View and discuss the latest research articles and FAQ's as well as numerous Detailed Drug Profiles
Want More? We have a full site section dedicated to Anabolic Steroid Articles and Anabolic Books
Gyno in aas user's
Gyno in AAS Users
This is a post from a good bro Deacon over on TID the OP is Doink the clown;
Gynaecomastia in AAS users
quote:AUTHOR'S NOTE :This is first finished version of the article, but its intended to be a work in progress, updated with more information as it becomes available. Thanks to all who participated in the various discussions, they've driven me to research, probably beyond what I would have normally done. And special thanks to the people who helped me acquire some of the needed studies. I hope you all enjoy it. (Big Cat)
Gynaecomastia is the development of breast tissue in males. It’s a side-effect often associated with anabolic androgenic steroid use/abuse, although it’s not all that prevalent in healthy males. One study with low-dose testosterone (200 mg/week of an ester amounting to roughly 140 mg of actual testosterone) showed a prevalence of roughly 8% (1) and likely in athletes and people using steroids for aesthetic purposes the incidence is significantly lower for various reasons including lower body-fat (adipose tissue is a primary source of aromatase, the enzyme that converts testosterone to estrogen) and the use of higher doses. Higher doses lead to higher circulation of androgens for an equal amount of aromatase that converts testosterone to estrogen. Androgens are capable of inhibiting the estrogen-induced proliferation of mammary epithelial cells and abolish estrogen-induced augmentation of ER- expression (2). They also further promote pro-apoptotic (cell-killing) effects in a wide variety of breast cancer cell lines (3).
To have this discussion we need to understand what gynaecomastia (gyno for short) is exactly. It is merely defined, as stated above, as the growth of breast tissue in males. An itchy or painful nipple is neither a symptom of gyno or the onset thereof, a distinction I wanted to make clear before going any further because all too often in this community users report these unrelated symptoms as being gyno or signs thereof, one of the primary reasons for the overconsumption of treatments (valid or otherwise) against the problem. The development is influenced by a number of factors including estrogens, progestins, GH, IGF’s and prolactin whose interaction isn’t always clear and sometimes ambiguous. This will make it essential to focus on what we know, since its often the uncertainties that are cited by pseudo-scientists as a cause or reason for various mechanisms. Before going deeper into the science and evidence in this regard, its perhaps interesting to look at the clinical history of gyno and its treatment. A distinction is usually made on the basis of size, and this is used a measure to gauge the level of permanent fibrosis. Fibrosis is often referred to as the point of no return and is invariably treated with surgery to remove the breast tissue. Only a biopsy can give absolute facts on fibrosis, and likely a number of conditions diagnosed as type 2 based on size are still perfectly treatable by other means, but not so much vice versa. If the tissue is over 3-4 cm it is considered type 2, before that it is considered type1. Gyno is prevalent in pre-pubescent boys (incidences of 70% are reported in some literature) and then disappears during puberty when androgens (testosterone/DHT) increase nearly 30-fold and estrogens increase only 3-fold. When gyno occurs during post-pubescent periods it’s almost invariably treated with anti-estrogens. Postpubertal men have significant levels of circulating estradiol, but their effects on mammary tissue are prevented by the simultaneous presence of high levels of testosterone (4).The notable exclusions are cases of hypogonadism (which are treated with androgen therapy of all things, the very thing so many people blame for rampant gyno) and hyperprolactinaemia due to tumors. Mild hyperprolactinaemia is usually caused by excess estrogen (5) and also treated with anti-estrogen therapy. It is of note that endocrinologists are quite content with this treatment, as there is no search for improved therapy for gyno. In short the authorities in the matter agree that a decreased androgen:estrogen ratio is the basis for the development of gyno in all of the above cases except prolactinoma. This is just a brief sketch and only pertains to naturally occurring cases of gyno and those AAS-users that are smart enough to seek diagnosis and council from a medical professional.
Cases where estrogen is the obvious cause
In most cases there is no argument that the cause of AAS-induced gyno is a decreased A:E ratio, caused by aromatization of an androgen to an estrogen, predominantly through the aromatase enzyme. Popular steroids like testosterone and methandienone operate in this manner. The prevalence is low in athletes and people who use for aesthetic reasons. This is because usually the doses administered invariably cause a higher androgen level than the amount of estrogen created from aromatization. Of great importance here is understanding what increased risk factors are for developing AAS induced gyno. First and foremost a tendency to develop gyno when not using AAS is a huge risk factor. If this is the case for you, you should get to the bottom of the cause first. If it is caused by hypogonadism, odds are using AAS may actually be a treatment for you. But in most other cases it’s an unusual level of estrogen formation. In those cases it’s important to decide whether you really want to pursue AAS use, and if so, to take precautions. Reducing the amount of aromatizable steroids to the strictly necessary amount (200 mg/week of testosterone) and combining them with non-estrogenic androgens is one method, preventive use of anti-estrogens is another. Preference is usually given to aromatase inhibitors when used for prolonged periods of time, but use of SERMS is also acceptable, we will go into the mechanism of these drugs later in this article. A higher body-fat percentage, as was alluded to earlier, is also a known risk factor since adipose tissue produces aromatase. Higher body-fat can also make the condition seem more drastic than it is, since fat deposits around the nipples will usually be larger. They can both obscure gyno or make it look worse than it is. Adressing this issue prior to AAS use, or concomitantly with AAS use will also be of huge benefit in later diagnosis. Lastly a low level of 5alpha-reductase can play a role. This enzyme converts testosterone to dihydrotestosterone (DHT). DHT has clear roles in controlling A:E ratio (it’s the reason we speak of A:E ratio and not T:E ratio). It can block aromatase (6), may competitively inhibit the estrogen receptor (7) and converts to the estrogen receptor beta specific 3alpha-androstanediol. We’ll explain the role of the latter when we discuss SERMS. Its not easy to diagnose a low 5AR level if it isn’t giving your problems, but some people will use 5AR inhibitors to stop androgenic side-effects and these form a huge risk for gyno. I highly advise against the use of such compounds. If you are unsure, or have no valid reason to believe you are at more risk, I would however advise to start on moderate testosterone only (400-500 mg a week – something I advise regardless since testosterone is by and large the most studied androgen, best for health and gains and the reference for all other AAS) and see what happens. If you think you are developing gyno, I would first and foremost get the opinion of a medical professional that it is in fact gyno.
