Article

Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men

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Abstract

Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known. To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function. Eight-week randomized controlled trial conducted between February and June 1998. Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training. Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men. Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration. Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation. Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.

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... In women pronounced increases not only in circulating androstenedione but also in testosterone have been described following administration of 100 mg androstenedione (Kicman et al. 2003) (Fig. 19.3). In contrast, in men the effects of oral androstenedione have been variable: in some trials serum total testosterone concentrations were not affected by 100 mg androstenedione (Brown et al. 2000;King et al. 1999). However, 300 mg androstenedione induced increases in testosterone levels (Leder et al. 2000). ...
... However, 300 mg androstenedione induced increases in testosterone levels (Leder et al. 2000). Importantly, clear increases in estrogens were observed after oral ingestion of androstenedione in young and elderly men (Brown et al. 2000;King et al. 1999;Leder et al. 2000), an effect quite similar to oral DHEA administration.Kicman et al. 2003). ...
... In 30–56 year-old men androstenedione (3 × 100 mg/day) for 28 days slightly reduced HDL-cholesterol without affecting prostate specific antigen (PSA), suggesting some androgenic activity (Brown et al. 2000). Serum HDL-cholesterol was also reduced in an eight-week randomized trial in 20 young men receiving oral androstenedione (300 mg/day) (King et al. 1999). Androstenedione failed to enhance muscle adaptation to resistance training in this population (King et al. 1999). ...
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Man, together with higher primates, has adrenals secreting large amounts of dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS. The physiological role of these steroid hormones is still not fully understood. However, in recent years a growing number of careful investigations have helped to better appreciate the function of DHEA(S). Dehydroepiandrosterone is distinct from the two other major adrenocortical steroids - cortisol and aldosterone - in declining with advancing age. Moreover, administration of DHEA to experimental animals has demonstrated a multitude of beneficial effects on the prevention of cancer, heart disease, diabetes and obesity (Svec and Porter 1998). This has led to the assumption that the age-related decline of DHEA may play a role in the degenerative changes observed in human aging and that administration of DHEA may reverse some of these changes. Moreover, the still ongoing availability of DHEA as a food supplement in the USA and its marketing as an anti-aging drug resulted in large scale self-administration without medical supervision. However, in rodents circulating levels of DHEA and DHEAS are several orders of magnitude lower than in humans and no age-related decline in DHEA concentrations has been documented. This indicates that experimental studies in laboratory animals receiving high doses of DHEA have little bearing for human physiology. This chapter, therefore, will focus mainly on data generated in humans. Dehydroepiandrosterone (sulfate), or DHEA(S), will refer to both DHEA and DHEAS. In addition, clinical studies concerning androstenedione, another less widely used steroid hormone precursor, will also be covered.
... Besides being key intermediates in the biosynthesis of biologically potent androgen, DHEA and androstenedione are also along that route precursors for estrogen production (2,3). Interest in oral androstenedione administration to young men as a means of enhancing bioavailable testosterone is rather recent (4)(5)(6)(7). The consensus emerging from these studies is that the bioconversion to testosterone is quantitatively of minor importance, with little or no influence on muscle strength. ...
... The influence of oral DHEA loading on the urinary androgen excretion profile in the human species (8)(9)(10) and in the horse (11) has been addressed by several authors. The consequences of androstenedione ingestion have been mainly investigated in man by analysis of plasma androgens (4)(5)(6)(7), and urinary determinations remain scarce (12). No work has yet been published on putative physiological effects of DHEA and androstenedione supplementations in the equine species. ...
... Basal androgen levels were assessed in urine and blood collections made at the time of drug administration and two days previously. Post-administration times of sampling were at 1,2,4,7,9,12,18,24,36, and 48 h. Twenty-milliliter volumes of blood were drawn in heparinized tubes and centrifuged, and the plasma was frozen immediately. ...
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Dehydroepiandrosterone (DHEA) and androstenedione are weak androgens, which need conversion to more potent testosterone in order to enhance anabolic action. Consequences of oral dosing at 1 mg/kg on the urinary and plasma androgen profile of mare and gelding have been evaluated with an analytical method involving conjugate fractionation and selective hydrolysis, group separation, and quantitation by gas chromatography-mass spectrometry with selected ion monitoring of trimethylsilyl ethers. Peak levels of testosterone total conjugates in urine (range 300-6000 microg/L) were attained a few hours after dosing. Renal clearance was fast, so the testosterone detection period lasted only 20 to 33 h, the longest time being generated by androstenedione. The urinary testosterone/epitestosterone ratio for detection of exogenous testosterone in the mare was inoperative after DHEA administration because there was a concomitant increase of epitestosterone, which thereby acted as a masking agent. Androstanediols and androstenediols, as well as some 17-ketosteroids, were additional markers. A transient increase of circulating free testosterone has been evidenced, and this would support possible anabolic/androgenic action by supplementation with DHEA and androstenedione along the oral route.
... The ingestion of weak androgens, such as androstenedione and androstenediol, is claimed by nutritional supplement marketers to increase serum testosterone concentrations. Although comparing results across studies and subject populations should be done with caution, serum total testosterone concentrations are unchanged within a few hours of ingesting 100 –200 mg androstenedione [3,11,12,13] or 8 –12 hours after ingesting 100 –300 mg [4,9,11,12,13] androstenedione. The addition of herbal extracts does not change the testosterone response to androstenedione ingestion within six hours of intake [11,12]. ...
... The ingestion of weak androgens, such as androstenedione and androstenediol, is claimed by nutritional supplement marketers to increase serum testosterone concentrations. Although comparing results across studies and subject populations should be done with caution, serum total testosterone concentrations are unchanged within a few hours of ingesting 100 –200 mg androstenedione [3,11,12,13] or 8 –12 hours after ingesting 100 –300 mg [4,9,11,12,13] androstenedione. The addition of herbal extracts does not change the testosterone response to androstenedione ingestion within six hours of intake [11,12]. ...
... Although comparing results across studies and subject populations should be done with caution, serum total testosterone concentrations are unchanged within a few hours of ingesting 100 –200 mg androstenedione [3,11,12,13] or 8 –12 hours after ingesting 100 –300 mg [4,9,11,12,13] androstenedione. The addition of herbal extracts does not change the testosterone response to androstenedione ingestion within six hours of intake [11,12]. In vitro, androstenediol is converted to testosterone 3 times more readily than androstenedione [2] , suggesting that androstenediol ingestion would more effectively increase serum testosterone concentrations than androstenedione. ...
