Article source: MESO-Rx

Wired Magazine identifies promising medical and pharmaceutical candidates that may represent the next generation of performance enhancement for Olympic athletes. As with any performance enhancing drug, bodybuilders are always the first guinea pigs to experiment with these drugs in the real world. After they receive the seal of approval from the bodybuilding community, the new drugs are ready for athletes in other professional sports where procedures are refined to avoid detection by anti-doping agencies. Here is a list of Wired’s top ten list they feel will represent the future of doping that almost make anabolic steroids obsolete (“Cheats of Strength: 10 Next-Gen Olympic Doping Methods,” August 15).

• myostatin-inhibitor gene;
• hypoxia-inducible factor (HIF) stabilizers;
• vascular endothelial growth factor (VEGF);
• beta-endorphin gene;
• insulin-like growth factor (IGF-1);
• selective androgen receptor modulators (SARMs);
• synthetic blood substitutes e.g. Oxycyte;
• EPO-stimulating agents;
• muscle-fiber gene GW1516;
• mustard oil to increase EPO

Insulin-like Growth Factor 1 (IGF-1) peptides

SARMS – selective androgen receptor modulators S4 by CEM

Originally published at: Next Generation Performancing Enhancing Drugs for Bodybuilders

Article source: MESO-Rx

Researcher Jason Thomas, a graduate student in the doctoral program for synthetic organic chemistry at City University in New York, takes us inside the mind of a designer steroid chemist in an interview with Culturekiosque. Thomas describes a powerful tool that has the potential to create an infinite number of undetectable, designer anabolic steroids.

Once steroid designers specify the essential features and desired biological activity for steroid drug design, hundreds of novel designer steroids could be synthesized or simulated through Dynamic Combinatorial Chemistry (DCC) ["Designer Steroids: Speeding Evolution (and Filling Stadium Seats)" August 8].

Until now, human attempts to change testosterone’s anabolic, androgenic or estrogen-related properties have been relatively slow due to the fact that they have been addressed one at a time. A steroid designer imagines a certain compound, synthesizes it, and then tests it for effectiveness. This can take a matter of weeks or years. However, this process is about to undergo a drastic change. Dynamic Combinatorial Chemistry is a complicated process, so instead of explaining how it works I will simply provide the bottom line. Once steroid chemists have invested the necessary time into the chemical strategy for DCC, hundreds of novel steroid compounds can be synthesized and tested within a matter of minutes. The entire process is orchestrated by computers. The pharmaceutical sector has recently employed this process, and steroid manufactures will soon follow suit, if they haven’t already.

Since the four ring carbon structure was extremely complicated for synthetic chemists to create, they have historically created most steroidal compounds from diosgenin, a steroidal substance occuring naturally in the Mexican wild yam. This has limited the number of undetectable performance enhancing drugs that rogue chemists could synthesize for tested elite athletes. But with combinatorial chemistry, chemists are not limited by the four-ring steroid construction.

Steroid designers have been limited by the structure of the molecule. But that is going to change, because there are now new ways to make the molecule all together. Until now, you started with diosgenin. You go to progesterone, then you make all other anabolic steroids. You can only do but so much because that basic structure is all there. Now, they are putting these things together from different pieces and in the next few years they might find something as anabolic as pure testosterone but with none of the side effects. For the moment, this is not possible as long as they use diosgenin as the initial compound. In my opinion, designer steroids are going to blow up in the next couple of years. Instead of making 50 different molecules they will be able to make 50 million different combinations. It will be like evolution all over again [without the limitations of time]. (emphasis added)

The steroid chemist behind the BALCO steroid scandal, Patrick Arnold of Ergopharm, explains that this is how pharmaceutical companies are creating a new class of drugs known as Selective Androgen Receptor Modulators (SARMs) that are not “steroids” but could potentially have significant performance enhancing effects. SARMs have long promised all the benefits of anabolic steroids with none of the side effects. Furthermore, Patrick Arnold suggests “anabolic” performance enhancing non-steroidal drug that bypass the four-ring steroid structure could be effective at eluding detection by anti-doping agencies.

This is the type of thing they use in the development of SARMS, which are non steroidal androgens/anabolics.

Why confine you to the four ring structure of steroids when that is too easy for the drug testers to figure out (steroid backbones have unique signatures on the mass spec)? And (in the case of legit medicine) too politically incorrrect.

The use of dynamic combinatorial chemistry to create novel (undetectable) designer steroids could prove a more serious challenge to anti-doping agencies than other emerging doping methods such as synthetic blood doping and gene doping.

Originally published at: Infinite Number of Undetectable Designer Steroids with Combinatorial Chemistry

Article source: MESO-Rx

Q: Are SARMS effective for post cycle therapy (PCT)? I’ve read about studies showing that SARMs are only suppressive at dosages greater than 50mg per day. So wouldn’t SARMS be ideal for PCT since they didn’t interfere with testosterone production?

A: It needs to be kept in mind that there are situations where low dose anabolic steroid also will not be found to cause “significant” suppression in a study.

The fact that SARMS, at anabolically-ineffective doses, have been found in the literature to not exhibit statistically-significant suppression — which does not mean no suppression — does not mean that they don’t cause it.

