HGH & thyroid

[plzr8]

i was reading over some studies @ Pubmed this week and came across two interesting studies regarding the use of synthetic growth hormone and its affect on thyroid levels....

its a been a debatable topic for some time now regarding thyroid meds & supplmentation during GH cycles as the thyroid is known to be supressed during synthetic GH use....T3 or T4? are meds needed at all?


first study was conducted on patients who are initially euthyroid...
BACKGROUND AND OBJECTIVE: There are numerous, often contradictory reports on the effects of growth hormone (GH) therapy on thyroid function. The aim of this study was to assess the effect of such therapy on serum concentrations of thyroid hormones in GH-deficient children euthyroid prior to the treatment, and to determine the necessity of thyroid hormone administration in these patients. MATERIAL AND METHODS: The study included 32 GH-deficient patients in the first stage of sexual development, in whom disorders of thyroid function could be excluded. The inclusion criteria were based on clinical examination and levels of thyroxine (T4), triiodothyronine (T3), free thyroxine (fT4), free triiodothyronine (fT3), reverse triiodothyronine (rT3), thyrotropin (TSH) before and after stimulation with thyrotropin-releasing hormone (TRH). Recombinant growth hormone (rGH) (Genotropin 16U, Pharmacia) was administered at a dose of 0.7 U/kg/week. Fasting blood samples were drawn before treatment and after 3, 6, 9 and 12 months of therapy. Thyroid hormones were measured using RIA and IRMA methods. RESULTS: There were no physical signs of hypothyroidism in the patients examined during 12 months of rGH administration, and the satisfactory growth rate was achieved. T4 levels decreased in the first 3 months but remained within the normal range, and then returned to the values prior to the treatment. A similar trend was observed for fF4, with 28.5% of patients exhibiting fF4 levels below the normal in the 3rd month. An increase during the first 3 months of therapy was observed in the cases of T3 (statistically non-significant) and fT3, and these values then fell to levels within the normal range of patients' age. During treatment, TSH levels decreased but remained within the normal range. CONCLUSIONS: A transient decrease in T4 concentrations in the 3rd month with unchanged T3 and an increase in fT3 concentrations probably result from the effect of rGH on the peripheral metabolism of thyroid hormones. The results obtained do not support the use of thyroid hormone therapy with levothyroxine during the first year of rGH therapy in patients who are initially euthyroid.
PMID: 14756384 [PubMed - indexed for MEDLINE]


second study was conducted on patients with an idiopathic isolated GH deficiency
The use of GH treatment in subjects with a GH deficiency has led to contrasting results concerning its impact to develop thyroid hyperfunction, whereas many others have underlined the possible onset of hypothyroidism. A number of studies have been carried out over short periods in subjects with multiple tropin deficiencies, in healthy adults or adults with GH deficiencies, in healthy adults or adults with GH deficiencies. The aim of the present study was to assess the effect of prolonged treatment with biosynthetic GH on thyroid function in children with an isolated idiopathic GH deficiency. The study included 8 children (mean age 10.4 +/- 0.8 years) with GH deficiencies treated with biosynthetic GH and 8 children with familial retarded stature of a similar age (mean age 10.3 +/- 0.7 years) who represented the control group. Serum levels of T3, T4, FT3, FT4 and TSH were measured at the start of the study and after one year of continuous GH treatment in subjects with GH deficiency; the same tests were performed in the control group on recruitment and after one year's observation without therapy. T4 and FT4 levels diminished, but not significantly, whereas there was a significant increase in plasma levels of T3 and FT3 (p less than 0.01); TSH values were significantly reduced in the treated group (p = 0.025). No significant variations in thyroid parameters were found in the control group. These data support the hypothesis of an increased peripheral conversion of T4 into T3 due to GH therapy; in conclusion, however, no significant variation in thyroid function was observed following GH replacement therapy, even if prolonged, in subjects with an idiopathic isolated GH deficiency.
PMID: 1495450 [PubMed - indexed for MEDLINE]



both studies seem to indicate that if there is no pre-existing thyroid problem, then meds (such as t3 or t4) should not be required to maintain a healthy thyroid during extended use of synthetic GH

reason im posting this to get some general feedback from GH users who have had their thyroid levels (T3,T4,FT3,FT4,TSH) tested either while on GH cycles, or post cycle...also with & without thyroid meds such as t3 and t4

i know this topic has been discussed several times, just curious if there have been any recent updates or threads i have overlooked from the past...after digging through several old threads of some knowledgable guys on this board, it seems some feel strongly about both sides...

ok, opening this up to discussion

[Fixr]

I have not read anything new recently, but what you have posted seems to be in stark contrast to the stickie on this topic posted by Anthony Roberts. I am very curious to hear other peoples opinions and any blood work results they might have to share.

[plzr8]

bumping for additional feedback...

[goose]

I put my hand upon my gland,Ha HA.Many paths to this answer.This is just me.I despise T4 and T3. I dont know why anyone would want to fool around with a healthy gland that is functioning normally.Its not your thyriods fault your abusing it with HGH.Afraid of a little hard work? Afraid you will not get the results with HGH unless you use T3? Using HGH in a disguise of a poor diet? Scared of the Demon under your bed with T3? Do tread mills frighten you? Rude boy who is scared of these study? Scared of yo bitch is going to screw another guy,who has a huge penis? Im scared if I dont take T3 with HGH and Im gonna die,LOL.I think the use of T3 shows alot about the individual using it.Now I'm talking in general here.Some people do have slow metabolisms due to a sluggish thyroid (not me) So a drug like T3 is advantageous for them.In the end its a risk either way,Im old school and my logic is the less drugs you use the better,I know stupid.Im going to risk HGH with no tyriod meds.Screw a study.Check out the anti-age clan that use HGH,they dont use these meds.

[plzr8]

I put my hand upon my gland,Ha HA.Many paths to this answer.This is just me.I despise T4 and T3. I dont know why anyone would want to fool around with a healthy gland that is functioning normally.Its not your thyriods fault your abusing it with HGH.Afraid of a little hard work? Afraid you will not get the results with HGH unless you use T3? Using HGH in a disguise of a poor diet? Scared of the Demon under your bed with T3? Do tread mills frighten you? Rude boy who is scared of these study? Scared of yo bitch is going to screw another guy,who has a huge penis? Im scared if I dont take T3 with HGH and Im gonna die,LOL.I think the use of T3 shows alot about the individual using it.Now I'm talking in general here.Some people do have slow metabolisms due to a sluggish thyroid (not me) So a drug like T3 is advantageous for them.In the end its a risk either way,Im old school and my logic is the less drugs you use the better,I know stupid.Im going to risk HGH with no tyriod meds.Screw a study.Check out the anti-age clan that use HGH,they dont use these meds.

appreciate the insight bud!

yah, i had decided that i was gonna start off with no thyroid meds....and if i "feel" any 'hypothyroid effects' then i would consider a t3 or t4 dosage...additionally plan to get my thyroid levels tested after 2-3 months

[goose]

Peace bro!!!! Good plan....