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The effectiveness of an androgenic nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogen was investigated in healthy 3 to 58 year old men. Subjects were randomly assigned to consume a nutritional supplement (AND-HB) containing 300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid and 1.350-mg Tribulus terrestris per day (n = 28), or placebo (n = 27) for 28 days. Subjects were stratified into age groups to represent the fourth (30 year olds, n = 20), fifth (40 year olds, n = 20) and sixth (50 year olds, n = 16) decades of life. Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate specific antigen and lipid concentrations were measured before supplementation and weekly for four weeks. Basal serum total testosterone, estradiol, and prostate specific antigen (PSA) concentrations were not different between age groups. Basal serum free testosterone concentrations were higher (p < 0.05) in the 30- (70.5 +/- 3.6 pmol/L) than in the 50 year olds (50.8 +/- 4.5 pmol/L). Basal serum androstenedione and dihydrotestosterone (DHT) concentrations were significantly higher in the 30- (for androstenedione and DHT, respectively, 10.4 +/- 0.6 nmol/L and 2198.2 +/- 166.5 pmol/L) than in the 40- (6.8 +/- 0.5 nmol/L and 1736.8 +/- 152.0 pmol/L) or 50 year olds (6.0 +/- 0.7 nmol/L and 1983.7 +/- 147.8 pmol/L). Basal serum hormone concentrations did not differ between the treatment groups. Serum concentrations of total testosterone and PSA were unchanged by supplementation. Ingestion of AND-HB resulted in increased (p < 0.05) serum androstenedione (174%), free testosterone (37%), DHT (57%) and estradiol (86%) throughout the four weeks. There was no relationship between the increases in serum free testosterone, androstenedione, DHT, or estradiol and age (r2 = 0.08, 0.03, 0.05 and 0.02, respectively). Serum HDL-C concentrations were reduced (p < 0.05) by 0.14 mmol/L in AND-HB. These data indicate that ingestion of androstenediol combined with herbal products does not prevent the formation of estradiol and dihydrotestosterone.
... Because blood samples in the current study were collected approximately 10 h after the previous 100-mg dose of ASD, it was not possible to assess peak hormonal changes after ASD ingestion. Our previous research indicates that after ingesting 100 mg ASD, peak increases in serum ASD concentrations occur approximately 120-300 min after ingestion, while changes in serum estradiol concentrations are not evident during the 6 h after ingestion, and serum total testosterone concentrations are not altered (3,4). Although transient increases in serum total testosterone after ingestion of 100 mg of ASD cannot be ruled out, the present results support our previous findings (3,4) and those of others (2,5,10) that total testosterone concentrations are not chronically increased by ingestion of ASD in doses of up to 300 mg per day, when taken in 100 mg doses. ...
... Our previous research indicates that after ingesting 100 mg ASD, peak increases in serum ASD concentrations occur approximately 120-300 min after ingestion, while changes in serum estradiol concentrations are not evident during the 6 h after ingestion, and serum total testosterone concentrations are not altered (3,4). Although transient increases in serum total testosterone after ingestion of 100 mg of ASD cannot be ruled out, the present results support our previous findings (3,4) and those of others (2,5,10) that total testosterone concentrations are not chronically increased by ingestion of ASD in doses of up to 300 mg per day, when taken in 100 mg doses. The current study extends these findings by demonstrating that ingestion of 100 mg of ASD three times daily does not alter serum total testosterone concentrations in middle-aged men. ...
... A novel finding was that, whereas serum total testosterone was unaffected, serum free testosterone increased by 37-51% in these 30-to 56-yr-old men. These results are in contrast to our previous finding that 100 mg of ASD three times daily does not chronically increase serum free testosterone concentrations in 23-yr-old men (3,4). Consistent with the previously observed age-related declines in serum free testosterone concentrations (7-9), the serum free testosterone concentrations in the current subjects were lower than in the younger subjects in our previous research (3,4). ...
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Article
In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investi- gated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n 5 28), or placebo (n 5 27) for 28 days. Serum ASD , dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplemen- tation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1- 4 in ASD (P , 0.05). There was no relationship between age and changes in serum ASD (r2 5 0.024), free testosterone (r2 5 0.00), or estradiol (r2 5 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 5 0.244; P , 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplemen- tation period (P , 0.05). These results suggest that the ingestion of 100 mg ASD , three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations. (J Clin Endocri- nol Metab 85: 4074 - 4080, 2000)
... More importantly, no study has shown that Andro or its related compounds significantly increases strength and/or lean mass by way of increasing blood testosterone levels. Five studies [46][47][48][49][50] lasting 8-12 weeks, using healthy males (ages 19-60) who were given 100 mg or 300 mg oral Andro or its related compounds per day in conjunction with strength training regimens, failed to detect significant increases in strength or muscle mass. ...
... The long-term health effects of prolonged Andro (or its related compounds) supplementation are unknown. However, recent studies have noted acute adverse effects [35,38,[41][42][43][46][47][48]50]. At least seven studies [35,38,[41][42][43]46,48] have reported a significant increase in blood estrogen levels (estrone and estradiol) in healthy males with oral Andro supplementation. ...
... However, recent studies have noted acute adverse effects [35,38,[41][42][43][46][47][48]50]. At least seven studies [35,38,[41][42][43]46,48] have reported a significant increase in blood estrogen levels (estrone and estradiol) in healthy males with oral Andro supplementation. Elevated estrogen levels in males are associated with gynecomastia and other feminizing effects, as well as an increased risk of cardiovascular disease [9]. ...
Article
The use of drugs to enhance performance has been a feature of athletic competition since ancient times. This review discusses the use of anabolic steroids and stimulants by athletes to improve performance during the later half of the nineteenth century and during most of the twentieth century. Included are discussions of the development and medical background of testosterone and anabolic steroids, how the use of steroids progressed from medical use to use in sport and, with the rapid expansion of testosterone and steroid use in sport during the 1960s and 1970s, the emergence of adverse health effects that lead to the initial banning of steroids in sports and the development of drug testing programmes. Links between stimulant use, war and sport during the 1930s and 1940s, the impact of stimulant use on post-war sport, and the prevalence of stimulant use in North American society and sport prior to 1970, including the deaths of several elite cyclists, are discussed in the second part of this review.
... These results partially conflict with those of King et al, 10 who showed that despite a 100% increase in serum androstenedione levels, neither free nor total testosterone levels increased in young men. The difference in results between the studies may relate to the distinct age difference in populations. ...