If he does not advise treatment, the best way to treat it acutely is with a SERM (Selective estrogen receptor modulator), tamoxifen being the most used and best studied. tamoxifen will block the Estrogen receptor alpha in breast tissue, the receptor that plays the most important role in breast cell proliferation (replication) (8). Because it stops the actions of circulating estrogens at the receptor its effect will be somewhat faster than those of aromatase inhibitors, which will take some time to reduce circulating estrogen and start having an effect. If we would look at the blood levels of estradiol when using an Aromatase inhibitor (AI) or a SERM we’d see very different things. The Aromatase inhibitor (AI) will reduce the level of estrogens, whereas a SERM will increase it (short term only), because the SERM is keeping the estrogens from binding the receptor. The end result with regards to estrogen receptor alpha is the same however : no estrogens are activating this receptor, so proliferation is halted. The reason we prefer tamoxifen however is because there is a second estrogen receptor, estrogen receptor beta. Both are stimulated similarly by estradiol (the primary estrogen) but have different roles. Estradiol shows a slightly higher affinity for the alpha receptor. This is actually how estrogenic effects are regulated. The alpha receptor causes proliferation of cells, the beta receptor inhibits proliferation and increases differentiation, or the maturing process into a fully functioning cell. So when estrogen increases proliferation starts, and when it reaches a certain threshold more binds to the more abundant beta receptor slowing proliferation and increasing differentiation. This is relevant because though tamoxifen also binds the beta receptor it does so with less affinity than estradiol and its unclear as to whether it activates or blocks the beta receptor. The net result is that proliferation is halted by tamoxifen’s negative effect on the alpha receptor, but estradiol is left in circulation to activate the beta receptor. The beta receptor offers us several benefits I may choose to address in an addendum later on, but here specifically it will further inhibit proliferation (tissue growth) and increase differentiation. Terminal differentiation aborts the proliferative capacity of a cell. So each cell that terminally differentiates is one more cell that won’t be replicating. These cells now await apoptosis (cell death) at the hand of androgen-mediated action (2,3,10,15,17,18,25,…). On top of that it reduces the risk of breast cancer and if breast cancer should ensue, it at least increases chances of it being benign (growth of tumor cells is dependent on uncontrollable proliferation). It seems that tamoxifen may impart the same benefit in the prostate (9). Aforementioned metabolite of DHT, 3alpha-androstanediol, is also a beta receptor specific estrogen (9) that promotes protective effects in breast and prostate tissue and can help stop and reduce breast growth. Another key reason why 5-alpha-reductase levels are a critical factor in determining risk for gyno.
One thing I do want to impart on people is that tamoxifen treatment must continue for some time to be effective. Too often tamoxifen is reported to be ineffective for acute treatment because it isn’t used sufficiently long. tamoxifen inhibits the growth of breast tissue, but does not reduce it on its own. This is mediated by your androgen levels as a male and an AAS user. These cells do not dissolve, they are ultimately destroyed by genomic signals. This takes some time. On top of that early cessation risks rebound effects. tamoxifen does not address circulating estradiol so early cessation will only lead to estradiol immediately binding ERalpha again, and barring any changes, starting problems all over again. Longer treatment with tamoxifen reduces ERalpha density (2), which only further promotes the beta-receptor mediated positive effects. It’s perfectly possible for tamoxifens effect to become visible after cessation, no doubt this is one primary reasons why treatments prescribed by quacks are sometimes deemed effective : they are administered at the time the cells are being destroyed, so that to a lay person it may seem that the medication is actually reducing his gyno. If ACTUAL tissue shrinks within days, its probably not what you are on right now, so if you took something because you thought tamoxifen did not work, and “it cleared up in three days” (I’m not kidding, I hear this stuff every day) its likely it was the tamoxifen and not the other drug.
If it turns out you are prone to gyno (early onset of gyno with testosterone only at moderate doses) you can always opt to make the needed changes in the future (preventive treatment with an Aromatase inhibitor (AI) or a SERM).
