His complete text:
Nandrolone was first made commercially available as a prescription synthetic anabolic by Organon as Deca-Durabolin, a brand of nandrolone decanoate, in 1962. It was almost immediately embraced by the athletic community, and rose to unseen popularity in the late 70’s, a status it maintained through most of the ‘90’s. Since then nandrolone has been distributed in several forms, by several companies, under a multitude of brand names, as demonstrated by the Table above.
The popularity of nandrolone decreased severely during the nineties, although it remains one of the more popular drugs of choice because many falsely believe it to be a safe drug, or at the very least safer than alternatives. The decrease in popularity was partially the result of the many fakes produced during that time (nandrolone was in a sense becoming a victim of its own popularity) and of course the ban on steroid use and concomitant testing for anabolic androgenic steroids in many athletic federations, as of 1988. Nandrolone has easy to detect metabolites, and with methods for screening becoming more and more sensitive, for many athletes using this drug became an impossibility without risking getting caught and sanctioned.
Around the same time as the time Organon was researching synthetic nandrolone as a commercial drug, researchers uncovered that nandrolone was also a naturally occurring metabolite in humans. There is still some confusion as to which came first actually, the synthetic nandrolone, or the discovery of natural nandrolone. There is also no clarity about the origin of nandrolone in the human body, although a study by Reznik et al22 using HCG to stimulate steroidogenisis shows a strong correlation between excretion of urinary nandrolone metabolites and the rise in plasma estradiol, the estradiol:testosterone ratio, but not to plasma testosterone. Data that may suggest that nandrolone is a by-product of the aromatization of testosterone to estradiol. At least two of the three proposed mechanisms for the final steps in the aromatization process in a study by Wright and Akhtar28 seem to support this notion if a small portion of the created radicals is not reactive enough to form a double bond, and instead attracts a hydrogen atom, leading to formation of nandrolone instead of estradiol.
Nandrolone differs in structure from testosterone, the principle natural androgen, only by the omission of the 19th carbon (the methyl group attached to carbon 10), hence the name 19-Nor testosterone.
Characteristics
Anabolic Characteristics : Nandrolone is often characterized as being more anabolic than testosterone. This assumption is however usually based on either the binding affinity of nandrolone relative to testosterone at the androgen receptor, and the anabolic:androgenic ratio of the product. Neither of these however can be directly extrapolated to predict the anabolic activity of nandrolone.
The anabolic:androgenic ratio determines the difference between the increase in weight in a smooth muscle (usually the levator ani) and the increase in weight in an androgen responsive target tissue, namely the ventral prostate. This ratio is meant to indicate the difference of the drugs anabolic activity, relative to its virilizing capabilities, in contrast to that of testosterone, given the arbitrary value of 1:1. It does however not say anything about the absolute ability of a product to increase weight in a striated muscle cell. The anabolic:androgenic ratio of many products can be found in a multitude of ancient studies, but many agree this ratio has lost any and all meaning. Secondly it is worth noting that the anabolic:androgenic ratio of a product can differ strongly with the length of the ester attached to it15,16. Ranging from 7:1 for nandrolone butyrate to 32:1 for nandrolone undecanoate. Given that the ratio can differ for different pharmacokinetic values and that neither value is truly indicative of androgenic potential on the one hand, or muscle-building properties on the other hand, any and all assumptions based on this ratio can be discarded.
The binding affinity, at first glance, seems to hold more promise. Since in striated muscle both nandrolone and testosterone bind unaltered to the androgen receptor. And nandrolone seems to do so with anywhere from 1 to 2.4 times the affinity of testosterone1,2. Given that number some have stated that nandrolone is up to 2.4 times more anabolic than testosterone. Experience teaches us otherwise. The same study1 seems to shed some extra light on this as it was primarily intended to demonstrate that different patterns of metabolism can influence the anabolic activity of products. But since both steroids bind to the AR unaltered in striated muscle cells one cannot account for a 2.4 time increase by referring to differences in metabolism to estrogens and so on. More likely the answer is to be found in the distinct activation profiles of androgen responsive promoter constructs17. While the study, previously discussed in depth, only shows how different anabolics react differently in activating DNA promoter constructs after binding the AR in a purely theoretical model, there is one thing that can be noted when looking at all three tested constructs. Namely that testosterone is a much more potent activator of most if not all constructs at any given dose. This could explain why testosterone is a much more potent anabolic in vivo than in vitro binding assays may allude to. Given this, one should also question the anabolic properties of a drug based on relative binding affinity comparative to other drugs.
