Synonyms:
Methoxygonadiene, methoxydienone, Max-LMG, M-LMG

History:
This compound first appears in patents dating to the 1960s filed by researchers Gordon Alan Hughes and Herchel Smith at Wyeth Laboratories, in which they synthesized a number of 13-alkylated 19-nor compounds, including some that would become the first synthetic contraceptives. ^[1][2] These patents would prove so profitable that after retiring from Wyeth, Smith was able to donate hundreds of millions of dollars to universities in the UK and US. ^[3]

Methoxygonadiene is a chemical intermediate in the synthesis of steroids such as Norbolethone, 18-methyl-nortestosterone, and Norgestrel/Levonorgestrel. ^[1]

Preparation of Norbolethone from Methoxydienone. ^[1]

This ready availability as a chemical intermediate, and its association with the BALCO scandal, are likely to be how it found its way into the “designer steroid” supplement market in 2005, when it was released by ALRI as Max-LMG (LMG stands for “Lean Mass Generator”).
Anabolic and Androgenic Activity:
Methoxygonadiene is believed to act as a ‘prodrug’, deriving pharmacological activity by being metabolised to an active compound. Methoxygonadiene is unlikely to have any ‘intrinsic’ anabolic activity due to the lack of a 17b-hydroxyl function.

Proposed scheme of metabolism of methoxygonadiene

The diagram above illustrates the commonly suggested metabolic route. According to the scheme proposed, after ingestion methoxydienone’s enol ether group (methoxy) will undergo hydrolysis to the 3-ketone and the remaining 5(10) double bond should isomerize readily under acidic conditions in the body to produce a 4-en-3-one conjugation. It will then further convert to the biologically active 17b-hydroxyl steroid, 18-methyl-19-nortestosterone.

18-methyl-19-nortestosterone is a potent anabolic by injection, holding an A:A ratio of approximately 54:27 (LA:VP vs. testosterone propionate). ^[4] and 90:625 (LA:VP vs. 19-nortestosterone). ^[5] No data is available on the oral activity of either methoxygonadiene or 18-methyl-19-nortestosterone.

Structure and Function:
Methoxydienone belongs to a class of steroids called gonanes. The most basic gonane is a steroid devoid of the C-10 and C-13 methyl groups and is generally referred to as the ‘steroid nucleus’.

Structure of the steroid nucleus; the simplest gonane.

Herchel Smith and Richard Edgren originally described hormones such as methoxygonadiene and norbolethone as “13-substituted bisnortestosterones”, though they soon switched to the gonane nomenclature system to avoid confusion.

“We initially started calling them 13-substituted, bisnor testosterones… However this became very cumbrous from a nomenclature standpoint and to get some consistency in our work, at least internally, we followed the IUPAC recommendations, starting from the gonane nucleus and building from there.” – Richard Edgren ^[5]

Since by the strictest definition all steroids can be considered gonanes, Edgren has expressed a preference for the term “carbon 18-homologated 19-nortestosterones”, or alternatively “levonorgestrel family of progestins” for 18-methyl hormones such as methoxygonadiene. ^[6]

When this was released as a dietary supplement in 2005, the accompanying advertising copy declared:

“Max LMG is structurally related to the so-called abortion pill RU-486…”

In fact it’s almost entirely unrelated, structurally, to the “abortion pill” RU-486 (Mifepristone), as can be seen by even a cursory glance at the molecular structures.

Left to right: methoxygonadiene, mifepristone (RU-486), and norgestrel.

It’s possible that the confusion may have arisen because Wyeth’s oral contraceptive Nordette (which contained ethinyl estradiol and levonorgestrel) was marked “Wyeth” on one side, and “486″ on the other. Since levonorgestrel can be made from methoxygonadiene, a comparison with that compound would have been much more appropriate.

“…being a 5-alpha-reduced analog prevents conversion to DHT. It is important to remember that being 5-alpha-reduced also means it is related to DHT.”

Methoxygonadiene is not 5-alpha-reduced, or even remotely related to DHT. It has a double bond from C5-C10, which it’s believed may isomerise in vivo to the more thermodynamically stable C4-C5 position.

“Naturally the lack of estrogenic activity translates into low water retention and solid gains.”

Contrary to the assertion above, this compound is noted by users for a high degree of water retention – and is certain to aromatise. Ironically, both of the compounds sold by ALRI under the name “LMG” (Lean Mass Generator) were renowned for doing the opposite: Ergomax LMG (desoxymethyltestosterone; “Pheraplex”) was also usually characterized as a “wet bulker” that caused significant water retention.

