Warning: The following information is intended only as a hypothetical consideration of ways in which human physiology may be altered, through pharmacological means, to achieve striking muscularity. The drugs discussed in this series of articles are, by and large, prescription drugs and should not be used without the supervision of a qualified physician. No attempt should be made to circumvent the laws in your area to obtain these drugs without a prescription. As always, Meso-Rx does not condone in any way the illegal acquisition and/or use of prescription drugs for purposes other than those approved by the FDA or other legally recognized regulatory bodies.
Bodybuilding is all about building muscle. In some arenas, this calls for whatever means necessary to grow bigger and leaner then anyone has before. Human progress together with fickle audiences demand that bodybuilders show up bigger and more unnatural looking year after year. As a spectator sport/culture, these two forces are critical to the future of bodybuilding. What would become of bodybuilding if you didn’t have to be bigger and leaner to place higher than you did the year before? I’ll tell you what would happen, audiences would dwindle, the money would dry up, competitors would get small and soft, and the hunger, the drive, the passion, for ever more powerful and massive physiques would extinguish, succumbing to the undertow of the seemingly homoerotic men’s fitness movement.
I left you with a bit of a teaser in the last installment by promising that you would learn just how to incorporate GH and IGF-1 into a bodybuilding regimen to achieve results far beyond what nature intended. Let me make it clear from the onset that GH and/or IGF-1, when used by themselves, are not nearly as effective as esterified androgens. You may ask, “Then why bother with GH or IGF-1 at all?” The answer is simple. There is a limit to how large you can grow with traditional androgen only regimens. This is not to say that a person cannot be successful in bodybuilding without the use of growth factors. That would be blatantly false. On the contrary, some guys can grow to very respectable proportions with androgens alone. My question to you is, “Must we, or more realistically, will we, stop there?” The history of science and man’s need to “go where no man has gone before” tells us that we will indeed continue to push the limits of nature and human evolution.
In part I of this article we described the mechanisms by which growth hormone (GH) and insulin-like growth factor-I (IGF-1) exert their effects on the body. The overwhelming majority of GH’s anabolic effects are realized through IGF-1 who’s production it stimulates in the liver and other peripheral tissues. GH levels are control by the hypothalamus which can either increase or decrease GH release from the pituitary by way of growth hormone releasing hormone (GHRH) or somatostatin (SS) respectively. The interrelationship between GH levels and IGF-1 levels is called the GH/IGF-1 axis. This axis is effected not only by GHRH and SS but also through negative feedback. GH and IGF-1, once released into circulation, travel back to the hypothalamus and pituitary to stop further GH release. GH and IGF-1 may also cause autocrine and paracrine negative feedback within the very cells of the pituitary and other tissues and organs that produce the hormones.
A holistic approach to optimally stimulate skeletal muscle growth
Androgens are only one of several mechanisms by which the body regulates muscle size and strength. If the goal is to grow as much muscle as humanly possible, one would be foolish not to ignore the other hormones, growth factors, and genes responsible for human muscle development. It would be like relying solely on the carburetor to make a dragster go faster. Sure, a bigger carburetor will significantly increase potential horsepower, but it will go even faster if you can increase the compression, alter the gear ratio, use more combustible fuels, use light weight materials, improve the aerodynamics, even adding computers has shown to be invaluable to achieve maximum performance from these machines. The human body is no different with respect to the need for a multi-system approach in order to achieve maximum performance.
Despite what we now know about GH and IGF-1, androgens are, for now, going to be the primary component of any hormone regimen. Androgens rely on the androgen receptor (AR) to activate genes associated with muscle growth and remodeling. Although there is only one known androgen receptor, different androgens are able to bring about different physiological effects by virtue of their ability to stabilize the receptor.1 For example, most of you are familiar with testosterone and its 5-a -reduced sibling dihydrotestosterone (DHT) (For a more detailed discussion of enzymatic conversion of steroid hormones see, Enzymatic Conversions and Anabolic-Androgenic Steroids by Bill Roberts). It is believed that DHT is primarily responsible for male pattern balding. If their is only one AR, how come DHT is able to accelerate hair loss while plain testosterone has only minimal effects? The answer lies in the fact that DHT is able to stabilize, or remain attached to the AR much longer than testosterone. This difference in association/dissociation properties of the two androgens gives rise to their diverse effects in your body.