We could as well say that Dianabol causes no suppression, as I can point to a study showing it to be “non-suppressive” (or more accurately, statistically significant suppression was not found.)

And for that matter, I can find the above at a dosing of 50 mg/day, which is more anabolic than I expect is the case for the SARM doses studied.

But, of course, Dianabol is in fact suppressive, as I expect is the case with the SARMs as well.

You’re not going to have the magic of activating the androgen receptor without getting the suppression that results from activating the androgen receptor.

I don’t know of reason to believe that, analogously to the SERMs, there is an effect with the SARMs where they are active in muscle but not in the hypothalamus and pituitary.

It really has seemed to me that the term SARM (selective androgen receptor modulator) is simply a gimmick to make the drugs sound fundamentally different from anabolic steroids and thus to perhaps escape the stigma that society has placed on anabolic steroids, rather than being a matter of real pharmacology.

Synthetic anabolic steroids are “selective” too — that is where the whole “anabolic/androgen ratio” thing, or ratio between activities at the levator ani of the rat vs the prostate, relative to testosterone — comes in.

The fact that the SARMs do not have a steroid skeleton doesn’t change anything pharmacologically, and doesn’t magically give them non-suppressive yet anabolic properties.

SARMS – selective androgen receptor modulators S4 by CEM

Originally published at: Are SARMs Effective for Post Cycle Therapy?

Article source: MESO-Rx

Nelson Vergel, author of “Testosterone: A Man’s Guide” discusses several recently approved and future testosterone-related products:

Underarm Spray:

In an attempt to reduce the risk of transference of testosterone to others, a company called Acrux  developed Axiron, a testosterone underarm product.  Axiron has been studied in 155 men in six countries and 26 sites. The product got approved last November (https://investor.lilly.com/releasedetail2.cfm?ReleaseID=532924 )

With this product men were permitted to use an underarm deodorant or antiperspirant during the trial. More than half of the men continued to apply an underarm deodorant or antiperspirant as part of their daily routine.  An analysis of these subgroups showed that this had no impact on the efficacy of Axiron treatment.

Two percent gel:

The same company that is hoping to launch Aveed (Nebido) in the United States, Endo Pharmaceuticals, recently got FDA approval for Fortesta (TM) (testosterone) 2% Gel for men diagnosed with low testosterone.  (http://www.fortestagel.com/ )

Aveed (Nebido outside the United States)

There is a new long-acting product being reviewed by the FDA in the United States called Aveed (Nebido is the brand name worldwide) that contains testosterone undecanoate, which is injected at a dose of 1,000 mg in Europe (the FDA may not allow that large of a dose in one injection, though) and which produces sustained total testosterone levels above 400 nanograms/dl in four to five months.

This testosterone ester may stay longer in your system so that less frequent injections may be needed. The injection is usually given once every 10 to 14 weeks, though the frequency will depend on your individual testosterone levels. After your first injection you may be asked to come back for another injection at week six. The company claims that only five injections a year are needed.

In an open-label study which enrolled 130 hypogonadal men with blood total testosterone levels below 300 ng/dL at study entry, Aveed was dosed as an intramuscular injection (750 mg) at baseline, at week four, and then every 10 weeks throughout the remainder of the 21-month study. Approximately 70 percent of patients completed all injections and 94 percent of them had total testosterone from 300 to 1,000 nanograms/ml through the entire study.

After  Nebido was approved in Europe a small number of European patients experienced respiratory symptoms immediately following an intramuscular injection of 1000 mg in a  4 cc injection volume, (versus the 750 mg, 3 cc injection volume used in the United States). The makers of Nebido believe, and the FDA concurs, that the reaction is likely the result of a small amount of the oily solution immediately entering the vascular system from the injection site.  This known yet uncommon complication of oil-based depot injections may be related to inappropriate injection technique or site.

The problem is characterized by short-term reactions involving an urge to cough or a shortness of breath. In some rare cases the reaction had been classified as serious or the patient had experienced other symptoms such as dizziness, flushing or fainting. In U.S. clinical trials of Nebido 750 mg (3 cc injection volume), the proposed dose in the U.S., there was a single, mild, non-serious case of oil-based coughing.

The U.S. manufacturer, Endo Pharmaceuticals, is gathering data to address concerns about the respiratory symptoms. It is not known how much longer it will take the get this product approved in the United States as of June 2010. And even if it gets approved, it may not be widely available for people to buy through private health insurance if the company decides to price it as high as gels.

Libigel (testosterone gel for women)

Results of Phase II

Treatment with LibiGel in BioSante’s Phase II clinical trial significantly increased satisfying sexual events in surgically menopausal women suffering from female sexual dysfunction (FSD). The Phase II trial results showed LibiGel significantly increased the number of satisfying sexual events by 238% versus baseline (p<0.0001); this increase also was significant versus placebo (p<0.05). In this study the effective dose of LibiGel produced testosterone blood levels within the normal range for pre-menopausal women and had a safety profile similar to that observed in the placebo group. In addition, no serious adverse events and no discontinuations due to adverse events occurred in any subject receiving LibiGel. The Phase II clinical trial was a double-blind, placebo-controlled trial, conducted in the United States.

