02-21-2012, 12:11 AM
SARMs: Successors to Anabolic Steroids?
Not ready for prime time.
by Jerry Brainum
The Holy Grail of drug companies and scientists has been an anabolic compound that has minimal to no androgenic side effects. That was the original goal set shortly after testosterone was first isolated in 1935.
The word anabolic refers to such properties as building and maintaining muscle mass and bone mass and helping maintain red blood cell production.
Androgenic refers to properties related to inherent maleness, including development of male sex organs and a typical male body hair pattern, as well as undesirable effects, such as male-pattern baldness, prostate enlargement and acne. Thousands of anabolic drugs were researched, mainly during the â60s, to find pure anabolic compounds. Many were never released into the commercial market, though they did experience a renaissance as so-called pro-hormone supplements touted for boosting testosterone.
They did just thatâbecause they were discarded drugs, not food supplements. The drug companies, although always eager for major profits, had discarded them for various reasons, most related to excess toxicity.
As a result, the current drugs popularly known as anabolic steroids are, in fact, anabolic-androgenic steroids, because they have both anabolic and androgenic properties. Despite the ingenuity of more than 50 years of research, no scientist has yet been able to completely dissociate the androgenic from the anabolic in those drugs. Some steroids are more anabolic than others, but all have certain androgenic properties. That can be readily seen when female athletes use what they think are more anabolic drugs, only to discover that such drugsâdepending on the dose and length of time usedâproduce unmistakable androgenic effects. In women, such effects are often glaringly apparent: excess facial hair, deeper voice and even male-pattern hair loss. While men who use steroids donât gain any extra size in their sexual organs, women do, and the effect is permanent.
The often pronounced androgenic effects of anabolic steroids and testosterone itself have created problems for their medical therapeutic use.
For example, giving testosterone injections to hypogonadal menâmen clinically deficient in testosteroneâworks quite well to restore testosterone counts. The problem is that the long-acting testosterone esters that were first used for that purpose produced a superphysiological spike in blood testosterone. That was good for adding muscle size and strength, but it also increased the chances of a few unwanted effects. One such effect is a rise in red blood cell concentration, caused by testosterone-induced stimulation of erythropoietin, usually called EPO, in the kidneys.
EPO potently sparks the development of red blood cells. In fact, drug forms of EPO are used in sports for blood-doping purposes to increase endurance. In a nonathlete, however, the presence of too many red blood cells increases the viscosity, or thickness, of the blood, which is linked to strokes, among other problems.
Oral anabolic steroids were developed to overcome the usual rapid destruction in the liver of oral doses of testosterone. The oral steroids have structural modifications that blunt premature liver breakdown. True, that change prevents the major drawback of rapid destruction in the liver, but it also lets the oral steroid build up in the liver. Whether problems ensue is a matter of time and dosage, with longer drug use and higher doses more likely to lead to serious liver problems.
All oral steroids do induce temporary inflammation of the liver, recognized by an elevation in liver enzymes. The orals also bring on the rapid breakdown of high-density-lipoprotein cholesterol, or HDLâthe good kind, and lower HDL counts are linked to cardiovascular disease. In addition, as oral anabolic steroids are not pure anabolic compounds, youâre still subject to all the androgenic effects of testosterone, such as male-pattern baldness, acne, prostate enlargement and so on. Thatâs particularly the case with the oral drugs based on the structure of dihydrotestosterone, or DHT, a by-product of testosterone metabolism thought to be the major culprit in those side effects.
In regard to testosterone therapy for men who are deficient in testosteroneâusually men over 40âthe major fear of doctors is that giving them testosterone will lead to prostate cancer. Prostate cancer is far more common in older men; indeed, some studies show that about 80 percent of men eventually develop a localized prostate tumor, although they usually die from something else, such as heart disease or another form of cancer. As Iâve pointed out in this space previously, the notion that normal testosterone counts bring on prostate cancer is just not true, but itâs so deep-rooted in the medical psyche that drug developers have repeatedly gone back to the drawing board to come up with drugs that can provide the anabolic effects of steroids minus their androgenic effects. Such drugs ideally would have no effect on the prostate.
In 1998 the first of such drugs appeared. Termed âSARMs,â or selective androgen receptor modulators, they can interact directly with androgen receptors, just as do testosterone and anabolic steroids, but have few, if any, of those drugsâ androgenic side effects. Unlike steroids, which get their name from their cholesterol-based chemical structure, the newer SARMs are nonsteroidal. They donât look anything like anabolic steroids or testosterone, but they mimic the drugsâ anabolic effects. Several types of SARMs have been developed by a few drug companies. The hope is that they will supplant testosterone in the treatment of male hypogonadism. The initial SARMs, like testosterone, suppressed the release of the hypothalamic and pituitary hormones that control testosterone and sperm development. Since that would be an androgenic effect, itâs clear that the initial SARMs were also not pure anabolic drugsâcontrary to Internet chatter.