It is important to remember that androgens not only have physiological effects by virtue of the intracellular androgen receptor but also through steroid hormone binding proteins (SHBP). Most people will tell you that only free testosterone is biologically active. This is false. Steroid hormones have what are referred to as nongenomic actions. These effects are believed to be the result of SHBP actually embedded in the cell membrane of target tissues, thus acting as a second messenger system, similar to the way in which catecholamines work.2,3 (For a more detailed discussion of second messenger systems, see Pharmacological approaches to fat loss: Targeting the beta adrenergic receptor). It is well known among steroid specialists, and many users, that not all synthetic derivations of testosterone produce the same results, unit per unit. In fact, when not using standard testosterone products, you can achieve synergy between different drugs. One example might be to combine methandrostenolone (Dianabol) with nandrolone decanoate (Deca). Using the two together produces more gains in size and strength than dose using either alone. This is not the result of simply increasing the quantity of steroids in the system. If total units of steroid remain constant, a combination of the two drugs is more effective than either alone. The ability of steroid hormones to interact at the cell surface gives rise to the secondary effects of some drugs such as stanozolol (Winstrol) and oxymetholone (Anadrol) among others.
Another important property of androgens is their propensity to aromatize. This process involves the removal of a methyl group resulting in the conversion of testosterone into estrogens. This process is accomplished through the aromatase or P450 enzyme system (once again I would refer you to Enzymatic Conversions and Anabolic-Androgenic Steroids by Bill Roberts for more information). This may sound like something very undesirable but in reality it is critical to getting maximum growth from androgen administration.
Androgens that boost GH/IGF-1 levels
Although this isn’t exactly an article about androgens per se, they play an integral role in the modulation of GH when trying to put on more size. In order to understand this relationship we must look back to those awkward years of pimples, sore nipples, and rapid growth. No, I’m not talking about your first testosterone cycle, I’m talking about puberty. During puberty there is a disruption in your body’s ability to accurately regulate GH levels leading to increased GH, IGF-1, and insulin levels. This combined with elevated testosterone production characterizes puberty. Research has shown that this disruption is caused by the aromatization of testosterone as well as some direct actions of androgens.4,5,6,7,8 In a recent study by Fryburg9 the effects of testosterone and stanozolol were compared for their effects on stimulating GH release. Testosterone enanthate (only 3 mg per kg per week) increased GH levels by 22% and IGF-1 levels by 21% whereas oral stanozolol (0.1mg per kg per day) had no effect whatsoever on GH or IGF-1 levels. A couple of notes about this study. It was only 2-3 weeks long and although stanozolol did not effect GH or IGF-1 levels, it had a similar effect on urinary nitrogen levels. Urinary nitrogen is fraught with confounding variables when used to determine skeletal muscle anabolism and/or catabolism and thus should not be considered an accurate indicator of skeletal muscle growth. Using labeled tracer amino acids as well as 3-methylhistidine is a far more reliable way of determining actual contractile protein synthesis and breakdown respectively. Nevertheless, this study may well explain the observation that many bodybuilders do not respond as well to testosterones with complete estrogenic blockade.
Too much Cytadren or especially Arimidex will prevent gyno and probably a little water bloat, but it will also cut into your muscle gains by virtue of a less robust GH burst activity and lower subsequent IGF-1 levels. In vitro have also shown that some androgens increase muscle satellite cells sensitivity to fibroblast growth factor and IGF-1.10 Remember that satellite cells are required for a muscle cell to grow. Bovine muscle satellite cells were able to fuse 20% more readily when treated with trenbolone and estradiol.11,12 One may surmise that it was not only the trenbolone but also the estradiol that was causing the significantly increased feed efficiency and muscle growth by way of increased GH and IGF-1 production both in the liver as well as in muscle cells. From these studies it is clear that IGF-1 is critical to get maximum anabolic activity from androgens. This means that androgens that increase GH production (i.e. those that aromatize to some degree) will most likely give you the greatest and most rapid gains in muscle mass.
Which androgens are tops for BIG gains?