Progress and Plans in Phase III

On January 24, 2008, the US FDA notified BioSante that it had completed and reached agreement with BioSante on a Special Protocol Assessment (SPA) for BioSante’s Phase III safety and efficacy clinical trials of LibiGel in the treatment of hypoactive sexual desire syndrome (HSDD).

Both Phase III safety and efficacy trials are underway and are double-blind, placebo-controlled trials that will enroll approximately 500 surgically menopausal women each for six-months of treatment.

The last issue beyond efficacy has been the question of safety of testosterone therapy in women, even though there are no data to indicate that low dose testosterone causes any serious adverse events in women. Therefore, in addition to the two Phase III safety and efficacy trials described above, BioSante is conducting one Phase III cardiovascular safety study of LibiGel. The safety study is a randomized, double-blind, placebo-controlled, multi-center, cardiovascular events driven study of between 2,400 and 3,100 women exposed to LibiGel or placebo for 12 months. At the end of 12 months BioSante intends to submit a LibiGel new drug application (NDA) for review and possible approval by FDA. BioSante will continue to follow the women enrolled in the safety study for an additional four years after the NDA submission and possible approval of LibiGel.

BioSante already fully enrolled the women in this multi-national cardiovascular-events-driven safety trial. Therefore, BioSante expects to be able to submit the LibiGel NDA for a potential approval and launch in 2011.( http://www.biosantepharma.com/LibiGel.php )

Androxal® (isomer of clomiphene or Clomid) for men
A company called Repros in Houston is attempting to get eventual approval of their clomiphene isomer Androxal . They completed a small Phase 2b proof-of-concept trial in men being treated for low testosterone levels who want to improve or maintain their fertility and/or sperm number and function.

While it remains to be seen if this clomiphene isomer has any effect on sexual function as a sole therapy without testosterone replacement remains to be seen.  I personally have my reservations about this claim.

Selective Androgen Receptor Modulators

Oral selective androgen receptor modulators (SARMs) are investigational agents.  Studied since 1998, they are still very much in the infancy of their development and marketing. SARMs may be able to provide the benefits of increased muscle mass and bone density, and fat loss that testosterone and other traditional anabolic/androgenic steroids provide but without the unwanted side effects (liver dysfunction or prostatic enlargement). SARMs are not intended to be a form of testosterone replacement therapy. I know, I know – so why am I talking about them? Besides replacement therapy, testosterone and other anabolics can be useful in the treatment of certain aspects of disease.  This is a topic close to my heart since this kind of medical use saved my life and that of many others.  Excuse me while I digress from the current topic.

Weight loss is common in a number of medical conditions (e.g., HIV/AIDS, burns, trauma, cancer, chronic obstructive pulmonary disease).   The loss of too much weight, especially muscle mass, increases the risk of complications, including death.

Cancer cachexia, or the unintentional loss of muscle mass and body weight, may lead to a loss of protein stores, severe weakness and fatigue, immobility and a loss of independence.  It can impair the ability to tolerate and to respond to cancer treatments. An estimated 1.3 million cancer patients in the United States have cancer cachexia. Cancer-induced muscle wasting is thought to be responsible for greater than 20 percent of cancer deaths.

There are no drugs currently approved for the treatment of cancer cachexia.. Physicians often prescribe different medications that have the side of effect of increased appetite in an attempt to fight weight loss. Megace, a progesterone-based appetite stimulant, is commonly used to increase weight. Unfortunately most of this weight consists of fat (lean body mass, not fat gain, has been correlated to increased survival.) Megace also increases the chances for blood clots and bone death.

Anabolics like nandrolone undecanoate and oxandrolone have been prescribed by progressive physicians to treat wasting in patients with non-androgen dependent cancers (colon, throat, lung, stomach, etc.). Androgens are contraindicated for people with prostate and breast can­cer, as they can worsen these types of cancers. Anabolics are usually prescribed along with testosterone replacement even if the patient starting them for wasting syndrome has normal testosterone levels. Anabolics have the same inhibiting effect as testosterone on the HPGA and they decrease testosterone blood levels if no testosterone is used in combination with them. Many doctors fail to remember this and treat wasting patients with anabolics alone, which results in loss of sexual function in patients using them for a few weeks. So, testosterone replacement therapy is essential when prescribing oxandrolone or nandrolone to patients with HIV, cancer, or other debilitating wasting conditions.

Oxandrolone (brand name: Oxandrin), an oral anabolic agent, is FDA approved as “adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of bone pain frequently accompanying osteoporosis.” (From the product’s package insert). Adjunctive means it is an additive or supportive therapy but it does not treat the underlying condition directly. In some patients and depending on the dose and duration, oxandrolone can increase liver enzymes and/or decrease high density cholesterol (HDL), the good cholesterol. Both side effects reverse when the drug is stopped. The usual dose for men is 20 mg/day (it can be used in women with wasting at 5-10 mg/day). As previously mentioned, testosterone is needed with it since it reduces testosterone and potentially sexual function after a few weeks in some patients. It is expensive at $1200 per month for 20 mg/day but insurance companies pay for it with some restrictions.