So is there actual scientific data that can give us exclusion about the exact anabolic nature of nandrolone ? Alas, no. Extensive experience with the drug in bodybuilding circles has given us the chance to estimate the phenotypical anabolic properties of the drug at some 60-70% that of testosterone. So contrary to what you may hear or read from some sources, nandrolone is not a more anabolic drug than testosterone, at least not in muscle. Such claims are all too often based on data that cannot be extrapolated to proper real-life situations.
Androgenic Characteristics : Nandrolone is often falsely perceived as a ‘safe’ drug because of its low androgenic potential. Whilst again, anabolic:androgenic ratio’s do not accurately reflect the androgenic potential, it is however still a safe bet to classify nandrolone as low androgenic. It is rapidly deactivated by the 5-alpha-reductase enzyme to 5-alpha-dihydronandrolone. 5-alpha-reductase is present in high concentration most androgen responsive tissues like prostate, scalp, skin, genitalia, etc. Dihydronandrolone has 3-4 times less affinity for the androgen receptor than nandrolone2 itself does. This is sharp contrast to what occurs with testosterone under similar conditions. Testosterone is altered to 5-alpha-dihydrotestosterone (DHT) by the same enzyme, and DHT is several times more androgenic than testosterone. Because of the difference between DHT and DHN given the same binding of testosterone and nandrolone in said tissues2 one could easily classify nandrolone as being 10 times less androgenic than testosterone.
However the relevance of such a figure can be called into question. Under medical conditions this can make a major difference, as it often concerns treating females, children, or the elderly, with pharmaceutically effective doses for the duration of a single cycle, people who are usually more responsive to androgenic side-effects. For a healthy male bodybuilder under the age of 45 the androgenic activity of commonly used steroids in effective doses for muscle building never exceeds acceptable levels.
Nonetheless, scaremongering by guru’s in the late ‘70’s and early ‘80’s, based on wrongfully extrapolated data from medical settings, has scared most of the bodybuilding community into over-exaggerating the androgenic risk involved with steroid use. This has lead to nandrolone being adopted as the number 1 drug of use/abuse among both competitive and non-competitive athletes from the late 1970’s up until the late ‘90’s. Even after that it remained unseemingly popular with most non-competitive athletes. However as will soon become evident when reading this profile, unlike in most medical settings, nandrolone is everything but a good choice for the bodybuilder.
Estrogenic/Progestagenic Characteristics : The estrogenic and progestagenic nature of nandrolone have been a topic of much debate over the years. Estrogen-sensitive nandrolone users have always complained about inexplicable estrogen-like symptoms that cannot be treated with conventional anti-estrogen therapies. Because of its more estrogen-like structure due to the lack of a 19th carbon atom, nandrolone shows considerably less affinity than testosterone for the aromatase enzyme that converts androgens to estrogens. Nandrolone has only approximately 1/5th the affinity for aromatase of testosterone in vitro18. There is more than ample evidence to suggest that in vivo this is probably a lot less. As occurs with all steroids that do not readily form estrogen or estrogen metabolites yet somehow seem to display what is perceived as estrogenic characteristics, a multitude of wild and unsubstantiated theories soon sprang up. This has caused and still causes great confusion amongst most steroid users.