When estrogen is the cause but it’s not obvious
With some drugs estrogenic problems like gyno will occur, when its not seemingly possible. A prime example of this is the drug oxymetholone. This is a DHT-derived androgen, that does not possess the structural capacity to be aromatized. But it still caused notable estrogenic effects. Here too wild theories were thrown around about mediation by the progesterone receptor and what not, even though evidence was available that it showed no appreciable binding to that receptor (11). In these cases its likely that the effect is mediated by either the steroid binding directly to the estrogen receptor (it has been postulated for oxymetholone, but isn’t likely to be the primary cause because steric properties make it unlikely to be a potent estrogen if it is one) or the cause of metabolization to a compound that can bind and activate the estrogen receptor. With most steroids we can exclude these mechanisms because affinity for the ER is well documented for most compounds, and the metabolites are well characterized. Usually those metabolites are the standard hydroxylated ones, primarily at the 3-keto moiety, but also at various other positions on the steroid backbone depending on enzymatic affinity. Hydroxylation generally reduces activity at class I nuclear receptors, and form the key to glucoronidation, the process the body uses to attach long hydrophilic molecules to steroids to make them water-soluble so they can be excreted in urine. Oxymetholone however metabolizes in so many different ways, and many of its metabolites fall outside of the realm of known compounds (12). So its not a far fetch that one of these metabolites is directly estrogenic.
In these cases treatment is fairly limited to SERMs, both short term and long term, because aromatase inhibitors will have no effect. Obviously if you are prone to gyno, the primary solution is to stay away from overly estrogenic compounds like oxymetholone.
When none of the above fits
That’s when the shit hits the fan and the pseudo-science guru’s come crawling out of the woodwork with “theories”. I parenthesize the word because theory in the scientific context implies a plausible ground to base the theory on, when most of these “theories” go against conventional wisdom and even established fact.
Progestagenic action is often cited as a cause. Not so much as it used to (primarily because it’s been refuted and the guru’s have moved on to newer things that allow them to sell stuff, like prolactin – progesterone problems aren’t as easily treated). Progestagenic action is the ability for an androgen to bind and activate the progesterone receptor. Progesterone is often referred to as the other female hormone and is known to play a role in breast development, and can aggravate estrogenic action on breast in rodents , but doesn’t seem to share this effect in primates (2). This is often the case for androgens in the 19-nor line (missing the 19th carbon of the steroid structure of natural androgens) which are known progestins. The problem with this postulation is two-fold however. The first is that progesterone is not known to cause gyno in the absence of estrogen (14), and the second is the fact that androgens reduce the expression of the progesterone receptor (15). Combine that with the fact that the androgenic potential for this line of androgens (trenbolone and nandrolone most notably) far exceeds their progestagenic potential (based on RBA for AR and PR –16) which implies that the level of PR reduction is greater (more androgen binds to the AR causing the reduction) than the level of PR activation. It would also imply that if this was an issue, it would resolve itself over time as PR expression would continue to decline. PR activity also has no effect on androgenic potential to decrease breast tissue and progestins themselves show a distinct ability to decrease breast tissue (3). Note : The above may not apply for drugs with an equal or greater progestagenic RBA as androgenic RBA. This includes designer steroids like THG and supplements containing dienolone precursors like Tren extreme. Fact of the matter is that while these drugs do possess a decent (in the case of THG excellent) anabolic activity, they are all really better classified as progestins than progestagenic androgens. Their use is tantamount to chemical castration, and problems ensuing from poor recovery and hypogonadal conditions is frankly to be expected. With dienolone, potent estrogenic action in similar fashion to nandrolone, is also not to be excluded. I can see why an athlete would resort to a designer steroid, but anyone else that does is a blatant idiot and frankly deserves what he gets.
The thing is that gyno occurs quite frequently with nandrolone, whereas I’ve yet to witness a confirmed case of trenbolone gyno. This despite the fact that both the progestagenic capacity is greater and the difference between AR and PR activation is smaller than for nandrolone. With nandrolone however we’ve been able to elucidate the mechanism of its effect. Whereas tren clearly shows the effects of a progestin in its action, nandrolone seems to exert none of the typical progestagenic effects. In fact it seems to perfectly fit the bill of an estrogenic steroid, something that was widely believed and accepted before people had access to medline. Nandrolone does aromatize, but to a much lesser degree (19). It’s also been shown to bind the estrogen receptor, but doesn’t seem to activate it unless at micromolar doses in vitro (20), something that would take massive consumption to mimic in vivo. One study however did estimate nandrolone’s estrogenic potential at 60% that of estradiol (21). With those figures a higher prevalence of gyno with this steroid than with testosterone isn’t that hard to imagine, especially when you know that the same enzyme that converts testosterone to DHT (5-alpha-reductase), the metabolite with the most profound effect on estrogen inhibition in the breast also converts nandrolone to DHN, which is a significantly WEAKER androgen (thus causing a massive A:E imbalance). But where does the estrogenic action come from ? Researchers already established (22) that aromatase, PR and ER did not play a role because the co-administration of inhibitors for each compound had no significant effect on the estrogenic potential. The elucidation of its mechanism came through a study on the synthetic steroid estren, a direct precursor to nandrolone (23). It showed that estren was able to mediate estrogenic effects by binding the AR and activating Estrogen Response Elements (ERE’s) in the DNA. Consider ERE’s like little signs that say “hey estrogen receptor, bind here and do your thing”. Apparently estren cause the AR to confuse itself with an ER. Estren however is a highly unstable metabolite, which rapidly converts to nandrolone under physiological circumstances. The time-frame of estrens effect (increased ERE activation while it is increasingly metabolized to nandrolone) and estrens low RBA to the AR compared to nandrolone clearly shows that this effect is mediated by nandrolone. So nandrolone causes estrogenic effects by binding the androgen receptor.