Nandrolone decanoate (brand name: Deca Durabolin), an injectable anabolic steroid, is the most studied anabolic agent for wasting syndrome. It requires a weekly injection of 200-400 mg plus testosterone replacement (100-200 mg testosterone cypionate a week or 5-10 grams of testosterone gel per day). Nandrolone is legally prescribed in an off-label manner to treat wasting syndrome since it is indicated for the management of the anemia of renal insufficiency and has been shown to increase hemoglobin and red cell mass. No liver toxicity has been observed, but decreases in HDL and other side effects typical of testosterone have been observed in those using higher doses.   Nandrolone is no longer available in regular pharmacies but it is available cheaply in compounding pharmacies by prescription (there is a list in the Appendix section). The average cost for 200 mg/week is $40 per month and it may produce the same effects on lean body mass than oxandrolone at 20/day.

The only drug that is actually approved in the United States for HIV wasting syndrome that does not require an off label prescription is Serostim (human growth hormone made by Serono), although doctors prescribe oxandrolone and nandrolone a lot more  due to cost and lower side effects. Depending on the dose used, Serostim can cost $3000 to $6000 per month.  This product can cause joint aches, water retention, and diabetes.  More details on treatment of wasting syndrome can be found in “Built to Survive” which I co-authored with Michael Mooney (the book is available on Amazon.com in a print or electronic version and has been translated into Spanish).

So back to the SARMs:

Ostarine is an oral agent that has demonstrated the ability to increase lean body mass and improve muscle strength and performance in postmenopausal women, elderly men, and men and women with cancer cachexia. Ostarine is made by the company GTx’s and has been studied in seven Phase I, Phase II, and Phase IIb clinical trials in 582 subjects.

It had no serious adverse events reported. Ostarine also exhibited no apparent change in measurements of serum prostatic specific antigen (PSA), sebum production (which causes acne), or decreases in blood levels of LH (which hints that it may not affect the HPGA at the doses tested).

SARMs have anecdotally not helped increase sexual function, so they probably will not replace testosterone for treatment of hypogonadism. They also decrease the body’s production of testosterone, just like anabolic steroids do.  So, testosterone replacement will most probably be still required with their use for illness or aging associated loss of lean body mass.  We await more data on these interesting compounds as they may have the same clinical benefits as anabolic steroids without the stigma and possibly without their side effects.

Axiron – underarm testosterone treatment

Originally published at: Recently Approved and Future Testosterone Related Products

Article source: MESO-Rx

Q: Are SARMs (selective androgen receptor modulators) a good idea to add to your post cycle therapy (PCT)? And if so, why do you not see them being used during PCT by many people? And lastly, does anyone think SARMs are going to eventually replace anabolic steroids? Any info would be greatly appreciated.

A: I don’t think they are good to add to PCT.

I haven’t found any evidence that any SARM gives less suppression for given anabolic effect than is the case for anabolic steroids such as say Primobolan, Masteron, or oxandrolone.

I know I’m beating this point into the ground but it’s something that others just don’t say enough — actually I virtually never, anywhere, see people making this point except where the subject at hand is statistics: The phrases “no significant (x) was found” or even “There was no change in (x)” appearing in scientific papers are basically weasel language. The technical meaning is VERY different than what it could appear to mean.

The meaning is only that, because of random variation and the small number of subjects, no effect COULD have been detected that smaller than some given amount — which sometimes is quite large! — and the study found that they saw no effect of at least that size.

It does not at all mean that a very substantial, important effect may not have occurred!

For whatever reason, many scientists prefer to write in a manner that makes it appear that there most likely was no effect without telling directly how large or small their threshold of detection was. I guess it’s better sounding to omit “But we couldn’t have found any effect smaller than X anyway,” particularly where X is a large amount!

So you can have reports in scientific literature such as anabolic steroids, at the dose studied, providing NO muscle mass gains or performance enhancement.

Correct conclusion, what change there was, they couldn’t detect to statistical significance. Not the the benefit may not be significant, in the sense we may mean the word!

All that was to bring some sense to the fact that a study can, with this way of using words, make it appear that SARMs are non-inhibitory whether or not that is so.

I don’t at all think that that is the case. Taking a SARM during PCT is I think the equivalent of taking a pharmaceutical anabolic steroid during PCT.

In some instances a careful use can make sense, but in general, it sets back recovery.

And even in those instances, I’d just use the anabolic steroid.

(Editor’s note: For more discussion, see “SARMs S4 and PCT?“.

Ask Bill Roberts about anabolic steroids

Originally published at: SARMs for Post Cycle Therapy?

Article source: MESO-Rx

Will Selective Androgen Receptor Modulators Replace Anabolic Steroids?

Oral selective androgen receptor modulators (SARMs) are investigational agents. Studied since 1998, they are still very much in the infancy of their development and marketing. SARMs may be able to provide the benefits of increased muscle mass and bone density, and fat loss that testosterone and other traditional anabolic/androgenic steroids provide but without the unwanted side effects (prostatic enlargement). SARMs are not intended to be a form of testosterone replacement therapy. So, why am I talking about them?