... One would hypothesize that an older population of men would most likely benefit from testosterone precursor supplementation since testosterone synthesis declines after the age of 30 years. 19 However, despite the apparent effect on total testosterone that was observed in this study, as was observed in the study by King et al, 10 there were no significant increases in free testosterone that could account for why the changes in strength and body composition were independent of supplementation as previously reported. 10 Ninety-eight percent of the body's total testosterone is protein bound. ...
... 19 However, despite the apparent effect on total testosterone that was observed in this study, as was observed in the study by King et al, 10 there were no significant increases in free testosterone that could account for why the changes in strength and body composition were independent of supplementation as previously reported. 10 Ninety-eight percent of the body's total testosterone is protein bound. 20 However, unbound testosterone is most metabolically active when it is enzymatically converted by the microsomal isoenzyme 5␣-reductase-2 to dihydrotestosterone. 20 Thus, in the present study, one would not expect any potentiation in resistance training adaptation with the use of androstenediol or androstenedione since neither supplement significantly increased free testosterone levels. ...
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Background Since the passage of The Dietary Supplement Health and Education Act in 1994, there has been a flood of new "dietary" supplements promoting anti-aging benefits such as the enhancement of growth hormone or testosterone levels. Androstenediol and androstenedione are such products. This study's purpose was to elucidate the physiological and hormonal effects of 200 mg/d of oral androstenediol and androstenedione supplementation in men aged 35 to 65 years while participating in a 12-week high-intensity resistance training program. Methods Fifty men not consuming any androgenic-enhancing substances and with normal total testosterone levels, prostate-specific antigen, hemoglobin, and hematocrit, and with no sign of cardiovascular or metabolic diseases participated. Subjects were randomly assigned to a placebo, androstenediol (diol), or androstenedione (dione) group using a double-blind study design. Main outcomes included serum sex hormone profile, body composition assessment, muscular strength, and blood lipid profiles. Results During the 12 weeks of androstenedione or androstenediol use, a significant increase in the aromatization by-products estrone and estradiol was observed in both groups ( P = .03). In the dione group, total testosterone levels significantly increased 16% after 1 month of use, but by the end of 12 weeks, they returned to pretreatment levels. This return to baseline levels resulted from increases in aromatization and down-regulation in endogenous testosterone synthesis based on the fact that luteinizing hormone was attenuated 18% to 33% during the treatment period. Neither androstenediol nor androstenedione enhanced the adaptations to resistance training compared with placebo for body composition or muscular strength. However, both androstenediol and androstenedione supplementation adversely affected high-density lipoprotein cholesterol (HDL-C) levels, coronary heart disease risk (representing a 6.5% increase), and each group's respective (low-density lipoprotein cholesterol [LDL-C]/HDL-C)/(apolipoprotein A/apolipoprotein B) lipid ratio (diol: +5.2%; dione: +10.5%; P = .05). In contrast, the placebo group's HDL-C levels increased 5.1%, with a 12.3% decline in the (LDL-C/HDL-C)/(apolipoprotein A/apolipoprotein B) lipid ratio. These negative and positive lipid effects occurred despite no significant alterations in body composition or dietary intakes in the supplemental groups or placebo group, respectively. Conclusions Testosterone precursors do not enhance adaptations to resistance training when consumed in dosages recommended by manufacturers. Testosterone precursor supplementation does result in significant increases in estrogen-related compounds, dehydroepiandrosterone sulfate concentrations, down-regulation in testosterone synthesis, and unfavorable alterations in blood lipid and coronary heart disease risk profiles of men aged 35 to 65 years.
... The anabolic action of AAS is particularly interesting since its affects protein metabolism by stimulation of protein synthesis and inhibition of protein breakdown, which could induce muscle growth and enhance adaptation to resistance training (Yesalis & Bahrke 1995; Brown et al. 2006). Since the AAS use in sport is banned, different nutritional strategies have been developed in the past decades to circumvent this problem and administer other exogenous testosterone analogues (King et al. 1999). In the past 2o years, different steroid prohormones or prosteroids (e.g. ...
... In the past 2o years, different steroid prohormones or prosteroids (e.g. androstenedion, dehydroepiandrosterone, androstenediol, 19-nor androstenediol, 19-nor androstenedione, 1- testosterone) have been developed and aggressively marketed in athletic environment as legal nutritional supplements that are expected to convert to active anabolic steroid hormones in the body and enhance exercise performance (Brown et al. 1999; Brown et al. 2000; Earnest et al. 2000; Leder et al. 2000; Brown et al. 2001; Kanayama et al. 2001). The efficacy and safety of these prohormones are not well established but are highly promoted to have the same androgenic effects on building muscle mass and strength as AAS (Baulieu et al. 2000; Brown et al. 2006). ...
... Oral administration of 100 mg androstenedione increased serum testosterone levels in a small study of two women (6), but did not increase serum testosterone levels in a study of healthy young men (7). Recently, we reported that orally administered androstenedione at a dose of 300 mg daily (but not 100 mg) increases serum testosterone levels in healthy young men (8). ...
... Furthermore, whereas several studies have now documented that 100-mg or smaller FIG. 2. Mean Ϯ SEM serum testosterone glucuronide levels during d 1 frequent blood sampling in the control (circles), 100 mg group (squares), and 300 mg group (triangles; n ϭ 5/group in control and 100 mg groups and n ϭ 6 in 300 mg group). doses of androstenedione fail to increase serum testosterone levels in men (7,8,11,12), administration of 100 mg androstenedione in this study increased serum testosterone glucuronide levels dramatically. The metabolism of androgens is characterized by enzymatic conversion to more polar inactive compounds (phase I reactions) and conjugation by glucuronic acid or sulfate (phase II reactions) (13). ...