References:
[1] US Patent US3959322: Synthesis of 13-alkyl-gon-4-ones. Smith, Herchel
[2] US Patent US3547909: Hughes GA. Synthesis of Gona-2,5(10)-Dienes. 1970.
[3] Herchel Smith Biography – University of Cambridge
[4] Buzby GC, Walk CR, Smith H. Totally Synthetic Steroid Hormones. X. Some (±)-13β-Ethyl-7α-methylgonane Derivatives. J. Med. Chem. 1966 Sep 1;9(5):782–4.
[5] Biological effects of synthetic gonanes. Edgren RA, Peterson DL, Jones RC, Nagra CL, Smith H, Hughes GA. Recent Prog Horm Res. 1966;22:305-49.
[6] Nomenclature of the gonane progestins. Edgren RA, Stanczyk FZ. Contraception. 1999 Dec;60(6):313

© Total Flex Blog 2013

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The five winners, who each receive a bottle of Triumphalis, a bottle of Advanced Muscle Science Epi-1-Test™, and a bottle of Antaeus Labs Talos cycle-support:

J.S. from New Jersey
J.R. from North Yorks, UK
K.P. from Ohio
D.S. from Pennsylvania
M.M. from Ohio

The five runners-up, who each receive a bottle of Triumphalis:

L.S. from Massachusetts
D.E. from Ohio
G.W. from Virginia
S.T. from Texas
T.M. from Melbourne, Australia

Congratulations to the winners, and thank you to our sponsors and all those that entered.

The post Anniversary Prize-Draw Results appeared first on Total Flex Blog.

History:
Experiments at Syntex in the early 1960s established that steroids that lacked a C-3 oxygen atom, but had a double bond somewhere in the A-ring (particularly C2-C3), could still be effective anabolic agents; the oral activity of desoxymethyltestosterone in particular was noted. ^[2]
Additional research by the same team demonstrated that substitution with a methyl group to C2 unsaturated compounds increased oral activity further.

J. Med. Chem. 1963 Mar 1;6(2):162–6. ^[3]

J. Med. Chem. 1962 Mar 1;5(2):406–8. ^[4]

Anabolic Androgenic Ratio:
Preliminary testing indicated that it was very strong, with an anabolic to androgenic ratio of around 1000:200. The 2-methylene analogue was markedly weaker – though still potent. ^[3]

J. Med. Chem. 1963 Mar 1;6(2):162–6. ^[3]

“The 2,17a-dimethyl derivative, a 3-deoxy steroid, had the remarkable activity of 1,040% on the levator ani, 97% on the ventral prostate, and 320% on the seminal vesicle.” ^[5]

Endocrinology. 1963 Feb 1;72(2):259–66 ^[5]

Androgens and Anabolic Agents. 1969. Academic Press. p. 215 ^[6]

The “family” of structurally-related compounds illustrated above are all powerful anabolic agents (as can be seen by the anabolic:androgenic ratios quoted below) – and dimethandrostenol may be the strongest of all.

LA = Levator ani (demonstrates anabolic potency). VP = Ventral prostate, and SV = Seminal vesicles (markers of androgenic potency)

Structure and Function:
Dimethandrostenol can be considered to be like methasterone (superdrol) with an additional double bond, or like desoxymethyltestosterone (phera-plex) with an additional 2-methyl group.
The presence of the adjacent double-bond causes the C-2 methyl group of dimethandrostenol to be planar (as with stenbolone and methyl stenbolone), unlike 2-methyl groups on saturated A-rings (like masteron and superdrol), which have to be in the alpha or beta position (alpha, in those examples).

Metabolism:
Dimethandrostenol cannot aromatize to form estrogenic metabolites, as it has no C4-5 double bond (it is ’5α-reduced’). For the same reason, it is not a substrate for (cannot be transformed by) the enzyme 5α-reductase (the enzyme that catalyzes the reaction that turns testosterone to DHT).
Potential metabolic transformations could include the reduction of the delta-2 double bond, formation of a 2-methylene metabolite, and various hydroxylation reactions. In desoxymethyltestosterone the double bond is fairly readily reduced; in dimethandrostenol it’s likely that the adjacent methyl group increases resistance to reduction of the double bond.
The toxicity of oral steroids appears to be closely related to both potency and resistance to metabolism. Given that this compound is extremely potent, and is likely to be fairly resistant to metabolism, it’s fair to assume it has a toxicity profile similar to other drugs of its class (i.e. those already mentioned).