Besides replacement therapy, testosterone and other anabolics can be useful in the treatment of certain aspects of disease. This is a topic close to my heart since this kind of medical use saved my life and that of many others. I spent years researching it to co-write the book “Built to Survive: A Comprehensive Guide to the Medical Use of Anabolic Therapies, Nutrition and Exercise for HIV+ Men and Women” (published in 1999 and then two more editions a few years later and available on amazon.com). Excuse me while I digress from the current topic.

Unintentional weight loss is common in a number of medical conditions (e.g., HIV/AIDS, burns, trauma, cancer, chronic obstructive pulmonary disease). The loss of too much weight, especially muscle mass, increases the risk of complications, including death. Dr. Donald Kotler from New York was able to plot body cell mass data versus mortality from different pathologies and found that once you lose 50% of your normal body cell mass, you die. So, there seems to be a minimum amount of lean tissue that the body needs to stay alive and functioning. Fat mass has not been correlated to increased survival, although losing fat has been proven to improve cardiovascular risks.

Cancer cachexia, or the unintentional loss of muscle mass and body weight, may lead to a loss of protein stores, severe weakness and fatigue, immobility and a loss of independence. It can impair the ability to tolerate and to respond to cancer treatments. An estimated 1.3 million cancer patients in the United States have cancer cachexia. Cancer-induced muscle wasting is thought to be responsible for greater than 20 percent of cancer deaths.

There are no drugs currently approved for the treatment of cancer cachexia. Physicians often prescribe different medications that have the side of effect of increased appetite in an attempt to fight weight loss. Megace, a progesterone-based appetite stimulant, is commonly used to increase weight. Unfortunately most of this weight consists of fat (lean body mass, not fat gain, has been correlated to increased survival.) Megace also increases the chances for blood clots, high blood sugar and bone death.

Anabolics like nandrolone undecanoate and oxandrolone have been prescribed by progressive physicians to treat wasting in patients with non-androgen dependent cancers (colon, throat, lung, stomach, etc.) and HIV associated wasting. Androgens are contraindicated for people with prostate and breast cancer, as they can worsen these types of cancers.

Anabolics are usually prescribed along with testosterone replacement even if the patient starting them for wasting syndrome has normal testosterone levels. Anabolics have the same inhibiting effect as testosterone on the HPGA and they decrease testosterone blood levels if no testosterone is used in combination with them. Many doctors fail to remember this and treat patients who are wasting with anabolics alone, which results in loss of sexual function in patients using them for a few weeks. So, testosterone replacement is essential as an adjunctive therapy when prescribing oxandrolone or nandrolone to patients with HIV, cancer, or other debilitating wasting conditions.

Oxandrolone (brand name: Oxandrin), an oral anabolic agent, is FDA approved as “adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of bone pain frequently accompanying osteoporosis.” (From the products package insert).

Adjunctive means it is an additive or supportive therapy but it does not treat the underlying condition directly. In some patients and depending on the dose and duration, oxandrolone can increase liver enzymes and/or decrease high density cholesterol (HDL), the good cholesterol. Both side effects reverse when the drug is stopped. The usual dose for men is 20 mg/ day (it can be used in women with wasting at 5-10 mg/day). As previously mentioned, testosterone is needed with it since it reduces testosterone and potentially sexual function after a few weeks in some patients. It is expensive at $1200 per month for 20 mg/day but insurance companies pay for it with some restrictions.

Nandrolone decanoate (brand name: Deca Durabolin), an injectable anabolic steroid, is the most studied anabolic agent for wasting syndrome. It requires a weekly injection of 200-400 mg plus testosterone replacement (100-200 mg testosterone cypionate a week or 5-10 grams of testosterone gel per day).

Nandrolone is legally prescribed in an off-label manner to treat wasting syndrome since it is indicated for the management of the anemia of renal insufficiency and has been shown to increase hemoglobin and red cell mass. No liver toxicity has been reported in the many studies, but decreases in HDL and other side effects typical of testosterone have been observed in those using higher doses. Nandrolone is no longer available in regular pharmacies but it is available cheaply in compounding pharmacies by prescription (there is a list in the Appendix section). The average cost for 200 mg/week is $40 per month and it may produce the same effects on lean body mass than oxandrolone at 20 mg/day. Both nandrolone and oxandrolone can have the same side effects of testosterone (polycythemia and gynecomastia).

The only drug that is actually approved in the United States for HIV wasting syndrome that does not require an off label prescription is Serostim (human growth hormone made by Serono), although doctors prescribe oxandrolone and nandrolone a lot more due to cost and lower side effects. Depending on the dose used, Serostim can cost $3000 to $6000 per month. This product can cause joint aches, water retention, and irreversible diabetes. More details on treatment of wasting syndrome can be found in the previously mentioned book “Built to Survive” which I co- authored with Michael Mooney (the book is available on Amazon.com in a print or electronic version and has been translated into Spanish).

Low doses of growth hormone (growth hormone replacement therapy) are commonly prescribed in antiaging and men’s clinics. It is a controversial topic that is beyond of the scope of this book. A lot of details are provided in ‘Built to Survive.”

So back to the SARMs:

SARMs are aimed to have the same benefits as anabolics but without the side effects.

