androgens can act directly on the hypothalamus to block LH and testosterone production. Not enough is know about the temporal relationship between hypothalamic GnRH pulses, LH production, and test secretion to conclude that taking dbol when test peaks will have no effect on the GnRH signal(s) responsible for that peak. Moreover, some research has shown that 5 and 10 mg of dbol administered daily can reduce endogenous testosterone by 66 and 73% respectively, WITHOUT depressing LH, leaving open the possibility that the dbol is having a direct effect on testicular testosterone production without any hypothalamic or pituitary action. So we may not even fully understand all the mechanisms by which dbol (and other AAS) affects testosterone production (12). Lacking a complete knowledge of androgen actions, how can re reasonably conclude bridging does not suppress endogenous testosterone production?
If someone wants to stay “on” all the time and call it bridging, that is fine and is his or her choice. I just don’t think they should try to justify the practice by claiming it is not suppressive of the HPTA or of endogenous testosterone production. I’m not making a value judgement here. There may not even be any serious health consequences to taking low doses of something like dbol between cycles, but on the other hand there in fact may be health implications. We saw above, for example, how very low doses of certain oral AAS can have dramatic effects on HDL. Steroids have traditionally been cycled to help avoid any long-term detrimental health effects associated with their use. Now we have certain individuals essentially advocating being “on” all the time, and using what are potentially the most dangerous steroids, 17 alpha alkylated orals, for this purpose. Am I overstating potential risks? Perhaps, but since there is little research to guide us, I’d rather err on the side of caution. If an individual wants to bridge, that is their business, but I don’t think they should jump on the soapbox encouraging others to do so.
Q: Often times you hear people talking about taking a break from taking steroids so their receptors can clean out otherwise their gains will come to a halt. Is there any truth to this?
A: Receptors are continually being degraded and remanufactured in cells, so they never really clog up and require cleaning. I think this is a sort of fanciful way of talking about receptor upregulation/downregulation, which is a complex topic. “Do gains slow because receptors downregulate (decrease in number and/or sensitivity) during a cycle?” is probably a more accurate way of posing the question. There are conflicting data in this regard. Short-term in vitro and in vivo studies generally show that androgens upregulate the androgen receptor (AR) in skeletal muscle. For example, in humans given 15 mg of oxandrolone daily for 5 days, the skeletal muscle AR density nearly doubled (13). When exposed to testosterone in vitro, skeletal muscle AR expression increased significantly (14).
In longer-term studies the picture is somewhat different. One study looked at AR expression in androgen treated sedentary rats vs nontreated exercised rats over 8 weeks. The androgen treated rats showed a decrease in the number of receptors, whereas the exercise trained rats showed an increase. (15) Unfortunately, the authors failed to address the question of interest to bodybuilders, and that would be the combined effects of exercise and androgen use on skeletal muscle AR regulation.
In long term studies in humans we get yet a different picture. In work conducted by Sheffield-Moore et. al., (16) older men were supplemented with testosterone so as to bring their testosterone levels into the mid to high physiological range. Androgen receptor expression had more than doubled after one month of treatment, yet by 6 months had returned to baseline. If this downregulation occurs when supraphysiological doses of testosterone are used, it could very well explain why gains tend to slow during a long cycle.
So, unfortunately the data are equivocal. The definitive experiment of combining supraphysiological AAS with resistance training and looking at AR regulation does not appear to have been carried out yet. Would exercise combined with AAS maintain increased AR expression, or would the addition of exercise serve to offset the AAS induced AR downregulation observed in the study by Bricout et al? Do the extremely high doses of AAS used by bodybuilders lead to more or less downregulation ( or even upregulation ) compared to what was seen by Sheffield-Moore et al? These are just a couple of questions that require further research, and could lead to answers on why exercise combined with AAS use is so much more productive than simply using steroids alone when it comes to building muscle mass.
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