References:
[1] Sekera MH, Ahrens BD, Chang Y-C, Starcevic B, Georgakopoulos C, Catlin DH. Another designer steroid: discovery, synthesis, and detection of “madol” in urine. Rapid Communications in Mass Spectrometry. 2005;19(6):781–4.
[2] Bowers A, Cross AD, Edwards JA, Carpio H, Calzada MC, Denot E. Steroids. CCV.1 Ring A Modified Hormone Analogs. Part I. Some Ring A Olefins. J. Med. Chem. 1963 Mar 1;6(2):156–61.
[3] Cross AD, Edwards JA, Orr JC, Berköz B, Cervantes L, Calzada MC, et al. Steroids. CCVI.1 Ring A Modified Hormone Analogs. Part II. 2-Methylene Androstanes and 2-Methyl-Δ1, Δ2 and Δ3-Androstenes2. J. Med. Chem. 1963 Mar 1;6(2):162–6.
[4] Cross AD, Edwards JA, Bowers A. Steroids. CLXXX.1 2-Methyl-Δ2-androstenes and 2-Methylene-androstanes. A New Class of Potent Anabolic Agents. J. Med. Chem. 1962 Mar 1;5(2):406–8.
[5] Dorfman RI, Kincl FA. Relative Potency of Various Steroids in an Anabolic-Androgenic Assay Using the Castrated Rat. Endocrinology. 1963 Feb 1;72(2):259–66.
[6] Vida, J. Androgens and Anabolic Agents. 1969. Academic Press. p. 215
[7] Kincl FA, Dorfman RI. Anabolic-androgenic potency of various steroids in a castrated rat assay. Steroids. 1964;3(1):109–22.
[8] Kincl, F. A. 1963. Unpublished data. In: Dorfman RI (ed) Methods in Hormone Research, Vol IV. Academic Press, New York, p32.
[9] Zaffaroni A. The effect of alkyl- and electronegative group substitution on steroidal hormone activity. Acta Endocrinol Suppl (Copenh). 1960;34(Suppl 50):139–45.
[10] Nutting EF, Klimstra PD, Counsell RE. Anabolic-Androgenic Activity of a-Ring Modified Androstane Derivatives. Acta Endocrinol. 1966 Dec 1;53(4):635–43.

© Total Flex Blog 2013

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The prizes:
Five winners will each receive a bottle of Triumphalis, a bottle of Advanced Muscle Science Epi-1-Test™, and a bottle of Antaeus Labs Talos cycle-support.
Five runners-up will each receive a bottle of Triumphalis, the exciting new prohormone from Iron Legion.

How to enter:
Find the words listed in the grid. Words may be written forwards, backwards, up, or down (but not diagonally). One of the words listed cannot be found in the grid. Submit your name and address and this word using the contact page to be in with a chance of winning. Closing date for entries is the 10th May.
Ed: Please note that the contest is now closed.

Terms and conditions:
Entrants must be 18 or over. Winners will be chosen at random from all correct entries received by the closing date. One entry per postal address. The winner accepts full responsibility for the use of the prize(s). No cash alternative is available. No responsibility is taken for items lost in transit. It is the responsibility of the entrant to ensure prizes are compliant with local laws and import regulations.
Entrants’ personal data will not be shared with third parties for marketing purposes. Names and addresses of the winners will be shared with the sponsor(s) to arrange delivery of the prize(s). A name or preferred pseudonym will be used to announce the winners on the blog.

The post The Total Flex Blog Anniversary Prize-Draw appeared first on Total Flex Blog.

Structural Image:

Nomenclature:
17β-Hydroxy-17α-methyl-5α-androstano[3,2-c]arsole, or
17b-Hydroxy-17a-methyl-5a-androstano[3,2-c]arsole

Synonyms:
Metandrostanarsole
Methandrostanarsole
17a-methyl-5a-androstan-arsole

Structure:
Androstanarsole bears a strong structural resemblance to other heterocyclic steroids like stanozolol and furazabol, but instead of a furazane or pyrazole ring, this steroid has an arsole heterocyclic ring fused to carbons 2 and 3. Instead of the nitrogen heteroatoms seen in ‘winstrol’ and ‘furaza’, this steroid has an arsenic atom in the heterocyclic ring.