Ostarine is an oral agent that has demonstrated the ability to increase lean body mass and improve muscle strength and performance in postmenopausal women, elderly men, and men and women with cancer cachexia. Ostarine is made by the company GTx’s and has been studied in seven Phase I, Phase II, and Phase IIb clinical trials in 582 subjects.

It had no serious adverse events reported, although I have yet to see the data. Ostarine also exhibited no apparent change in measurements of serum prostatic specific antigen (PSA), sebum production (which causes acne), or decreases in blood levels of LH (which hints that it may not affect the HPGA at the doses tested). I have not seen LDL or HDL and hematocrit or hemoglobin data on this product to assess its effect on lipids and red blood cells, respectively. I am also curious about its effect on liver enzymes.

SARMs have anecdotally not helped increase sexual function, so they probably will not replace testosterone for treatment of hypogonadism. They also decrease the body’s production of testosterone, just like anabolic steroids do. So, testosterone replacement will most probably be still required with their use for illness or aging associated loss of lean body mass. We await more data on these interesting compounds as they may have the same clinical benefits as anabolic steroids without the stigma and possibly without their side effects.

For more information read: Testosterone: A Man’s Guide

Selective Androgen Receptor Modulators (SARMs)

Originally published at: Selective Androgen Receptor Modulators for HIV Wasting and Cancer Cachexia

Article source: MESO-Rx

Q: “How should I incorporate SARMs (selective androgen receptor modulators) into my steroid cycle or into PCT?”

You should not do so.

Various authors in the scientific literature have tried to make it appear that in contrast to anabolic steroids, SARMs somehow will have an improved side effect profile or an increase in dissociation between anabolic and androgenic effects. But other than in the regard of liver toxicity with oral use, where most oral anabolic steroids have an issue and the SARMs do not, the evidence isn’t there. There isn’t even a reasonable argument as to how they might offer an improvement.

In my opinion, the only difference between these compounds and anabolic steroids is in a structural feature that makes no difference to the user but apparently makes a difference to society, namely whether the compound has a steroid skeleton or not.

You could call them politically correct androgens that have had the socially-unacceptable word “steroid” removed from them.

And that’s it.

That really is no reason to include them in an anabolic steroid cycle, nor is there any other reason.

There’s even less reason to include them in PCT, as they are suppressive of LH production.

Using SARMs During Steroid Cycles or During PCT

Originally published at: The Use of SARMs During Steroid Cycles or PCT

Article source: MESO-Rx

Q: Are SARMs (selective androgen receptor modulators) a good idea to add to your post cycle therapy (PCT)? And if so, why do you not see them being used during PCT by many people? And lastly, does anyone think SARMs are going to eventually replace anabolic steroids? Any info would be greatly appreciated.

A: I don’t think they are good to add to PCT.

I haven’t found any evidence that any SARM gives less suppression for given anabolic effect than is the case for anabolic steroids such as say Primobolan, Masteron, or oxandrolone.

I know I’m beating this point into the ground but it’s something that others just don’t say enough — actually I virtually never, anywhere, see people making this point except where the subject at hand is statistics: The phrases “no significant (x) was found” or even “There was no change in (x)” appearing in scientific papers are basically weasel language. The technical meaning is VERY different than what it could appear to mean.

The meaning is only that, because of random variation and the small number of subjects, no effect COULD have been detected that smaller than some given amount — which sometimes is quite large! — and the study found that they saw no effect of at least that size.

It does not at all mean that a very substantial, important effect may not have occurred!

For whatever reason, many scientists prefer to write in a manner that makes it appear that there most likely was no effect without telling directly how large or small their threshold of detection was. I guess it’s better sounding to omit “But we couldn’t have found any effect smaller than X anyway,” particularly where X is a large amount!

So you can have reports in scientific literature such as anabolic steroids, at the dose studied, providing NO muscle mass gains or performance enhancement.

Correct conclusion, what change there was, they couldn’t detect to statistical significance. Not the the benefit may not be significant, in the sense we may mean the word!

All that was to bring some sense to the fact that a study can, with this way of using words, make it appear that SARMs are non-inhibitory whether or not that is so.

I don’t at all think that that is the case. Taking a SARM during PCT is I think the equivalent of taking a pharmaceutical anabolic steroid during PCT.

In some instances a careful use can make sense, but in general, it sets back recovery.

And even in those instances, I’d just use the anabolic steroid.

(Editor’s note: For more discussion, see “SARMs S4 and PCT?“.

Ask Bill Roberts about anabolic steroids

Originally published at: SARMs for Post Cycle Therapy?

Article source: MESO-Rx

Will Selective Androgen Receptor Modulators Replace Anabolic Steroids?

Oral selective androgen receptor modulators (SARMs) are investigational agents. Studied since 1998, they are still very much in the infancy of their development and marketing. SARMs may be able to provide the benefits of increased muscle mass and bone density, and fat loss that testosterone and other traditional anabolic/androgenic steroids provide but without the unwanted side effects (prostatic enlargement). SARMs are not intended to be a form of testosterone replacement therapy. So, why am I talking about them?

Besides replacement therapy, testosterone and other anabolics can be useful in the treatment of certain aspects of disease. This is a topic close to my heart since this kind of medical use saved my life and that of many others. I spent years researching it to co-write the book “Built to Survive: A Comprehensive Guide to the Medical Use of Anabolic Therapies, Nutrition and Exercise for HIV+ Men and Women” (published in 1999 and then two more editions a few years later and available on amazon.com). Excuse me while I digress from the current topic.