This causes a huge problem in treatment, since the only way to stop this effect is to block the AR, and with it the anabolic effect of nandrolone. Technically there is some evidence that ERE’s can be blocked using piperedinediones (24) but I’m not aware of any formulations containing such products, nor is there any data on their safety. This is crucial : THE ONLY WAY TO STOP NANDROLONE’S ESTROGENIC EFFECT IS TO NOT USE IT. While I would think its logical that if a certain compound gives you more problems, or harder to treat problems, that you cease use of that product, especially since there are plenty of other products available that offer the same benefits, I would stress this extra for nandrolone. It’s easily replaced with a drug like boldenone, which is completely different, but produces the same outward results, probably a little leaner. But it’s easy to see why this compound would be great food for all the alternate “theory” guru’s, and their primary proof for “estrogen-management doesn’t work in every case”. Fact is it does, but in this case the only way to manage it is not to take it.
What about trenbolone ?
One could propose a similar mechanism for trenbolone, but it absolutely doesn’t have the characteristics of a highly estrogenic drug. It doesn’t aromatize, has no appreciable binding to the ER (16). It produces none of the typical things one associates with an estrogenic drug. I have to honestly say that while gyno is more common with nandrolone than aromatizable steroids, I’ve yet to see a single confirmed report of tren gyno. But any stimulatory activity of trenbolone on the breast in the absence of estrogen is highly questionable to say the least, especially since the literature demonstrates that trenbolone “counteracts the mammary stimulus of estrogens showing ultrastructural images of cell autolysis and necrosis” (25). This is in accordance with previously listed studies demonstrating the negative effect of androgens on estrogen-mediated breast proliferation (2,10).
The fact that trenbolone has some binding affinity for the PR often lays at the basis of these claims, but the truth is that while we know that trenbolone binds the PR, we have no idea whether it is an agonist or antagonist. Something some people want to bend into their own view, suggesting mixed agonist/antagonist gene expression profiles to fit their theories. We currently assume it’s a progestin because of its effect on erectile dysfunction and the fact that a great many steroids in the 19-Nor line are known progestins. But the opposite is just as likely because progestins are sometimes administered to treat erectile dysfunction, and while progesterone treatment is typically known to increase body fat, no such effect is perceived with trenbolone. Quite the contrary. What people seem to forget is that its largely irrelevant, because in vivo research in primates has shown no effect of ovariectomy (removal of progesterone) nor replacement with progesterone (pure progesterone receptor agonism) on the proliferation of breast tissue, demonstrating that no degree of agonism, whether partial or complete, would have any effect in breast tissue development (2). This is in contrast to the additive effect of progesterone to estrogen in murine models, but rodents have a different oestrous cycle regulation, where they have to continue breastfeeding while already being able to conceive again. The fact that no degree of PR activation had any effect, also excludes any indirect effects such as PR-mediated prolactin increases or other crazy things of the sort that have been previously suggested.
Though it’s practically impossible this problem even really exists, I don’t want to exclude it entirely, and still offer some suggestions. Again I would like to state that if this compound is giving you some form of unexplicable, or worse, untreatable gyno, YOU SHOULDN’T BE USING IT. I really don’t see what the big problem is here. I can see a reluctance to stop using AAS altogether, but don’t really see the point in sticking to one particular drug that is giving you more problems than you care for. If use has to be continued I would argue for preventive use of an Aromatase inhibitor (AI) here over a SERM. I’m usually not a fan, but since if this problem exists it is yet to be elucidated, its best to take estrogen completely out of the equation. Anecdotal reports of such incidences frequently report pain and such, or freak lactation. Genotoxic effects cannot be excluded here and an endocrinologist should be consulted, and you should inform him of your use of this particular drug, and if so, of any failure of anti-estrogenic drugs to work over prolonged periods of time. Keep in mind previous notes made in this article on the correct and sufficiently long use of anti-estrogenic drugs.
The prolactin theory
Prolactin is the latest theory and pet peeve of the pseudo-scientists, most likely because progesterone was getting old, disproven (2) and was hard to make money off of since common anti-progestins are heavily regulated and hard to get a hold off, and the fact that PR inhibition has been linked with the occurance of gyno more than its treatment (26). In my quest to find out what gave rise to this theory I actually found the man that claims to have started it, and even he failed to provide even one single reason to assume this is anything more than a hoax. It doesn’t help that this person has a monetary stake in the sale of dopamine agonist drugs typically used to lower prolactin in patients irresponsive to standard treatments like androgen administration or anti-estrogen treatment, nor does his long standing reputation of making money off of people in these fraudulent manners.
Research conducted on androgen-insensitive mammals who have been ovariectomized, castrated and/or adrenalectomized (27) demonstrate a drastic decrease in prolactin because of the removal of estrogen-producing organs, while treatment in primates with an anti-androgen (18) seems to increase prolactin. This is consistent with the known regulation of prolactin by sex steroids, showing that estrogens are needed to increase and maintain increased prolactin, and that androgens inhibit this action in vivo (28). The theory is predominantly used to explain the action of the typical progesterone receptor-binding androgens like nandrolone and trenbolone, showing that protagonists of the prolactin theory hold some (frequently expressed) belief that the PR plays a role in the prolactin increase, but progesterone too attenuates the estrogen-mediated increase in prolactin (28,35), and repressed the downstream signaling cascade of prolactin (13,35) in the breast specifically. This ties into the known method of lactogenic induction in post-partum women, which is accompanied by a drastic drop in progesterone, because sex steroids in general inhibit the PRL activity at the PRLR (42). Furthermore blood panels of users of anabolic androgenic steroids, including trenbolone and nandrolone, have been shown to have a slight decrease in circulating prolactin if anything, as one would expect with high androgen treatment. The one case where we do know gyno with lactation develops is in the use of low dose testosterone (29,30) and there we do in fact see a rise serum prolactin mediated by the imbalance in A:E ratio. It is also plausible to see this with improper post-cycle therapy after the use of heavily HPTA suppressing androgens (such as for example trenbolone) after cessation of the drug for some time, also linked to an imbalanced A:E ratio.