History:
Unlike most commercially available steroids, this one did not feature in Julius Vida’s 1969 publication “Androgens and Anabolic Agents”, and does not appear to have been experimentally synthesized by any steroid research labs of the time, hence the anabolic and androgenic activity is unknown.
Androstanarsole was released as a dietary supplement in April 2013 by The Right ‘Onourable Lord Lucan Labs.
Administration:
This product has been formulated as a suppository, for the rectal route of administration. The rectum has an abundance of blood vessels, causing a rapid uptake of the steroid molecule through the mucous membrane into the blood stream. Rectally administered, androstanarsole has a higher bioavailability and faster onset than similar oral products, and avoids the “first-pass effect” of the liver.

Warning: Androstanarsole capsules may contain metal fragments and large shards of glass.

© Total Flex Blog 2013

No connection to, or association with, the 7th Earl of Lucan or his estate is implied or intended.

The post Androstanarsole appeared first on Total Flex Blog.

The active ingredient is labeled 2a,17a-dimethyl-5a-androstane-3,17b-diol, however the trivial name “superdiol” is less of a mouthful.
This compound is known to be a metabolite of methasterone (superdrol) in both humans and animals. ^[3][4][5]

Structure of “superdiol”

Though the conversion of the ‘diol’ form to methasterone has not been studied, diols have a long track record as metabolic precursors to active (and typically illegal) compounds: 1-androstenediol was sold as a precursor to 1-testosterone, Halodrol-50 as a precursor to Oral Turinabol, methyl-1-androstenediol (“Alpha One”) as a precursor to methyl-1-testosterone (M1T), and methyl-1,4-androstadiene-diol (M14ADD) as a precursor to methandrostenolone (Dianabol).

References:
[1] PHF Supplements: Celtic Labs
[2] Classification of two steroids, prostanozol and methasterone, as Schedule III anabolic steroids under the Controlled Substance Act. Final rule. Fed Regist. 2012 Jul 30;77(146):44456–62.
[3] Gauthier J, Goudreault D, Poirier D, Ayotte C. Identification of drostanolone and 17-methyldrostanolone metabolites produced by cryopreserved human hepatocytes. Steroids. 2009 Mar;74(3):306–14.
[4] Lootens L, Meuleman P, Leroux-Roels G, Van Eenoo P. Metabolic studies with promagnon, methylclostebol and methasterone in the uPA+/+-SCID chimeric mice. J. Steroid Biochem. Mol. Biol. 2011 Nov;127(3-5):374–81.
[5] G. Rodchenkov, T. Sobolevsky, V. Sizoi. New designer anabolic steroids from internet. Recent Adv. Doping Anal. 2006, 14, 141.

© Total Flex Blog 2013

The post Celtic Labs “Superdiol” appeared first on Total Flex Blog.

Nomenclature:
3,3-azo-17a-methyl-5a-androstan-17b-ol or
3,3-azo-17α-methyl-5α-androstan-17β-ol

Synonyms:
Methyldiazirinol

History:
This compound was first synthesized by researchers at Lederle Laboratories, a subsidiary of American Cyanamid, who were examining a series of diazirines and diaziridines (the steroid in question is a diazirine). Their results were reported in 1965. ^[1] They patented the invention in 1966. ^[2]
Lederle/American Cyanamid also synthesized (appropriately enough) some 2a-cyano-substituted compounds similar to the Anabolic Innovations ‘prohormone’ Cynostane, ^[3][4] though their major contribution to the field of steroids was the 16-oxygenated corticosteroid triamcinolone in the late 1950s. ^[5]

US Patent #19640392022 ^[2]

Prog Med Chem. 1991;28:233-300. ^[7]

Androgens and Anabolic Agents. 1969. Academic Press, p90. ^[6]

Androgens and Anabolic Agents. 1969. Academic Press, p194. ^[8]

• Stanozolol (Winstrol) has a pyrazole heterocyclic ring fused to the steroid at carbons 2 and 3.
• Furazabol has a furazane ring at the same position.
• Methylepitiostanol (“Epistane”) has an episulphide moiety at carbons 2 and 3.
• Methyldiazirinol has a diazirine moiety at carbon 3.

Heterocyclic steroids

Receptor bonding in these cases has been improved by the substitution of the 3-ketone for a more highly nucleophilic heteroatom; either sulphur or nitrogen. Methylepithiostanol has a sulphur atom in the place of the oxygen function of the natural steroids, while stanozolol, furazabol, and methyldiazirinol possess a nitrogen atom.