So the question now stands, which androgens are best with consideration to GH for maximum muscle tissue growth? Well, the answer is probably the testosterones, specifically esterified versions such as enanthate, cypionate, etc.. Esterification of the testosterone molecule increases it’s lipid solubility and leads to a more prolonged release of the drug into the blood stream after deposition in fat tissue. However, the down side to these products is there high incidence of side effects. As explained above, their ability to aromatize and thus increase GH and IGF-1 levels is, in my opinion, part of what makes them superior mass and strength drugs compared to nonaromatizable drugs such as methenolone (Primobolan), stanozolol (Winstrol), and oxandrolone (Anavar) among others. The conversion of testosterone to DHT may also be of some benefit in performance as DHT is known to alter intracellular Ca+ levels through nongenomic mechanisms (i.e. without the androgen receptor). The effect is neurological stimulation, or a sense of well being and mental endurance during intense training.
Obviously the beneficial properties of testosterone esters are inseparably linked to the negative side effects such as male pattern baldness and gyno. The very best remedy for this is to shave your head and to surgically remove the offending gyno once and for all. Surgery can even turn out to be financially cost effective when comparing the cost of real antiestrogens/aromatase inhibitors over the course of several years.
I believe that the testosterones are sufficiently anabolic to use by themselves, nevertheless, if one wanted to combine another steroid with a testosterone I would recommend trenbolone acetate because of its high affinity for the androgen receptor and its very successful application in human as well as animal husbandry (love those beefy cows). Of course, for a larger specimen of say a lean 240-250 pounds under 6 feet tall, a combination of a testosterone ester as your base (800 mg per week), and then adding Deca (300-400 mg per week) and Winstrol Depot (just enough to favorably combat the progesterone induced side effects of the Deca i.e. 50mg per day) would undoubtedly give good results but you are looking at quite a hit to the pocket book for legitimate products. All in all, you want to combine a drug that aromatizes, and then add those that don’t if you can afford it. That way you can control the side effects simply by adding complimentary antiestrogens, or if worse comes to worse, decreasing the dose of the aromatizing drug while maintaining the dose of the secondary anabolics. Each individual will be slightly different in their propensity to develop estrogen related side effects so the appropriate course of action may differ from one person to the other. If not using these drugs on a continual basis it is desirable to take a break from the testosterone esters, in which case any non-aromatizable drug would work though I think trenbolone would be a good first choice for most people. There are other sources for planning drug cycles and I would recommend you read them if you are a intermittent user (see Bill Roberts’ Anabolic Pharmacology Archives). It may be that you don’t have access to the testosterones I mentioned above. It may also be that you simply disagree with my high opinion of the testosterones. This being the case I suggest you turn to the valuable and extensive contributions of Bill Roberts to MESO-Rx for more information on other possible combinations.
Addressing unwanted side effects
When using testosterones to boost GH and thus IGF-1 it is not necessary to go completely without complimentary antiestrogens and/or estrogen antagonists. A good approach is to use a combination of aminoglutethimide (Cytadren) an aromatase inhibitor, and clomiphene (Clomid) an estrogen antagonist.
Assuming that you are not exceeding 600-800 milligrams of Testosterone per week I would suggest taking only 1/4 tablet of Cytadren, 2-3 times per day, or every 8-6 hours respectively. This may be less than would be necessary to completely block estrogen related side effects. When using an aromatase inhibitor, the idea is not to completely block aromatization, but to keep it within a reasonable rate. Clomid may also be necessary especially if taking higher doses of testosterone or exogenous IGF-1. IGF-1 is known to have lead to gyno in some cases involving the elderly.13,14 This is presumably because of its ability to co-activate estrogen receptors in breast tissue. The usual practice when taking Clomid is to take a higher dose on the first day and then reduce the dose thereafter. Like Deca, Clomid’s long half life leads to an accumulative effect when taken daily. Once again I would recommend a dosing pattern slightly below the usual. Take one 50 milligram tablet three times per day on the first day, then ½ tablet per day thereafter. If side effects become unbearable on this dosing pattern, increase the antiestrogen (i.e. Clomid) first, then the aromatase inhibitor (i.e. Cytadren).
Finally, it may be necessary to add a small bit of finasteride to the mix in the form of Proscar or Propecia. However, I would prefer that you try Nizoral combined with Minoxidil first. If that is not enough, add the finasteride. Just how much depends on how bad you are losing your hair and how much you value sexual performance. If using Proscar, try taking one half tablet (2.5 mg) per day. It isn’t necessary to take with meals. If using Propecia, just take one tablet per day.