I’ve had this discussion at length on several message boards, including with the “inventor” of the theory and his disciples (regrettably at the expense of my leisure time, sleep and family life) in the hope of finding at least one morsel of evidence that suggests this theory holds ground, or is even stooled on a plausibility. When I pointed out that their theory goes against the grain and 40+ years of scientific research, they quickly turned the discussion to paracrine secretion of prolactin in the mammary gland and upregulation of the prolactin receptor. Before we delve into that subject, I want to explain my main beef with this postulation : It’s hard to completely disprove due to lack of specific research, but that also entails there is no research demonstrating this does occur, hence no reason to “assume” this theory in the first place. Especially since it forces you to accept that autocrine/paracrine regulation is linearly opposed to the systemic regulation of prolactin.
What we do know about autocrine/paracrine secretion and effects of prolactin doesn’t really bode well for the theory either however. There are two things we need to address here. The first is the activity of prolactin in benign breast tissue in males, and the second is the ability of prolactin to stimulate or cause gyno. We know that prolactin exerts its effects through the membrane bound prolactin receptor (PRLR), which then activates the Jak/stat kinase pathway in the cell leading to increased expression of target genes and that this receptor is required for the activity of prolactin (31,32). However studies done specifically in men with gynaecomastia demonstrate that only 20% of cases are PRLR positive (33), allowing us to simply state that at least 80% of gyno cases aren’t even susceptible to the effect of prolactin. This argument was frequently countered with the postulation that progestagenic effects upregulate PRLR, but it is widely documented (33,34) that there is no correlation between progesterone/PR expression and prolactin/PRLR expression.
Having established that, we haven’t even addressed whether or not prolactin can cause gyno on its own. We’ve already demonstrated that it has no correlation with the progesterone receptor and that androgen mediation attenuates the activity of estrogen on prolactin. There is however also evidence that there is no correlation between gyno and prolactin, with plenty of cases of hyperprolactinaemia showing no signs of gynaecomastia, and vice versa, plenty of gyno cases showing no elevation in prolactin or prolactin activity. It has been suggested several times in fact that prolactin has no real effect in breast development in the absence of estrogens (5,34), further establishing anti-estrogen treatment as the primary treatment for gyno, with or without prolactin. Taken together the probability of PRLR positive gyno that isn’t responsive to estrogen management is extremely small. Combine that with the aforementioned unique dispersal of these occurrences to the places frequented by charismatic pseudo-scientists and you get the picture of a typical hoax.
A few scarce individuals have been presented with lactation. The literature does make mention of galactorrhea in adolescents (43), and it was later linked to their reluctant (understandable … as I assume many of those who report it on boards will be equally reluctant to admit) admission that they self-manipulated their nipples as they developed gyno. Its an understandable phenomenon to touch your nipples when presented with gyno, but its advisable not to, likely the same mechanism takes place as when post-partum women are suckled by their infants, which in turn stimulates milk secretion. It’s important to know that both in the aforementioned case studies prolactin levels were low, and that the studies on suckling-induced galactorrhea mention there is no correlation between prolactin level and milk production (44), although some prolactin is needed (some meaning low normal levels can be sufficient). The key points here is that the onset was self-manipulation of the nipples after the onset of gyno, so that it may be wise to not play with yourself while you administer your anti-estrogen treatment to treat the gyno, as well as the fact that this can and does occur with low prolactin levels, meaning treating against prolactin with dopamine agonists may not be effective, and may actually exacerbate the problem when the drug is discontinued due to dopamine D2-receptor downregulation.
The sense and nonsense of dopamine agonists
In regards to the previous paragraphs I do want to address this issue further. The only thing that still keeps the prolactin theory alive is that the protagonists of the theory seem to recommend treatment with dopamine agonists, drugs typically used in the treatment of hyperprolactinoma, because agonism of pituitary D2-receptors seems to be the primary controlling factor in preventing prolactin release from the lactotrophs. The argument that keeps coming back is that these people claim these products work, where others have failed. There are several key points to address here.
Let us first start by weeding out the irrelevant information. Many people who have never even experienced gyno, or don’t have experience with dopamine agonists claim they work. Why exactly I do not know, I can only assume some form of sympathy for the pseudo-scientists in question. Many others keep the option that it may work alive, because they experience unrelated effects, such as a resolution to libido and erectile dysfunction problems. Low libido and erectile dysfunction have been known to be associated with elevated prolactin levels. But dopaminergic and adrenergic drugs have a longstanding history of being able to enhance libido and sexual function independent of any effects on prolactin. This already eliminates a large amount of anecdotal claims. But lastly we can weed out those who are either plain lying, experiencing a placebo effect or where extraneous factors play a role. Imagine those people who claim that estrogen control did not work, but after adding a dopamine agonist, there gyno cleared up in 48 hours. I hate to break the news, but tissue doesn’t build up overnight, it also doesn’t break down overnight, this takes genomic signaling to induce apoptosis in the cell. There are a variety of reasons (presuming these people are on the level) why there can be a perceived effect here. Latent effects of anti-estrogens, reduction of inflammation or increased lipolysis in the area can all either have an effect unrelated to the drug, or simply masking the condition, if it was actually a problem to begin with. The fact that none of these people had a problem that could be linked specifically to prolactin, or ever demonstrated elevated prolactin in their blood results, only further supports this.