Stability
Diazirines are not terribly stable chemical structures, being known to be susceptible to decay from both ultraviolet light and heat. This relative instability is partly due to the ring strain on three membered rings, and partly due to the nucleophilic nature of the nitrogen atoms.
Instability in UV light is not something that is unique to diazirines, or to this steroid; many steroids have been found to be subject to photodegradation, including testosterone, testosterone propionate, methyltestosterone, nandrolone, dienolone, and trenbolone. ^{[9][10][11][12]}
The American Cyanomid Company discovered that the 3,3-azo steroids pyrolized largely to 2-ene compounds at 135°+ (via a singlet state carbene), though that is not expected to happen in vivo. This degradation with heat is not unique to methyldiazirinol either; the structurally similar steroid methylepitiostanol (epistane) also pyrolizes under heat (to the same 2-ene compound, desoxymethyltestosterone), making accurate testing by GC/MS impossible. ^[13][14]
In practice this ‘instability’ is likely to be of little consequence. The Lederle researchers found that “Unlike the diaziridines, the diazirines were found to be very stable, relatively nonpolar compounds”. ^[1] The same storage advice should be heeded as with all other steroidal products: keep in a cool, dark, dry place.

Availability
Methyldiazirinol was never commercialised by its inventors, though they continued to explore the possibilities of the diazirine group in other (non-steroidal) molecules. ^[15][16]

In 2013 methyldiazirinol was released onto the dietary supplement market as Iron Legion Triumphalis.

References:
[1] Church RFR, Kende AS, Weiss MJ. Diazirines. I. Some Observations on the Scope of the Ammonia-Hydroxylamine-O-sulfonic Acid Diaziridine Synthesis. The Preparation of Certain Steroid Diaziridines and Diazirines. J. Am. Chem. Soc. 1965 Jun 1;87(12):2665–71.
[2] Church RFR. 2,2 And 3,3-Hydrazi-Steroids of the Androstane and Pregnane Series. 1969
[3] Kissman H, Hoffman A, Weiss M. Communications- Synthesis of Certain Steroidal α-Cyano Ketones. J. Org. Chem. 1961 Jul 1;26(7):2610–1.
[4] Kissman HM, Hoffman AS, Weiss MJ. The Synthesis of Certain α-Cyano Keto Steroids. J. Org. Chem. 1962 Sep 1;27(9):3168–75.
[5] Bernstein S. Historic reflection on steroids: Lederle and personal aspects. Steroids. 1992 Aug;57(8):392–402.
[6] Androgens and Anabolic Agents. 1969. Academic Press, p90.
[7] Singh H, Jindal DP, Yadav MR, Kumar M. Heterosteroids and drug research. Prog Med Chem. 1991;28:233–300.
[8] Androgens and Anabolic Agents. 1969. Academic Press, p194.
[9] Albini A, Fasani E, Albini A, Fasani E. Photochemistry of drugs: An overview and practical problems. Drugs Photochemistry and Photostability. 2007.
[10] Van der Merwe PJ, Pieterse JW. Stability of zeranol, nandrolone and trenbolone in bovine urine. Analyst. 1994 Dec;119(12):2651–3.
[11] Debono M. The photodimerization of 17β-hydroxy-estra-4,9(10)-dien-3-one. Steroids. 1968 Oct;12(4):485–9.
[12] Qu S, Kolodziej EP, Cwiertny DM. Phototransformation rates and mechanisms for synthetic hormone growth promoters used in animal agriculture. Environ. Sci. Technol. 2012 Dec 18;46(24):13202–11.
[13] Okano M, Sato M, Ikekita A, Kageyama S. Analysis of non-ketoic steroids 17α-methylepithiostanol and desoxymethyl- testosterone in dietary supplements. Drug Testing and Analysis. 2009;1(11-12):518–25.
[14] Does “Epistane” convert to “Phera”? – Total Flex Blog.
[15] Church RFR, Weiss MJ. Diazirines. II. Synthesis and properties of small functionalized diazirine molecules. Observations on the reaction of a diaziridine with the iodine-iodide ion system. J. Org. Chem. 1970 Aug 1;35(8):2465–71.
[16] Church RFR, Maleike RR, Weiss MJ. Diazirines. 3. Synthesis of a series of diazirine-containing molecules and their pharmacological evaluation. J. Med. Chem. 1972 May 1;15(5):514–8.