Unintentional weight loss is common in a number of medical conditions (e.g., HIV/AIDS, burns, trauma, cancer, chronic obstructive pulmonary disease). The loss of too much weight, especially muscle mass, increases the risk of complications, including death. Dr. Donald Kotler from New York was able to plot body cell mass data versus mortality from different pathologies and found that once you lose 50% of your normal body cell mass, you die. So, there seems to be a minimum amount of lean tissue that the body needs to stay alive and functioning. Fat mass has not been correlated to increased survival, although losing fat has been proven to improve cardiovascular risks.

Cancer cachexia, or the unintentional loss of muscle mass and body weight, may lead to a loss of protein stores, severe weakness and fatigue, immobility and a loss of independence. It can impair the ability to tolerate and to respond to cancer treatments. An estimated 1.3 million cancer patients in the United States have cancer cachexia. Cancer-induced muscle wasting is thought to be responsible for greater than 20 percent of cancer deaths.

There are no drugs currently approved for the treatment of cancer cachexia. Physicians often prescribe different medications that have the side of effect of increased appetite in an attempt to fight weight loss. Megace, a progesterone-based appetite stimulant, is commonly used to increase weight. Unfortunately most of this weight consists of fat (lean body mass, not fat gain, has been correlated to increased survival.) Megace also increases the chances for blood clots, high blood sugar and bone death.

Anabolics like nandrolone undecanoate and oxandrolone have been prescribed by progressive physicians to treat wasting in patients with non-androgen dependent cancers (colon, throat, lung, stomach, etc.) and HIV associated wasting. Androgens are contraindicated for people with prostate and breast cancer, as they can worsen these types of cancers.

Anabolics are usually prescribed along with testosterone replacement even if the patient starting them for wasting syndrome has normal testosterone levels. Anabolics have the same inhibiting effect as testosterone on the HPGA and they decrease testosterone blood levels if no testosterone is used in combination with them. Many doctors fail to remember this and treat patients who are wasting with anabolics alone, which results in loss of sexual function in patients using them for a few weeks. So, testosterone replacement is essential as an adjunctive therapy when prescribing oxandrolone or nandrolone to patients with HIV, cancer, or other debilitating wasting conditions.

Oxandrolone (brand name: Oxandrin), an oral anabolic agent, is FDA approved as “adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of bone pain frequently accompanying osteoporosis.” (From the products package insert).

Adjunctive means it is an additive or supportive therapy but it does not treat the underlying condition directly. In some patients and depending on the dose and duration, oxandrolone can increase liver enzymes and/or decrease high density cholesterol (HDL), the good cholesterol. Both side effects reverse when the drug is stopped. The usual dose for men is 20 mg/ day (it can be used in women with wasting at 5-10 mg/day). As previously mentioned, testosterone is needed with it since it reduces testosterone and potentially sexual function after a few weeks in some patients. It is expensive at $1200 per month for 20 mg/day but insurance companies pay for it with some restrictions.

Nandrolone decanoate (brand name: Deca Durabolin), an injectable anabolic steroid, is the most studied anabolic agent for wasting syndrome. It requires a weekly injection of 200-400 mg plus testosterone replacement (100-200 mg testosterone cypionate a week or 5-10 grams of testosterone gel per day).

Nandrolone is legally prescribed in an off-label manner to treat wasting syndrome since it is indicated for the management of the anemia of renal insufficiency and has been shown to increase hemoglobin and red cell mass. No liver toxicity has been reported in the many studies, but decreases in HDL and other side effects typical of testosterone have been observed in those using higher doses. Nandrolone is no longer available in regular pharmacies but it is available cheaply in compounding pharmacies by prescription (there is a list in the Appendix section). The average cost for 200 mg/week is $40 per month and it may produce the same effects on lean body mass than oxandrolone at 20 mg/day. Both nandrolone and oxandrolone can have the same side effects of testosterone (polycythemia and gynecomastia).

The only drug that is actually approved in the United States for HIV wasting syndrome that does not require an off label prescription is Serostim (human growth hormone made by Serono), although doctors prescribe oxandrolone and nandrolone a lot more due to cost and lower side effects. Depending on the dose used, Serostim can cost $3000 to $6000 per month. This product can cause joint aches, water retention, and irreversible diabetes. More details on treatment of wasting syndrome can be found in the previously mentioned book “Built to Survive” which I co- authored with Michael Mooney (the book is available on Amazon.com in a print or electronic version and has been translated into Spanish).

Low doses of growth hormone (growth hormone replacement therapy) are commonly prescribed in antiaging and men’s clinics. It is a controversial topic that is beyond of the scope of this book. A lot of details are provided in ‘Built to Survive.”

So back to the SARMs:

SARMs are aimed to have the same benefits as anabolics but without the side effects.

Ostarine is an oral agent that has demonstrated the ability to increase lean body mass and improve muscle strength and performance in postmenopausal women, elderly men, and men and women with cancer cachexia. Ostarine is made by the company GTx’s and has been studied in seven Phase I, Phase II, and Phase IIb clinical trials in 582 subjects.