[MrNice]

I put my hand upon my gland,Ha HA.Many paths to this answer.This is just me.I despise T4 and T3. I dont know why anyone would want to fool around with a healthy gland that is functioning normally.Its not your thyriods fault your abusing it with HGH.Afraid of a little hard work? Afraid you will not get the results with HGH unless you use T3? Using HGH in a disguise of a poor diet? Scared of the Demon under your bed with T3? Do tread mills frighten you? Rude boy who is scared of these study? Scared of yo bitch is going to screw another guy,who has a huge penis? Im scared if I dont take T3 with HGH and Im gonna die,LOL.I think the use of T3 shows alot about the individual using it.Now I'm talking in general here.Some people do have slow metabolisms due to a sluggish thyroid (not me) So a drug like T3 is advantageous for them.In the end its a risk either way,Im old school and my logic is the less drugs you use the better,I know stupid.Im going to risk HGH with no tyriod meds.Screw a study.Check out the anti-age clan that use HGH,they dont use these meds.

I think that using thyroid meds is a much less important decision than using GH in the first place, there are studies of people regaining normal thyroid output after 30 years of thyroid replacement therapy, which to me suggests its almost impossible to suppress the thyroid, rather than the thyroid rapidly recovering after 30 years of continuous suppression.

Anyway, I think I have a slow metabolism, so when I use GH i will almost definitely use thyroid hormones...but I am a former fatty, my whole body type is definitely in favor of storing fat. (215lbs of PURE fatness at 18 y/o..seriously, I cut to 160 and was still around 18-20% bf..NO muscle whatsover!!!) and my body type is def in favor of storing fat as opposed to gaining muscle...

[goose]

With respect to these meds, for the most part what has already been expressed as the experience of most I know holds true .... you aren't going to see any radical difference one way or the other. You can make a case for some small assist with protein synthesis, and potentially a small assist with weight loss, but nothing that is going to make or break an HGH unless you have some underlying health issues to begin with.Fact is I have been using HGH for over 3 years,its garbage for me.

[MrNice]

With respect to these meds, for the most part what has already been expressed as the experience of most I know holds true .... you aren't going to see any radical difference one way or the other. You can make a case for some small assist with protein synthesis, and potentially a small assist with weight loss, but nothing that is going to make or break an HGH unless you have some underlying health issues to begin with.Fact is I have been using HGH for over 3 years,its garbage for me.

Really?

****....problem is I trust your judgement more than 99% of those I hear, and being a former psychology student I know the power of placebo so previous experience doesn't convince me.


Your opinion on HGH how have you ran it to make that opinion?

[goose]

DNP is the only time I Support the use of T3.You need the combat at any length when your dealing with the potential of those sides.I have ran HGH using both protocols,results wise the same,blood work good.So I have seen the Freudian slip from you....So you studied psychology and I have to give you respect for that? I will find a few threads on here from people who have there glands shut down for extended periods.....The weight piling on.Your attempts are a scientific endeavor,perhaps,you suffer from Dehumanization and the constant pain in your mind.

[MrNice]

shut it you ugly duckling.

My point on psychology was that I trust what you're saying cuz I know you don't sugarcoat the truth. The placebo I was speaking of is that which people may report when running GH, I mean, I wouldn't be surprised if a large majority of people running GH psychosomatically invented side-effects and results.

I didn't mean you were making things up, My point was I trusted your opinion over others who had reported great gains.

Dumbasss

[MrNice]

silly goose

[goose]

Im done here......I going to get my great mate Redbaron on this.He is number one.What he says is final,LOL......

[goose]

DONT READ THIS POST NEXT ONE!!!!!

Karl Hoffman

www.*************.net and www.avantlabs.com


One of the more commonly encountered assertions in the bodybuilding literature is that " href="http://www.steroid.com/">steroids (AAS) suppress thyroid function. What is the origin of this claim? Is it supported by evidence published in the scientific literature? And perhaps most important is it of any clinical significance, meaning if it does occur is it serious enough to worry about? Before reviewing the evidence for and against AAS induced thyroid impairment a short review of thyroid physiology is probably in order.

The thyroid gland secretes principally the hormone thyroxine (T4) along with small amounts of triiodothyronine (T3). The majority of the " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 by the enzyme deiodinase. Most of this transformation takes place in the " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=42">estrogen s are bound to sex hormone binding globulin (SHBG), most of the thyroid hormone in circulation is bound to thyroid binding globulin (TBG). And as with SHBG and sex hormones, the levels of TBG influence the levels of total thyroid hormone in circulation. If TBG is ***ressed, total T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 and T4 that remain unbound to TBG (0.05% of T4 and 0.5% of " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 if TBG is low, but still have normal levels of free " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 is normal. Similarly when TBG is elevated total T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 levels. These include " href="http://www.steroid.com/">steroids. So to recap, if a person were using AAS and had their total T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 and T4 are low. This observation will be critical to our discussion of the effects of AAS on the thyroid gland. In a similar vein, a woman using OC might have elevated T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 is inadequate because these values are strongly influenced by TBG levels. Other laboratory tests are required to determine whether low T4, say, is being caused by actual hypothyroidism, or reflects the use of a drug that is simply lowering TBG. One such test is the thyroid hormone binding ratio (THBR; T3 resin uptake). This test is essentially a measure of the number of TBG sites that are occupied by thyroid hormone. In a person who is hyperthyroid (high T4) there are fewer unbound TBG sites/more occupied sites (since obviously there is more thyroid hormone available to bind to them). In this case " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 resin uptake is low. In the case where thyroid function is normal but TBG is elevated (oral contraceptives) it turns out " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 resin uptake reading HIGH.

We can tabulate these various possible outcomes to give a clearer picture of how these two tests can be used to distinguish thyroid dysfunction from mere altered levels of TBG:


<DIV align=center>SERUM T4<B>SERUM " href="http://www.steroid.com/inject.php">injection of synthetic TRH is administered. The body’s normal response is to secrete increased levels of TSH up to a peak at 20 minutes and then to decrease TSH secretion. In hyperthyroidism, TSH is being suppressed by circulating thyroid hormones so there is a suppressed response to TRH. In primary hypothyroidism, which is due to thyroid dysfunction with normal pituitary function, levels of thyroid hormones are very low and TSH levels are ordinarily raised; however, TSH increases greatly on TRH stimulation yielding an exaggerated response - it reaches a higher peak and does not decline for over an hour. In secondary hypothyroidism (where the pituitary is malfunctioning, not the thyroid) it doesn't matter how much TRH there is, the pituitary cannot make TSH so there is an absent response to TRH stimulation.

Now that we have reviewed the elements of thyroid physiology and gone over the basic tests to determine thyroid function, we are ready to review the literature regarding the effects of " href="http://www.steroid.com/">steroids on the thyroid. At the beginning of this review, we asked the question “what is the origin of the claim that AAS impair the thyroid?” The answer perhaps lies in a 1993 paper by Deyssig & Weissel (1). The authors looked at the effects of self-administered AAS use in an admittedly small group of five bodybuilders. Eight additional subjects served as controls. In the AAS using group, total T4, Total " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 with no effect on the free hormone levels and hence no effect on TSH. Indeed in this study there was no difference in free T4 and TSH between the AAS group and the controls. Basal free " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 response was significantly lower in the AAS group. Recall that in hypothyroidism there is an exaggerated TSH response to TRH. Quoting from the study, “These " href="http://www.steroid.com/">anabolic " href="http://www.steroid.com/">steroids, as are used by some athletes, may impair thyroid function to an extent that is not clinically detectable and probably not relevant.” (Italics added.)