© Total Flex Blog 2013

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The compounds below have been experimentally produced and tested by pharmaceutical companies for their selective androgen receptor modulating properties. Your task is to identify them.

Please leave your answers in the comments.

The post Name That Steroid: Round 7 – Name That SARM appeared first on Total Flex Blog.

In 1967, boldenone undecyclenate was being clinically evaluated by Ciba. At that time the drug was known by its internal moniker of BA-29038. Elderly men and women (aged 70-95) were given BA-29038 at a dosage of 50mg every two weeks for a period of 16 weeks. The expected increase in hematocrit (the percentage of blood made up of red blood cells) turned out to be relatively minor (from 41.74±3.1 to 43.3:±4.1), and was not statistically significant. ^[1] That the effects on erythropoiesis were so mild is not too surprising, given the extremely modest dosages involved (bodybuilders often inject doses 20 or more times greater than that used in this study on a weekly basis).

Another study, conducted in 1973 on horses by Squibb (makers of Equipoise^TM) also failed to show an increase in hematocrit in the study period (although again, it was injected at a low dose – so low that no statistically relevant anabolic effect was noted). ^[2]

If the clinical studies don’t support an erythropoietic effect, is there any good reason to suspect one? To understand the answer to this question it’s necessary to understand a little advanced steroid metabolism.

Most readers will be aware that testosterone is metabolized in tissues such as skin, scalp, prostate, and liver, by the enzyme 5alpha-reductase to 5α-dihydrotestosterone (DHT), a more potent androgen. Less well-known is that in the liver, there is also a 5beta-reductase enzyme (encoded by the AKR1D1 gene) that catalyzes reduction of the double bond to form 5β-reduced, or 5β-H metabolites.

A-ring metabolism: 5α- and 5β- reduction of 3-keto-4-ene steroids ^[3]

Stereochemical representation of the 5α-H (trans) and 5β-H (cis) isomeric forms of the steroid nucleus. ^[4]

Relatively small structural changes can significantly change the way steroids are metabolized.
Unsaturation (the addition of a double bond) of a delta-4 steroid between C1 and C2 favours 5β-reduction of the delta-4 double bond over the 5α-H isomer.
This observation is important because it means that for those compounds with a “1,4-diene” structure – such as boldenone – reduction of the Δ4 double bond proceeds in favour of 5β-H metabolites.

A ring metabolism: Reduction of the double bonds in 3-keto-1,4-diene steroids produces 5β-H metabolites. ^[3]

Clin. Chem. 1996 Jul 1;42(7):1001–20. ^[3]

“The reduction of the C-4,5-double bond [of boldenone] is stereospecific and yields the 5β-configuration. No 5α-metabolite is detected.” – Wilhelm Schänzer ^[3]

So what does this have to do with erythropoiesis?
In the late 1960s and early 1970s a number of experiments were conducted to determine the erythropoietic effects of a series of steroids. Some Δ4, 5α-H and 5β-H steroids of the androstane and pregnane series were found to be erythropoietic. The erythropoietic effects of testosterone and 5α-H steroids was found to be reversible by the co-administration of anti-erythropoietin antibodies – indicating that their effects are mediated directly by an increase in erythropoietin. Conversely, the erythropoietic effects of the 5β-H steroids were not adversely affected by the addition of anti-erythropoietin, which suggested that their erythropoietic effects were achieved by a different mechanism of action. ^[5]
The enzyme δ-aminolevulinic acid synthase (ALA synthase) is the rate-limiting step in heme synthesis, both in the liver and in erythroid tissues. In these experiments the researchers found that 5β-H steroid metabolites were more effective at stimulating the induction of δ-aminolevulinic acid synthase than 5α-H steroids.
When radioactively-labelled iron uptake was used to measure hemoglobin production in mice, it was observed that “compounds with a 5β-H configuration produced a significant increase in Fe⁵⁹ incorporation relative to the control while those with a 5α-H configuration did not.” ^[6]
5β-H steroids of the pregnane series were also observed to increase hemoglobin synthesis in chick blastoderm ^[7] and in human bone marrow cultures, ^[8] and increase red cell mass in squirrel monkeys. ^[9] Of the steroids studied, the progesterone metabolite pregnanedione was among the most effective at inducing erythropoiesis.

