Anti-inflammatory Benefits of Androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol, beta AET)


Androstene-3 beta-7 beta-17 beta-triol (AET) represents a key naturally occurring 7-hydroxy dehydroepiandrosterone (DHEA) metabolite. Produced from the adrenal gland, DHEA and its sulfate are the major circulating adrenal steroids in humans. Serum levels peak in young adults, but then steadily decline with age, falling over 80% by age 70. DHEA serves as a precursor of male and female sex hormones. (1, 3, 5, 6)


DHEA demonstrates a plethora of anti-aging properties in rodents, including anti-inflammatory, anti-obesity, anti-diabetic, immune enhancing activities, and opposes certain activities of endogenous glucocorticoids (GC). As the literature grew, DHEA became widely used as an anti-aging, anti-stress dietary supplement. Despite these well-documented activities in animal models, DHEA supplementation in humans has yielded inconclusive results and the value of DHEA replacement in humans is controversial. Such widely different outcomes in rodents and humans have been referred to as ‘the DHEA conundrum’. Moreover, the potential therapeutic use of DHEA is limited by its side effects due to its conversion to sex hormones.


One possibility to explain these discrepancies is that a metabolite(s) of DHEA, rather than DHEA itself, may be necessary for its full action in human physiology. DHEA undergoes extensive conversion and derivatization to multiple products by phase 1 reactions involving the cytochrome P450 system, and studies have shown that these phase 1 products can be more potent than parental DHEA. Phase 1 reactions frequently decline in elderly subjects, and since such subjects have been the major participants in human DHEA treatment studies, it is possible that biologically active metabolites of DHEA were not produced in adequate amounts in previous human studies. It is also possible that qualitative changes in DHEA metabolism between rodents and humans will account for these differences.


DHEA oxidation via the action of the enzyme CYP7B leads to the 7-hydroxy derivatives of C-19 steroids, which are collectively present in low nanomolar concentrations in human circulation and are not readily metabolized to potent androgens or estrogens. Many of the functions initially attributed to DHEA from observations in rodents are now thought to be properties of these oxygenated metabolites, particularly AET.

 

Molecular Structure of Androstenetriol


AET possesses some of the anti-inflammatory and GC-opposing activities that have been attributed to DHEA, but with greater apparent potency. Studies with AET demonstrate it markedly up regulates host immune response, prevents immune suppression, modulates inflammation and improves survival after lethal infections by pathogens and lethal radiation. (1, 3, 5, 6)


AET has been shown to be protective against traumatic shock. Traumatic shock activates the hypothalamic-pituitary-adrenal axis (HPA) to mediate a cascade of defensive mechanisms that often include overwhelming inflammatory response and immunosuppression, which may lead to multiple organ failure. In a relevant traumatic hemorrhagic shock rodent model that applies to both combat and civilian sectors, AET provided a significant protective effect and improved survival. In a murine thermal injury model that includes glucocorticoid-induced osteopenia, AET significantly preserved bone mineral content, restored whole body bone mineral content and bone growth, suggesting reversal of GC-mediated adverse effects.


Since AET is a naturally occurring compound there is no patent protection leaving the door wide open for AET analogue research. Harbor BioSciences, Inc. – http://www.harborbiosciences.com/ (Public, OTC:HRBR – http://www.google.com/finance?q=OTC:HRBR ) is exploring a synthetic derivative of AET for the treatment of diseases with underlying chronic inflammation. HRBR has developed 17alpha-Ethynyl-5-androsten-3beta, 7beta, 17beta-triol (HE3286), a synthetic derivative AET. (1, 2, 4, 7)


Within the past two years, animal model studies of HE3286 successfully demonstrate the treatment of lung inflammation without immune suppression, the reduction of established disease of rheumatoid arthritis, and both glucose-lowering and cholesterol-lowering effects. Harbor BioSciences most ambitious project to date is their recently released data regarding that plasma levels of AET positively correlate with BMI in healthy men and women.(1) These observations suggest a compensatory role for AET in preventing the development of metabolic syndrome and obesity. The AET structural core may provide the basis for novel pharmaceuticals to treat this disease, HE3286. Stay tuned.