Moreover, when one scrutinizes the data, one sees that out of the five AAS-using subjects, only two had stimulated TSH values higher than the controls, one was only marginally but not significantly higher than in controls, and two had stimulated TSH values in the control range. In addition, no pre-study baseline stimulated TSH values were measured in any subjects. One could argue these facts call into question the authors’ conclusions of “mild impairment of thyroid function”.

How high were the “high doses” used by the participants? The subjects were using a number of different AAS including " href="http://www.steroid.com/Dianabol.php">Dianabol, stacking them as bodybuilders typically do. The average total dose for all drugs combined was 1.26 grams/week, with a range of 740 – 1950 mg/week.

Alen et. al. (2) conducted a study along similar lines. Seven power athletes " href="http://www.steroid.com/Testosterone-Enanthate.php">testosterone, Dianabol, stanozolol, and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3, total T4 and TBG were all ***ressed during the study period, while " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3, which is reflected in the elevated T3U-values [T3 resin uptake]. Increased availability of T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3. The measurements of thyroid function parameters performed support this reasoning. In general our findings suggest that thyroid hormones at the cellular level were not disturbed in our athletes.

While the approximate 20% drop in free T4 observed by Alen et al is suggestive of some degree of thyroid impairment, the consequences of this need to be interpreted carefully. First, free T4 stayed well within the normal range. Second, since free " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3, the metabolically active hormone. Lum et al. have shown that when serum T4 levels drop, the body upregulates the peripheral conversion of T4 to " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 could have been significantly smaller than the observed 20% drop in free T4.

We see here contradictory findings between the two studies discussed so far as regards TSH levels: Deyssig & Weissel observed no change in unstimulated TSH levels, while Alen et al observed a decline in TSH, although the values remained well inside the normal range. The finding consistent between the two studies is the AAS suppressed TBG and the consequent decline in total T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 resin uptake observed by Alen but not measured by Deyssig. Again, quoting from (2): “In relation to the changes in thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis.”

In a third study, this time performed by Malarkey et al in AAS-using females, the authors looked at Total T4, FreeT4, TSH, and TBG (4). The authors observed that

Thyroxine-binding proteins also were decreased in the " href="http://www.steroid.com/">anabolic " href="http://www.steroid.com/">anabolic " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=42">estrogen , and " href="http://www.steroid.com/Testosterone-Enanthate.php">testosterone would be expected to have only a minor effect, the increased androgen and " href="http://www.steroid.com/Anavar.php">oxandrolone group showed a significant decrease in T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 resin uptake is characteristic of hypothyroidism. This is the conclusion the authors arrived at as well, that the " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 resin uptake were low relative to placebo the values fell within the normal range, making the diagnosis of “hypothyroidism” a relative one rather than a clinical one. Clinically all subjects would be classified as euthyroid. And as in the other studies the authors here concluded “these changes were most likely due to the effects of sex " href="http://www.steroid.com/Anavar.php">oxandrolone group than either the placebo or " href="http://www.steroid.com/Methyltestosterone.php">methyltestosterone administration to normal subjects (6). The researchers found that total T4, total " href="http://www.steroid.com/Winstrol.php">stanozolol, another nonaromatizing " href="http://www.steroid.com/Testosterone-Enanthate.php">testosterone by 50% and LH by 30%. TBG, T4 and " href="http://www.steroid.com/">anabolic " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 and T4 fell as a result of the reductions in TBG levels. The lack of change in TSH or Free T4 indicates that important physiological changes of thyroid function do not occur during treatment with " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 and increases in " href="http://www.steroid.com/Trenbolone-Acetate.php">trenbolone in particular suppresses thyroid function was done in sheep (9). However, in this study only total T4 was measured, not free T4, so we cannot conclude from this research that bioavailable " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 and T4, and TBG. As we have discussed, androgens typically lower TBG, along with total T4 and " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 and TBG. If there is a direct effect of AAS on the thyroid, pituitary, or hypothalamus the studies conducted so far shed little light on the mechanism due to their inconsistent results. And as stressed by Deyssig & Weissel any direct effect of " href="http://www.steroid.com/">steroids on the thyroid would likely be of no clinical significance due to its small magnitude.

From a practical standpoint for those concerned that " href="http://www.steroid.com/">steroids might suppress the thyroid it is a simple matter to incorporate low dose (25 to 50 mcg/day) T3 into a " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 alone while the other was given a combination of " href="http://www.steroid.com/Testosterone-Enanthate.php">testosterone enanthate, 200 mg/week. After 28 days of bed rest, the men in the " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 plus " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3 group, whereas the " href="http://www.steroid.com/Testosterone-Enanthate.php">testosterone-treated subjects experienced nearly a 2-kg increase in lean mass (i.e. 1.7 ± 0.9 kg). Of course we don’t know how much mass the test plus " href="http://www.ar-r.com/shop/product_info.php?cPath=23&products_id=92">T3. Nevertheless these are still impressive gains considering the subjects were forced to lie in bed for 28 days with no exercise, and considering that no special dietary measures were imposed to preserve or increase muscle mass.


References:

(1) Deyssig R, Weissel M. Ingestion of androgenic-anabolic " href="http://www.steroid.com/">steroid effects on serum thyroid, pituitary and " href="http://www.steroid.com/Testosterone-Enanthate.php">testosterone and " href="http://www.steroid.com/">steroids. Am J Obstet Gynecol. 1991 Nov;165(5 Pt 1):1385-90.

(5) Lovejoy JC, Bray GA, Greeson CS, Klemperer M, Morris J, Partington C, Tulley R. Oral " href="http://www.steroid.com/">anabolic steroid administration in male normal volunteers. Psychoneuroendocrinology. 2003 Apr;28(3):317-31

(7) Small M, Beastall GH, Semple CG, Cowan RA, Forbes CD. Alteration of hormone levels in normal males given the " href="http://www.steroid.com/Winstrol.php">stanozolol. Clin Endocrinol (Oxf). 1984 Jul;21(1):49-55

(8) Spitz IM, Margalioth EJ, Yeger Y, Livshin Y, Zylber-Haran E, Shilo S. Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure. Horm Metab Res. 1984 Sep;16(9):492-7.

(9) Donaldson IA, Hart IC, Heitzman RJ. Growth hormone, insulin, prolactin and total thyroxine in the plasma of sheep implanted with the " href="http://www.steroid.com/Trenbolone-Acetate.php">trenbolone acetate alone or with oestradiol. Res Vet Sci. 1981 Jan;30(1):7-13.

