Help!!! Please check what I'm taking. Worried about gyno

[musclenz]

Cheers HP, respect & appreciate your agreement in principle given your PT experience with athletes. Just the point raised about using Nandrolone without Test is subject to differing opinions in the broader AAS using community from my observations. Although it has an Anabolic/Androgenic ratio of 125:37 & due to nandrolones chemical structure it only aromatizes slightly, it is a strong progestin with a binding affinity of 20% to the progesterone receptor, so side effects are still very possible with progesterone gyno & prolactin buildup resulting in libido & ED issues being quite a problem in some users. Originally, Boldenone was designed or used by BBers to replace Nandrolone because of the above but I have found they have very good synergy if stacked together as you suggest but I have normally always included Test in this stack but I see no reason to not use those 2 together without test.

[bulking]

AR receptors DON'T down-regulate this is a myth.

They up-regulate in response to supraphysiological androgen levels.

But they dont stay up-regulated....

[musclenz]

AR receptors DON'T down-regulate this is a myth.

They up-regulate in response to supraphysiological androgen levels.

But they dont stay up-regulated....

Go on Bulking you might as well dispell the whole myth

[bulking]

Well Ive never actually come across someone who believed AR receptors down-regulated permanently. How something that is constantly refreshed by the system can be downregulated is beyond me.

But as to down-regulation DURING the cycle ill touch on that. I have heard this discussed by people as to being the reason gains stop or slow after a certain time, 6-8 weeks generally.

In a nutshell the androgen receptors upregulate in response to high levels of Androgens. Like I said they dont stay upregulated but revert to normalcy over time. This is one of the reasons for diminshed gains after 6-8 weeks, other factors have an influence as well myostatin etc ( btw MusNZ I have the log of the guy running the myostatin inhibitors you were asking about ill email them to you later)

Heres a couple layman's articles to read for those interested. Hate to quote bill roberts but hes right about some things.

-----------------------------------------------------------------------

1] Androgen Receptor Regulation

by Bill Roberts

http://www.mesomorphosis.com/articles/p ... lation.htm

2] Androgen Receptors Downregulate - Don't They?

By Bryan Haycock

http://www.thinkmuscle.com/ARTICLES/hay ... ors-01.htm

Heres an interesting study for those who want a little more depth

Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment , Indrani Sinha-Hikim, The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 10 5245-5255

The mechanisms by which androgens induce skeletal muscle hypertrophy are not well understood (3). In pioneering studies, Kochakian (39) and Kenyon et al. (40) reported that testosterone supplementation promotes nitrogen retention in castrated males of many mammalian species, including eunuchoidal men. These early observations of androgen effects on nitrogen retention led to the hypothesis that androgens stimulate protein synthesis. Recent studies provided further evidence that testosterone promotes muscle anabolism by stimulating fractional muscle protein synthesis, inhibiting muscle protein degradation, and by increasing the efficiency of amino acid reuse by the skeletal muscle (4, 12, 41).

However, the muscle protein synthesis hypothesis does not explain a number of observed effects of androgen administration on body composition; it cannot easily explain the reciprocal decrease in fat mass and the observed increase in the number of satellite cells and myonuclei during testosterone administration. Recently, we reported that testosterone promotes the commitment of a pluripotent, mesenchymal cell line into the myogenic lineage and inhibits the differentiation of these precursor cells into the adipogenic lineage (20). The hypothesis that androgens regulate body composition by modulating the commitment of pluripotent mesenchymal cells provides a unifying explanation for the reciprocal changes in fat and muscle mass during androgen administration (3); it is consistent with the observed increase in satellite cell number after androgen administration (3). Our observation that mesenchymal precursor cells within the skeletal muscle, including satellite cells, are the predominant site of AR expression supports the hypothesis that mesenchymal precursor cells resident within the skeletal muscle are the target of androgen action.