1. Auci DL, Ahlem CN, Kennedy MR, Page TM, Reading CL, Frincke JM. A Potential Role for 5-Androstene-3[beta],7[beta],17[beta]-triol in Obesity and Metabolic Syndrome. Obesity. http://www.nature.com/oby/journal/vaop/ncurrent/abs/oby2010204a.html


2. Conrad D, Wang A, Pieters R, et al. HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. Journal of Inflammation 2010;7(1):52. http://www.journal-inflammation.com/content/7/1/52


3. Loria RM. Antiglucocorticoid function of androstenetriol. Psychoneuroendocrinology 1997;22 Suppl 1:S103-8.


4. Lu M, Patsouris D, Li P, et al. A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats. American Journal of Physiology – Endocrinology And Metabolism 2010;298(5):E1036-E48. http://ajpendo.physiology.org/content/298/5/E1036.full


5. Malik AK, Khaldoyanidi S, Auci DL, et al. 5-androstene-3?,7?,17?-triol (?-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis. PLoS ONE;5(10):e13566. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013566


6. Marcu AC, Paccione KE, Barbee RW, et al. Androstenetriol Immunomodulation Improves Survival in a Severe Trauma Hemorrhage Shock Model. The Journal of Trauma 2007;63(3):662-9.


7. Offner H, Firestein GS, Boyle DL, et al. An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis. Journal of Pharmacology and Experimental Therapeutics 2009;329(3):1100-9. http://jpet.aspetjournals.org/content/329/3/1100.full


8. Stiles AR, McDonald JG, Bauman DR, Russell DW. CYP7B1: One Cytochrome P450, Two Human Genetic Diseases, and Multiple Physiological Functions. Journal of Biological Chemistry 2009;284(42):28485-9.

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1,4,6 Androstatriene-dione (ATD)

Diagram of molecule

Chemical Name(s):

Androsta-1,4,6-triene-3,17-dione
1,4,6-androstatriene-3,17-dione
Chemical Formula: C19H22O2
Molecular Weight: 282
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 4%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: 2 days
Legal Status (US): Not listed as a controlled substance
Average Dose: 25-100mg/day
Average Cycle Length: 4-8 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

ATD is a steroidal aromatase inhibitor, known as a suicidal inhibitor because it permanently binds to the aromatase enzyme.

ATD is used for its aromatase inhibiting and testosterone boosting effect. Its effectiveness at lowering estrogen appears to be stronger than 6-oxo. It converts to 1,4,6-testosterone, which would also be expected to cause falsely high readings for a testosterone analysis.

The 1,4,6-testosterone metabolite of ATD can also bind to the androgen receptor (AR) and induce androgenic (or possibly anti-androgenic) effects similar to what is seen from 6-oxo. This would be expected since 1,4,6-testosterone has about one third the binding affinity for the AR, therefore it may interefere with the anabolic or androgenic action of hormones which bind the androgen receptor.

ATD would also be expected to interfere with production of natural testosterone by acting upon the hypothalamus pituitary testicular axis (HPTA), therefore this compound should not be used during post cycle therapy (PCT), however it could successfully be used during a cycle to help keep estrogen in control. Anecdotal reports and animal studies have also shown ATD inhibits libido and general sexual potency.

Common Clones:

Arom-X by Advanced Muscle Science (AMS)
AIFM by Anafit
ATD MAX by Anabolic Formulations
ATD-JET by Molecular Developments
Reversitol by IForce


Related Discussion

The Official 1,4,6 Androstatriene-dione (ATD) Thread
Posted by Eric

References

Effect of an inhibitor of aromatization, 1,4,6 androstatriene-3,17-dione (ATD) on LH release and steroid binding in hypothalamus of adult female rats.

Exp Brain Res. 1986;64(3):407-10.
Slama A, Gogan F, Sarrieau A, Vial M, Rostene W, Kordon C.

Effects of ATD on male sexual behavior and androgen receptor binding: a reexamination of the aromatization hypothesis.
ME Kaplan and MY McGinnis
Horm Behav, Mar 1989; 23(1): 10-26.

Anabolic Pharmacology
Seth Roberts (2009)

Androstenetrione (6-OXO)

Diagram of molecule

Chemical Name(s):

4-androsten-3,6,17-trione
3,6,17-androstenetrione
androst-4-ene-3,6,17-trione
6-ketoandrostenedione
Chemical Formula: C19H24O3
Molecular Weight: 300
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 4%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: 3-6 hours
Legal Status (US): Not listed as a controlled substance
Average Dose: 300-600mg/day
Average Cycle Length: 4-8 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

6-OXO is a steroidal aromatase inhibitor, known as a suicidal inhibitor because it permanently binds to the aromatase enzyme.

It is used for its anti-estrogen and testosterone boosting effects.

There is debate about whether or not 6-oxo actually lowers estrogen or increases testosterone. Several human studies have shown an increase in estrone levels following 6-oxo supplementation. However, one of the primary metabolites of 6-oxo is 6-oxoestrone which may have given a false positive for elevated estrone levels. The human study also concluded that 6-oxo raised testosterone levels, however it is possible that 6-oxotestosterone (which is another metabolite of 6-oxo) gave a false positive for the testosterone level as well.

