Nandrolone may increase the hypoglycemic activities of Bromocriptine.
This drug is an anabolic steroid that has recently caused a great deal of controversy after a number of big name athletes have been banned from competition after failing tests for this drug. These include Linford Christie, Mark Richardson and Dougie Walker (all well known British sprinters), Merlene Ottey (the Jamaican former 200 m world champion), and Dieter Baumann (the German 500 m runner). After protesting their innocence, all were subsequently cleared by their national athletics organisations, although the International Amateur Athletics Federation fueled the controversy further by overturning the reinstatement of Christie and Walker. As well as athletes, French soccer star Christophe Dugarry tested positive for nandrolone after a match last year, and following a Wimbledon quarter final in 1998 Czech tennis player Petr Korda also failed a test. But the fact that so many sportsmen have tested positive for the same substance in such a short space of time has led to speculation that the testing procedure may be flawed, or inaccurate.
British sprinter Linford Christie, who controversially failed a test for nandrolone earlier this year.
The drug known as nandrolone (also known commercially as Deca-Durabolin) has the IUPAC name 17β-hydroxy-19-nor-4-andro-sten-3-one, and is an anabolic steroid (a muscle-building chemical) which occurs naturally in the human body, but only in tiny quantities. It is very similar in structure to the male hormone testosterone, and has many of the same effects in terms of increasing muscle mass, without some of the more unwanted side-effects such as increased body hair or aggressive behaviour. As such, it is being actively examined in clinical tests as a possible treatment for wasting diseases, and to strengthen and increase body tissue and musculature in HIV infected men. In this form it is usually injected in its decanoate form, after first being dissolved in a suitable edible oil.
However, what is detected in the drug tests is the metabolism product of this molecule, called 19-norandrosterone, which is excreted from the body in urine, making it easy to obtain samples. A limit of 2 ng per ml of urine (set by the International Olympic Committee) is the maximum concentration thought possible to occur in human body by ‘natural means’, and if this is exceeded the drug test is considered positive. Since some samples given by athletes have shown levels up to 100 times higher than this, the conclusion is that the athletes must have been taking extra quantities of the drug to enhance their performance.
The diagrams above show the structures of the steroid nandrolone and its metabolite 19-norandrosterone. The structural differences between them consist of a reduction of a double bond to a single bond accompanied by a reduction of a carbonyl to a hydroxyl group in the first ring, and an oxidation of a hydroxyl sidegroup to a carbonyl in the fourth ring. These differences are shown in blue.
Below for comparison, are the more familiar steroid hormones, testosterone and progesterone. You can see that nandrolone and testosterone are almost identical, differing only by one methyl group, shown in red. Progesterone (the female pregnancy hormone) is also very similar, perhaps giving some credence to the boxer’s claim mentioned below…
So, if the tests are flawed, what could be going wrong? Many excuses have been put forward to suggest why nandrolone is present in much higher concentrations than it should be. Bobsleigh racer Lenny Paul said that his positive test was due to eating a plate of spaghetti bolognese which contained beef from cattle that had been fed steroids. Although the UK Sport Nandrolone Review Group said that there was only a ‘remote’ possibility of meat consumption leading to a positive test, the athlete was cleared by his sporting body. Another sportsman, a boxer, said he failed his test after having sex with his pregnant wife! He too, was cleared.
Another possible explanation, often cited by athletes caught with positive tests, is that the nandrolone in their system arose from the use of protein milkshakes and the amino acid creatine, which are perfectly legal and used as dietary supplements to increase weight. But it is difficult to see how nandrolone could be produced from the benign components of these substances, unless they had been accidentally or deliberately contaminated. Subsequent testing, however, ruled out any deliberate contamination.
A much more likely theory has recently emerged from the results of a preliminary investigation at Aberdeen University. The findings are that dietary supplements themselves are harmless and produce no increased levels of nandrolone. Exercise alone, too, doesn’t cause any problems. But a combination of both dietary supplements (none of which contain a banned substance) and exercise, can result in a positive nandrolone test. The reason for this is still unclear, but one theory is that there is a link between heavy training, the dehydration that goes with it, and their effects upon the components of high protein diets. Until more work is done, however, the ‘nandrolone mystery’ goes on…
This drug esters are well absorbed from intramuscular sites with an absorption half-life of about 6–7 days (Wijnand et al., 1985). The chemical nature of the ester influences absorption rate and peak plasma concentrations, higher peak plasma concentrations (∼ 30 nM) being achieved after the phenpropionate compared with the decanoate (∼ 14 nM). Plasma concentrations of nandrolone relate well to biological effects in terms of endocrine parameters (suppression of plasma testosterone and inhibin concentrations; Minto et al., 1997). Nandrolone itself, like testosterone, is well absorbed from the gastro-intestinal tract but rapidly inactivated in the liver. Its main metabolites are 19-norandrosterone and 19-noretiocholanolone (Le et al., 2002).
