Written by Seth Roberts
23 March 2010

 

 

 

Anabolic Pharmacology

By Seth Roberts

 

Methyltestosterone

 

            Pharmacology is the study of drugs and their effects. Anabolic Pharmacology is the study of drugs that have a growth-promoting effect in muscle. This column will explore Anabolic Pharmacology by profiling a different anabolic drug and its effects each month. The focus of discussion this month will be the anabolic androgenic steroid, Methyltestosterone.

            Methyltestosterone is a very crude synthetic derivative of testosterone. In fact, it was probably the first orally available steroid ever marketed. Methyltestosterone is simply the C-17 alpha-alkylated version of testosterone. This added methyl group allows the molecule to survive long enough when taken orally to have an effect. The effect however, is considered to be rather small. Methyltestosterone has a short half-life, about 2.5 hours, and because of this, the drug needs to be taken frequently to have any real effect on muscle anabolism.1 Most people see little to no effect even when using large doses, but some athletes still use it to try and beat drug tests and maybe increase aggression a little just prior to competition.

            Methyltest is liver-toxic, due to the added methyl group, but no more so than other orals. The reputation for being more liver-toxic is due to the large amounts needed to make this drug worth taking. Most people do not knowingly use this drug, but methyltest is found in a lot of the counterfeit dianabol that is available on the black market.

            Methyltestosterone is converted by aromatase to the long-lived estrogen, methylestradiol. However, methyltestosterone is a fairly potent inhibitor of the aromatase enzyme, so, with continued use, estrogenicity peaks and then decreases. However, when methyltestosterone is stopped, there can be a rebound estrogenic effect. This steroid is also converted by 5-alpha reductase to methylDHT which is inactivated in skeletal muscle but very active in the prostate, hair follicles and other androgen target tissues, resulting in androgenic side effects.2

            The binding affinity of methyltestosterone is about equal to that of testosterone; however, the longer plasma half-life and the conversion to methylDHT result in a drug that has an anabolic-to-androgenic ratio of about 1 to 1.3,4 Methyltestosterone has been shown in the scientific literature to be a direct antagonist of the glucocorticoid receptor.5

                        This drug has no real effect on CBG levels or cortisol levels but it does have a rather large suppressive effect on TBG with small compensatory increases in TBPA.6 The binding affinity of methyltest is about equal to that of estradiol, resulting in displacement of a good amount of estradiol and testosterone from SHBG.7 It is likely that methylandrostenediol is formed through the metabolism of methyltest, and methylandrostenediol has been shown to induce hypertension through potent inhibition of 11-beta hydroxylase.8 Methyltestosterone is cheap and readily available in pharmaceutical preparations and the black market.

            Seth Roberts is a former pharmaceutical research scientist with over 10 years of pharmacological research in the discovery and development of novel therapeutics. If you want to learn more about anabolic steroids, pick up Seth’s new book ANABOLIC PHARMACOLOGY at www.Ergogens.com. [© Seth Roberts, 2009. All rights reserved. For informational purposes only, not to be considered as medical advice or an endorsement of the use of illegal substances.]

           

            Got a question for Seth Roberts? You can ask him directly on the MD website and have Seth personally answer your question! Go to www.musculardevelopment.com, MD Forums, MD Staff and Pros, Q and A for Seth Roberts.

 

References:

            1. Shinohara Y, Baba S, Kasuya Y et al. Stable-isoptope methodology in the bioavailability study of 17 α-methyltesosterone using gas chromatography-mass spectrometry. J Pharm Sci, 1986; 75:161-4.

            2. Tóth M, Zakár T. Classification of anabolic steroids using the method of competitive metabolism. Exp Clin Endocrinol, 87(2):125-32, 1986.

            3. Ojasoo T, Delettre J, Mornon JP, Turpin-VanDycke C, Raynaud JP: Towards the mapping of the progesterone and androgen receptors. J Steroid Biochem, 27(1-3):255-69, 1987.

            4. Pavlatos AM, Fultz O, Monberg MJ, Vootkur A, Pharmd: Review of oxymetholone: a 17alpha-alkylated anabolic-androgenic steroid. Clin Ther, Jun;23(6):789-801; discussion 771, 2001.

            5. Raaka BM, Finnerty M, Samuels HH. The glucocorticoid antagonist 17 alpha-methyltestosterone binds to the 10 S glucocorticoid receptor and blocks agonist-mediated dissociation of the 10 S oligomer to the 4 S deoxyribonucleic acid-binding subunit. Mol Endocrinol, 1989 Feb;3(2):332-41.

            6. Barbosa J, Seal US, Doe RP: Effects of anabolic steroids on hormone-binding proteins, serum cortisol and serum nonprotein-bound cortisol. J Clin Endocrinol Metab, Feb;32(2):232-40, 1971.

            7. Pugeat MM, Dunn JF, Nisula BC: Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab, Jul;53(1):69-75, 1981.

            8. McCall AL, Stern J, Dale SL, Melby JC. Adrenal steroidogenesis in methylandrostenediol-induced hypertension. Endocrinology, 103(1):1-5, 1