Adapted from: PNAS. 1970 Mar 1;65(3):564–8. ^[6]

Since boldenone produces almost exclusively 5β-H steroid metabolites, it could be that boldenone acts as a metabolic precursor to a pool of erythropoietic 5β-H steroids (though boldenone’s major metabolites have not been tested for this activity). In its unchanged form it is also expected to also elicit the same erythropoietin-mediated effects found with other anabolic steroids.

The reasons outlined above lend some credibility to the theory (already widely-held among bodybuilders) that boldenone could have an erythropoietic effect greater than that experienced with other steroids.☨

☨This is a theoretical exposition, and neither a statement of fact nor opinion.

References
[1] D ASDM, Papanayiotou P, Marketos S. Renal effects of a new anabolic steroid (29’038-Ba) in old age. Pharmacol. Clin. 1968 Oct 1;1(2):43–6.
[2] O’Connor JJ, Stillions MC, Reynolds WA, Linkenheimer WH, Maplesden DC. Evaluation of boldenone undecylenate as an anabolic agent in horses. Can Vet J. 1973 Jul;14(7):154–8.
[3] Schänzer W. Metabolism of anabolic androgenic steroids. Clinical Chemistry. 1996 Jul 1;42(7):1001–20.
[4] Levere RD, Gidari AS. Steroid metabolites and the control of hemoglobin synthesis. Bull N Y Acad Med. 1974 May;50(5):563–75.
[5] Gordon AS, Zanjani ED, Levere RD, Kappas A. Stimulation of Mammalian Erythropoiesis by 5β-H Steroid Metabolites*. Proc Natl Acad Sci U S A. 1970 Apr;65(4):919–24.
[6] Gorshein D, Gardner FH. Erythropoietic Activity of Steroid Metabolites in Mice. PNAS. 1970 Mar 1;65(3):564–8.
[7] Levere RD, Kappas A, Granick S. Stimulation of hemoglobin synthesis in chick blastoderms by certain 5beta androstane and 5beta pregnane steroids. Proc Natl Acad Sci U S A. 1967 Sep;58(3):985–90.
[8] Necheles TF, Rai US. Studies on the control of hemoglobin synthesis: the in vitro stimulating effect of a 5-beta-H steroid metabolite on heme formation in human bone marrow cells. Blood. 1969 Sep;34(3):380–4.
[9] Besa EC, Gorshein D, Hait WA, Gardner FH. Effective Erythropoiesis Induced by 5β-Pregnane-3β-Hydroxy-20-One in Squirrel Monkeys. J Clin Invest. 1973 Sep;52(9):2278–82.
[10] Necheles TF. Studies on the control of hemoglobin synthesis: a model of erythroid differentiation based upon the in vitro effect of erythropoietin and 5 beta-H steroids. Hamatol. Bluttransfus. 1972;10:53–9.
[11] Gross M, Goldwasser E. On the mechanism of erythropoietin-induced differentiation. XIV. The apparent effect of etiocholanolone on initiation of erythropoiesis. Exp. Hematol. 1976 Jul;4(4):227–33.
[12] Garavini C, Cristofori M. The effect of 5 alpha-dihydrotestosterone and 5 beta-dihydrotestosterone on erythropoiesis of the newt, Triturus cristatus carnifex (Laur.). Gen. Comp. Endocrinol. 1984 May;54(2):188–93.

© Total Flex Blog 2013

The post Steroids, Athletic Performance, and Red Blood Cells. Part 2/2. appeared first on Total Flex Blog.

Some methods for increasing red blood cell count (sometimes called “blood boosting”) include:
- Administration of erythropoietin
- Training at altitude
- Using a hypobaric chamber
- Blood transfusions
- Steroids

The increase in endurance gained from so-called “blood boosting” products and techniques has made them highly popular among endurance athletes, most notably in cycling. The widespread use of autologous blood transfusions and erythropoietin (at the time undetectable) in cycling in the 1990s and beyond led to many records being broken – and the eventual downfall and vilification of its most iconic figure, Lance Armstrong.

“I viewed it as very simple. You had things that were oxygen-boosting drugs that were incredibly beneficial for performance, or endurance sports – whether it’s cycling or running or whatever. And that’s all you needed. My cocktail was only EPO, but not a lot, transfusions, and testosterone.” – Lance Armstrong ^[1]

Erythropoietin
Erythropoietin is the hormone that stimulates the production of erythrocytes (red blood cells) in the bone marrow, a process that takes about seven days. Mature red blood cells contain hemoglobin, which carries oxygen from the lungs to the tissues, where it is used by the cells to facilitate the conversion of nutrients to energy in a process called respiration. The red blood cell is then carried back to the lungs to repeat the process.

