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Bodybuilding Pharmocology: Nandrolone Zone

Nandrolone in drug tests, steroids and fertility.

Among the issues being discussed about the recent controversy over the increased incidence of positive drug tests for nandrolone is whether that steroid is made in the human body naturally and in sufficient amounts to lead to a positive doping test. Nandrolone is a generic name for various anabolic steroids, such as Durabolin and Deca-Durabolin. The drug forms of nandrolone are always injectable, although the 19-nor forms of pro-hormones also convert into nandrolone in the body and thus are capable of producing a positive test for nandrolone.

Nandrolone is excreted from the body as two major metabolites: 19-norandrosterone (NA) and 19-noretiochoanolone (NE). The drug-testing procedure looks for those metabolites, and if they’re found in a concentration of two nanograms per liter or more, the test is positive for nandrolone use. When taken orally, nandrolone drugs are mostly metabolized in the liver, which explains why the drug versions are always found in injectable form.

Research shows that nandrolone and its metabolites are produced naturally in both male and female horses. In horses and in pregnant women nandrolone metabolites are converted into estrogen by aromatase enzymes that exist in the placenta. More recently, trace levels of the nandrolone metabolite NA were found in men, raising the question of whether men produce enough to lead to a positive drug test.

Since intense physical exercise increases urine levels of NA two- to fourfold, researchers hypothesized that the metabolic stress that leads to changes in blood glucose levels may stimulate the production of higher-than-normal levels of nandrolone metabolites, such as NA. Both exercise and sports fit into that category, but the researchers instead produced similar metabolic effects by giving 10 healthy men enough insulin to lead to hypoglycemia, or low blood glucose.1

To determine if nandrolone is produced in the course of normal androgen synthesis, the subjects also got injections of human chorionic gonadotropin (HCG), a hormone known to stimulate testosterone synthesis in the body.

The insulin injection led to a drop in plasma levels of both testosterone and estrogen. Such declines are commonly observed under low-blood-glucose conditions, since the stress reaction linked to low blood glucose results in an increase in cortisol release. The cortisol binds to receptors in the testes that are needed for testosterone synthesis, thus blocking the synthesis. In the brain cortisol also blocks the release of luteinizing hormone (LH), the pituitary hormone that controls testosterone synthesis in the body.

In this study, however, HCG, which is similar in structure to LH, did lead to an increase in the nandrolone metabolite NA in all 10 subjects, while NE rose in four out of 10 subjects. Since HCG is known to stimulate the aromatization process in the testes’leading to an increase in estrogen’the researchers believe that nandrolone metabolites are produced in the pathway leading from androgen to estrogen synthesis in the human body. While this study confirmed that nandrolone metabolites are indeed produced naturally in the human body, the amount produced never exceeded more than one nanogram per liter’clearly less than the two-nanogram level required to produce a positive drug test. Thus, it appears unlikely that anyone would fail a drug test for nandrolone from the metabolites produced naturally in the body.

Steroids and Fertility

International health organizations have recently explored the use of testosterone as a male contraceptive. The research is based on the fact that when taken in amounts far greater than what the body produces naturally, testosterone suppresses sperm production through several mechanisms. As levels of testosterone rise in the blood, the brain senses that rise, leading to a negative feedback inhibition of gonadotropin release. The gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are synthesized in the brain’s pituitary gland, control the production and maturation of sperm in the testes.

Since anabolic steroid drugs are synthetic versions of testosterone, many can duplicate the effect of natural testosterone in the negative feedback effect that occurs in the brain. That, in turn, has led to concerns that extensive use of anabolic steroids may impair fertility.

Past studies examining that issue of the effect of steroids on male fertility have usually found that using steroids does indeed lead to rapid changes indicative of decreased fertility, including changes in the number, shape and movement of sperm. Men taking typical anabolic steroid drug stacks show either no or low numbers of viable sperm cells. They also display low testosterone levels (after a cycle) and low levels of both LH and FSH. Those effects can occur as rapidly as two weeks after initiating a steroid cycle, especially if testosterone injections are part of the stack.