(10) Zachwieja JJ, Smith SR, Lovejoy JC, Rood JC, Windhauser MM, Bray GA. Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest. J Clin Endocrinol Metab. 1999 Jan;84(1):207-12</P>

[goose]

Karl Hoffman
www.*************.net and www.avantlabs.com

One of the more commonly encountered assertions in the bodybuilding literature is that anabolic steroids (AAS) suppress thyroid function. What is the origin of this claim? Is it supported by evidence published in the scientific literature? And perhaps most important is it of any clinical significance, meaning if it does occur is it serious enough to worry about? Before reviewing the evidence for and against AAS induced thyroid impairment a short review of thyroid physiology is probably in order.
The thyroid gland secretes principally the hormone thyroxine (T4) along with small amounts of triiodothyronine (T3). The majority of the T3 in the circulation (about 80%) is formed from the conversion of T4 to T3 by the enzyme deiodinase. Most of this transformation takes place in the liver and kidney. T3 is considered the physiologically active hormone; in this sense T4 can be thought of as a prohormone.
The production within and secretion from the thyroid gland of T4 is under the control of Thyroid Stimulating Hormone (TSH), which is secreted from the pituitary gland. Higher levels of TSH lead to higher rates of hormone production and secretion from the thyroid. TSH in turn is regulated by another hormone secreted from the hypothalamus, thyrotropin-releasing hormone (TRH). TSH levels are also regulated in a negative feedback manner by the levels of circulating thyroid hormone. If extra hormone is administered, transcription of the TSH gene is decreased and less TSH is produced by the pituitary, leading to suppression of natural thyroid hormone production. Similarly, a decrease in the rate of thyroid hormone secretion leads to enhanced TSH production in an attempt to return to homeostasis.
Just as the bulk of circulating androgens and estrogens are bound to sex hormone binding globulin (SHBG), most of the thyroid hormone in circulation is bound to thyroid binding globulin (TBG). And as with SHBG and sex hormones, the levels of TBG influence the levels of total thyroid hormone in circulation. If TBG is ***ressed, total T4 and T3 levels will go down. An increase in TBG leads to higher values of total thyroid hormone. Note however that the small percentage of T3 and T4 that remain unbound to TBG (0.05% of T4 and 0.5% of T3), the so-called free fraction, is the portion considered physiologically active. So it is quite possible to have lowered total T3 if TBG is low, but still have normal levels of free T3. This condition is not indicative of thyroidal impairment since the bioactive free T3 is normal. Similarly when TBG is elevated total T4 and T3 are high, again with the possibility that physiologically active free hormone levels remain normal.
A number of drugs and medical conditions are capable of elevating TBG and hence total T4 and T3 levels. These include estrogen, oral contraceptives (OC), pregnancy, acute infectious hepatitis, and cirrhosis. Likewise there are drugs and medical conditions that lower TBG. These include cortisol, growth hormone, and very important to this discussion, anabolic steroids. So to recap, if a person were using AAS and had their total T4 and T3 measured, because TBG is low, those total values would register as low, but that would not necessarily mean that the bioactive (free) levels of T3 and T4 are low. This observation will be critical to our discussion of the effects of AAS on the thyroid gland. In a similar vein, a woman using OC might have elevated T4 and T3 because oral contraceptives raise TBG. This would not necessarily warrant a diagnosis of hyperthyroidism, as her free thyroid levels could be perfectly normal.
So we see that in order to assess thyroid function, measuring only the total T4 and/or T3 is inadequate because these values are strongly influenced by TBG levels. Other laboratory tests are required to determine whether low T4, say, is being caused by actual hypothyroidism, or reflects the use of a drug that is simply lowering TBG. One such test is the thyroid hormone binding ratio (THBR; T3 resin uptake). This test is essentially a measure of the number of TBG sites that are occupied by thyroid hormone. In a person who is hyperthyroid (high T4) there are fewer unbound TBG sites/more occupied sites (since obviously there is more thyroid hormone available to bind to them). In this case T3 resin uptake is high. Conversely, in hypothyroidism there are fewer occupied TBG binding sites, and T3 resin uptake is low. In the case where thyroid function is normal but TBG is elevated (oral contraceptives) it turns out T3 resin uptake registers LOW; conversely when TBG is lowered (AAS use), a lab report would show T3 resin uptake reading HIGH.
We can tabulate these various possible outcomes to give a clearer picture of how these two tests can be used to distinguish thyroid dysfunction from mere altered levels of TBG:

SERUM T4SERUM T3T3 RESIN UPTAKEHyperthyroidismHighHighHighHypothyroidismLow LowLowNormal, on OCHighHighLowNormal, on AASLowLowHigh
TABLE 1