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Androstenedione is a steroid hormone and the major precursor to testosterone. It is available without prescription and taken with the expectation that it will be converted to testosterone endogenously and increase strength and athletic performance. The metabolism of orally administered testosterone has not been well studied. We randomly assigned 37 healthy men to receive 0, 100, or 300 mg oral androstenedione in a single daily dose for 7 d. Single 8-h urine collections were performed on the day before the start of the androstenedione administration and on d 1 and 7 to assess excretion rates of free and glucuronide- conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone. Serum testosterone glucuronide concentrations were measured by frequent blood sampling over 8 h on d 1 in 16 subjects (5 each in the 0 and 100 mg group and 6 in the 300 mg group). In the control group, mean (±se) d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 3 ± 1, 215 ± 26, 175 ± 26, and 0.4 ± 0.1 μg/h, respectively. In the 100 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 47 ± 11, 3,836 ± 458, 4,306 ± 458, and 1.6 ± 0.2 μg/h, respectively. In the 300 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 115 ± 39, 8,142 ± 1,362, 10,070 ± 1,999, and 7.7 ± 1.5μ g/h, respectively. Urinary excretion rates of all metabolites were greater in both the 100 and 300 mg groups than in controls (P < 0.0001). Urinary excretion rates of testosterone (P = 0.007), androsterone (P = 0.009), etiocholanolone (P= 0.0005), and dihydrotestosterone (P < 0.0001) were greater in the subjects who received 300 mg androstenedione than in those who received 100 mg. In the treated groups, excretion of free testosterone accounted for less than 0.1% of the total excreted testosterone measured. Serum testosterone glucuronide levels increased significantly during frequent blood sampling in both the 100 and 300 mg groups compared with controls (P = 0.0005 for the 100 mg group; P < 0.0001 for the 300 mg group). The net mean changes in area under the curve for serum testosterone glucuronide were −18 ± 25%, 579 ± 572%, and 1267 ± 1675% in the groups receiving 0, 100, and 300 mg/d androstenedione, respectively. We conclude that the administration of both 100 and 300 mg androstenedione increases the excretion rates of conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone and the serum levels of testosterone glucuronide in men. The magnitude of these increases is much greater than the changes observed in serum total testosterone concentrations. These findings demonstrate that orally administered androstenedione is largely metabolized to testosterone glucuronide and other androgen metabolites before release into the general circulation.
... ter higher doses are ingested. However, high dose supplementation and resistance training failed to increase muscle fiber cross sectional when compared to placebo ingestion and training (King, et al., 1999) . This combination has also failed to promote changes in strength or lean body mass (Welle,Jozefowicz & Statt, 1990). ...
... pitch, changes in hair growth patterns, including facial hair, increased abdominal fat accumulation, and appearance of secondary male characteristics. In young males, both acute and chronic increases in estrogen have been observed following high and low dose precursor supplementation even if testosterone did not increase (Rasmussen, et. al., 2000;King, et. al., 1999). It is very possible that the increases in estrogen concentrations experienced by males could have feminizing effects, including gynecomastia (breast development). Great care should be given to the prac-· tical implications associated with the use of precursor supplements. ...
... 5 In a recent study, in which an- drostenedione was administered either as a single 100-mg dose or as 100 mg 3 times daily to healthy men, testosterone concentrations did not increase, although estrogenlevelsdid. 6 Ourdataconfirmthat individual 100-mg doses of androstenedione are insufficient to increase testosterone concentrations in healthy men. However, our data also demonstrate that a higher dose does increase serum testosterone concentrations. ...
... Muscle size and strength did not change when 100 mg of androstenedione was administered 3 times daily to healthy men without prior weight-lifting experience. 6 As this dose was not sufficient to raise testosterone levels, it remains unknown if doses of androstenedione that increase testosterone levels would have significant effects on muscle size and function. Finally, because androstenedione itself is a weakly androgenic steroid, 14 increases in androstenedione itself could have anabolic effects. ...
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Article
Androstenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown. To determine if oral administration of androstenedione increases serum testosterone levels in healthy men. Open-label randomized controlled trial conducted between October 1998 and April 1999. General clinical research center of a tertiary-care, university-affiliated hospital. Forty-two healthy men aged 20 to 40 years. Subjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days. Changes in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups. Mean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were -2% (7%), -4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P<.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids. Our data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men.
... Based on our results with the human PXR, we would not expect physiological concentrations of ADIONE and DHEA in humans to be high enough to significantly activate PXR. Physiological concentrations of ADIONE in blood are in the low nanomolar range, and even in individuals who supplement with over-the-counter ADIONE, levels do not reach the micromolar range (King et al., 1999). Physiological concentrations of DHEA in human plasma are approximately 1 to 8 M (measured as the 3␤sulfate conjugate), with younger adults having higher levels than older adults (Nafziger et al., 1991). ...
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Dehydroepiandrosterone (DHEA) is a steroid produced by the human adrenal gland. Administration of pharmacological doses of DHEA to rats changes expression of many genes, including the cytochrome P450 family members CYP4A1 and CYP3A23. It is known that induction of CYP4A expression by DHEA requires the peroxisome proliferator-activated receptor alpha (PPAR(alpha)). In the current study, PPAR(alpha)-null mice were used to examine the role of PPAR(alpha) in expression of CYP3A. In wild-type mice, 150 mg/kg DHEA-sulfate induced Cyp4a and Cyp3a11 mRNAs by 5- and 2-fold, respectively. Induction of Cyp4a expression by DHEA-sulfate was not observed in PPAR(alpha)-null mice, whereas induction of Cyp3a11 expression by DHEA-sulfate was similar between genotypes. This suggests that PPAR(alpha) is not involved in induction of Cyp3a11 expression by DHEA. Because expression of CYP3A family members can be induced by activation of another member of the nuclear receptor superfamily, the pregnane X receptor (PXR), we examined the ability of DHEA to activate PXR. In transient transfection assays, DHEA and its metabolites androst-5-ene-3beta,17beta-diol (ADIOL), androst-5-ene-3,17-dione, and androst-4-ene-3,17-dione were activators of PXR. Maximal induction of a PXR-responsive reporter gene of approximately 3-fold was observed at concentrations of 50 to 100 microM, indicating that these steroids are relatively weak activators of PXR. Human and murine PXR exhibited different specificities for DHEA and its metabolites. ADIOL activated reporter gene expression in the presence of murine but not human PXR. Results of these studies suggest that the induction of rodent CYP3A expression upon treatment with high doses of DHEA occurs through activation of PXR.
... Administration of 300 mg androstenedione/day for up seven days (Leder et al., 2000) or 300 mg androstenedione/day for 28 days (Brown et al., 2004b) increased serum concentrations and excretion of androgens in men. However, administration of 200 mg androstenedione/day for 28 days (Beckham and Earnest, 2003) or 300 mg androstenedione/day for 8 weeks (King et al., 1999) did not increase serum testosterone levels in men. Prolonged androstenedione exposure to men (200 mg/day for 12 weeks) elevated serum concentrations of androstenedione, estradiol, and estrone, but not testosterone (Broeder et al., 2000). ...