The demonstration of AR expression in multiple cell types, including fibroblasts, vascular endothelial and smooth muscle cells, and mast cells within the human skeletal muscle is intriguing. Fibroblasts in other tissues have been shown to express AR. Endoneurial fibroblasts of the sciatic nerve show prominent AR immunostaining (42). Although there were only a few mast cells in tissue sections, we noted dense distribution of AR on the metachromatic granules within the mast cells. Mast cells participate in a multitude of inflammatory and immune responses and stimulate local cell proliferation (43, 44); these mast cell reactions might be important in skeletal muscle repair and remodeling in response to injury or hypertrophic stimuli.

The aggregation of the immunogold particles within the nucleoli of satellite cells and myonuclei is a novel finding; testosterone administration was associated with increased nucleolar aggregation of immunogold particles. The nucleoli are the site of processing and partial assembly of the three major RNA classes. We do not know whether nucleolar aggregation of AR is related to androgen stimulation of protein synthesis.

There was a qualitative increase in the density of AR within satellite cells and myonuclei after administration of a supraphysiologic dose of testosterone enanthate. Similarly, in enriched satellite cell cultures, incubation with androgens increased the expression of AR protein, measured by Western blot analysis. The changes in AR mRNA levels, measured by real-time PCR, were very modest. These data are consistent with those of Sheffield-Moore et al. (12) and Kadi et al. (17, 18), who also reported an increase in AR expression in the skeletal muscle biopsies from men receiving androgenic steroids. These studies, including our own, used supraphysiologic doses of testosterone or other anabolic steroids; we do not know whether physiologic replacement doses of testosterone can produce similar up-regulation of AR in the skeletal muscle. In a mesenechymal, pluripotent cell line, C3H 10T1/2, testosterone and DHT up-regulate the expression of AR (20). Speculation that androgens might augment the responsiveness of the skeletal muscle to further androgen administration by up-regulating their own receptor needs further evaluation (12).

We only evaluated the expression of the classical AR; it has been speculated that some actions of androgens might be mediated through nongenomic, membrane binding sites (45, 46, 47). The precise nature of these nongenomic binding sites is not known, although it has been suggested that nongenomic effects might involve G protein signaling (47).

In summary, although multiple cell types within the human skeletal muscle express AR protein, satellite cells, and myonuclei are the predominant sites of AR expression. ARs aggregate within the nucleoli of satellite cells and myonuclei. Testosterone and DHT up-regulate AR expression in vivo and in vitro. These data are consistent with the proposal that androgens induce skeletal muscle hypertrophy by acting at multiple sites within the muscle through multiple mechanisms, including modulation of pluripotent stem cell commitment and differentiation and regulation of muscle protein synthesis; further studies are needed to elucidate the molecular basis of androgen action on human skeletal muscle.

End of study.

Ok so this begs the question how do you combat the lack of upregulation after time. Well starting the cycle on reasonable dosages then upping the dose later in the cycle is one way. Another is to add compounds with Strong AR binding affinity later in the cycle ie tren as an injectable and Tbol as an oral. I dont recommend finishing a cycle on tren though it shuts you down hard, alow a few weeks break from it before you end.

[ThePman]

You guys do realize that even contraction of a muscle increases the AR count, right?

Not that I care to get into the drug debate, but muscle growth is a topic I know a tiny bit about.

[Optimass]

I want to throw in a wild card now. I believe that bigger, stronger genetically gifted mesomorphs are normally higher in natty test production & that they respond to smaller doses of AAS & have better results. While smaller bodied ectomorphs & endomorphs do not naturally produce & carry as much free test as the mesos do. I think age also plays a big part in the equation. Now I have no scientific studies to support my hypothesis but I have taken into account those guys I have been involved with & it just seems to have some credence, in my books anyway.

Not sure thats a wild card statement mate. As you say, if you have spent enough time in gyms and around like minded people, it's easy enough to identify the gifted individuals. They grow faster, are generally stronger and have more dominant behavioural characteristics. (both as nattys and enhanced).

