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Big Cat's Corner: Issue 7!

Read about how estrogen can be anabolic, if testosterone is crucial for muscle growth, if DHEA is good for fat loss and more...

Estrogen As An Anabolic? More Important Than You Think.

This illustrious issue has been hotly debated in the past. Does estrogen have an anabolic contribution to make? That it does is not so much an issue any more, several studies have demonstrated that indeed growth is promoted with strong androgens, more so in the presence of estrogen. This is also the reason many cattle implants today contain a form of estrogen as well, next to a potent androgen.

The debate today mainly centers around whether or not supraphysiological doses of estrogen can benefit growth more than a permissive, physiological dose of estrogen. Extensive experience as well as a lot of indirect evidence has taught me that this is definitely the case.

Of course, if I could have proven it conclusively before, it wouldn't have been much of a debate. Now, however, evidence clearly demonstrates that estrogen is anabolic in a dose responsive way. Even more important it clearly shows how levels of estrogen can help determine whether you are more likely to become a strength athlete or an endurance athlete.

In the past estrogen has been shown to increase local IGF-1, probably through a decrease in systemic liver-derived IGF-1 and a subsequent increase in circulating growth hormone. It has been shown to activate the mitogen activated protein kinase cascade (1), one of the ways in which IGF-1 and insulin exert anabolic effects, and it has been shown to increase cyclo-oxygenase activity (2) which would result in an enhanced immune-response and increased manufacture of prostaglandins.

Several prostaglandins have been implicated in enhancing both muscle anabolism and fat loss, by sensitizing tissues to the effects of testosterone and IGF-1. However none of these effects have been shown to occur specifically in skeletal muscle tissue, and for none of them it has been determined whether or not the effects are enhanced with increased doses of estrogen or not.

Estrogen works through so many ways that are anabolic or potentially anabolic, and a few of those are bound to increase in supraphysiological doses, but nonetheless, previously this was all conjecture.

One system we do know however that is dose responsive to estrogen, is the renin-angiotensin system. Estrogen increases the activity of this system, renin converts angiotensinogen to Angiotensin I, and then Angiotensin converting enzyme (ACE) converts it to Angiotensin II (AngII). Angiotensin II in turn stimulates aldosterone release. AngII and aldosterone are the main hormonal factors implicated in elevated blood pressure and water retention.

As any seasoned steroid user knows, estrogen has a very dose responsive reaction on this system. Drugs with a very rapid and high increase in estrogen or estrogenic actions, like testosterone suspension, Anadrol and Dianabol, cause massive increases in blood pressure, headaches and water retention.

The pink ones are Anabol (Dianabol) and the yellow ones are Stanabol (Winstrol). These are very popular right now. They are 5 mg tabs and they sell for less than 30 cents a tab.

Many tissues express a local Renin-angiotensin System (RAS), including skeletal muscle tissue, that exists partially through uptake of systemic RAS components and partially through de novo synthesis of its components (AngII, ACE). One study in particular linked this skeletal muscle RAS to exercise performance (3), and the results were quite remarkable to say the least.

High ACE, and consequently AngII, resulted in a poorer athletic performance, but greater muscular strength and muscular hypertrophy. Subjects with higher levels of ACE had a higher level of Type II fiber and intracellular glucose stores, whereas people with lower ACE had higher Type I fiber, higher degree of vascularization and higher levels of interstitial glucose.

This higher interstitial glucose means a lot of the glucose is excreted from intracellular stores and can be readily mobilized. All these things are supportive a greater endurance and greater athletic performance. In the former situation, performance would suffer, but strength would increase to a much greater extent.

The implication of this is quite profound, since it offers a reason for genetic phenotyping. In humans ACE expression is dependent on insertion (I) or deletion (D) of a 287 base pair sequence in intron 16. That means three phenotypes exist, I/I, I/D and D/D.

The distribution of these phenotypes among Caucasian males is 25%, 50% and 25%. That means if you fall in the former or latter category, you have a genetic tendency to become better at endurance or strength sports. I/I has the lowest RAS expression, and D/D has the highest RAS expression.It also offers a point of manipulation to reach your desired goal. Logically said manipulation would be most successful in the I/D phenotype, since promoting or reducing RAS activity could push you in either direction, while the promoting RAS in I/I or inhibiting it in D/D would most likely push you towards more of an I/D type.

Since estrogen is a dose-dependent activator of the RAS, it not only increases muscle strength and hypertrophy, it also helps determine to a large degree how much Type I or Type II fiber a certain muscle group has. Type II muscle fibers grow faster and bigger than Type II fibers and promote more explosive strength, while Type I fibers are well vascularized, grow slowly, but are more fit for longer, lower intensity tasks. By inhibiting estrogen, we may therefore be slowing our muscle gains, both short term, but especially long term.