Article
Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of androstenedione in male and female F344/N rats and B6C3F1 mice. In subchronic studies, dose limiting effects were not observed. A chronic (2-year) exposure by gavage at 10, 20, or 50 mg/kg in rats and male mice, and 2, 10, or 50 mg/kg in female mice (50 mg/kg, maximum feasible dose) was conducted. Increased incidences of lung alveolar/bronchiolar adenoma and carcinoma occurred in the 20 mg/kg male rats and increases in mononuclear cell leukemia occurred in the 20 and 50 mg/kg female rats, which may have been related to androstenedione administration. In male and female mice, androstenedione was carcinogenic based upon a significant increase in hepatocellular tumors. A marginal increase in pancreatic islet cell adenomas in male (50 mg/kg) and female (2, 10, 50 mg/kg) mice was considered to be related to androstenedione administration. Interestingly, incidences of male rat Leydig cell adenomas and female rat mammary gland fibroadenomas decreased. In conclusion, androstenedione was determined to be carcinogenic in male and female mice, and may have been carcinogenic in rats.
... Assim como a DHEA, a androstenediona tem sido utilizada com o intuito de elevar os níveis de testosterona 48 . Todavia, King et al. 49 , em 1999, demonstraram que a suplementação de androstenediona não elevou as concentrações plasmáticas de testosterona nem promoveu adaptações do músculo esquelético no treinamento de resistên- cia. ...
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Os hormônios esteróides anabólicos androgênicos (EAA) compreendem a testosterona e seus derivados. Eles são produzidos nos testículos e no córtex adrenal, e promovem as características sexuais secundárias associadas à masculinidade. Na medicina, os EAA são utilizados geralmente no tratamento de sarcopenias, do hipogonadismo, do câncer de mama e da osteoporose. Nos esportes, são utilizados para o aumento da força física e da massa muscular; entretanto, os efeitos sobre o desempenho atlético permanecem, ainda, controversos. Os EAA podem causar diversos efeitos colaterais, como psicopatologias, câncer de próstata, doença coronariana e esterilidade. Estudos epidemiológicos apontam a problemática acerca do uso de EAA, nos esportes; todavia, no Brasil não existem publicações substanciais sobre esse tema. Esta revisão analisa esse assunto, procurando despertar a curiosidade e o interesse dos leitores para a produção científica de novos trabalhos relacionados ao tema.
... Assim como a DHEA, a androstenediona tem sido utilizada com o intuito de elevar os níveis de testosterona 48. Todavia, King et al. 49 , em 1999, demonstraram que a suplementação de androstenediona não elevou as concentrações plasmáticas de testosterona nem promoveu adaptações do músculo esquelético no treinamento de resistência. ...
... TT plus AAS. In the search for appropriate androgens taken by athletes, Brown et al. (2000b) focused their attention on exogenous androstenedione and androstenediol, steroids which in the human body are converted into more biologically active compounds. Assuming that TT would enhance the rate of that conversion, and in consequence increase the effectiveness of relatively small amounts of those pro-hormones, the same authors carried out more comprehensive studies on the biological effect of TT taken concurrently with androstenediol (Brown et al., 2001) or androstenedione (Brown et al., 2000a). ...
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Herbal and nutritional supplements are more and more popular in the western population. One of them is an extract of an exotic plant, named Tribulus terrestris (TT). TT is a component of several supplements that are available over-the-counter and widely recommended, generally as enhancers of human vitality. TT is touted as a testosterone booster and remedy for impaired erectile function; therefore, it is targeted at physically active men, including male athletes. Based on the scientific literature describing the results of clinical trials, this review attempted to verify information on marketing TT with particular reference to the needs of athletes. It was found that there are few reliable data on the usefulness of TT in competitive sport. In humans, a TT extract used alone without additional components does not improve androgenic status or physical performance among athletes. The results of a few studies have showed that the combination of TT with other pharmacological components increases testosterone levels, but it was not discovered which components of the mixture contributed to that effect. TT contains several organic compounds including alkaloids and steroidal glycosides, of which pharmacological action in humans is not completely explained. One anti-doping study reported an incident with a TT supplement contaminated by a banned steroid. Toxicological studies regarding TT have been carried out on animals only, however, one accidental poisoning of a man was described. The Australian Institute of Sport does not recommend athletes' usage of TT. So far, the published data concerning TT do not provide strong evidence for either usefulness or safe usage in sport.
... Une étude à répartition aléatoire à double insu avec placebo a montré que des doses supraphysiologiques de testostérone et un programme d'exercice entraînaient une augmentation importante de la masse maigre et de la force musculaire. Cependant, selon d'autres études, les prohormones telles que l'androstènedione (un autre supplément alimentaire populaire) et la DHEA ne peuvent offrir ces mêmes avantages 7 10 Les effets psychiques des SAA peuvent être importants. Vrai. ...
Article
Depuis l'entrée de son fils dans la Ligue de hockey junior majeure du Québec, Papa se demande si fiston ne devrait pas utiliser des stéroïdes pour prendre de la masse musculaire et augmenter ses chances de succès. Vous rencontrez Papa au Pavillon de l'éducation physique et des sports de l'Université Laval, et il vous soumet ses questions. Mettez vos connaissances à l'épreuve pour voir si vous pouvez conseiller vos patients afin qu'ils fassent un choix éclairé. Vrai Faux 1. Moins de 1 % des jeunes étudiants du secondaire et du collégial auraient utilisé des stéroïdes. I I I I 2. Les stéroïdes anabolisants androgéniques (SAA) sont tous des produits naturels.
... Of these, only creatine and HMB have reproducible evidence of increases in muscle mass and strength in individuals engaged in resistance exercise (2,3,5,13,18,20,23,24,26,27,34,35). Prohormones tested in exercising human subjects to date, DHEA and androstenedione , have not been associated with increased muscle mass and strength in human studies (8,9,25,36,40,44,48). Previous studies of supplements utilized in vivo animal cell models. ...