Another interesting element to these articles is that despite the supposed increase in testosterone (enough to cause significant improvements in body composition if given via injection) no improvements where found for fat free mass (FFM) or strength. Therefore, 6-oxo is either a weak AI that doesn’t really inhibit estrogen at the recommended dose and simply converts to metabolites which give false readings, or it actually does increase testosterone, while the 6-oxo metabolites antagonize the androgen receptor enough to block any anabolic effect from testosterone.

Either way, no ergonomic or real world benefit could be found after 6-oxo supplementation.

Its also worth mentioning that 6-oxo should never be used post cycle, as its steroidial effects would likely interfere with recovery of natural testosterone production.


Related Discussion

The Official Androstenetrione (6-OXO) Thread
Posted by Eric

References

Immunological interference of the synthetic aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) and its metabolite(s) in the radioimmunoassay for testosterone.

MD Donaldson and MG Forest
Steroids, Dec 1980; 36(6): 717-21

Testosterone dose-response relationships in healthy young men
Shalender Bhasin, et al.
Am J Physiol Endocrinol Metab, Dec 2001; 281: E1172 – E1181.

1-Androsterone

Diagram of molecule

Chemical Name(s):

1-androsten-3b-ol-17-one
1-Dehydroepiandrosterone
Chemical Formula: C19H28O2
Molecular Weight: NA
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 8%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Not listed as a controlled substance
Average Dose:
200-300mg/day Transdermally
400-600mg/day standalone (oral)
200-400mg/day when stacking (oral)
Average Cycle Length: 4-6 weeks

Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

1- Androsteronetm (1-DHEA) is a non-methylated (non 17aa) pro-steroid that must convert to 1-androstenediol (1-AD), 1-androstenedione (original 1-AD) and/or 1-testosterone to be active. The double bond in the 1st position seems to slightly enhance its ability to resist excretion by the liver.

1-Androsterone occurs naturally in the body, and is a naturally occurring metabolite of DHEA. (2) The 17b-HSD enzyme converts 1-Androsterone to 1-Androstenediol, and the 3b-HSD converts it to 1-Androstenedione. Both of these 1-AD metabolites can then be converted to 1-Testosterone. Although the 1-AD metabolites are known to have some anabolic and androgenic effects on their own, 1-Testosterone is probably where most of the effects come from with this steroid.

There is no conversion to estrogen so users will not experience bloat with this compound, nor will it have a dramatic effect on blood pressure. However one unique side effect that users have reported with this compound is a feeling of lethargy. (It appears that stacking 1-Androsterone with a nuero-active hormone such as DHEA can help reverse this effect)

1-Androsterone (and primarily its metabolites) have relatively potent androgenic effects, therefore gyno is almost never an issue. However, because of the androgenic potency, this compound could pose a mild hair loss risk for those prone to MPB. Because this steroid is non-17aa there should be less concern about it negatively affecting the HDL/LDL ratio.

Results from this compound generally take a couple weeks to be realized. Moderate gains of lean muscle mass and strength can be expected, but users should not expect rapid increases in size or weight with this compound since extra-cellular and intra-cellular water retention are very minimal. This makes the gains from this steroid fairly easy to maintain post cycle.

1-Androsterone will stack well with almost any compound. For more dramatic gains in size and strength it is recommended to stack this compound with an aromatizing steroid or possibly one of the progestational compounds listed elsewhere.

Common Clones:

1-T by Primordial Performance
1-Androsterone by Advanced Muscle Science (AMS)

Related Discussion

The Official 1-Androsterone Thread
Posted by Eric

References

1. 17beta-hydroxy-5alpha-androst-1-en-3-one (1-testosterone) is a potent androgen with anabolic properties.

A Friedel, et al.
Toxicol Lett, Aug 2006; 165(2): 149-55.

2. “Metabolism of 1-Dehydroandrostanes in Man”
Galletti and Gardi, et al.
J Steroid Biochem, 3 (1972), 933-936

Methoxygonadiene

Diagram of molecule

Chemical Name(s):

13-ethyl-3-methoxy-gona-2,5(10)-diene-17-one
13b-ethyl-3-methoxy-2,5 (10)-gona-diene-17-one
Chemical Formula: C20H28O2
Molecular Weight: 300
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 20%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Not listed as a controlled substance
Average Dose:
50-75mg/day standalone
25-50mg/day when stacked
Average Cycle Length: 4 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[][][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Libido

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

Methoxygonadiene is not a 17aa steroid so liver toxicity is not as harsh as with 17aa steorids, however the ethyl group on C-18 may make it slightly more toxic than a non-ethylated steroid (while increasing its oral bio-availability). The progestational activity of methoxygonadiene (once it is converted to its active metabolites) is considered to be slightly stronger than nandrolone.