Perhaps the test most commonly performed test to determine thyroid status measures Thyroid Stimulating Hormone (TSH) levels. Typically in hypothyroidism, the thyroid is not secreting adequate levels of T4, and in an attempt to stimulate the thyroid, the pituitary secretes excess TSH. So in hypothyroidism, TSH is HIGH. The opposite is observed in hyperthyroidism: the excess thyroid hormone in circulation acts back on the pituitary to suppress TSH production. TSH is LOW in hyperthyroidism.
The above applies to so-called primary hypothyroidism/hyperthyroidism where the thyroid gland itself is malfunctioning. In secondary hyper/hypothyroidism the problem lies at the levels of the pituitary or hypothalamus. In this case the pituitary secretes insufficient TSH to stimulate the thyroid, resulting in hypothyroidism with low TSH. In secondary hyperthyroidism the pituitary secretes excess TSH, resulting in hyperthyroidism associated with elevated TSH.
Before the advent of highly sensitive TSH assays, it was common to perform a TRH challenge test. Recall the hypothalamus secretes TRH, in turn stimulating the pituitary to secrete TSH. In the TRH test, a bolus injection of synthetic TRH is administered. The body’s normal response is to secrete increased levels of TSH up to a peak at 20 minutes and then to decrease TSH secretion. In hyperthyroidism, TSH is being suppressed by circulating thyroid hormones so there is a suppressed response to TRH. In primary hypothyroidism, which is due to thyroid dysfunction with normal pituitary function, levels of thyroid hormones are very low and TSH levels are ordinarily raised; however, TSH increases greatly on TRH stimulation yielding an exaggerated response - it reaches a higher peak and does not decline for over an hour. In secondary hypothyroidism (where the pituitary is malfunctioning, not the thyroid) it doesn't matter how much TRH there is, the pituitary cannot make TSH so there is an absent response to TRH stimulation.
Now that we have reviewed the elements of thyroid physiology and gone over the basic tests to determine thyroid function, we are ready to review the literature regarding the effects of anabolic steroids on the thyroid. At the beginning of this review, we asked the question “what is the origin of the claim that AAS impair the thyroid?” The answer perhaps lies in a 1993 paper by Deyssig & Weissel (1). The authors looked at the effects of self-administered AAS use in an admittedly small group of five bodybuilders. Eight additional subjects served as controls. In the AAS using group, total T4, Total T3, and TBG were ***ressed relative to the control group. Recall this is consistent with the widespread observation that by lowering TBG, AAS lower total T4 and total T3 with no effect on the free hormone levels and hence no effect on TSH. Indeed in this study there was no difference in free T4 and TSH between the AAS group and the controls. Basal free T3 was not measured. So far everything is consistent with normal thyroid function accompanied by AAS induced ***ression of TBG.
The authors next performed a TRH test. Upon administration of THR, TSH values climbed significantly higher in the AAS group, and the T3 response was significantly lower in the AAS group. Recall that in hypothyroidism there is an exaggerated TSH response to TRH. Quoting from the study, “These T3 and TSH reactions to TRH point to a mild impairment of thyroid function as a consequence of the use of anabolic steroids.” However, stressing the fact that all unstimulated parameters were consistent with the simple suppression of TBG by AAS, the authors conclude that “the results of our cross-sectional study show that high doses of androgenic-anabolic steroids, as are used by some athletes, may impair thyroid function to an extent that is not clinically detectable and probably not relevant.” (Italics added.)
Moreover, when one scrutinizes the data, one sees that out of the five AAS-using subjects, only two had stimulated TSH values higher than the controls, one was only marginally but not significantly higher than in controls, and two had stimulated TSH values in the control range. In addition, no pre-study baseline stimulated TSH values were measured in any subjects. One could argue these facts call into question the authors’ conclusions of “mild impairment of thyroid function”.
How high were the “high doses” used by the participants? The subjects were using a number of different AAS including testosterone, nandrolone, stanozolol, and Dianabol, stacking them as bodybuilders typically do. The average total dose for all drugs combined was 1.26 grams/week, with a range of 740 – 1950 mg/week.
Alen et. al. (2) conducted a study along similar lines. Seven power athletes stacking testosterone, Dianabol, stanozolol, and nandrolone were monitored for (among other things) thyroid function during a 12 week period. In this study, total T3, total T4 and TBG were all ***ressed during the study period, while T3 resin uptake was elevated. All of these changes are again consistent with AAS induced suppression of TBG, with no direct effect on thyroid function. Interestingly, TSH dropped during the first 8 weeks of the study, and then began to climb. Free T4 dropped marginally but stayed within the normal range. The authors interpreted the data thusly:
It is tempting to suggest that decreases in serum TBG led to decreased protein binding of the thyroid hormones, T4 and T3, which is reflected in the elevated T3U-values [T3 resin uptake]. Increased availability of T4 and T3 would then lead to a compensatory decrease in serum TSH, and this, via decreased thyroid stimulation, would further decrease total concentrations of circulating T4 and T3. The measurements of thyroid function parameters performed support this reasoning. In general our findings suggest that thyroid hormones at the cellular level were not disturbed in our athletes.
While the approximate 20% drop in free T4 observed by Alen et al is suggestive of some degree of thyroid impairment, the consequences of this need to be interpreted carefully. First, free T4 stayed well within the normal range. Second, since free T3 was not measured, we do not know if there was any change in free T3, the metabolically active hormone. Lum et al. have shown that when serum T4 levels drop, the body upregulates the peripheral conversion of T4 to T3, maintaining metabolic homeostasis (3). So it is possible that any drop in free T3 could have been significantly smaller than the observed 20% drop in free T4.
We see here contradictory findings between the two studies discussed so far as regards TSH levels: Deyssig & Weissel observed no change in unstimulated TSH levels, while Alen et al observed a decline in TSH, although the values remained well inside the normal range. The finding consistent between the two studies is the AAS suppressed TBG and the consequent decline in total T4 and T3, and an increase in T3 resin uptake observed by Alen but not measured by Deyssig. Again, quoting from (2): “In relation to the changes in thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis.”
In a third study, this time performed by Malarkey et al in AAS-using females, the authors looked at Total T4, FreeT4, TSH, and TBG (4). The authors observed that
Thyroxine-binding proteins also were decreased in the steroid users, as reflected by the low thyroxine binding index and the decrease in total serum thyroxine levels. These latter changes had no significant influence on the biological activity of thyroid hormone, however, because the free thyroxine concentration and the thyroid stimulating hormone level were within normal limits. These findings are similar to those of a previous report of decreased thyroxine-binding globulin in men who were using anabolic steroids [2].
Note here though that while TSH was “within normal limits” it was nevertheless elevated significantly compared to controls (2.5 mU/L vs 0.8 mU/L).
The difference between this study and the previous one by Alen is that in (4) free T4 was unchanged, while in (2) there was a drop in free T4. Also here TSH was elevated in the AAS users while in Alen et al it was ***ressed. In the current study the combination of normal free T4 but elevated TSH is suggestive of subclinical hypothyroidism. However, to truly meet the criteria required for that diagnosis TSH would have to be elevated above 5.0 mU/L (although some physicians have argued that that threshold should be lowered). Technically, these subjects would be considered euthyroid (normal).
One criticism of the studies examined thus far is that in each case the subjects used a cocktail of anabolic steroids, including ones that aromatize and others that do not. Might there be a difference in the thyroidal effects of the two classes of drugs? A study by Lovejoy et al (5) addressed that question as part of research looking at the broader differences between the metabolic effects of oral (oxandrolone) and parenteral (testosterone) steroids. Lovejoy’s group administered each drug separately to groups of subjects. Testosterone aromatizes to estrogen, and estrogen has an opposite effect on TBG from pure androgens: the former elevates TBG while the latter lowers it. If the primary effects of AAS on measured thyroid parameters result from changes in TBG, then testosterone would be expected to have only a minor effect, the increased androgen and estrogen levels tending to cancel each other’s effects. Indeed this was the case in (5). Testosterone had no significant effect on any parameter measured (T4; TSH; T3 resin uptake; or free thyroxine index, a calculated measure of free T4).
Oxandrolone on the other hand does not aromatize. The oxandrolone group showed a significant decrease in T4 and T3 resin uptake, with no change in TSH. Referring to Table 1 above, we see that the combination of low T4 and low T3 resin uptake is characteristic of hypothyroidism. This is the conclusion the authors arrived at as well, that the oxandrolone group experienced mild hypothyroidism. Again, as in the study by Deyssig & Weissel, even though T4 and T3 resin uptake were low relative to placebo the values fell within the normal range, making the diagnosis of “hypothyroidism” a relative one rather than a clinical one. Clinically all subjects would be classified as euthyroid. And as in the other studies the authors here concluded “these changes were most likely due to the effects of sex steroids on thyroid binding globulin (TBG).” The authors also observed that the Free T4 Index was higher in the oxandrolone group than either the placebo or testosterone groups.
A recent study looked at the effects of short-term methyltestosterone administration to normal subjects (6). The researchers found that total T4, total T3, and TBG were lowered, as we have come to expect. However, TSH and free T4 were elevated as well compared to the subjects’ baseline values. Again all hormone values remained within the normal range. The authors speculate that the elevated TSH and free T4 could be due to increased sensitivity of the thyroid to TRH or decreased sensitivity to hormonal feedback, suggesting some form of mild impaired thyroid function. As with the study by Deyssig, if this functional impairment were real, it would be subclinical and of dubious relevance. Note also that the elevated TSH measured by Daly et al differs from the ***ressed TSH observed by Alen et al. Daly et al speculate that this may be due to the fact that they sampled blood after six days vs 4 weeks and longer in the study by Alen et al.
A 1984 study by Small et al examined the effects of 10 mg daily of stanozolol, another nonaromatizing steroid, for 14 days in nine healthy subjects (7). This dosage was enough to lower testosterone by 50% and LH by 30%. TBG, T4 and T3 were lowered significantly, with no change in free T4 or TSH. This is the “standard model” of action of androgens on thyroid parameters stressed in endocrinology texts: no change in thyroid function, merely a lowering of TBG with the expected lowering of total thyroid hormone levels, but no effect on the physiologically relevant free hormone levels. To quote from the study,
“The changes found in thyroid hormones are in accord with the well known effects of anabolic steroids on thyroid function tests. Both T3 and T4 fell as a result of the reductions in TBG levels. The lack of change in TSH or Free T4 indicates that important physiological changes of thyroid function do not occur during treatment with stanozolol.”

We can summarize the results of the studies for comparative purposes by tabulating the data in Fig 2.