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Postnatal muscle stem cells, recognized as myogenic satellite cells, were isolated from sheep skeletal muscle and used in these experiments. Forty-one different metabolic compounds that are commonly found in commercially-available oral supplements were exposed to primary muscle stem cell cultures, in an effort to ascertain whether any one compound could alter satellite cell proliferation or differentiation (a first step towards elucidating the metabolomics or nutrigenomics of these stem cells). These compounds included energetic moieties, amino acid analogs, fatty acids and analogs including different forms of conjugated linoleic acid, minerals and mineral conjugates, insect hormones, caffeine, plant extracts, and extracts from over-the-counter supplements, and were obtained by key manufacturers in a form that would be commercially available. The compounds were sterilized and then exposed to myogenic satellite cell cultures at different levels (ranging from toxic to physiologic) to ascertain if there would be an effect. The results suggested that exposure of satellite cells to only a few compounds resulted in any measurable effect(s). Ten compounds elicited increases in proliferation, and four compounds promoted increases in differentiation. These results suggest avenues for the exploration of enhancing muscle stem cell activity of interest for muscle wasting disorders, sarcopenia of aging and physical performance.
... The key anabolic steroid required for an increase in muscle mass is testosterone (Mooradian, Morley & Korenman 1987). It can be provided from the blood either directly (via testosterone from the testes) or indirectly (via the conversion within the tissue of androgen precursors such as androstenedione which is usually produced by the adrenals, King et al. 1999 ). Testosterone is critical for the behavioural and physiological changes necessary for breeding in vertebrates (Baum 2002). ...
Article
1. At high latitudes, evolutionary adaptations focus on those that maximize survival, with hibernation being a major one used by many smaller mammals. Typically, mammalian hibernators overwinter in sites that are ≈0°C. However, in arctic regions, such sites do not exist, necessitating hibernation at sites well below 0°C. Lipid, the normal fuel of most hibernators, may not provide sufficient glucose needed by certain tissues to permit survival, with muscle breakdown being required. Critical to enhancing muscle stores are high concentrations of anabolic androgens prior to hibernation when the gonads are inactive.
... Unlike the parenteral administration of testosterone, however, DHEA does not produce a notable elevation in serum testosterone levels or enhance skeletal muscle hypertrophy. 230 Several adverse effects were reported and the International Olympic Committee considers DHEA an illegal steroid, banning its use. A recent analysis of sixteen commercial DHEA products revealed that only half the products contained the actual amount of DHEA stated on the product label, with actual levels varying between 0% and 150% of the label content. ...
Chapter
There is widespread recognition that diet plays an important role in the incidence of many diseases. Whereas basic nutrients, including vitamins and minerals, are important for growth and development, the focus of functional foods is to provide health benefi ts beyond those provided by basic nutrients. Although the mechanisms are not completely clear, when eaten on a regular basis as part of a varied diet, functional foods may lower the risk of developing diseases such as cancer or heart disease.
... The most important and common side effects of anabolic steroids are gynecomastia, infertility, impotence in men [7] and a deeper voice, increased body hair, cliteromegaly, infrequent or absent menstrual periods in women [8]. Both men and women also have increased risk of severe acne, liver abnormalities and tumors, high blood pressure, heart circulatory problems [9], increased aggressiveness [10], psychiatric disorders [11], injection disease such as HIV or hepatitis [12] and decrease serum high density lipoprotein (HDL) and increase low density lipoprotein (LDL) [13]. ...
... ‫واﻟﺘﺎرﯾﺦ‬ ‫اﻟﻐﺬاﺋﯿﺔ،‬ ‫اﻟﻤﻜﻤﻼت‬ ‫ﻧﻮع‬ ‫اﻟﺮﯾﺎﺿﺔ،‬ ‫ﻣﺰاوﻟﺔ‬ ‫ﻣﺪة‬ ‫اﻟﺴﻦ،‬ ‫ذﻟﻚ‬ ‫ﻓﻲ‬ ‫ﺑﻤﺎ‬ ‫ﻣﺘﻄﻮع‬ ‫ﻛﻞ‬ ‫ﻣﻦ‬ ‫اﻟﺪﻗﯿﻘﮫ‬ ‫ﺎت‬ ‫ﻣﺜﻞ‬ ‫اﻟﻜﯿﻤﻮﺣﯿﺎﺗﯿﮫ‬ ‫اﻟﻤﻌﺎﯾﯿﺮ‬ ‫ﺑﻌﺾ‬ ‫ﻗﯿﺎس‬ ‫وﺗﻢ‬ ‫ﻟﻸﻣﺮاض،‬ ‫اﻟﻌﺎﺋﻠﻲ‬ ‫اﻟﺪراﺳﺔ‬ ‫ﻗﯿﺪ‬ ‫اﻟﻤﺠﻤﻮﻋﺘﯿﻦ‬ ‫اﻣﺼﺎل‬ ‫ﻓﻲ‬ . ‫اﻟﻤﺠﻤﻮﻋﺘﯿﻦ‬ ‫ﻣﻦ‬ ‫ﻛﻼ‬ ‫ﻟﺪى‬ ‫اﻟﻤﺪروﺳﮫ‬ ‫اﻟﻤﻌﺎﯾﯿﺮ‬ ‫ﻓﻲ‬ ‫ﻣﻌﻨﻮﯾﺔ‬ ‫ﻓﺮوق‬ ‫وﺟﻮد‬ ‫ﻋﺪم‬ ‫اﻟﻨﺘﺎﺋﺞ‬ ‫اظﮭﺮت‬ ) ‫ﻣﺘﺨﺬه‬ ‫وﻏﯿﺮ‬ ‫ﻣﺘﺨﺬة‬ ‫ﺑﺮوﺗﯿﻨﯿﮫ‬ ‫ﻣﻜﻤﻼت‬ ( ‫ﻣﺆﺷﺮﻛ‬ ‫ﻓﻲ‬ ‫ﻛﺒﯿﺮة‬ ‫اﺧﺘﻼﻓﺎت‬ ‫اﻟﻨﺘﺎﺋﺞ‬ ‫اظﮭﺮت‬ ‫ﺑﯿﻨﻤﺎ‬ ، ‫ﯾﺘﻨﺎوﻟﻮن‬ ‫اﻟﺬﯾﻦ‬ ‫اﻟﻌﻀﻼت‬ ‫ﺑﻨﺎة‬ ‫اﻟﺸﺒﺎن‬ ‫ﻟﺪى‬ ‫اﻟﺠﺴﻢ‬ ‫ﺘﻠﺔ‬ ‫ﻣﺨﺘﻠﻔﺔ‬ ‫ﻣﺼﺎدر‬ ‫ﻣﻦ‬ ‫اﻟﺒﺮوﺗﯿﻦ‬ ‫ﻣﻜﻤﻼت‬ ) ‫اﻟﻤﺘﺤﺪة‬ ‫واﻟﻤﻤﻠﻜﺔ‬ ‫وﺳﻮﯾﺴﺮا‬ ‫وﻣﺎﻟﯿﺰﯾﺎ‬ ‫اﻟﻤﺘﺤﺪة‬ ‫اﻟﻮﻻﯾﺎت‬ ( ‫ﺑﺎﻟﻤﺠﻤﻮﻋﮫ‬ ‫ﻣﻘﺎرﻧﺘﮭﻢ‬ ‫ﻋﻨﺪ‬ ‫ﻻ‬ ‫اﻟﺘﻲ‬ ‫ﺑﺮوﺗﯿﻨﻲ‬ ‫ﻣﻜﻤﻞ‬ ‫اي‬ ‫ﺗﺘﻨﺎول‬ .Bodybuilding supplements are dietary supplements commonly used by those involved in bodybuilding and athletics (Powers and Howley 2001).Bodybuilding supplements may be used to replace meals, enhance weight gain, promote weight loss or improve athletic performance(King, 1999;Mansky and Strauss, 2002). ...
