Characterisation of the pharmacological profile of desoxymethyltestosterone (Madol), a steroid misused for doping.

* Diel P,
* Friedel A,
* Geyer H,
* Kamber M,
* Laudenbach-Leschowsky U,
* Schanzer W,
* Thevis M,
* Vollmer G,
* Zierau O.

Center for Preventive Doping Research, Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, 50927 Cologne, Germany. diel@dshs-koeln.de

Desoxymethyltestosterone (DMT), also known as Madol, is a steroid recently identified to be misused as a doping agent. Since, the knowledge of functions of this substance is rather limited, it was our aim to characterise the pharmacological profile of DMT and to identify potential adverse side effects. DMT was synthesised, its purity was confirmed and its biological activity was tested. The potency of Madol (DMT) to transactivate androgen receptor (AR) dependent reporter gene expression was two times lower as compared to dihydrotestosterone (DHT). Receptor binding tests demonstrate that DMT binds with high selectivity to the AR, binding to the progesterone receptor (PR) was low. In vivo experiments in orchiectomised rats demonstrated that treatment with DMT resulted only in a stimulation of the weight of the levator ani muscle; the prostate and seminal vesicle weights remained unaffected. Like testosterone, administration of DMT resulted in a stimulation of IGF-1 and myostatin mRNA expression in the gastrocnemius muscle. In the prostate proliferation was stimulated by TP (testosteronepropionate), but remained unaffected by DMT. Remarkably, treatment with DMT, in contrast to TP, resulted in a significant increase of the heart weight. In the liver, DMT slightly stimulates the expression of the tyrosine aminotransferase gene (TAT). Our results demonstrate that DMT is a potent AR agonist with an anabolic activity. Besides the levator ani weight, DMT also modulates the gene expression in the musculus gastrocnemius. The observed stimulation of TAT expression in the liver and the significant increase of the heart weight after DMT treatment can be taken as an indication for side effects. Summarizing these data it is obvious that DMT is a powerful anabolic steroid with selective androgen receptor modulators (SARM) like properties and some indications for toxic side effects. Therefore, there is a need for a strict control of a possible misuse.

PMID: 17254722 [PubMed - indexed for MEDLINE]

Obviously no dosage was given but....

Well now.....interesting. What is the year this is from?

You must spread some Reputation around before giving it to jasonschaffin again.

Originally Posted by yeahright

Well now.....interesting. What is the year this is from?

Very good post. Bump to yeahright's question...I think I'm going to have to read more into this as DMT is one of my favorites.

Just judging from the way I have felt on PP...I totally believe this study might be relevant to us. My heart feels "congested" for lack of a better word on PP cycles. That and the shortness of breath are very disconcerting.

Now the question is how relevant is this to humans and is it a permanent effect or is it only during the cycle?

Originally Posted by bioman

Just judging from the way I have felt on PP...I totally believe this study might be relevant to us. My heart feels "congested" for lack of a better word on PP cycles. That and the shortness of breath are very disconcerting.

Now the question is how relevant is this to humans and is it a permanent effect or is it only during the cycle?

This would explain the shortness of breath feeling reported by some users.

Originally Posted by yeahright

Well now.....interesting. What is the year this is from?

From the abstract:

Received 18 October 2006; revised 13 December 2006; accepted 14 December 2006. Available online 27 December 2006.

Very interesting.

And before some idiot comes in and starts saying "Duuude, PP even makes your heart freakin heeeuuge!"

Hypertrophic Cardiomyopathy..aka enlarged heart is a BAD thing. lol

I thought LVH was a temporary side if you run a short cycle, and then take a year off. As in, LVH occurs, but decreases slowly after the cycle is over... and this with any anabolic?

I would assume that is the case. Most highly anabolic compounds will cause this but I've always wondered where the threshold is between temporary HCM and a permanent condition.

Intuitively, we see pro wrestlers and other perma-cycle folks dropping dead early due to heart complications..probably because they never come off. What I am interested in is how often us non-pros can use anabolics without suffering the same fate..or if it is an inevitable consequence of using and lifting(since lifting also causes an increase in HCM).

Originally Posted by bioman

I would assume that is the case. Most highly anabolic compounds will cause this but I've always wondered where the threshold is between temporary HCM and a permanent condition.

Intuitively, we see pro wrestlers and other perma-cycle folks dropping dead early due to heart complications..probably because they never come off. What I am interested in is how often us non-pros can use anabolics without suffering the same fate..or if it is an inevitable consequence of using and lifting(since lifting also causes an increase in HCM).

Furthermore, are there certain compounds which preferentially act upon cardiac tissue? It would seem logical that androgens will effects cardiac tissue. However, if there is an androgen which does so as a primary effect raher than a small secondary effect, that would definately be a product to avoid.

I think heart tissue is effected differently.



The odd thing is that I've had heart palpiations mainly due to anxiety and stress wayyyy before i ever started taking AAS. Now that I'm using AAS, I have zero. So what exactly does that mean?

