Soon after the publication of a landmark 1990 study concerning the effects of growth hormone on older men, GH gained a reputation for its ability to reverse the aging clock. The male subjects given GH injections showed a significant loss of bodyfat and a gain in lean mass. Other changes, such as a thickening of the skin and an increase in immune function, seemed to show that the hormone could reverse at least some of the ravages of age.
A few aspects of that study, however, didn’t receive as much publicity. First of all, the subjects were considered deficient in growth hormone, based on circulating insulinlike growth factor 1 (IGF-1) levels. GH promotes the synthesis of IGF-1, and while GH itself is degraded in about an hour, IGF-1 circulates for more than 12 hours, bound to specific carrier proteins in the blood that delay hormone catabolism. IGF-1 levels are considered the biochemical barometer of GH release in the body.
Furthermore, the beneficial changes disappeared when the men stopped taking the hormone. Nonetheless, only the age-reversing effects were publicized, and even today some anti-aging clinics dispense GH. But the question remains: Does GH offer any true anti-aging effects?
And what about other hormones, such as testosterone? Many older men show levels of testosterone similar to those of castrated males. In the past that was considered a normal aspect of aging. Yet older women are routinely provided with forms of estrogen to combat estrogen deficiency. More recent research shows that men, too, may benefit from taking supplemental testosterone.
Bodybuilders are interested in those hormones for a different reason. Experience shows that combining GH with testosterone increases the anabolic effects of both hormones. Some bodybuilders also add a third anabolic hormone to the mix, insulin. (Excess insulin, however, unlike the other two hormones, appears to promote aging.)
A new study examined the effects of these hormones in a group of older people.1 Lasting 26 weeks, it featured a randomized, double-blind, placebo-controlled design; some of the subjects received actual hormones, while others were given a placebo. The subjects’57 women and 74 men, ages 65 to 88’received combinations of GH and either estrogen/progesterone (women) or testosterone injections (men).
Combining GH with sex hormones led to a significant increase in lean mass and loss of bodyfat. Men who took both GH and testosterone showed lean-mass increases three times greater than those who took testosterone alone. The men’s strength increased only with the GH-and-testosterone combo.
As for side effects, edema, or water retention, was common in the women who took GH, while carpal-tunnel syndrome, a nerve impingement of the wrist, was common in the men who got GH and testosterone. The men who took GH alone were more likely to experience joint pains. Some of the men in the GH group also showed signs of glucose intolerance, a precursor to diabetes, but some of the men in the placebo group showed the same symptoms.
Another recent study that examined the effect of GH on aging and longevity had 205 healthy subjects with an age range of 19 to 93.2 The researchers found that older men who have IGF-1 levels similar to those of young men do not show the age-dependent decrease in serum testosterone levels and lean mass seen in many older adults, nor do they display the usual fat gain. Men also showed a sharper decline in IGF-1 with age than women, which suggests that the reason women tend to live longer is the more gradual decline of GH/IGF-1 they experience.
According to still another new study, people who maintain higher IGF-1 levels may also keep their marbles longer.3 It showed that serum levels of IGF-1 appear to regulate the levels in the brain of a protein called beta-amyloid, a buildup of which is considered a major cause of Alzheimer’s disease. By helping to clear the brain of excess beta-amyloid, IGF-1 may help prevent the onset of that terrible disease.
Steroids and the Liver: Unusual Findings
Of all the body’s organs affected by anabolic steroids, the liver ranks first. That makes sense, since the primary function of the liver is to detoxify all the substances you eat. Oral anabolic steroids are particularly tough on the liver because they’re structurally manipulated to resist breakdown. As a result, taking oral anabolic steroids in either large amounts or for an extended time can lead to liver damage. The good news is that the damage is usually reversed when the person stops using steroids.
In the past these liver problems were often attributed to a steroid-induced toxic hepatitis (hepatitis is a general term referring to an inflammation of the liver and may be caused by viruses, bacteria or drugs). Liver inflammation brought on by steroids obstructs the normal flow of bile, a condition called cholestasis. After a while that obstruction can lead to actual destruction of liver cells and, if not treated, liver failure.
Most past cases of liver impairment attributed to anabolic steroids followed a typical pattern, with the first sign being elevated liver enzymes. That was followed by other clinical signs, such as jaundice, a yellow discoloration of the skin and eyes, pointing to a buildup of bile. Some new studies, however, involving bodybuilders who took too many or too large a dose of anabolic steroids point to a newly recognized aspect of steroid-related liver toxicity.
One case described a 26-year-old bodybuilder who was admitted to a hospital with a 10-day history of jaundice, nausea and malaise’all signs of liver problems.4 A month earlier he’d been on a steroid program consisting of the following drugs:
‘ Testosterone enanthate injections’500 milligrams, twice weekly
‘ Stanozolol (Winstrol)’40 milligrams daily by mouth
‘ Methylandrostenediol (Dianabol)’30 milligrams daily by mouth
The bodybuilder, now a patient, had used that program for five weeks but had taken lower doses of steroids periodically for nine years. His liver enzymes were far more elevated than in past cases of reported steroid abuse, and he seemed to be storing iron in his liver. Iron buildup in the liver is usually seen only in a hereditary condition called hemochromatosis, but that was ruled out in this case. Still, excessive iron in the liver can destroy liver cells, and that’s precisely what had occurred.