T4T3TSHT3 resin uptakeFree T4TBGDeyssiglowlow0-0lowAlenlowlowlowhighlowlowLovejoy (test)0-000-Lovejoy (ox)low-0lowhigh-Malarkeylow-high-0lowDalylowlowhigh-highlowSmalllowlow0-0low
Table 2. Summary of measured thyroid parameters ( 0, no change; - unmeasured; )

Fluoxymesterone at 10 mg per day caused the by now familiar drop in TBG and total thyroid hormone levels with no effect on free parameters (8). Quoting from this study,
“Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged.”
Thus far we have looked at studies involving humans. One study that is often cited in the bodybuilding literature as evidence that trenbolone in particular suppresses thyroid function was done in sheep (9). However, in this study only total T4 was measured, not free T4, so we cannot conclude from this research that bioavailable T3 was affected in any way.
Can we make any sense out of the seeming hodgepodge of conflicting data? The only parameters that are consistent from study to study, where they were measured, are ***ressed total T3 and T4, and TBG. As we have discussed, androgens typically lower TBG, along with total T4 and T3 since the latter are a function of TBG levels. This however does not necessarily reflect thyroid dysfunction since the physiologically significant free fractions of these hormones typically remain in the normal range. If TBG levels change rapidly, however, a period of disequilibrium will exist during which thyroid function will be perturbed. This could explain the low free T4 and TSH observed by Alen as follows: The abrupt drop in TBG leads to a drop in bound T4, but free T4 remains elevated. This causes a shift in hormone from the blood to tissues because of a steeper free T4 concentration gradient. This increases the degradation rate of hormone in peripheral tissues. The increased tissue concentration of T4 signals the pituitary to lower TSH production, which will be reflected by temporarily lowered free T4 until the appropriate thyroid hormone/TBG ratio, and plasma/tissue ratio is reestablished. Alen et al discuss this possibility, and the process is illustrated graphically here:

http://www.thyroidmanager.org/Chapter5/5a-frame.htm
In conclusion then AAS seem to have little if any effect on thyroid function per se. The reports by Deyssig & Weissel, and Daly et al suggest the possibility of a direct action of AAS on the thyroid or pituitary, but their results are inconsistent: The former researchers detected elevated stimulated TSH while the latter saw an increase in basal TSH. Free T4 was unchanged in former group, while it was elevated in the latter. The only consistently reported effect is a ***ression in total T4, total T3 and TBG. If there is a direct effect of AAS on the thyroid, pituitary, or hypothalamus the studies conducted so far shed little light on the mechanism due to their inconsistent results. And as stressed by Deyssig & Weissel any direct effect of anabolic steroids on the thyroid would likely be of no clinical significance due to its small magnitude.
From a practical standpoint for those concerned that anabolic steroids might suppress the thyroid it is a simple matter to incorporate low dose (25 to 50 mcg/day) T3 into a cycle to enhance fat loss while at the same time only minimally if it all compromising gains in muscle mass (10). In (10) one group of subjects was given T3 alone while the other was given a combination of T3 and testosterone enanthate, 200 mg/week. After 28 days of bed rest, the men in the T3 group lost an average of 3.9 kg of body weight (i.e. from 82.0 ± 7.1 to 78.1 ± 7.1 kg). Body weight in the T3 plus testosterone-treated subjects declined by only 1.0 kg (78.9 ± 4.9 to 77.9 ± 4.9 kg). Lean body mass declined by 1.5 kg in the T3 group, whereas the T3 plus testosterone-treated subjects experienced nearly a 2-kg increase in lean mass (i.e. 1.7 ± 0.9 kg). Of course we don’t know how much mass the test plus T3 group would have gained had they foregone the T3. Nevertheless these are still impressive gains considering the subjects were forced to lie in bed for 28 days with no exercise, and considering that no special dietary measures were imposed to preserve or increase muscle mass.

References:
(1) Deyssig R, Weissel M. Ingestion of androgenic-anabolic steroids induces mild thyroidal impairment in male body builders. J Clin Endocrinol Metab. 1993 Apr;76(4):1069-71
(2) Alen M, Rahkila P, Reinila M, Vihko R. Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes. Am J Sports Med. 1987 Jul-Aug;15(4):357-61
(3) Lum SM, Nicoloff JT, Spencer CA, Kaptein EM Peripheral tissue mechanism for maintenance of serum triiodothyronine values in a thyroxine-deficient state in man. J Clin Invest. 1984 Feb;73(2):570-5.
(4) Malarkey WB, Strauss RH, Leizman DJ, Liggett M, Demers LM. Endocrine effects in female weight lifters who self-administer testosterone and anabolic steroids. Am J Obstet Gynecol. 1991 Nov;165(5 Pt 1):1385-90.
(5) Lovejoy JC, Bray GA, Greeson CS, Klemperer M, Morris J, Partington C, Tulley R. Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases a**ominal fat in obese, older men Int J Obes Relat Metab Disord. 1995 Sep;19(9):614-24.
(6) Daly RC, Su TP, Schmidt PJ, Pagliaro M, Pickar D, Rubinow DR. Neuroendocrine and behavioral effects of high-dose anabolic steroid administration in male normal volunteers. Psychoneuroendocrinology. 2003 Apr;28(3):317-31
(7) Small M, Beastall GH, Semple CG, Cowan RA, Forbes CD. Alteration of hormone levels in normal males given the anabolic steroid stanozolol. Clin Endocrinol (Oxf). 1984 Jul;21(1):49-55
(8) Spitz IM, Margalioth EJ, Yeger Y, Livshin Y, Zylber-Haran E, Shilo S. Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure. Horm Metab Res. 1984 Sep;16(9):492-7.
(9) Donaldson IA, Hart IC, Heitzman RJ. Growth hormone, insulin, prolactin and total thyroxine in the plasma of sheep implanted with the anabolic steroid trenbolone acetate alone or with oestradiol. Res Vet Sci. 1981 Jan;30(1):7-13.
(10) Zachwieja JJ, Smith SR, Lovejoy JC, Rood JC, Windhauser MM, Bray GA. Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest. J Clin Endocrinol Metab. 1999 Jan;84(1):207-12

[goose]

This helps your case MR nice!!


Few Common Bodybuilding Myths
by Karl Hoffman
www.*************.net and www.avantlabs.com

Based on my experience of having been either a moderator or administrator on three Anabolic Fitness boards, I’ve put together a collection of what I feel are, for lack of a better term, a few of the most prevalent “bodybuilding myths.” These are topics that are discussed often and at great length, usually accompanied by much misinformation. In some cases “myth” might be an inappropriate term. A better term might be “bodybuilding dogma based on little or no evidence.” Some might even argue that is unfair in some cases, and that these are simply “controversial topics.” These are not myths held by the general public about bodybuilders and drugs, such as “anabolic steroids invariably cause ‘roid rage,’ or anabolic steroids lead to permanent impotence. They are rather what I believe are widespread misconceptions within the bodybuilding community itself about problems encountered and practices employed by the participants themselves.