Your heart is too big to palp? lol, just kidding.

Before getting into lifting I used to feel my mytral valve prolapse all the time...now I never feel it. Dunno what that means either.

Given that there are so many variations with the designer roids, there certainly could be one that preferentially binds to cardiac tissues over skeletal. There are fewer AR in the heart, but they are definitely there.

You bastards! I posted a link to this same study last week, lol. It was in Thesinner's Designer Steroid/Prohoromone thread.

Anyway, what could one do to help combat this problem. Obviously abstaining from using DMT would be one, but what, if anything else, could help prevent this side?

Originally Posted by stxnas

You bastards! I posted a link to this same study last week, lol. It was in Thesinner's Designer Steroid/Prohoromone thread.

Anyway, what could one do to help combat this problem. Obviously abstaining from using DMT would be one, but what, if anything else, could help prevent this side?

"You must spread some Reputation around before giving it to stxnas again."

Haha. No worries. I only linked it, Jason posted it. The reps should go to Jason since he got you guys to read it.

Hmm, didn't see that one comming...umm, no pun intended.

So viagra reverses LVH?

Wonder if Icariin would do the same.

Originally Posted by bioman

Wonder if Icariin would do the same.

Ezatly my toughts...

Good post Jason. I remember reading about this somewhere not here. I wonder what the dose and length was? I assume ErgoMax-LMG would do the same since they are so simliar?

Originally Posted by bioman

Your heart is too big to palp? lol, just kidding.

Before getting into lifting I used to feel my mytral valve prolapse all the time...now I never feel it. Dunno what that means either.

Given that there are so many variations with the designer roids, there certainly could be one that preferentially binds to cardiac tissues over skeletal. There are fewer AR in the heart, but they are definitely there.

We must also remember that this study was done on rats. Humans may have a completely different concentration of AR in the heart...

Because desoxymethyltest isn't being utilized by a pharm company, I highly doubt that we'll see any future studies on humans unfortunately. I would be interested to know the differences in heart AR in humans vs rats...

The number of AR in the heart muscle versus skelletal muscle should understood very well and widely availible. However, the affinity of these androgens for those AR's may not be...

Conclusions—Androgen receptors are present in cardiac myocytes from multiple species, including normal men and women, in a context that permits androgens to modulate the cardiac phenotype and produce hypertrophy by direct, receptor-specific mechanisms. There are clinical implications for therapeutic or illicit use of androgens in humans.
Androgen Receptors Mediate Hypertrophy in Cardiac Myocytes -- Marsh et al. 98 (3): 256 -- Circulation

possible good news

Sports Med. 2004;34(8):513-54. Links
Effects of androgenic-anabolic steroids in athletes.

* Hartgens F,
* Kuipers H.

Department of Surgery, Outpatient Clinic Sports Medicine, University Hospital Maastricht, and Sports Medicine Center Maastricht, Maastricht, The Netherlands. fhartgens@home.nl

Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. They can exert strong effects on the human body that may be beneficial for athletic performance. A review of the literature revealed that most laboratory studies did not investigate the actual doses of AAS currently abused in the field. Therefore, those studies may not reflect the actual (adverse) effects of steroids. The available scientific literature describes that short-term administration of these drugs by athletes can increase strength and bodyweight. Strength gains of about 5-20% of the initial strength and increments of 2-5 kg bodyweight, that may be attributed to an increase of the lean body mass, have been observed. A reduction of fat mass does not seem to occur. Although AAS administration may affect erythropoiesis and blood haemoglobin concentrations, no effect on endurance performance was observed. Little data about the effects of AAS on metabolic responses during exercise training and recovery are available and, therefore, do not allow firm conclusions. The main untoward effects of short- and long-term AAS abuse that male athletes most often self-report are an increase in sexual drive, the occurrence of acne vulgaris, increased body hair and increment of aggressive behaviour. AAS administration will disturb the regular endogenous production of testosterone and gonadotrophins that may persist for months after drug withdrawal. Cardiovascular risk factors may undergo deleterious alterations, including elevation of blood pressure and depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol levels. In echocardiographic studies in male athletes, AAS did not seem to affect cardiac structure and function, although in animal studies these drugs have been observed to exert hazardous effects on heart structure and function. In studies of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to be strongly affected by AAS. Generally, AAS seem to induce increments of aggression and hostility. Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose and drug dependent. AAS dependence or withdrawal effects (such as depression) seem to occur only in a small number of AAS users. Dissatisfaction with the body and low self-esteem may lead to the so-called 'reverse anorexia syndrome' that predisposes to the start of AAS use. Many other adverse effects have been associated with AAS misuse, including disturbance of endocrine and immune function, alterations of sebaceous system and skin, changes of haemostatic system and urogenital tract. One has to keep in mind that the scientific data may underestimate the actual untoward effects because of the relatively low doses administered in those studies, since they do not approximate doses used by illicit steroid users. The mechanism of action of AAS may differ between compounds because of variations in the steroid molecule and affinity to androgen receptors. Several pathways of action have been recognised. The enzyme 5-alpha-reductase seems to play an important role by converting AAS into dihydrotestosterone (androstanolone) that acts in the cell nucleus of target organs, such as male accessory glands, skin and prostate. Other mechanisms comprises mediation by the enzyme aromatase that converts AAS in female sex hormones (estradiol and estrone), antagonistic action to estrogens and a competitive antagonism to the glucocorticoid receptors. Furthermore, AAS stimulate erythropoietin synthesis and red cell production as well as bone formation but counteract bone breakdown. The effects on the cardiovascular system are proposed to be mediated by the occurrence of AAS-induced atherosclerosis (due to unfavourable influence on serum lipids and lipoproteins), thrombosis, vasospasm or direct injury to vessel walls, or may be ascribed to a combination of the different mechanisms. AAS-induced increment of muscle tissue can be attributed to hypertrophy and the formation of new muscle fibres, in which key roles are played by satellite cell number and ultrastructure, androgen receptors and myonuclei. Copyright 2004 Adis Data Information BV