The suggested treatment by prolactin guru’s by the way is to combine dopamine agonist treatment with an aromatase inhibitor and a low-calorie diet. Both a low-calorie diet and dopamine agonists have a role in fat loss that is well-established, and will reduce gyno mass short term without actually addressing the problem. In the mean time the anti-estrogen is likely doing its job, and that’s why some people do experience regression. By virtue of this protocol I could administer butter with an Aromatase inhibitor (AI) and a low calorie diet and then claim that butter cleared up my gyno, or I could administer a dopamine agonist with high dose estrogen and claim that the dopamine agonist actually gave me gyno. Just to give you an idea of how credible the findings are by these people and what sort of logic they apply to come up with their theories. On top of that one can argue the sense of using a low-calorie diet. Its supposedly to eliminate insulin as a factor in gyno formation. I freely admit I haven’t looked into that, so I couldn’t tell you if this is sound reasoning or not, but I can tell you there is something wrong with the logic of using a low-calorie diet on a cycle used to gain muscle mass. If you are going to do that, wouldn’t it be safer and cheaper to just stop using the drug that’s causing the problem instead of wasting all that money and gear ?
More important is the manner in which androgens decrease prolactin. They have been shown to reduce expression of Mono-amine oxydase enzymes, reducing the metabolism of dopamine (36), which in turn leads to more available dopamine in the brain, and also upregulating the dopamine D2-receptors (37), enhancing dopaminergic action. This is consistent with reports of high dose nandrolone only cycles slightly decreasing prolactin. So it turns out that androgens actually tend to decrease prolactin in the very same manner that dopaminergic drugs like cabergoline and pramipexole do.
And throughout all of this, when all factual rebuttal was impossible, at least one person tried to win me over for this argument by stating that there was no harm in adding a dopamine agonist, that there can only be a benefit from eliminating prolactin from the equation. This shows a severe lack of judgment and ethics. First of all the aim is always to use as little drugs as possible, and certainly not administer drugs to treat against a non-existing condition with no indication therefore either. Each drug has its own added risks and side-effects, and that’s not accounting for the possible drug-drug interactions associated with multi-pharmacology. For this reason alone, one should never add more drugs than strictly necessary. So lets have a look at the risks associated with the use of dopamine agonists, and for that matter, associated with chronically low prolactin. Nausea, orthostatic hypotension, headaches, abdominal discomfort, nasal congestion, fatigue and constipation are all not uncommon with use of these products. Somewhat more worrying however, as my co-author once pointed out, is that dopamine-agonist induced decreases in prolactin severely hamper the immunity, giving rise not only to opportunistic infection, but can even increase the chance of developing cancer (38). Combined with the fact that AAS generally have a similar effect on immunity, and increase levels of IGF-1, which is a known factor in the development of various cancers, you are putting yourself at an increased level of risk, needlessly.
One last point I want to address in regards to this is that if you do choose to use dopamine agonists, whether it is because you heard its good for fat loss, to address libido issues or because you are bonehead and still want to take it for prolactin issues you don’t have, is that you should cease use a while before you cease the use of your androgens, and should certainly avoid using it when not using AAS. This is because some level of prolactin is needed for testosterone synthesis (39,40), likely for the effect of LH on the leydig cells (41), and low prolactin can lead to lowered testosterone levels, just as easily as high prolactin can. This can severely hamper your recovery. I also stress that these drugs should be taken out of your regimen some time before stopping, because dopamine agonists downregulate dopamine D2-receptors, so cessation of use can actually lead to an increase in systemic prolactin, which can also cause problems with recovery. So both stopping use immediately prior to stopping AAS use and continuing use past AAS use can severely hinder recovery of natural testosterone after a cycle, costing you gains and possibly leading to problems with mood, sexual function and, yes, even gyno (although I’d assume you’d be using SERMs by then).
Gynaecomastia is a condition that is quite rare in users of high dose androgens, such as athletes and people who use AAS for aesthetic reasons, and there are distinct factors that predict sensitivity to the condition. AAS-induced gynaecomastia, since its emergence, has been solely and successfully treated with estrogen management by laymen and medical professionals alike. Successful acute and preventive treatments for estrogenic side-effects have been established anecdotally in the community at large, and are widely supported by the existing literature. One should recognize that a certain amount of circulating estrogen has positive effects on health and well-being , as well as fat loss and possibly muscle and strength gains. For this reason it is wise to adhere to common sense and not self-administer additional pharmaceuticals for problems that aren’t there.
When problems do arise, and you have reason to believe that you are getting gynaecomastia, go see a medical professional about the condition first and foremost. The smart thing to do at this point is also to cease use of the likely causative agent, and start proper post cycle therapy (pct) to let yourself recover. Getting this condition while on high dose androgens could indicate underlying problems that pose severe threats to your health. Oftentimes your doctor will do no more than observe the condition at first. Most likely a preliminary blood test will already identify absolute estrogen or relative estrogen values as the culprit and treatment will be given accordingly. If your doctor refuses to treat, anti-estrogenic drugs are widely available, but if you do choose to self-administer these drugs, make sure you understand them and their correct use. If you are the person who is likely to believe aforementioned pseudo-scientists, this is especially relevant. For acute treatment the SERMs are widely documented to be effective, most notably clomiphene, tamoxifen and raloxifene.