[Specter]

I want to throw in a wild card now. I believe that bigger, stronger genetically gifted mesomorphs are normally higher in natty test production & that they respond to smaller doses of AAS & have better results. While smaller bodied ectomorphs & endomorphs do not naturally produce & carry as much free test as the mesos do. I think age also plays a big part in the equation. Now I have no scientific studies to support my hypothesis but I have taken into account those guys I have been involved with & it just seems to have some credence, in my books anyway.

Not sure thats a wild card statement mate. As you say, if you have spent enough time in gyms and around like minded people, it's easy enough to identify the gifted individuals. They grow faster, are generally stronger and have more dominant behavioural characteristics. (both as nattys and enhanced).

more dominant behavioural characteristics...

Hey Opti....just intersted in the comment there, but does that mean better self control and focus with these individuals?

[Optimass]

Was more getting at the " Alpha male" aspect of it - physical implications of AAS are normally discussed in the forum but the psychological is often over looked when making comparisons.

The alpha animals are given preference to be the first to eat and the first to mate, among some species the only animals in the pack allowed to mate. Other animals in the community are usually killed or ousted if they violate this rule.

Sounds like your average day in the office doesn't it? :pfft:

.... or the gym for that matter - the alpha males always get more 20 plates on leg nights than the others :grin: god help the poor soul tha violates this rule

[musclenz]

Well Ive never actually come across someone who believed AR receptors down-regulated permanently. How something that is constantly refreshed by the system can be downregulated is beyond me.

But as to down-regulation DURING the cycle ill touch on that. I have heard this discussed by people as to being the reason gains stop or slow after a certain time, 6-8 weeks generally.

In a nutshell the androgen receptors upregulate in response to high levels of Androgens. Like I said they dont stay upregulated but revert to normalcy over time. This is one of the reasons for diminshed gains after 6-8 weeks, other factors have an influence as well myostatin etc ( btw MusNZ I have the log of the guy running the myostatin inhibitors you were asking about ill email them to you later)

Heres a couple layman's articles to read for those interested. Hate to quote bill roberts but hes right about some things.

-----------------------------------------------------------------------

1] Androgen Receptor Regulation

by Bill Roberts

http://www.mesomorphosis.com/articles/p ... lation.htm

2] Androgen Receptors Downregulate - Don't They?

By Bryan Haycock

http://www.thinkmuscle.com/ARTICLES/hay ... ors-01.htm

Heres an interesting study for those who want a little more depth

Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment , Indrani Sinha-Hikim, The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 10 5245-5255

The mechanisms by which androgens induce skeletal muscle hypertrophy are not well understood (3). In pioneering studies, Kochakian (39) and Kenyon et al. (40) reported that testosterone supplementation promotes nitrogen retention in castrated males of many mammalian species, including eunuchoidal men. These early observations of androgen effects on nitrogen retention led to the hypothesis that androgens stimulate protein synthesis. Recent studies provided further evidence that testosterone promotes muscle anabolism by stimulating fractional muscle protein synthesis, inhibiting muscle protein degradation, and by increasing the efficiency of amino acid reuse by the skeletal muscle (4, 12, 41).

However, the muscle protein synthesis hypothesis does not explain a number of observed effects of androgen administration on body composition; it cannot easily explain the reciprocal decrease in fat mass and the observed increase in the number of satellite cells and myonuclei during testosterone administration. Recently, we reported that testosterone promotes the commitment of a pluripotent, mesenchymal cell line into the myogenic lineage and inhibits the differentiation of these precursor cells into the adipogenic lineage (20). The hypothesis that androgens regulate body composition by modulating the commitment of pluripotent mesenchymal cells provides a unifying explanation for the reciprocal changes in fat and muscle mass during androgen administration (3); it is consistent with the observed increase in satellite cell number after androgen administration (3). Our observation that mesenchymal precursor cells within the skeletal muscle, including satellite cells, are the predominant site of AR expression supports the hypothesis that mesenchymal precursor cells resident within the skeletal muscle are the target of androgen action.