On the other hand, SARMs are not subject to conversion by the enzymes aromatase and 5-alpha reductase. That means they cannot be converted into estrogen or DHT. Even so, the first generation of SARMs shared some of the same side-effect profile as oral anabolic steroidsâfor example, depression of HDL and transient rises in liver enzymes, indicative of minor liver stress. Some suggest that, as with anabolic steroids, those effects may be linked to the oral intake of SARMs. Using another delivery methodâsuch as injections or topical creamâmay eliminate those problems. Injections would not be popular for therapeutic purposes, however, just as testosterone injections are not favored by many men considering testosterone therapy. Patient resistance resulted in the development of the currently preferred forms of T therapy, such as topical skin creams.
Research has shown that some of the beneficial effects of testosterone are linked to its conversion into estrogen by way of the ubiquitous enzyme aromatase: a rise in protective HDL and even an increase in libido. Ongoing research shows that estrogen in the brain may be associated with sex drive in men. SARMs wouldnât do that.
What about building muscle? Are SARMs as effective as anabolic steroids? Studies of the first generation of SARMs showed that they induced modest gains in lean mass in healthy subjectsâbut nowhere near what happens with testosterone or anabolic steroids. For example, one study found that SARMs produced a gain of 1.0 to 1.5 kilograms of lean mass over four to six weeks. Meanwhile, studies of injectable testosterone show gains of five to seven kilograms of lean mass in about the same period. Some of the newer generations of SARMs may be considerably more potent than the original versions in that regard, but that remains to be seen.
The potential muscle-building properties of SARMs havenât gone unnoticed by athletic antidoping organizations. One such group, the World Anti-doping Agency, added all SARMs to its prohibited list in January 2008, even though SARMs are still considered experimental drugs and have not been offered for commercial sales by any legitimate companies. The key word here is legitimate, for SARMs have been available on the Internet for at least two years. Like other exotic, putatively anabolic compounds available online, they have achieved cult status, despite little or no evidence of their role in adding muscle size or strength. The price of Internet SARMs varies, but it isnât cheap: $140 to $179. Thatâs more expensive than anabolic steroids, which do have a proven track record.
To be continue...
Not ready for prime time.
by Jerry Brainum
The Holy Grail of drug companies and scientists has been an anabolic compound that has minimal to no androgenic side effects. That was the original goal set shortly after testosterone was first isolated in 1935.
The word anabolic refers to such properties as building and maintaining muscle mass and bone mass and helping maintain red blood cell production.
Androgenic refers to properties related to inherent maleness, including development of male sex organs and a typical male body hair pattern, as well as undesirable effects, such as male-pattern baldness, prostate enlargement and acne. Thousands of anabolic drugs were researched, mainly during the â60s, to find pure anabolic compounds. Many were never released into the commercial market, though they did experience a renaissance as so-called pro-hormone supplements touted for boosting testosterone.
They did just thatâbecause they were discarded drugs, not food supplements. The drug companies, although always eager for major profits, had discarded them for various reasons, most related to excess toxicity.
As a result, the current drugs popularly known as anabolic steroids are, in fact, anabolic-androgenic steroids, because they have both anabolic and androgenic properties. Despite the ingenuity of more than 50 years of research, no scientist has yet been able to completely dissociate the androgenic from the anabolic in those drugs. Some steroids are more anabolic than others, but all have certain androgenic properties. That can be readily seen when female athletes use what they think are more anabolic drugs, only to discover that such drugsâdepending on the dose and length of time usedâproduce unmistakable androgenic effects. In women, such effects are often glaringly apparent: excess facial hair, deeper voice and even male-pattern hair loss. While men who use steroids donât gain any extra size in their sexual organs, women do, and the effect is permanent.
The often pronounced androgenic effects of anabolic steroids and testosterone itself have created problems for their medical therapeutic use.
For example, giving testosterone injections to hypogonadal menâmen clinically deficient in testosteroneâworks quite well to restore testosterone counts. The problem is that the long-acting testosterone esters that were first used for that purpose produced a superphysiological spike in blood testosterone. That was good for adding muscle size and strength, but it also increased the chances of a few unwanted effects. One such effect is a rise in red blood cell concentration, caused by testosterone-induced stimulation of erythropoietin, usually called EPO, in the kidneys.
EPO potently sparks the development of red blood cells. In fact, drug forms of EPO are used in sports for blood-doping purposes to increase endurance. In a nonathlete, however, the presence of too many red blood cells increases the viscosity, or thickness, of the blood, which is linked to strokes, among other problems.