If risk factors are in play, or if you have suffered gynaecomastia during past AAS use, especially if it came on early, preventive treatment with aromatase inhibitors may be wiser. Keep in mind however that this will not address estrogenic problems caused by drugs that do not aromatize to estrogens but are still estrogenic in nature, such as nandrolone and oxymetholone. One should take care to avoid these drugs. Long term treatment with SERMs is acceptable as well, but usually more costly.
1.Wu FC, Farley TM, Peregoudov A, Waites GM. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. Fertil Steril. 1996 Mar;65(3):626-36.
2.Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J. 2000 Sep;14(12):1725-30.
3. Kandouz M, Lombet A, Perrot JY, Jacob D, Carvajal S, Kazem A, Rostene W, Therwath A, Gompel A. Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):463-71.
4. Rochefort H, Garcia M. The estrogenic and antiestrogenic activities of androgens in female target tissues. Pharmacol Ther. 1983;23(2):193-216.
5. Ismail AA, Barth JH. Endocrinology of gynaecomastia. Ann Clin Biochem. 2001 Nov;38(Pt 6):596-607.
6. Perel E, Stolee KH, Kharlip L, Blackstein ME, Killinger DW. The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. J Clin Endocrinol Metab. 1984 Mar;58(3):467-72.
7. Casey RW, Wilson JD. Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor. J Clin Invest. 1984 Dec;74(6):2272-8.
8. Saji S, Jensen EV, Nilsson S, Rylander T, Warner M, Gustafsson J-Å 2000 Estrogen receptors and ß in the rodent mammary gland. Proc Natl Acad Sci USA 97:337–342
9. Koehler KF, Helguero LA, Haldosén LA, Warner M, Gustafsson JA. Reflections on the discovery and significance of estrogen receptor beta. Endocr Rev. 2005 May;26(3):465-78.
10. Dimitrakakis C, Zhou J, Wang J, Belanger A, LaBrie F, Cheng C, Powell D, Bondy C. A physiologic role for testosterone in limiting estrogenic stimulation of the breast. Menopause. 2003 Jul-Aug;10(4):292-8
11. Desaulles PA. [Anabolic hormones from the experimental point of view.] Helv Med Acta. 1960 Dec;27:479-503.
12. Bi H, Du P, Massé R. Studies on anabolic steroids--8. GC/MS characterization of unusual seco acidic metabolites of oxymetholone in human urine. J Steroid Biochem Mol Biol. 1992 Apr;42(2):229-42.
13. Buser AC, Gass-Handel EK, Wyszomierski SL, Doppler W, Leonhardt SA, Schaack J, Rosen JM, Watkin H, Anderson SM, Edwards DP. Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells. Mol Endocrinol. 2007 Jan;21(1):106-25.
14. Nomura K, Suzuki H, Saji M, Horiba N, Ujihara M, Tsushima T, Demura H, Shizume K. High serum progesterone in hyperthyroid men with Graves' disease. J Clin Endocrinol Metab. 1988 Jan;66(1):230-2.
15. Hofling M, Löfgren L, von Schoultz E, Carlström K, Söderqvist G. Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue in postmenopausal women. Gynecol Endocrinol. 2008 Jul;24(7):405-10.
16. Ojasoo T, Raynaud JP. Unique steroid congeners for receptor studies. Cancer Res. 1978 Nov;38(11 Pt 2):4186-98.
17. Tiefenbacher K., Daxenbichler G. The Role of Androgens in Normal and Malignant Breast Tissue. Breast Care 2008;3:325-331
18.Herbert DC, Schuppler J, Poggel A, Günzel P, El Etreby MF. Effect of cyproterone acetate on prolactin secretion in the female rhesus monkey. Cell and Tissue Research. 1977 Sep; 183 (1):51-60.
19. Ryan K. Biological aromatization of steroidsJ. Biol. Chem., Feb 1959; 234: 268 - 272.
20. Bovee TF, Helsdingen RJ, Rietjens IM, Keijer J, Hoogenboom RL. Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types. J Steroid Biochem Mol Biol. 2004 Jul;91(3):99-109
21. J. Shields-Botella, I Duc, E. Duranti, F. Puccio, P. Bonnet, R. Delansorne, J. Paris. An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. Journal of Steroid Biochemistry & Molecular Biology 87 (2003) 111-122.
22. J. Botella,t E. Duranti, V. Viader, I. Duc, R. Delansorne, J. Paris. Lack of Estrogenic Potential of Progesterone- or 19-Nor-progesterone-derived Progestins as Opposed to Testosterone or 19-Nor- testosterone Derivatives on Endometrial Ishikawa Cells. Steroid Biochem. Molec. Biol. Vol. 55, No. 1, pp. 77-84, 1995.
23. Centrella M, McCarthy TL, Chang WZ, Labaree DC, Hochberg RB. Estren (4-estren-3alpha,17beta-diol) is a prohormone that regulates both androgenic and estrogenic transcriptional effects through the androgen receptor. Mol Endocrinol. 2004 May;18(5):1120-30.