ESTROGENIC FAT
Estrogen makes a person fat, doesn’t it? Well, women do have a higher body fat content in general than do men, especially in the gluteofemoral (hips and buttocks) region. Is estrogen really the cause of this gender dimorphism in adiposity? Probably not. In fact, there are a wealth of data that implicate estrogen as both an anorectic and antiadipogenic hormone. It is much more likely that progesterone is the culprit in supporting higher levels of gluteofemoral fat in women (1). The model described in (1) has progesterone as the lipogenic hormone. Before menopause, both estrodiol and progesterone are secreted by the ovaries. After menopause, estrone becomes the primary circulating estrogen produced from aromatization of adrenal androgens (primarily the aromatization of androstenedione to estrone by adipose tissue), while progesterone levels drop dramatically since adrenal production of progesterone is minimal.
In premenopausal women, progesterone increases lipoprotein lipase activity, which is greater in the gluteofemoral region, while estrogen suppresses it. Lipoprotein lipase is the body’s primary fat storage enzyme; it is responsible for allowing fats to leave the circulation and enter adipocytes. The progesterone wins out however and before menopause, women tend to have more gluteofemoral fat and less a**ominal fat.
Why do women have more gluteofemoral fat while men have more central (a**ominal) fat? One popular theory is that women hold fat in the gluteofemoral region where it is far removed from the liver and has fewer fat mobilizing enzymes/more fat retaining enzymes than in men. Men hold fat in the visceral and a**ominal subcutaneous region where it is closer to the liver and richer in fat mobilizing enzymes. Proximity to the liver is a factor because the portal circulation connects a**ominal fat ***osits directly to the liver. Free fatty acids released from a**ominal ***osits can act directly on the liver to promote gluconeogenesis, providing the body with a ready supply of glucose for “fight or flight” situations.
From an adaptational viewpoint, women's fat is designed to be stored until needed for lactation and child rearing. Men's fat on the other hand is designed to be readily mobilized for fight or flight situations during defense and hunting. This theory may be a bit simplistic as well as sexist; but it does make sense to some degree.
Most likely the notion of estrogenic fat originated from the belief that estrogen upregulates alpha 2 receptors in fat cells, retarding lipolysis. This may be just one facet of estrogen’s actions. If one looks at the net result of estrogen’s effects, to quote a leading expert in the field
“Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Oestrogens seem to exert net effects similar to those of testosterone.” (2)
For example, animal studies have shown that testosterone promotes alpha 2 adrenoreceptor mediated antilipolytic activity, just as it promotes beta adrenoreceptor mediated lipolysis.
Interestingly, recent research has even attributed at least part of testosterone's fat burning properties to its local aromatization to estradiol (3). For instance when testosterone is administered along with an aromatase inhibitor, LPL activity increases, showing that the testosterone itself is devoid of any ability to lower LPL. (4)
There are a number of animal studies where estradiol administration led to significant weight and fat loss. Citing just one, for example:
"The administration of 17 beta-estradiol (500 micrograms/kg, 2 or 4 weeks) to male rats significantly reduced the body weight...Basal lipolysis and adren****e-induced lipolysis [due to increase in HSL action] were also significantly enhanced in the epididymal adipose tissue from the male rat treated either with 7 mg/kg estradiol 12 h ahead or with 500 micrograms/kg estradiol for 2 weeks. These results indicate that estradiol exerts strong effects on metabolism of the adipose and these effects seems to be mediated through cyclic-AMP." (5)
This research indicates that in addition to the abovementioned inhibition of LPL, estrogen also stimulates the lipolytic enzyme hormone sensitive lipase.
Some of the most compelling evidence for the antiadipogenic effect of estrogen in both males and females comes from studies of estrogen receptor knockout mice and humans with aromatase deficiency. Both the afflicted humans and the knockout mice exhibit obesity. A detailed look at this topic can be found here:


I also mentioned that estrogen is a potent hunger-suppressing hormone. Research is a bit sketchier here, but the effect is thought to be due to an estrogen-induced inhibition in melanin-concentrating hormone (MCH) sign****g (6). MCH is a neuropeptide found in the hypothalamus that is also thought to be involved in leptin’s regulation of appetite. Leptin, an anorectic hormone secreted from the adipose tissue, acts on the specific receptor present on its target neurons in the brain, and suppresses the expression of both MCH and its receptor. So we see that the actions of both estrogen and leptin are at least partly mediated through interactions with MCH.

LONG TERM USE OF T3 WILL ULTIMATELY DAMAGE YOUR THYROID
This notion was dispensed with in Mind & Muscle #10. Here is a brief recap of the relevant findings.
The first study that looked at thyroid function and recovery under the influence of exogenous thyroid hormone was undertaken by Greer (7). He looked at patients who were misdiagnosed as being hypothyroid and put on thyroid hormone replacement for as long as 30 years. When the medication was withdrawn, their thyroids quickly returned to normal.
Here is a remark about Greer's classic paper from a later author:
"In 1951, Greer reported the pattern of recovery of thyroid function after stopping suppressive treatment with thyroid hormone in euthyroid [normal] subjects based on sequential measurements of their thyroidal uptake of radioiodine. He observed that after withdrawal of exogenous thyroid therapy, thyroid function, in terms of radioiodine uptake, returned to normal in most subjects within two weeks. He further observed that thyroid function returned as rapidly in those subjects whose glands had been ***ressed by several years of thyroid medication as it did in those whose gland had been ***ressed for only a few days" (8)
These results have been subsequently verified in several studies (8,9) and a large number of trials where T3 was used to treat obesity. So, contrary to what has been stated in the bodybuilding literature, there is no evidence that long-term thyroid supplementation will somehow damage your thyroid gland.

ANDROGENS SUPPRESS THE IMMUNE SYSTEM
This is a grossly oversimplified description of the effects of androgens on immunity. The immune system is comprised of two “arms,” so called humor and cellular immunity. Humoral immunity involves the production of antibodies, and is primarily responsible for targeting extracellular pathogens. Cellular, or cell-mediated immunity involves the action of white blood cells including macrophages, neutrophils, and NK (natural killer) cells. These cells mount an attack on invading pathogens and are responsible for the clearance of intracellular pathogens, virus infected cells, and tumor cells. The cell-mediated response is also responsible for the development of inflammation.
Immune cells known as helper T cells, or Th cells, determine which response—humoral or cellular—the body will mount. There are three subsets of Th cells, Th0, Th1 and Th2 cells. The Th1 cells drive the cellular response, whereas Th2 cells control the humoral response. The two Th subsets are mutually inhibitory. Chemicals called cytokines secreted by Th1 cells suppress Th2 cells, and vice versa. The Th0 cells are precursor cells that can give rise to both Th1 and Th2 cells. This process is illustrated schematically here:


Numerous studies have shown that androgens as well as high levels of estrogens such as occur during pregnancy stimulate Th2 cells and hence promote humoral immunity. So in this sense, androgens are immune stimulating. However, as mentioned, the two arms of the immune system inhibit each other, so by virtue of stimulating Th2 cells and humoral immunity, cellular immunity is suppressed. A nice schematic illustration of this process can be found here:


How exactly do androgens stimulate humoral immunity? One idea is that androgens directly stimulate the production of the cytokine interleukin 10, IL-10, by T cells (10). As illustrated in the first link above, when Th2 cells secrete IL-10, this cytokine has a direct suppressive effect on Th1 cells and hence on the cellular immune response.
Probably the most important clinical effect of the suppression of cellular immunity by androgens is the resulting suppression of the inflammatory response. Androgens have been used with varying degrees of success to ameliorate the symptoms of some autoimmune inflammatory diseases like rheumatoid arthritis. Bodybuilders and other athletes commonly remark how certain anabolic steroids, like testosterone and nandrolone, help to alleviate the inflammation associated with injury or overuse.