In the stomach acid, the C-3 methoxy group is rapidly cleaved off and the double bond on the A ring at C-2 is lost. At this point, a 3-oxo is formed and a metabolite known as 13b-ethyl-nor-androstenedione is created, which is chemically similar to norbolethone, and probably where this compound gets most of its effects.

13b-ethyl-nor-androstenedione is about equal to testosterone in anabolic potency, yet less androgenic. This would make this compound fairly light on the hairline with minimal chance of acne or other androgenic side-effects.

With low androgenic activity, this compound may negatively affect the libido and erectile function. The lack of androgenic potency and progestational effects make this compound likely to cause gyno symptoms. Users could stack this compound with testosterone or one of its non-aromatizing metabolites to preserve DHT levels and possibly prevent these side-effects.

Users experience rapid weight gain from this compound partly due to subcutaneous water retention from the progestational activity. Therefore the overall gains from this compound may lead to a bloated appearance. Because of the progestational effects, users should avoid stacking this compound with other gyno aggravating compounds. Methoxygonadiene can aromatize to estrogen in small amounts, however not to any significant degree, therefore an aromatase inhibitor would provide little protection against this compounds side-effects.

Common Clones:

Revolt by KiloSports
M-LMG by Competitive Edge Labs (CEL)
X-MASS by Generic Labs
Deiselbolan by Mrsupps


Related Discussion

The Official Methoxygonadiene Thread
Posted by Eric

References

Anabolic Pharmacology
Seth Roberts (2009)

norDHEA

Diagram of molecule

Chemical Name(s):

5-estren-3b-ol-17-one
Nordehydroepiandrosterone
Chemical Formula: C18H26O2
Molecular Weight: 274
CAS: NA
Q Qatio: NA
Anabolic #: NA
Androgenic #: NA
Oral Bioavailability: Estimated at 4%
AR Binding Affinity: NA
SHBG Binding Affinity: NA
Half Life: NA
Legal Status (US): Not listed as a controlled substance
Average Dose:
300-600mg/day standalone
200-300mg/day when stacked
Average Cycle Length: 4-6 weeks
Stimulator
Inhibitor

-5
-4
-3
-2
-1

0
1
2
3
4
5

Muscle Gain

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Strength Gain

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Fat Gain (negative indicates fat loss)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Water Retention (extra-cellular bloat)

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Aggression

[]
-5
-4
-3
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-1

0
1
2
3
4
5

Libido

[][]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Acne

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Hair Loss

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Prostate Enlargement

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Liver Toxicity

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Lethargy

[]
-5
-4
-3
-2
-1

0
1
2
3
4
5

Characteristics

norDHEA is a non-methylated (non-17aa) pro-steroid. (naturally occurring in trace amounts in humans)

norDHEA can convert to the illegal anabolic steroid nandrolone by converting to norandrostenediol/norandrostenedione, and then to nandrolone. Nandrolone is known to have stronger anabolic effects than testosterone, yet weaker androgenic effects.

norDHEA will aromatize to estrogen less than regular DHEA, but because it is a nor compound it lacks strong androgenic metabolites. For instance, after nandrolone interacts with 5a-reductase, the metabolite dihydronandrolone (DHN) is formed, which is a weaker nor-version of DHT.

Ironically, the lack of estrogen conversion from norDHEA is probably balanced by the lack of androgenic potency and progestational effects, which makes the possibility of bloating and experiencing gyno about as likely as with regular DHEA.

One difference between norDHEA and DHEA that should be considered is the fact that norDHEA will have less androgenic effects, which may pose less risk of androgenic related hair loss and/or acne. This may be a smart choice for some men, and a decent choice for women looking for a moderately anabolic compound without much androgenic effect. (to avoid masculinizing side-effects)

Because of the low bio-availability, high doses must be used to notice gains in lean muscle mass and strength. Even with higher doses, the gains will be mild to moderate. Some bloat should be expected from the estrogenic and progestational effects of the nor-steroids. Because this steroid is non-17aa there should be less concern about it negatively affecting the HDL/LDL ratio.

Like the other DHEA derivatives, norDHEA would be useful in a transdermal application since the enzymes needed for the conversions to more powerful metabolites are concentrated in the skin and absorption through the skin using a good transdermal delivery cream could allow for 5-10x higher absorption than oral.

This compound would stack well with almost any other steroid, except those with progestational activity.

Common Clones:

Decavol by Advanced Muscle Science (AMS)


Related Discussion

The Official norDHEA Thread
Posted by Eric

References

Anabolic Pharmacology
Seth Roberts (2009)

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