These findings vindicate a number of theories I have defended for a long time. First and foremost that estrogen is indeed a dose-dependent anabolic steroid, especially in combination with androgens, in supra-physiological doses, such as seen with several high-estrogenic drugs. For a very long time we have known that drugs with extremely poor androgenic qualities like oxymetholone and methandrostenolone are very strong anabolics.

Many have denied the role of estrogen in this, instead sinning against ockham's razor and finding all sorts of far-fetched theories. We first dismissed the growth as being mostly water. A lot of it was, since RAS increases water retention, but obviously not all mass gained could be explained by water. Then some people attempted to explain it by claiming it was the result of more androgenic by-products.

But no by-product had sufficient androgenic effects, or was expressed to a large enough degree to explain why these drugs performed as good as less estrogenic drugs, sometimes outperforming them despite imminently lower androgenic binding. Following ockham's razor, the logical conclusion was that the higher degree of anabolism was a result of their higher degree of estrogen receptor activation, either direct (oxymetholone) or indirect via aromatization to potent estrogens (methandrostenolone).

Cattle ranchers have known this for a long time. Cattle implants contain a certain amount of estradiol, which not only improves the total amount of muscle mass, but also the quality of the meat. More Type II fibers equates more meat, and more usable quality meat since it is less vascularized.

The downsides are however that we again corroborate the fact that being good at predominantly endurance activities, rules out being extremely good at building muscle mass and vice versa. Through activation of RAS, local and systemic, estrogen would reduce aerobic capacity and Type I fiber formation in favour of Type II muscle. It would also increase blood pressure and water retention.

The same holds true the other way around, endurance activity may very well lower estrogen, since regular exercise has been shown to lower blood pressure and favour Type I muscle growth. The implications of that, would once again be huge, since it puts a negative aspect on doing cardio during bulking phases.

The take home message however is that estrogen is indeed a potent anabolic aid, especially in combination with androgens, and that this effect is very much dose-responsive and thus holds up in higher, supraphysiological doses. Together with a previously discussed item in this column, regarding increased estrogenic problems after the use of anti-estrogenic drugs, this seriously questions the importance some bodybuilders attach to anti-estrogens.

Clearly the uneducated use of anti-estrogenic drugs needs some re-examination, and bodybuilders need to see that estrogen can not only be a major contributor to growth, but not using anti-estrogens will often prevent many of the problems their use supposedly cures. So unless you are extremely prone to estrogenic side-effects, I would seriously think twice about incorporating potent anti-estrogenic drugs during the course of a steroid or prohormone cycle.


  1. Wade CB, Robinson S, Shapiro RA, Dorsa DM. Estrogen receptor (ER)alpha and ERbeta exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway. Endocrinology. 2001 Jun;142(6):2336-42.
  2. Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA. Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5.
  3. Jones A, Woods R. Skeletal muscle RAS and exercise performance. Int J Biochem Cell Biol. 2003 Jun;35(6):855-66.

The Relevance Of Testosterone During Bulking

We all know that testosterone is crucial in muscle growth. It directly increases protein synthesis by being a promoter of transcription when it binds the nuclear androgen receptor, supports proliferation, differentiation and fusion of satellite cells by increasing calcium influx and activating calcineurin and it promotes the local production of growth factors like IGF-I. testosterone may however also be relevant to us in determining the type of weight gained during bulking.

One study examined the effect of testosterone on pluripotent stem cells. These stem cells can develop into either pre-adipocytes or muscle satellite cells. Testosterone not only inhibited the formation of pre-adipocytes, but also the proliferation and differentiation of existing pre-adipocytes, while promoting the transformation of the pluripotent stem cells to muscle satellite cells.

This indicates a clear long term benefit for elevated testosterone levels as well, since they increase the number of cells that can potentially donate nuclei to the muscles, thereby increasing androgen receptor density and the effect of testosterone on promoting transcription of DNA.

This is synergistic with testosterone's effect on calcineurin activity, which causes the cells to proliferate (via NFAT2 activation) and differentiate into myoblasts (via NFAT3 activation) as well as fuse with existing myotubes (via NFAT2 related paracrine IL-4 release).


  1. Bhasin S, Taylor WE, Singh R, Artaza J, Sinha-Hikim I, Jasuja R, Choi H, Gonzalez-Cadavid NF.
  2. The mechanisms of androgen effects on body composition: Mesenchymal pluripotent cell as the target of androgen action.
  3. Journal of Gerontology, medical sciences 2003, (58A) 12: 1103-1110.