It had no serious adverse events reported, although I have yet to see the data. Ostarine also exhibited no apparent change in measurements of serum prostatic specific antigen (PSA), sebum production (which causes acne), or decreases in blood levels of LH (which hints that it may not affect the HPGA at the doses tested). I have not seen LDL or HDL and hematocrit or hemoglobin data on this product to assess its effect on lipids and red blood cells, respectively. I am also curious about its effect on liver enzymes.

SARMs have anecdotally not helped increase sexual function, so they probably will not replace testosterone for treatment of hypogonadism. They also decrease the body’s production of testosterone, just like anabolic steroids do. So, testosterone replacement will most probably be still required with their use for illness or aging associated loss of lean body mass. We await more data on these interesting compounds as they may have the same clinical benefits as anabolic steroids without the stigma and possibly without their side effects.

For more information read: Testosterone: A Man’s Guide

Selective Androgen Receptor Modulators (SARMs)

Originally published at: Selective Androgen Receptor Modulators for HIV Wasting and Cancer Cachexia

Article source: MESO-Rx

Q: “How should I incorporate SARMs (selective androgen receptor modulators) into my steroid cycle or into PCT?”

You should not do so.

Various authors in the scientific literature have tried to make it appear that in contrast to anabolic steroids, SARMs somehow will have an improved side effect profile or an increase in dissociation between anabolic and androgenic effects. But other than in the regard of liver toxicity with oral use, where most oral anabolic steroids have an issue and the SARMs do not, the evidence isn’t there. There isn’t even a reasonable argument as to how they might offer an improvement.

In my opinion, the only difference between these compounds and anabolic steroids is in a structural feature that makes no difference to the user but apparently makes a difference to society, namely whether the compound has a steroid skeleton or not.

You could call them politically correct androgens that have had the socially-unacceptable word “steroid” removed from them.

And that’s it.

That really is no reason to include them in an anabolic steroid cycle, nor is there any other reason.

There’s even less reason to include them in PCT, as they are suppressive of LH production.

Using SARMs During Steroid Cycles or During PCT

Originally published at: The Use of SARMs During Steroid Cycles or PCT

Q: “You’ve previously written that SARMs such as Ostarine are more hype than reality. They imitate the name of SERMs, claiming to be “Selective Androgen Receptor Modulators” to have a name that might go over better with the public than “anabolic steroids” does. Well you didn’t say exactly that but that was what I got out of it. Ostarine does seem to offer nothing over existing anabolic steroids, I see no reason to add it to a cycle. But I’ve just read about RAD-140. This one sounds like the real deal. What say you?”

A: RAD-140 is indeed very interesting.

First, as to terminology. An “agonist” is a molecule which activates a receptor. A full agonist, at high enough concentration in the blood or test medium, can achieve 100% effect from the receptors. A partial agonist, also called a weak agonist, can only ever achieve partial effect from the receptors. In some cases it binds the receptors, but no activity results. In some cases, the presence of a partial agonist can reduce the effect of a full agonist that is also present. For example, in humans estriol, a weak agonist, can reduce the effect of estradiol, a full agonist.

The concept of a modulator, as opposed to being a simple agonist of some type, is that when the molecule binds to a receptor, in some tissues the receptor will act in one way and in other tissues, a different way.

Tamoxifen (Nolvadex) or clomiphene (Clomid), for example, cause estrogen receptors in breast tissue to work differently than when estradiol binds the receptors, but in bone tissue causes the receptors to work in the same way as when estradiol binds.

So what would be the significance to androgens? In muscle cells we’d want the molecule to work in the same way that testosterone does. But in tissues that we don’t want androgenic effect, ideally we’d want the molecule to work differently at the androgen receptor than testosterone does.

In terms of the most commonly measured effect – levator ani growth vs prostate growth* – we already had this with the synthetic anabolic steroids. The difference in effect was calculated as the anabolic/androgenic ratio. Values for this ratio reached as high as a reported 20:1 with norbolethone, 16:1 with norethandrolone, and 12:1 for oxandrolone.

Ostarine and some others showed anabolic/androgenic ratios comparable to this, though a little better. Differences were arguably more quantitative than being in kind or class, particularly given that the assay method gives quite variable results from one study to another.

RAD-140, however, has shown an anabolic/androgenic ratio of about 90:1, and actually antagonizes (partially blocks) the effect of testosterone on the prostate. That’s an impressive demonstration.

Now as to whether RAD-140 has less activity in the scalp or, for women, the larynx than synthetic anabolic steroids, that would be a differing question which may have a differing outcome.

It’s a very interesting compound, and could be of value as part of a steroid stack due to its partial testosterone blocking effect in the prostate.

* In the rat, the muscle sometimes called the levator ani acts to elevate the penis. While it responds differently to anabolic steroids than skeletal muscle cells in general do, in the anabolic/androgenic ratio measurements levator ani growth is used as a guess factor for general effect on skeletal muscle growth. Prostate growth provides some useful information on effect on the prostate and is used as a guess factor for effect on other tissues such as the scalp and the larynx, but is of no proven value for estimating effect on those tissues.

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