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This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 +/- 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min (P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 +/- 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo (n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly (P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly (P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.
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Androstenedione is the immediate precursor of testosterone. Androstenedione intake has been speculated to increase plasma testosterone levels and muscle anabolism. Thus, androstenedione supplements have become widely popular in the sport community to improve performance. This study was designed to determine whether 5 days of oral androstenedione (100 mg/day) supplementation increases skeletal muscle anabolism. Six healthy young men were studied before the treatment period and after 5 days of oral androstenedione supplementation. Muscle protein turnover parameters were compared to those of a control group studied twice as well and receiving no treatment. We measured muscle protein kinetics using a three-compartment model involving infusion of l-[ring-2H5]phenylalanine, blood sampling from femoral artery and vein, and muscle biopsies. Plasma testosterone, androstenedione, LH, and estradiol concentrations were determined by RIA. After ingestion of oral androstenedione, plasma testosterone and LH concentrations did not change from basal, whereas plasma androstenedione and estradiol concentrations were significantly increased (P < 0.05). Compared to a control group, androstenedione did not affect muscle protein synthesis and breakdown, or phenylalanine net balance across the leg. We conclude that oral androstenedione does not increase plasma testosterone concentrations and has no anabolic effect on muscle protein metabolism in young eugonadal men.
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Much of the existing research on disordered eating has centered on the drive for thinness, which is most commonly observed in girls and women. The male standard of bodily attractiveness, however, is bigger, bulkier, and more muscular. Are boys and men motivated to be big and muscular in the same way that girls and women are motivated to be thin? The authors constructed a 15-item survey and administered it to 197 adolescents. The findings showed that the drive for muscularity measure displayed good reliability; that individuals high in the drive were more likely to be boys who were trying to gain both weight and muscle mass; that the drive was related to poor self-esteem and higher levels of depression among boys, but not among girls; and that the drive for muscularity was relatively unrelated to the drive for thinness.
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ABSTRACT: The purpose of this dissertation was to gain a better understanding of the relationship between the reading of men?s fitness magazines and concerns related to leanness and muscularity. Previous research had found an association between the reading of these magazines and internationalization of the fit ideal, body dissatisfaction, and eating disorder attitudes among college men. However, little was known about the nature of this relationship. The dissertation combined a quantitative content analysis of Men's Health and Men's Fitness magazines published from 1999 to 2003, with qualitative, in-depth interviews with 13 male undergraduates. Findings suggest that fitness magazines disseminate only one type of male physique as healthy, fit, and attractive: the lean and muscular physique, characterized by chiseled abdominal muscles. Dissemination of this ideal may have the positive effect of promoting involvement in healthy activities, such as exercising with weights. However, the ideal is an extreme, unrealistic representation, which may contribute to body dissatisfaction and engagement in unhealthy, appearance-driven pursuits. In fact, few men can achieve the ideal without doing so. Interviews with college men suggest that they may be internalizing the ideal and engaging in behaviors designed to attain it, such as limiting carbohydrates and/or fat in their diets, increasing consumption of protein, exercising (particularly with weights), and using performance-enhancing supplements such as whey protein, creatine, caffeine, and ephedra to reduce body fat and increase muscle mass. Some of these behaviors, particularly the use of supplements, could lead to serious health problems. Overall, the interviews did not suggest that exposure to the magazines was a significant factor in motivating either men's acceptance of the lean and muscular ideal or their involvement in behaviors linked to the pursuit of that ideal. Rather, findings suggest that other influences, such as previous involvement in competitive sports or interactions with friends who engage in these behaviors, may contribute to an interest in body change that precedes the reading of fitness magazines. More research is needed to determine whether-and if so among which readers-exposure to fitness magazines may serve to reinforce existing concerns related to achieving a lean and muscular physique. Text (Electronic thesis) in PDF format. System requirements: World Wide Web browser and PDF reader. Mode of access: World Wide Web. Title from title page of source document. Document formatted into pages; contains 224 pages. Thesis (Ph. D.)--University of Florida, 2004. Includes vita. Includes bibliographical references.
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Ergogenic aids are taken to enhance energy utilization by producing more, controlling its use, or increasing mechanical efficiency. Most athletes are looking toward enhancing performance by proper training modalities and methods; however, some look to the biochemical route for a "quick fix." Thus, the use of chemical agents is on the rise. Herein is provided information on the anabolic-androgenic agents androstenedione, dehydroepiandrosterone, and the "parent" compound, testosterone. The former two, at best, have equivocal activity, but testosterone is both anabolic and androgenic in doses that adolescents might receive. Growth hormone and insulin-like growth factor-1 are anabolic, nonandrogenic compounds with undoubted effects on the lean body mass compartment. Both are expensive, not readily available, and subject to the art of counterfeiting. Thus, very few data are available in non-growth hormone-deficient adolescents. The discussion of these agents ends with issues of fairness, ethics, and the message we attempt to project to our teenagers, whether athletes or not.
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Numerous ergogenic aids that claim to enhance sports performance are used by amateur and professional athletes. Approximately 50 percent of the general population have reported taking some form of dietary supplements, while 76 to 100 percent of athletes in some sports are reported to use them. Physicians can evaluate these products by examining four factors (method of action, available research, adverse effects, legality) that will help them counsel patients. Common ergogenic aids include anabolic steroids, which increase muscle mass. These illegal supplements are associated with a number of serious adverse effects, some irreversible. Creatine modestly improves athletic performance and appears to be relatively safe. Dehydroepiandrosterone and androstenedione do not improve athletic performance but apparently have similar adverse effects as testosterone and are also banned by some sports organizations. Caffeine has mild benefits and side effects and is banned above certain levels. Products that combine caffeine with other stimulants (e.g., ephedrine) have been linked to fatal events. Protein and carbohydrate supplementation provides modest benefits with no major adverse effects.