The demonstration of AR expression in multiple cell types, including fibroblasts, vascular endothelial and smooth muscle cells, and mast cells within the human skeletal muscle is intriguing. Fibroblasts in other tissues have been shown to express AR. Endoneurial fibroblasts of the sciatic nerve show prominent AR immunostaining (42). Although there were only a few mast cells in tissue sections, we noted dense distribution of AR on the metachromatic granules within the mast cells. Mast cells participate in a multitude of inflammatory and immune responses and stimulate local cell proliferation (43, 44); these mast cell reactions might be important in skeletal muscle repair and remodeling in response to injury or hypertrophic stimuli.

The aggregation of the immunogold particles within the nucleoli of satellite cells and myonuclei is a novel finding; testosterone administration was associated with increased nucleolar aggregation of immunogold particles. The nucleoli are the site of processing and partial assembly of the three major RNA classes. We do not know whether nucleolar aggregation of AR is related to androgen stimulation of protein synthesis.

There was a qualitative increase in the density of AR within satellite cells and myonuclei after administration of a supraphysiologic dose of testosterone enanthate. Similarly, in enriched satellite cell cultures, incubation with androgens increased the expression of AR protein, measured by Western blot analysis. The changes in AR mRNA levels, measured by real-time PCR, were very modest. These data are consistent with those of Sheffield-Moore et al. (12) and Kadi et al. (17, 18), who also reported an increase in AR expression in the skeletal muscle biopsies from men receiving androgenic steroids. These studies, including our own, used supraphysiologic doses of testosterone or other anabolic steroids; we do not know whether physiologic replacement doses of testosterone can produce similar up-regulation of AR in the skeletal muscle. In a mesenechymal, pluripotent cell line, C3H 10T1/2, testosterone and DHT up-regulate the expression of AR (20). Speculation that androgens might augment the responsiveness of the skeletal muscle to further androgen administration by up-regulating their own receptor needs further evaluation (12).

We only evaluated the expression of the classical AR; it has been speculated that some actions of androgens might be mediated through nongenomic, membrane binding sites (45, 46, 47). The precise nature of these nongenomic binding sites is not known, although it has been suggested that nongenomic effects might involve G protein signaling (47).

In summary, although multiple cell types within the human skeletal muscle express AR protein, satellite cells, and myonuclei are the predominant sites of AR expression. ARs aggregate within the nucleoli of satellite cells and myonuclei. Testosterone and DHT up-regulate AR expression in vivo and in vitro. These data are consistent with the proposal that androgens induce skeletal muscle hypertrophy by acting at multiple sites within the muscle through multiple mechanisms, including modulation of pluripotent stem cell commitment and differentiation and regulation of muscle protein synthesis; further studies are needed to elucidate the molecular basis of androgen action on human skeletal muscle.

End of study.

Ok so this begs the question how do you combat the lack of upregulation after time. Well starting the cycle on reasonable dosages then upping the dose later in the cycle is one way. Another is to add compounds with Strong AR binding affinity later in the cycle ie tren as an injectable and Tbol as an oral. I dont recommend finishing a cycle on tren though it shuts you down hard, alow a few weeks break from it before you end.

Bill Roberts is ok its Anthony Roberts you got to be wary of Two very good articles on the myth of AR down regulation & a scientific study to promote up-regulation. Nice work Bulking. I think Brian Haycock's article highlights some of the many other factors that influence AR activity that can result in diminishing returns in an AAS cycle. I am not sure there is any definitive answer to this.

[Pete_S]

Cheers HP, respect & appreciate your agreement in principle given your PT experience with athletes. Just the point raised about using Nandrolone without Test is subject to differing opinions in the broader AAS using community from my observations. Although it has an Anabolic/Androgenic ratio of 125:37 & due to nandrolones chemical structure it only aromatizes slightly, it is a strong progestin with a binding affinity of 20% to the progesterone receptor, so side effects are still very possible with progesterone gyno & prolactin buildup resulting in libido & ED issues being quite a problem in some users. Originally, Boldenone was designed or used by BBers to replace Nandrolone because of the above but I have found they have very good synergy if stacked together as you suggest but I have normally always included Test in this stack but I see no reason to not use those 2 together without test.