One such theory blamed a feminizing hormone called prolactin. However that theory never really held up since potent androgens tend to decrease prolactin and prolactin sensitivity whereas estrogens seem to increase its activity. There was also no evidence to assume that prolactin played any significant role in the most common of estrogenic side-effects in the absence of estrogen, which would fail to explain why conventional anti-estrogenic therapy did not work with nandrolone use/abuse, given that nandrolone aromatized considerably less and blood profiles of users generally showed low estradiol and estrone levels in the blood after several weeks of use. Fortunately this theory was only shortlived, and only maintained by a few obscure guru’s eager to draw attention to themselves by claiming to have found a solution, where there wasn’t a problem.
Another theory, that has persisted very long, and remains the most popular belief today was that nandrolone’s progestational activity lay at the base of the perceived estrogenic effects. This theory again held very little ground, but is commonly accepted because it was never thoroughly refuted since the rumour first started circulating. Indeed, nandrolone3 and several of its metabolites4,5 have been identified as being progestins. Meaning they can bind and activate the progesterone receptor. And equally supportive of the theory, studies have demonstrated that progestagenic activity can both stimulate and suppress estrogenic activity6. Whether that holds true for the more common estrogenic side-effects is not really known, but it leant a validity to this theory. However, again, progestins have never been shown to cause estrogenic side-effects in the absence of estrogen. So once again, this did not account for the lack of effect with conventional anti-estrogens.
A third and last theory that has only been circulating of late is that nandrolone was directly estrogenic, binding and activating the estrogen receptor (ER) without metabolizing. Most likely the rumour initiated after the proposed theory that oxymetholone, another non-aromatizing drug, may me directly estrogenic. It was a theory first proferred by Bill Llewellyn7, and found support with people like myself and organic chemist Patrick Arnold. A dutch pseudo-guru even suggested he had found proof in the fact that studies demonstrated that nandrolone bound the estrogenic receptor8. This infamous study however demonstrated that nandrolone had a more estrogenic effect at the ER than testosterone in millimolar doses. However testosterone is not a potent ER activator, nor are millimolar in vitro doses indicative of what a typical steroid user would have in his blood.
All of these theories were shot down by two other studies9,10. The first study is not immediately relevant, but that it contained a table with results from an older study, showing the relative estrogenic properties of several progestins, compared to estradiol.
As you can see from the table above, taken from that study, nandrolone was about 60% as estrogenic in nature as estradiol itself. So far nothing special. All this tells us is that nandrolone has very potent estrogenic action that cannot be explained by aromatization, which is what we already knew. At best this has some shock value by demonstrating just HOW estrogenic it really is. The second study however was undertaken by the same researchers to hopefully shed some light on the situation. It did not. But it disproved all commonly accepted theories supported to date. In the study the researchers administered nandrolone with either an aromatase blocker, a progesterone receptor blocker or an estrogen receptor blocker. As was to be expected the aromatase blocker had no effect whatsoever on the estrogenic activity of nandrolone. More surprisingly, neither did the progesterone receptor blocker. Which also strikes a blow for basically any involvement of progestational activity in the development of common estrogenic side-effects associated with AAS use. And lastly, and even more surprisingly, the estrogen receptor blocker’s effect on the estrogenic activity was just barely significant. This suggests that nandrolone’s direct binding (or that of its metabolites) to the estrogen receptor played a very limited role. At the end of that all we could state was that nandrolone was 60% as estrogenic as estradiol itself, but more than 55% of that could not be explained.