EPO administration has been found in a double-blind, placebo-controlled experiment to produce a significant increase in VO₂max (maximal aerobic capacity, an indicator of physical fitness) in male athletes after four weeks administration, ^[2] which is unsurprising given the clear relationship between VO₂max and hemoglobin. ^[3]

Total body hemoglobin and whole body maximal oxygen uptake (VO₂max) for 94 subjects age 7–30 years.
Br J Sports Med. 2003 Jun;37(3):190–1. ^[3]

The widespread use of EPO in professional athletics is believed to be responsible for a sharp drop in running times in long distance events, as illustrated by the graph below.

Mean finishing times of the top 20 athletes in the men’s 5000 m from 1985 to 2010
Drug Test Anal. 2012 Aug 29 ^[4]

Drawbacks of EPO include frequent injections, and that testing for EPO has been routine in many sports since the year 2000.

Steroids
It has been known for over 50 years that the sex steroids affect red blood cell production (erythropoiesis); androgens increase red blood cell count, and estrogens have the opposite effect. ^[5]
For this reason men have more red blood cells than women, and are able to regenerate blood losses after donations faster than female donors. ^[6]

“The stimulation of erythropoiesis by anabolic steroids is primarily mediated by ESF [erythropoietic stimulating factor; erythropoietin]. Androgens enhance the renal production of ESF in normal and hypoxic animals and in humans” ^[7]

A number of steroids have been clinically prescribed for treatment of anaemia (a medical condition consisting of a lack of red blood cells or hemoglobin), including fluoxymesterone, methandrostenolone, methyltestosterone, stanozolol, and oxymetholone.

Adverse effects from anabolic steroids include virilization (masculinization of women and children), hepatotoxicity, and an adverse shift in lipoprotein subfraction (they are bad for cholesterol levels). The risk of side-effects is increased for the treatment of anaemia (relative to other uses), as to achieve a clinically relevant erythropoietic effect they must be administered at high doses. ^[7][8]

“[To treat anaemia] The dosage of the anabolic steroid has to be considerably higher than necessary for the achievement of a good nitrogen-retaining [i.e. anabolic] effect alone. The dosage has to be around 1-2 mg of 17a-methyl-testosterone per kilogram of bodyweight per day, or its equivalent. Side-effects, consequently, tend to appear fairly frequently.” – H. L. Krüskemper ^[8]

There is a school of thought that suggests some androgens are better than others for the purpose of increasing red blood cell count – oxymetholone and boldenone are commonly believed to be superior – and another opposing view holds that all steroids appear to be roughly equally effective at increasing RBC. It’s true that most studies have failed to show any significant benefit of one synthetic anabolic agent over another, and in the case of oxymetholone it’s probably true that it is not significantly better than the others, even though it is the anabolic steroid that has been investigated most extensively for that purpose. ^[7] Boldenone, however, may be different, and in part two of this article you will see why.

References
[1] Oprah and Lance Armstrong: The Worldwide Exclusive Part 1
[2] Birkeland KI, Stray-Gundersen J, Hemmersbach P, Hallen J, Haug E, Bahr R. Effect of rhEPO administration on serum levels of sTfR and cycling performance. Med Sci Sports Exerc. 2000 Jul;32(7):1238–43.
[3] Joyner M. VO2MAX, blood doping, and erythropoietin. Br J Sports Med. 2003 Jun;37(3):190–1.
[4] Ernst S, Simon P. A quantitative approach for assessing significant improvements in elite sprint performance: Has IGF-1 entered the arena? Drug Test Anal. 2012 Aug 29;
[5] Mirand EA, Gordon AS. Mechanism of Estrogen Action in Erythropoiesis. Endocrinology. 1966 Feb 1;78(2):325–32.
[6] Kappas A, Palmer RH. Selected aspects of steroid pharmacology. Pharmacol. Rev. 1963 Mar;15:123–67.
[7] Evens RP, Amerson AB. Androgens and erythropoiesis. J Clin Pharmacol. 1974 Mar;14(2):94–101.
[8] Krüskemper, Hans Ludwig. 1968. Anabolic Steroids. Academic Press. p158.

Any quotes are for illustrative purposes only and are not to be taken as an endorsement or approval of any course of action or product.

© Total Flex Blog 2013

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