The primary debate related to the effect of anabolic steroids on fertility is whether the effect is temporary or permanent. Common sense suggests that in most cases the impaired fertility is temporary. The evidence for that is the existence of normal, healthy children sired by athletes who have previously used large amounts of various anabolic steroid drugs; however, some reports show that after extensive use, it may take longer to return to normal fertility, or the athlete’s fertility may even be permanently impaired.

One recent study involved a 20-year-old bodybuilder who initially showed both low testosterone levels and no discernible sperm cells at all.2 He’d begun using anabolic steroids 10 months earlier, gradually increasing doses of an oral drug, Bionabol, and an injectable drug, Retabolil. Bionabol is a version of the famous oral steroid Dianabol, while Retabolil is a version of a popular injectable steroid, Deca-Durabolin. Both drugs are made and sold in Bulgaria, where the study took place.

The subject’s impaired fertility showed up during a physical examination after he was admitted to the mental ward of a local hospital. He was sent there after showing ‘agitation and excessive aggression’ toward his relatives. The man’s testosterone level was low and remained low even five months after stopping all steroid use. After 10 months off the drugs his testosterone returned to normal values, as did his sperm count. Although the man was diagnosed with a ‘borderline personality disorder,’ the physicians who wrote the case study noted that his steroid use likely had nothing to do with his mental disorder, although the mental problem may have motivated him to use steroids.

Another recent study examined two groups of bodybuilders who followed the same exercise program for eight weeks.3 The only difference between the groups was that one group used steroids: weekly injections of Deca-Durabolin and Sustanon, the latter being a combination of fast-, medium- and slow-acting testosterone esters. The researchers increased the doses by 25 percent weekly until they were doubled over a four-to-five-week period, then gradually decreased them in the same way by the eighth week.

At the conclusion of the study the bodybuilders in the steroid group showed a significant decrease in sperm count, motility (movement) and normal morphology (shape). They also showed decreased levels of LH (50 percent), FSH (75 percent) and testosterone (50 percent) compared to baseline, or starting, levels. Prolactin, another pituitary hormone, increased, as did DHEA, an adrenal androgen. Those in the control group also showed decreased sperm motility with an increase in FSH levels. Men need FSH for sperm maturation and development.

The authors of the study didn’t disclose whether the sperm and hormone levels returned to normal after the bodybuilders stopped using steroids. As noted, most previous reports did find that fertility returned to normal, but in some of those cases some of the lagging reproductive systems needed a kick-start with other drugs, such as Clomid or HCG. HCG is similar in structure to LH and may help to rev a lagging male reproductive system. The consensus is that relatively short steroid cycles do temporarily depress fertility, but the effect is often individual, as some men’s systems return to normal more rapidly than others. The type of steroids used also likely plays a role, with some drugs possibly having a more potent effect on fertility than others. Such drugs would have a more profound competitive inhibition effect on the release of pituitary gonadotropins in the brain. As with any effect induced by steroids, these also relate to time and dosage. In short, the higher the dose, combined with the length of time the drugs are used, probably determines the long-term effects on male fertility. In some rare cases such depressive effects may be permanent; however, I know of no case in which that actually occurred in a bodybuilder who used steroids, and, as noted above, the existence of scores of healthy progeny of such drug-using athletes offers living testimony to the usually temporary nature of impaired fertility associated with anabolic steroids.

1 Reznik, Y., et al. (2001). Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation. J Clin Endocrin Metab. 86:146-150.
2 Boyadhev, N.P., et al. (2000). Reversible hypogonadism and azoospermia as a result of anabolic-androgenic steroid use in a bodybuilder with personality disorder. J Sports Med Phys Fitness. 40:271-4.
3 Torres-Calleja, J., et al. (2000). Effect of androgenic-anabolic steroids on semen parameters and hormone levels in bodybuilders. Fertility and Sterility. 74:1055-1056.

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