The good news is that after 12 weeks of medical treatment the patient’s liver values returned to normal. What was unique about the case was that his primary liver problems weren’t caused by a lack of bile flow or cholestasis but rather the actual liver-cell destruction. The next question was what had caused it.
Two suspects emerged out of this case, the first and most likely being oral steroids the bodybuilder took, especially Winstrol. While Winstrol has acquired a reputation as a ‘safe’ anabolic steroid, various studies show that it can destroy liver cells, especially when taken in too high a dose or for too long.
The second suspect was the increase of iron in the patient’s liver. Was it somehow related to the oral steroids? That seems likely, since the iron levels in his liver returned to normal after he was off the steroids for 12 weeks.
That was the first reported case of initial liver-cell destruction induced by anabolic-steroid use, rather than the usual pattern of initial liver swelling caused by an obstruction of bile flow. I think the finding of increased iron stores in this man’s liver is ominous. If it was related to oral anabolic-steroid use, that indicates that steroids are far more toxic to the liver than was previously recognized.
Fenoterol: Superior to Clenbuterol?
Clenbuterol is classified as a beta-2 agonist drug, meaning that it’s structurally similar to epinephrine and can interact with specific beta-adrenergic cellular receptors. Since clenbuterol’s activity focuses almost entirely on beta-2 receptors, it offers some benefits for diseases identified as problematic in beta-2 activity, such as asthma. Though never approved for use in the United States, clenbuterol is used to treat asthma in various European and Latin American countries.
One reason for that is its long half-life, meaning it stays in the body far longer than similar drugs prescribed to treat asthma. That leads to a far greater chance of side effects, mainly affecting the heart. Since the therapeutic value of clenbuterol isn’t significantly superior to that of other drugs in the same category, drug companies in the United States decided it wasn’t worth the risk to place it on the market.
But clenbuterol exhibits another property, first noticed in animals receiving it, that’s not typical of other asthma drugs. Since it was administered in doses based on weight, such larger animals as horses showed a repartitioning effect, whereby clenbuterol appeared to induce muscle gain, coupled with significant fat loss.
That news soon reached athletes, and clenbuterol became a favored drug based on its reputed anabolic and fat-loss effects. The truth, however, is that its anabolic effects are evident only at doses that are toxic to humans. As for fat loss, clenbuterol does induce a pronounced thermogenic effect, but it’s short-lived, due to the exquisite sensitivity of beta-adrenergic receptors, which shut down after about two to three weeks of continuous clenbuterol use.
Even so, clenbuterol is not the only asthma drug capable of promoting anabolic effects. Another drug, fenoterol, can produce similar effects. Like clenbuterol, fenoterol was never approved for use in the United States. Unlike clenbuterol, it’s a full beta-2 and a full beta-1 agonist drug. That means fenoterol should provide effects superior to those of clenbuterol.
A recent study involving rats compared equal doses of fenoterol and clenbuterol in their effects on rat skeletal muscle.5 The doses supplied were far higher than any human would take. The results showed that fenoterol was more potent in promoting muscle growth and fostered a 20 percent greater increase in muscle cross-section growth than clenbuterol. In addition, fenoterol promoted the growth of both slow- and fast-twitch muscle, while clenbuterol works only on fast-twitch muscle fibers.
On the other hand, fenoterol also induced potentially adverse changes in heart structure and activity similar to those associated with clenbuterol. In fact, the greater beta-1 adrenergic receptor activity of fenoterol over clenbuterol would indicate that fenoterol affects the heart more than clenbuterol. Sure enough, in countries such as Canada and New Zealand, where fenoterol is available for asthma treatment, several deaths from cardiovascular complications have been linked to its use.
Thus, although fenoterol may be more anabolically potent than clenbuterol, it’s also more dangerous. And considering that you’d have to take far higher doses than those used to treat asthma to gain any anabolic effect from fenoterol, the drug is clearly not suitable for human anabolic use’unless you’re bent on suicide.
1 Blackman, M.R., et al. (2002). Growth hormone and sex steroid administration in healthy older women and men. JAMA. 288:2282-2292.
2 Ruiz-Torres, A., et al. (2002). Aging and longevity are related to growth hormone/insulinlike growth factor 1 secretion. Gerontology. 48:401-407.
3 Carro, E., et al. (2002). Serum insulinlike growth factor 1 regulates brain amyloid-B levels. Nature Med. 8:1390-97.
4 Stimac, D., et al. (2002). Androgenic-anabolic steroid-induced toxic hepatitis. J Clin Gastroenterol. 35:350-352.
5 Ryall, J.G., et al. (2002). B2-agonist fenoterol has greater effects on contractile function of rat skeletal muscles than clenbuterol. Am J Physiol. 283:R1386-R1394. IM