Nandrolone esters are well absorbed from intramuscular sites with an absorption half-life of about 6–7 days (Wijnand et al., 1985). The chemical nature of the ester influences absorption rate and peak plasma concentrations, higher peak plasma concentrations (∼ 30 nM) being achieved after the phenpropionate compared with the decanoate (∼ 14 nM). Plasma concentrations of nandrolone relate well to biological effects in terms of endocrine parameters (suppression of plasma testosterone and inhibin concentrations; Minto et al., 1997). Nandrolone itself, like testosterone, is well absorbed from the gastro-intestinal tract but rapidly inactivated in the liver. Its main metabolites are 19-norandrosterone and 19-noretiocholanolone (Le et al., 2002).
19-Nortestosterone (19-NT or nandrolone) is a long-acting ester with potent androgenic effects and a high progestational activity (10 times that of T) but it is not aromatized. 19-NT has been shown to suppress LH and FSH effectively with full maintenance of androgen-dependent functions. With the combination of both androgenic and progestational activity, the potential for 19-NT to provide contraception as a single agent has been considered. Small trials with 19-NT alone or in combination with depot medroxyprogesteroneacetate (DMPA, see below) have confirmed that azoospermia is induced without any symptoms of androgen deficiency (despite low T
The main male sex hormone testosterone has well-known anabolic actions, and this property is retained in synthetic derivatives such as nandrolone (19-nortestosterone). Synthetic, 17-alpha-alkylated compounds (oxymetholone, stanozolol, oxandrolone, danazol) are orally active and, in animals, show selectivity for anabolic versus classic androgenic activity, although the evidence for such selectivity in the human is unclear. These agents are/have been used for their anabolic properties in several disease states, including anemia, post-menopausal osteoporosis, hereditary angioneurotic edema and AIDS-related wasting myopathy. They are subject to abuse by athletes.
Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis.
A randomized 2 × 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco–affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights.
Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 ± 2.2 kg (P < 0.0001).
Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.
Dialysis patients have limited physical functioning as measured by self-reported functioning (1,2), peak oxygen consumption (3–8), physical performance tests (9), and tests of muscle strength (10,11). One study highlighted the severity of debility, reporting that more than one third of hemodialysis patients were unable to perform the normal activities of daily living without assistance (12). In addition, physical functioning has been shown to be a major determinant of patients’ assessment of their global quality of life (13). Therefore, interventions to improve functioning in this population have the potential to improve quality of life significantly.
Muscle wasting and weakness are particularly attractive targets for intervention because they are related to loss of function and can be measured and targeted objectively for improvement. Small studies support the possible benefits of two strategies to increase muscle size and strength among patients who are on dialysis. Anabolic steroids, which frequently were used to ameliorate the anemia associated with ESRD before the introduction of recombinant erythropoietin, were noted to cause an increase in serum creatinine along with increases in hemoglobin and hematocrit (14). Although some agents were associated with significant adverse effects, nandrolone decanoate had few adverse effects as a result of its intramuscular route of administration and favorable erythropoietic to androgenic ratio (15).
More recently, nandrolone decanoate has been shown to increase lean body mass (LBM) and improve physical performance (16), and resistance exercise training has been shown to increase strength and improve physical performance (17). Neither of these preliminary results has been confirmed, and the relative benefits of these strategies or their potential additive or synergistic effects have not been examined.
Therefore, we designed a study to compare changes in LBM, muscle size and strength, physical performance, and self-reported functioning during a 12-wk period among hemodialysis patients who were randomly assigned to one of four groups: (1) Nandrolone decanoate, a synthetic testosterone derivative, by weekly intramuscular injection (ND); (2) weekly placebo injections (PL); (3) lower extremity resistance exercise training during dialysis sessions three times per week plus weekly placebo injections (EX); and (4) resistance exercise plus nandrolone injections weekly (EX+ND).