Oral anabolic steroids were developed to overcome the usual rapid destruction in the liver of oral doses of testosterone. The oral steroids have structural modifications that blunt premature liver breakdown. True, that change prevents the major drawback of rapid destruction in the liver, but it also lets the oral steroid build up in the liver. Whether problems ensue is a matter of time and dosage, with longer drug use and higher doses more likely to lead to serious liver problems.
All oral steroids do induce temporary inflammation of the liver, recognized by an elevation in liver enzymes. The orals also bring on the rapid breakdown of high-density-lipoprotein cholesterol, or HDLâthe good kind, and lower HDL counts are linked to cardiovascular disease. In addition, as oral anabolic steroids are not pure anabolic compounds, youâre still subject to all the androgenic effects of testosterone, such as male-pattern baldness, acne, prostate enlargement and so on. Thatâs particularly the case with the oral drugs based on the structure of dihydrotestosterone, or DHT, a by-product of testosterone metabolism thought to be the major culprit in those side effects.
In regard to testosterone therapy for men who are deficient in testosteroneâusually men over 40âthe major fear of doctors is that giving them testosterone will lead to prostate cancer. Prostate cancer is far more common in older men; indeed, some studies show that about 80 percent of men eventually develop a localized prostate tumor, although they usually die from something else, such as heart disease or another form of cancer. As Iâve pointed out in this space previously, the notion that normal testosterone counts bring on prostate cancer is just not true, but itâs so deep-rooted in the medical psyche that drug developers have repeatedly gone back to the drawing board to come up with drugs that can provide the anabolic effects of steroids minus their androgenic effects. Such drugs ideally would have no effect on the prostate.
In 1998 the first of such drugs appeared. Termed âSARMs,â or selective androgen receptor modulators, they can interact directly with androgen receptors, just as do testosterone and anabolic steroids, but have few, if any, of those drugsâ androgenic side effects. Unlike steroids, which get their name from their cholesterol-based chemical structure, the newer SARMs are nonsteroidal. They donât look anything like anabolic steroids or testosterone, but they mimic the drugsâ anabolic effects. Several types of SARMs have been developed by a few drug companies. The hope is that they will supplant testosterone in the treatment of male hypogonadism. The initial SARMs, like testosterone, suppressed the release of the hypothalamic and pituitary hormones that control testosterone and sperm development. Since that would be an androgenic effect, itâs clear that the initial SARMs were also not pure anabolic drugsâcontrary to Internet chatter.
On the other hand, SARMs are not subject to conversion by the enzymes aromatase and 5-alpha reductase. That means they cannot be converted into estrogen or DHT. Even so, the first generation of SARMs shared some of the same side-effect profile as oral anabolic steroidsâfor example, depression of HDL and transient rises in liver enzymes, indicative of minor liver stress. Some suggest that, as with anabolic steroids, those effects may be linked to the oral intake of SARMs. Using another delivery methodâsuch as injections or topical creamâmay eliminate those problems. Injections would not be popular for therapeutic purposes, however, just as testosterone injections are not favored by many men considering testosterone therapy. Patient resistance resulted in the development of the currently preferred forms of T therapy, such as topical skin creams.
Research has shown that some of the beneficial effects of testosterone are linked to its conversion into estrogen by way of the ubiquitous enzyme aromatase: a rise in protective HDL and even an increase in libido. Ongoing research shows that estrogen in the brain may be associated with sex drive in men. SARMs wouldnât do that.
What about building muscle? Are SARMs as effective as anabolic steroids? Studies of the first generation of SARMs showed that they induced modest gains in lean mass in healthy subjectsâbut nowhere near what happens with testosterone or anabolic steroids. For example, one study found that SARMs produced a gain of 1.0 to 1.5 kilograms of lean mass over four to six weeks. Meanwhile, studies of injectable testosterone show gains of five to seven kilograms of lean mass in about the same period. Some of the newer generations of SARMs may be considerably more potent than the original versions in that regard, but that remains to be seen.
The potential muscle-building properties of SARMs havenât gone unnoticed by athletic antidoping organizations. One such group, the World Anti-doping Agency, added all SARMs to its prohibited list in January 2008, even though SARMs are still considered experimental drugs and have not been offered for commercial sales by any legitimate companies. The key word here is legitimate, for SARMs have been available on the Internet for at least two years. Like other exotic, putatively anabolic compounds available online, they have achieved cult status, despite little or no evidence of their role in adding muscle size or strength. The price of Internet SARMs varies, but it isnât cheap: $140 to $179. Thatâs more expensive than anabolic steroids, which do have a proven track record.
To be continue...
What a RUSHHHHHHHH!!!!!!!!