Yours truly dug a little deeper and actually found the answer in a synthetic nandrolone metabolite, named estren (19-Nor-4-androstene-3α,17β-diol)11. Estren was found to only weakly bind the estrogen receptor, showing no real activity at that site and possessing a 300-fold lower binding affinity. Yet it mimicked the actions of estrogens in osteoblasts. Estren was however shown to be as active as DHT at activating certain androgen receptor related transcripts. The same study also demonstrated that estren was capable of activating estrogen specific constructs in the DNA through the androgen receptor. Estren is a metabolite of nandrolone through the 3α-HSD enzyme. So in first instance one might suggest we start looking for something that blocks this enzyme. However I mentioned that this steroid was synthetic. Nandrolone is a natural androgen. So why does estren not appear naturally in the body ? Well mostly because it is a very labile structure, that is quickly converted back to nandrolone. The problem however is that the researchers noted that despite similar activity on several constructs as DHT, it bound with a 200-fold lower activity to the androgen receptor. The researchers found that the high androgenic potency of estren resulted in its conversion to the more stable molecule nandrolone, almost 50% in 4-6 hours, and no less than 95% within 24 hours. From this it can be concluded that the effects of estren via the AR are mediated by its metabolite nandrolone, and it is in fact nandrolone that activates estrogen specific transcripts via binding and activating the androgen receptor. Now the study also noted that binding of DHT activated estrogen-related transcripts, so this is not uncommon, but DHT did so with a 30 to 100-fold lower potency than estren. The authors concluded :
“Finally, the unexpected estren-dependent activation(and by extension nandrolone-dependent activation) of ERE-driven gene expression in cells that express AR, which occurs with far greater potency relative to DHT, predicts the possibility of some troublesome feminizing effects in males, which still await examination."
This is indeed a further blow to nandrolone’s already damaged image as being a safe steroid. As my co-author astutely pointed out, one could potentially treat this problem with the addition of chemicals that block the estrogen response element, such as piperidinediones12. However I’m not aware of any commercial preparations with such products, and finding them may prove difficult. So until further notice the only way to block nandrolone’s very potent estrogenic effects is to block the androgen receptor, and with it any and all anabolic effect the drug may have.
Water-retention and blood Pressure : Blood pressure is rarely a concern with the use of nandrolone. Monitoring blood pressure continuously through the use of any cycle with anabolic androgenic steroids is of course advisory.
Water retention with nandrolone is quite frequently noticed. In fact in the past it has often been an excuse for athletes to incorporate nandrolone in their cycles. Nandrolone is reported to increase water in the synovia of joints, and have a ‘lubricating’ effect offering the bodybuilder a more pain and trouble free workout when lifting very heavily. This practice is of course advised against, as is any of the like, because such properties can mask underlying injuries and leave the athlete with severe damage to his person as the result of his heavy lifting. Water retention is often wrongfully associated with estrogen, quite possibly because it is often seen with aromatizing steroids. However several AAS have more direct effects on water retention, such as agonizing aldosterone, as is the case with nandrolone13. The increased activity of aldosterone results in more sodium and conversely more water being retained by the body.
Therefore it is never advisory to treat water retention, if that is the main problem, with an anti-estrogen. That is the Anabolic steroid equivalent of chasing a mosquito with a bazooka. Especially in the case of nandrolone, where irrelevant of how much of water retention is caused by estrogenic effects, and anti-estrogen would serve no purpose at all. A much better approach is to treat it with products specifically designed for the purpose, such as ACE-inhibitors (Captopril, Capoten) or mild diuretics. One might proffer this is dangerous, but under the care of a physician any and all risk is eliminated. The dangers of these products lay mostly in the acute risk of misusing the products, dangers that are easily circumvented with proper use and supervision. With most anti-estrogens nothing is known about their long term and repetitive use and the effect on our health. So using anti-estrogens as preventive measures in people most likely not suffering estrogenic side-effects, or treating something that is best treated another way, is highly advised against by all health professionals.
Effects of nandrolone on Immune response : Sex steroids promote very different effects on the immune response, and this may account for the gender difference seen in the prevalence of auto-immune diseases27. This same study indicates there are two main ways of responding to an immune challenge (in reality immunology is a more complicated and intricate interplay of immune cells and their secretion of cytokines), namely a T-helper1 cell response and a T-helper2-cell response (depending on which one predominates). Each establishes a different pro-inflammatory response. Men tend to produce the latter response more often, and women the former. Of note in this case is that women during gestation exhibit a more male response. This is because progesterone, which is the more abundant hormone during gestation, elicits a similar response to testosterone, whereas estradiol seems to be more prone to cause the other reaction.