24. Sidell N, Tanmahasamut P, Ewing DE, Hendry LB. Transcriptional inhibition of the estrogen response element by antiestrogenic piperidinediones correlates with intercalation into DNA measured by energy calculations. J Steroid Biochem Mol Biol. 2005 Jul 27;
25. Blanco A, Moya L, Flores R, Agüera E, Monterde JG. Effects of anabolic implants of oestradiol alone or in combination with trenbolone acetate on the ultrastructure of mammary glands in female lambs regarding their interference in prolactin secretion. J Vet Med A Physiol Pathol Clin Med. 2002 Feb;49(1):13-7.
26. Grunberg SM, Weiss MH, Spitz IM, Ahmadi J, Sadun A, Russell CA, Lucci L, Stevenson LL. Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg. 1991 Jun;74(6):861-6.
27. Weidenbach PW, Allison JE, Becker RR, Hollander R. Effects of testosterone and oestrogen on serum prolactin in the androgen-insensitive rat. J Reprod Fertil. 1980 Jan;58(1):169-71.
28. Tong Y, Simard J, Labrie C, Zhao HF, Labrie F, Pelletier G. Inhibitory effect of androgen on estrogen-induced prolactin messenger ribonucleic acid accumulation in the male rat anterior pituitary gland. Endocrinology. 1989 Oct;125(4):1821-8.
29. Adamopoulos DA, Nicopoulou S, Kapolla N, Vassilopoulos P, Karamertzanis M, Kontogeorgos L. Endocrine effects of testosterone undecanoate as a supplementary treatment to menopausal gonadotropins or tamoxifen citrate in idiopathic oligozoospermia. Fertil Steril. 1995 Oct;64(4):818-24.
30. Nicoletti I, Filipponi P, Fedeli L, Ambrosi F, Gregorini G, Santeusanio F. Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation. Acta Endocrinol (Copenh). 1984 Feb;105(2):167-72.
31. Hennighausen L, Robinson GW, Wagner KU, Liu W. Prolactin signaling in mammary gland development. J. Biol. Chem. 1997;272; 7567–7569.
32. Kelly PA, Djiane J, Postel-Vinay MC, Edery M. The prolactin/growth hormone receptor family. Endocr. Rev. 1991; 12; 235–251.
33.Ferreira M, Mesquita M, Quaresma M, André S. Prolactin receptor expression in gynaecomastia and male breast carcinoma. Histopathology. 2008 Jul;53(1):56-61
34. Farthing MJ, Green JR, Edwards CR, Dawson AM. Progesterone, prolactin, and gynaecomastia in men with liver disease. Gut. 1982 April; 23(4): 276–279.
35. Nishikawa S, Moore C, Nonomura N, Oka T. Progesterone and EGF inhibit mouse mammary gland prolactin receptor and beta-casein gene expression. Am J Physiol. 1994 Nov;267(5 Pt 1):C1467-72.
36.Birgner C, Kindlundh-H?gberg AM, Oreland L, Alsi? J, Lindblom J, Schi?th HB, Bergstr?m L. Reduced activity of monoamine oxidase in the rat brain following repeated nandrolone decanoate administration. Brain Res. 2008 Jul 11;1219:103-10.
37.Kindlundh AM, Lindblom J, Nyberg F. Chronic administration with nandrolone decanoate induces alterations in the gene-transcript content of dopamine D(1)- and D(2)-receptors in the rat brain. Brain Res. 2003 Jul 25;979(1-2):37-42.
38. Matera L, Mori M, Geuna M, Buttiglieri S, Palestro G. Prolactin in autoimmunity and antitumor defence. J Neuroimmunol 2000 Sep 1;109(1):47-55.
39. Marin-Lopez G, Vilchez-Martinez J, Hernandez-Yanez L, Torres-Morales A, Bishop W. Leydig cell function in hyper- or hypoprolactinemic states in healthy men. Invest Clin 1996 Sep;37(3):153-66.
40. Manna PR, El-Hefnawy T, Kero J, Huhtaniemi IT. Biphasic action of prolactin in the regulation of murine Leydig tumor cell functions. Endocrinology 2001 Jan;142(1):308-18.
41. Kovacevic R, Sarac M. Bromocriptine-induced inhibition of hydroxylase/lyase activity of adult rat Leydig cells. J Steroid Biochem Mol Biol 1993 Dec;46(6):841-5.
42. Aono T. [Hormonal control of lactation]. Nippon Sanka Fujinka Gakkai Zasshi. 1990 Aug;42(8):867-72.
43. Rohn RD. Benign galactorrhea/breast discharge in adolescent males probably due to breast self-manipulation. J Adolesc Health Care. 1984 Jul;5(3):210-2.
44. Howie PW, McNeilly AS, McArdle T, Smart L, Houston M. The relationship between suckling-induced prolactin response and lactogenesis. J Clin Endocrinol Metab. 1980 Apr;50(4):670-3.
Originally Posted by Doink the clown;
I found this really interesting. It seems to run contrary in many ways to the conventional logic.
I know I had good luck in the past with Ralixofene for shrinking existing gyno, but as stated it was a loooong protocol.
Users Browsing this Thread
There are currently 1 users browsing this thread. (0 members and 1 guests)
By Live2Train in forum Anabolic Steroid Forum
Last Post: 03-18-2015, 02:54 AM
By ricosuve in forum Anabolic Steroid Forum
Last Post: 01-13-2013, 08:36 AM
By joltan in forum Anabolic Steroid Forum
Last Post: 04-19-2008, 09:23 AM
By dude2003 in forum Anabolic Steroid Forum
Last Post: 06-09-2003, 05:14 PM
Tags for this Thread