PMID: 15248788 [PubMed - indexed for MEDLINE]

still doesn't tell us about every steroid though, especially the "new" designers

more somewhat good news ( I know its old but....)

: Anat Rec. 1989 Apr;223(4):414-9. Links
Heart contains receptors for dihydrotestosterone but not testosterone: possible role in the sex differential in coronary heart disease.

* Sheridan PJ,
* McGill HC Jr,
* Aufdemorte TB,
* Triplett RG,
* Holt RG.

Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.

The sex differential in coronary heart disease is well documented but poorly understood. Previous studies have demonstrated receptors for dihydrotestosterone (DHT) in the myocardium and smooth muscle cells of arteries from a number of species. In this autoradiographic study, we further investigated and characterized the in vivo uptake and retention of the androgen binding in the male baboon. Adult castrated male baboons were injected with 1 micrograms/kg bw 3H-testosterone; 1 hr after the injection, the animals were rapidly exsanguinated while under anesthesia. The heart and arterial system were removed and processed for autoradiography. As a negative control, one animal received both 3H-testosterone and 100-fold unlabeled testosterone. For positive controls, the pituitary gland, prostate, seminal vesicles, and other tissues were also removed and processed for autoradiography. In contrast to our previous finding with 3H-DHT, no nuclear uptake and retention of 3H-steroid was found in any of the cells in either the heart or the arterial system. In the positive control tissues, pituitary gland, prostate, seminal vesicles, and others, a very distinct nuclear uptake and retention of 3H-steroid was observed, which was completely inhibited by the simultaneous injection of 100-fold unlabeled testosterone. In the binding study, Scatchard analysis of the cytosol prepared from a 17-year-old female baboon demonstrated levels of androgen receptor (as determined by the use of radiolabeled R1881) comparable to that found in young adults.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 2540679 [PubMed - indexed for MEDLINE]

finasteride to be safe???

and the cure???

: Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2138-43.Click here to read Links
Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol.

* Juric D,
* Wojciechowski P,
* Das DK,
* Netticadan T.

Cardiovascular Research Center Univ. of Connecticut School of Medicine, Farmington, CT 06030-1110. ddas@neuron.uchc.edu).

This study was designed to examine the effects of the antioxidant resveratrol on cardiac structure and function in pressure overload (PO)-induced cardiac hypertrophy. Male Sprague-Dawley rats were subjected to sham operation and the aortic banding procedure. A subgroup of sham control and aortic-banded rats were treated with resveratrol for 2 wk after surgery. Echocardiographic analysis of cardiac structure and function along with Western blot analysis of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and redox factor-1 (ref-1) were performed in all groups after 4 wk of surgery. Banded rats showed significantly increased left ventricle-to-body weight ratio. Echocardiographic analysis showed that the interventricular septal wall thickness and left ventricular posterior wall thickness at systole and diastole were significantly increased in banded rats. Also, a significant increase in isovolumic relaxation time was observed in banded rats. Measured eNOS, iNOS, and ref-1 protein levels were significantly reduced in banded rats. Resveratrol treatment prevented the above changes in cardiac structure, function, and protein expression in banded rats. Aortic banding after 4 wk resulted in concentric remodeling and impaired contractile function due to PO on the heart. The 2-wk treatment with resveratrol was found to abolish PO-induced cardiac hypertrophy. Resveratrol may therefore be beneficial against PO-induced cardiac hypertrophy found in clinical settings of hypertension and aortic valve stenosis.

PMID: 17488730 [PubMed - in process]

Reservatrol. I wonder how much wine is an effective dose

It's not a brew, but it beats taking pills any day!

Nice work, Jason.

Somewhat comforting, but we need to see long term studies on large scale populations of AAS users..who all use consistently and report their usage consistently annnnnd that's just never gonna happen. lol

I like the rezveratrol news. Been using Arjuna to help offset some of the potential problems..but also take rez in my anti-ox mix.