DHEA vs 7-Oxo-DHEA For Fat Loss

Dehydroepiandrosterone has been sold as a nutritional supplement for quite some time now, long before prohormones started coming out. It has been sold with so many purposes its hard to keep track. It was marketed as the next fountain of youth, as so many things are these days, and to little or no avail. In the bodybuilding community it was briefly promoted as a muscle-gaining supplement, since it was a precursor to testosterone, but to little or no avail.

DHEA was never really specifically marketed as a fat loss supplement. Now, several years later, products are popping up left and right promoting an analog, 7-oxo-DHEA for fat loss.

This is however the most utterly stupid thing I have ever heard. 7-oxo-DHEA is quite poor at aiding fat loss, and may actually inhibit it, while the much cheaper and more readily available DHEA is an excellent and often overlooked diet aid. One study (1) that directly compares the effects of DHEA to 7-oxo-DHEA clearly demonstrates this: cells treated with DHEA had significantly reduced levels fatty acid content, where as cells treated with 7-oxo had significantly increased levels of fatty acids.

This correlated well with the level of expression of stearoyl coA desaturase (SCD1), and may be mediated by changes in this enzyme, as DHEA treated cells had a much lower expression of SCD1, and cells treated with 7-oxo had considerably elevated levels of SCD1. DHEA also inhibited differentiation of pre-adipocytes into adipocytes, probably through a reduction in the proliferation and differentiation factor PPARgamma (3), and the study also demonstrated that DHEA had a thermogenic effect in already differentiating cells, whereas 7-oxo promoted differentiation with no effect on thermogenesis at all.

This is corroborated in another study (2) that shows that DHEA increases expression of UCP1 and UCP3 in fat cells. Since every fat cell expressing UCP1 is by definition a brown fat cell, we can conclude that next to inhibiting the differentiation of pre-adipocytes into new fat cells, it also turns differentiating and differentiated fat cells into brown fat cells.

Brown fat cells are thermogenically active and contribute to the process of burning calories. Thanks to their expression of UCP1 they also manage to uncouple this process from energy production. A brown fat cell produces more heat than energy, meaning more calories are burned for the same amount of energy produced. So not only does DHEA prevent the formation of new fat cells, those that are formed are metabolically active, while 7-oXo has no such effects at all and invariably leads to a higher level of fat in the cell.

One the supposed benefits touted for 7-oxo by supplement manufacturers is its ability to inhibit cortisol formation (4) more so than DHEA. This very thing is its major downside. Cortisol is only adipogenic in visceral fat. When on a diet, visceral fat is the easiest and fastest to be mobilized. A correct diet will not allow for visceral fat gain at all. Cortisol is highly lipolytic in all other tissues however, meaning you lose a considerable ally in the war on fat.

This suppression of cortisol is most likely why 7-oxo treated cells have a much higher fat content and why it doesn't inhibit differentiation. Furthermore DHEA also has distinct roles in enhancing beta-adrenergic mediated fat loss (5) and as a neuro-active steroid it lowers food intake (6).

The combination of all these effects make fat loss probably the best supported and documented role for DHEA, more so than any other purpose it was previously marketed for, while its analog 7-oxo-DHEA is currently marketed for that very purpose, while it actually decreases fat loss through several different pathways.


  1. Gomez FE, Miyazaki M, Kim YC, Marwah P, Lardy HA, Ntambi JM, Fox BG. Molecular differences caused by differentiation of 3T3-L1 preadipocytes in the presence of either dehydroepiandrosterone (DHEA) or 7-oxo-DHEA. Biochemistry. 2002 Apr 30;41(17):5473-82.
  2. Ryu JW, Kim MS, Kim CH, Song KH, Park JY, Lee JD, Kim JB, Lee KU. DHEA administration increases brown fat uncoupling protein 1 levels in obese OLETF rats. Biochem Biophys Res Commun. 2003 Apr 4;303(2):726-31.
  3. Kajita K, Ishizuka T, Mune T, Miura A, Ishizawa M, Kanoh Y, Kawai Y, Natsume Y, Yasuda K. Dehydroepiandrosterone down-regulates the expression of peroxisome proliferator-activated receptor gamma in adipocytes. Endocrinology. 2003 Jan;144(1):253-9.
  4. Hampl R, Lapcik O, Hill M, Klak J, Kasal A, Novacek A, Sterzl I, Sterzl J, Starka L. 7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy? Physiol Res. 2000;49 Suppl 1:S107-12.
  5. Tagliaferro AR, Ronan AM, Payne J, Meeker LD, Tse S. Increased lipolysis to beta-adrenergic stimulation after dehydroepiandrosterone treatment in rats. Am J Physiol. 1995 Jun;268(6 Pt 2):R1374-80.
  6. Wright BE, Svec F, Porter JR. Central effects of dehydroepiandrosterone in Zucker rats. Int J Obes Relat Metab Disord. 1995 Dec;19(12):887-92.

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