In this the second installment of “Growing Beyond What Nature Intended” we learned that GH and IGF-1 play a complimentary role in the anabolic effects of testosterone. I am not alone in this opinion, in fact, leading researchers in the field attest that GH and thus IGF-1 are absolutely necessary for the full anabolic expression of androgens.9 This explains why some steroids simply out perform others. Those that do not interact with the GH/IGF-1 axis are not able to facilitate the anabolic activity of androgens and thus give you less than stellar gains in mass and strength. Generally, those drugs that do not aromatize will not optimally increase tissue production of IGF-1 and thus are inferior at increasing the activity of muscle satellite cells which are so critical to adaptive muscle growth.
We’re not finished yet…
Here’s what you can look forward to in the next installment of “Growing Beyond What Nature Intended”. Learn why previous reports of GH’s effects have been disappointing to say the least. Learn under which conditions that using GH in addition to androgens may be useful. Learn how IGF-1 can be used to sculpt a less than genetically gifted physique. Think you need insulin to look like a pro? Find out the truth. Finally, learn how to use thyroid medications to grow, rather than shrink, your physique. Until then, train smart and train heavy.
1. Evan T. Keller, William B. Ershler, and Chawnshang Chang. The androgen receptor: Mediator of diverse responses. Frontiers in Bioscience 1, d59-d71, March 1, 1996.
2. Rosner W., Hryb DJ., Khan MS., et al: Androgens, estrogens, and second messengers. Steroids 63:278-281, 1998
3. Wehling M. Specific, nongenomic actions of steroid hormones. Annu. Rev. Physiol. 59:365-393, 1997
4. Veldhuis JD., Metzger DL., Martha, Jr. PM., et al: Estrogen and testosterone, but not nonaromatizable androgen, direct network integration of the hypothalmo-somatotrope (growth hormone)-insulin-like growth factor axis in human: Evidence from pubertal pathophysiology and sex-steroid hormone replacement. J Clin. Endocrinol Metab. 82(10):3414-3420, 1997
5. Ulloa-Aguirre A., Blizzard RM., Garcia-Rubi E., et al: Testosterone and oxandrolone, a nonaromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life. J Clin. Endocrinol Metab. 71(4):846-854, 1990
6. Illig R., Prader A. Effect of testosterone on growth hormone secretion in patients with anorchia and delayed puberty. J Clin Endocrinol Metab 30:615-618, 1970
7. Mauras NM., Blizzard RM., Link K., et al: Augmentation of growth hormone secretion during puberty: Evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab. 64:596-601, 1987
8. Kerrigan JR., Rogol AD., The impact of gonadal steroid hormone action on growth hormone secretion during childhood and adolescence. Endocr Rev. 13:281-298, 1992
9. Fryburg DA., Weltman A., Jahn LA., et al: Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone releasing hormone-stimulated GH secretion in healthy men: Impact of gonadal steroid and GH secretory changes on metabolic outcomes. J Clin Endocrinol. Metab. 82(11):3710-37-19, 1997
10. Thompson SH., Boxhorn LK., Kong W., and Allen RE. Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor-I. Endocrinology. 124:2110-2117, 1989
11. Johnson BJ, Halstead N, White ME, Hathaway MR, DiCostanzo A, Dayton WR. Activation state of muscle satellite cells isolated from steers implanted with a combined trenbolone acetate and estradiol implant. J Anim Sci Nov;76(11):2779-86, 1998
12. Johnson BJ, White ME, Hathaway MR, Christians CJ, Dayton WR. Effect of a combined trenbolone acetate and estradiol implant on steady-state IGF-I mRNA concentrations in the liver of wethers and the longissimus muscle of steers. J Anim Sci Feb;76(2):491-7, 1998
13. Sullivan DH, Carter WJ, Warr WR, Williams LH. Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients. J Gerontol A Biol Sci Med Sci May;53(3):M183-7, 1998
14. Cohn L, Feller AG, Draper MW, Rudman IW, Rudman D. Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations. Clin Endocrinol (Oxf) Oct;39(4):417-25, 1993