In my experience my best bulking results have been running test with deca at a ratio of 2:1. I add some other compunds in at various stages but have tried equipose and don't rate it very much and now never use it. Using deca without test will shut you down hard and you don't get the synegistic effect of 1 + 1 = 3.

[spencer21]

To start with Sustanon & Trenbolone Acetate should be injected at least EOD. ED is even better for Tren. This helps to keep sides to a minimum. By shooting up twice weekly your blood levels will be all over the place. However, I realise that the dose you are using with Tren is a bit difficult to split up. What mg/ml is the Tren? If you are getting puffy itchy nips this is probably from increased progesterone activity which results in prolactin buildup. Tren works on a different pathway than Test. As Outkast suggested you need a estrogen inhibitor like Letrozole 2.5mg eod to start with to see if you can tidy it up. I would not think that prolactin would be too high on 100mg PW of Tren but if you have no sucess with the AI then you may need Cagergoline - Dostinex at .5mg 3 xPW. Once you have had gyno you will have a lot more respect to what drugs you asre using & will likely learn a lot more about using anti-estrogens in your cycle or at least having them on hand. Good luck.

Cheers for the coments. Was taking 1ml a week of the tren. Went back to the guy who got me started and he has given me Genox (tamoxifen) and said 20mg pill every morning. What are your thoughts on this.

[spencer21]

no offence dude but that display picture you had on here lastnight looked like an average 4th former who never stepped foot in a gym before.

i dont think you should be taking gear and i dont say that about many people! how old are you?

Was a really old pic of when I first started training back in the day. Am now 25. Have gotten really good results from the gear but still wish I had done it the hard way.

[spencer21]

my question to you is why did you start taking them in the first place? too many people "succumb" to taking steroids when their training and/or diet isn't even sorted. if i were you i would get off those roids before you've done your research and gained some more insight into bodybuilding

Yeah Dude

Fully regret it now and wish I had done it the hard way. Really just need someone to take me under there wing and help me with proper nutrition and training. I have great genes and know I can do it. I guess watch this space.

[JAFA]

Just wondering about the recommendation to use letrozole in the first three PCT weeks of a test e cycle. Just that Ive never seen this PCT method used before. Is there a significant risk of high levels of prolactin?

[musclenz]

To start with Sustanon & Trenbolone Acetate should be injected at least EOD. ED is even better for Tren. This helps to keep sides to a minimum. By shooting up twice weekly your blood levels will be all over the place. However, I realise that the dose you are using with Tren is a bit difficult to split up. What mg/ml is the Tren? If you are getting puffy itchy nips this is probably from increased progesterone activity which results in prolactin buildup. Tren works on a different pathway than Test. As Outkast suggested you need a estrogen inhibitor like Letrozole 2.5mg eod to start with to see if you can tidy it up. I would not think that prolactin would be too high on 100mg PW of Tren but if you have no sucess with the AI then you may need Cagergoline - Dostinex at .5mg 3 xPW. Once you have had gyno you will have a lot more respect to what drugs you asre using & will likely learn a lot more about using anti-estrogens in your cycle or at least having them on hand. Good luck.

Cheers for the coments. Was taking 1ml a week of the tren. Went back to the guy who got me started and he has given me Genox (tamoxifen) and said 20mg pill every morning. What are your thoughts on this.

Tamoxifen is not that effective if your Gyno is progesterone gyno but better than nothing. see how you go. 20mg ed is sufficient but best taken at night IMO.

[musclenz]

Just wondering about the recommendation to use letrozole in the first three PCT weeks of a test e cycle. Just that Ive never seen this PCT method used before. Is there a significant risk of high levels of prolactin?

Ummm your question is a little misconstrued. Letro can be used as part of a PCT after a TestE cycle. Aromasin is a better choice but often in NZ we have to make do with whats available in your area. Letro in itself will not deal to prolactin levels. You may require a dopamine receptor agonist like Prami, Dostinex, Cabasar, Bromocriptine. Because Letro is so effective at reducing estrogen in body, its effective at treating issues at the PR as prolactin cannot synthesize in the absence of estrogen.