ORAL ANABOLIC STEROIDS STIMULATE HEPATIC IGF-1 PRODUCTION
It’s never been completely clear to me exactly how this notion originated. As far as I can tell it was part of the dubious Class I/Class II theory of steroid action that was spawned on anabolic boards and now generally considered meritless. But many people still seem to believe that oral anabolic steroids such as methandrostenelone (Dianabol) and stanozolol (Winstrol) act directly on the liver to stimulate the production of insulin like growth factor (IGF-1) in***endently of any increase in growth hormone production. As most readers are aware, normally the pituitary gland secretes growth hormone (GH), and the GH then acts on the liver to stimulate the production of IGF-1. In fact, some “experts” have claimed that it is essential to include an oral steroid in any cycle for this reason.
Some oral androgens have been shown to increase IGF-1 levels, but these same drugs also elevate GH levels. So any increase in circulating liver-derived IGF-1 is almost certainly due to an increase in GH. There is not much research in this area to fall back on, but oxandrolone (10) and methandrostenolone (12) have both been shown to elevate GH in humans. Interestingly, when methandrostenolone was administered to rats whose pituitary glands had been removed, it demonstrated no anabolic effects, suggesting that GH secretion is important to the growth promoting effects of Dianabol (13).
Also, as was demonstrated in (14) and a number of other studies, plain old testosterone increases both GH and IGF-1 production. Perhaps most importantly, testosterone has been shown to stimulate the production of IGF-1 directly in muscle tissue, where it acts in an autocrine manner to stimulate growth (15). Locally produced IGF-1 is believed to play a more important role in muscle growth than does liver-derived IGF-1. So this renders moot the argument that it is necessary to incorporate an oral steroid in a cycle in order to elevate hepatic IGF-1 levels.

ANABOLIC STEROIDS DOWNREGULATE THE ANDROGEN RECEPTOR
Or is it upregulate? It seems there are two schools of thought on this, with the answer probably lying somewhere in between. Short-term in vitro and in vivo studies generally show that androgens upregulate the androgen receptor (AR) in skeletal muscle. For example, in humans given 15 mg of oxandrolone daily for 5 days, the skeletal muscle AR density nearly doubled (15). When exposed to testosterone in vitro, skeletal muscle AR expression increased significantly (16).
In longer-term studies the picture is somewhat different. One study looked at AR expression in androgen treated sedentary rats vs nontreated exercised rats over 8 weeks. To quote from the abstract:
Results show that contractile muscular activity always increased the quantity of receptors whereas the steroid treatment decreased it. Thus for EDL (extensorum digitorum longus) and SOL (soleus) of control trained rats the quantity of receptors was 0.78 and 0.82 fmol/mg protein, respectively, compared to 0.23 and 0.43 fmol/mg protein for sedentary testosterone-treated rats. (17)
In long term studies in humans we get yet a different picture. In work conducted by Sheffield-Moore et. al., (18) older men were supplemented with testosterone so as to bring their testosterone levels into the mid-to-high physiological range. Androgen receptor expression had more than doubled after one month of treatment, yet by 6 months had returned to baseline. This pattern suggested to the authors that cycling androgen replacement much as bodybuilders cycle AAS might be a viable strategy:
This pattern of AR expression raises the possibility that cycling of testosterone administration could produce effects on skeletal muscle analogous to continuous administration. Such a paradigm would be beneficial by administering significantly less testosterone for similar anabolic outcomes, thus minimizing the possibility of side effects.
So despite the passion with which advocates of either AR upregulation or downregulation defend their positions, the research is equivocal. Would exercise combined with AAS maintain increased AR expression, or would the addition of exercise serve to offset the AAS induced AR downregulation observed in the study by Bricout et al? These are just a couple of questions that require further research, and could lead to answers on why exercise combined with AAS use is so much more productive than simply using steroids alone when it comes to building muscle mass.

PROGESTERONE AND PROLACTIN INDUCED GYNECOMASTIA
Before delving into this subject, I’d like to say first and foremost, that in users of anabolic/androgenic steroids (AAS) the first step in combating the development of gynecomastia, or male breast enlargement, is to eliminate the causative agent: the anabolic steroid. Drug-induced gynecomastia almost invariably resolves on its own when a person quits taking the drugs responsible for it, if caught before permanent fibrosis develops. Unfortunately, most AAS users don’t want to employ this simple approach, for obvious reasons, so the foregoing will all be under the assumption that a person wants to prevent or treat gyno and still continue steroid use.
In the belief that certain anabolic steroids increase prolactin levels as well as act as agonists at the progesterone receptor, some have advocated the use of antiprolactin agents, like bromocriptine, or progesterone receptor blockers like RU-486 to treat AAS related gynecomastia, in lieu of more traditional drugs like tamoxifen.
In truth, the etiology of gynecomastia is unknown and a number of agents including estrogens, progestins, GH, IGF-1, and prolactin may be involved. However, most authorities believe that a decreased (T+DHT)/E ratio is central to the development of gyno, and that blocking the effects of estrogen, or increasing T + DHT levels, is central to ameliorating the problem.
Regarding prolactin, androgens decrease prolactin levels whereas estrogens increase prolactin. Non-aromatizing androgens have never been shown to elevate prolactin levels in humans, but testosterone has, due to its aromatization to estradiol (19). Prolactin secreting tumors, or prolactinomas, are often associated with gyno. But in these cases the prolactin is believed to induce gyno by suppressing testosterone production: “Prolactinomas that are sufficiently large to cause gynecomastia do so as a result of impairment of gonadotropin secretion and secondary hypogonadism”. (20). However, this is a moot issue in AAS users whose gonadotropin secretion is already blunted.
According to research cited in (20), prolactin may have a direct stimulatory effect on mammary tissue development, but only in the presence of high estrogen levels:
The presence of mild hyperprolactinaemia is therefore not uncommon in patients with estrogen excess. Significant primary hyperprolactinaemia, on the other hand, may directly stimulate epithelial cell proliferation in an estrogen-primed breast, causing epithelial cell proliferation and gynaecomastia.
So rather than focusing solely on lowering prolactin levels which may be elevated in users of aromatizing androgens, attacking estrogen should be the first line of action.
GH and IGF-1 are considered critical to the proliferation of mammary tissue. An excellent review of the role played by these hormones, as well as a general overview of gynecomastia can be found here:


Since elevated GH and IGF-1 are considered important to the anabolic effect of AAS, it would be impractical and counterproductive to attempt to prevent gynecomastia by blocking GH/IGF.
Progesterone acts in concert with estrogen to promote breast development, and at least part of any role played by synthetic progestins may be to stimulate IGF-1 production in the breast. But again, blocking the action of progesterone or synthetic progestins is not practical. Specific progesterone receptor antagonists like RU-486 block not only the progesterone receptor, but the androgen receptor as well, and have actually been associated with the development of gynecomastia (21). In any case, progesterone is thought to act on the breast to enhance the effects of estrogen (22) so once again, attacking estrogen is the easiest and most logical approach.
DHT gel (Andractim) or a generic knockoff might help as well. DHT is thought to act as an aromatase inhibitor (23) and perhaps compete directly with estrogen for binding at the estrogen receptor (24). DHT has been used in several case reports and controlled trials to successfully treat gynecomastia. So perhaps a viable strategy would be to combine DHT gel with tamoxifen. I would recommend tamoxifen rather than an aromatase inhibitor due to the simple fact that tamoxifen has been widely used in numerous controlled studies to succesfully treat gynecomastia, whereas the evidence to support the efficacy of aromatase inhibitors is scanty at best.
Undoubtedly, due to space limitations, I have left out a number of what are surely many readers’ pet myths. Perhaps in a future issue we can address more of these myths and questionable notions. Feedback is always welcome, and if readers wish to submit their ideas for myths that need to be examined in the future, please feel free to contact Mind & Muscle with your ideas.

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