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Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient, neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases.
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A growing body of data has revealed that specific nutrient deficiencies contribute to microvascular and cellular dysfunction following critical illness. Further, targeted administration of these 'pharmaconutrients' may reverse or improve this dysfunction and improve clinical outcome. Specific nutrient therapy with glutamine protects cellular metabolism and vascular function via induction of heat shock proteins, which are key proteins found to be deficient following acute illness. Arginine becomes rapidly deficient following trauma and surgery. This leads to significant immunosuppression, which when treated by arginine administration significantly reduces postoperative infection. Omega-3 fatty acids attenuate the inflammatory response and provide for resolution of ongoing inflammatory injury via production of resolvins/protectins. Antioxidants (vitamin C and selenium) and trace elements (zinc) become rapidly depleted in critical illness and replacement appears vital to ensure optimal cellular and microvascular function. Data on targeted metabolic (mitochondrial) therapies (i.e. co-enzyme Q10) show promise to improve myocardial function following cardiac surgery. These specific nutrients have newly discovered vital mechanistic roles in the optimization of cellular and microcirculatory function in critical illness and injury. A growing body of literature is demonstrating that correction of key nutrient deficiencies via therapeutic administration of these pharmaconutrients can improve clinical outcome in critically ill patients.
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The large improvement in sporting performances in recent decades is partly due to the volume of training that athletes are undertaking. In response to exercise training, testosterone will acutely increase, decrease or have no change in concentration, depending on many factors including exercise modality, intensity, and duration. Exercise training places a tremendous amount of stress on the body, and if excessive or not managed appropriately, it can compromise an athlete’s health and performance. As a result, the endocrine system can become disrupted, Male athletes with chronic training overload may develop the exercise-hypogonadal male condition with a corresponding reduction in resting testosterone levels, possibly due to both central and peripheral regulatory compromises. In addition to low testosterone, these males also exhibit a lack of corresponding luteinizing hormone secretion. Moreover and regrettably, athletes at all levels of competition have been recorded as using exogenous anabolic-androgenic steroids, leading to a pseudo-hypogonadism state. Although rare, some athletes are candidates for testosterone replacement therapy for medical conditions, however physicians should be aware of the sanctioned and permitted use of exogenous hormones by athletes as dictated by the World Anti-Doping Agency.
Chapter
Numerous publications have addressed the medical, ethical, and legal issues surrounding nonmedical hormone use by healthy individuals. The ethical and legal implications of hormone use in sports to enhance performance are clear—it is unethical and illegal. However, the medical implications surrounding this practice are far less certain, particularly when hormones are used to enhance appearance or performance in noncompetitive athletic settings. A considerable amount of misinformation exists among both users and their primary-care physicians. Many in the medical/scientific community are unaware of why some of these drugs are used, their basic mechanisms of action, and differences among agents within a class of drugs, such as anabolic-androgenic steroids. In addition, sensationalistic media coverage and anecdotal case reporting have further clouded our understanding of performance-enhancing drugs, has impeded research, and has suppressed potentially important clinical applications of these agents. Therefore, the purpose of this chapter is to 1. Provide an overview of hormones and related drugs commonly used to enhance performance and/or physical appearance; 2. Provide a critique of the various rationales given by individuals to support their use of performance-enhancing drugs; and 3. Discuss the basis for the prevailing dogmas surrounding the nonmedical use of hormones, particularly those involving side effects and overall risk.
Chapter
“Heart health is tantamount to fertility and erectile health,” and “first do no harm” are the mantras of this chapter. Lifestyle changes to improve fertility and erectile function are no longer a theory, but sufficient clinical data exists to emphasize a variety of heart healthy behaviors to enhance overall male health, and specific urologic concerns such as infertility and erectile dysfunction (ED). Nutraceuticals for fertility and erectile health appear to exist or be perceived by clinicians and patients on opposite ends of the treatment validation spectrum. Numerous fertility supplements have preliminary evidence and are utilized in urology in addition to assisted reproductive technologies (ART). In fact, their ongoing use continues to be validated by meta-analyses of randomized trials examining pregnancy and live birth rates. Yet the issue with fertility nutraceuticals is the lack of discrimination over which ones to potentially recommend and discourage based on their overall safety in medicine. A plethora of nutraceuticals has been suggested to be of benefit, but one or several have not in general been recommended. Clinicians need to review the latest list of these supplements and review cost, and especially overall safety and efficacy especially outside of the urologic specialty. For example, high-dose vitamin E supplements have been found to increase the risk of prostate cancer, and regardless of their potential positive data in fertility, there are numerous other options, which could parallel the benefits of vitamin E, but without the potential harm. Erectile dysfunction nutraceuticals have arguably one of the most sordid pasts in the dietary supplement milieu, and it is rightly deserved because the FDA has removed more of these supplements from the market compared to any other type of supplement based on nefarious activities, from the addition of PDE-5 contaminants, to the promotion of a variety of benefits without adequate research. However, despite such a problem with ED nutraceuticals, it appears to have created an unnecessary bias in this category from clinicians, which is not warranted because several nutraceuticals for ED have arguably stronger methodological clinical trials compared to fertility nutraceuticals. This chapter highlights some of the most promising nutraceuticals that have the ability to be utilized with conventional options such as PDE-5 inhibitors and/or ART, and it discourages the vast majority of other ED or fertility-enhancing compounds that simply have no efficacy or are not safe.
Chapter
Athletes who compete in endurance-based events are swimming, running, cycling, and skating faster than ever before, and, thus, world records in many events are being broken on a nearly annual basis (1). There are many factors that contribute to this improvement in human exercise performance. First, the coaches working with these athletes have improved scientific knowledge because of advances in the fields of sports medicine and exercise physiology. Second, sporting equipment changes have allowed some improvements in events (1,2). Third, and perhaps most important, is the greater level of exercise training that athletes are performing in our modern era (1–4). It is not uncommon, for example, for marathon runners to complete 150 to 250 km of intensive running per week or for tri athletes to spend 3 to 4 h per day in swimming, running, and cycling training. This large volume of exercise training results in physiological changes and adaptations that are highly beneficial to the human organism, such as enhanced cardiac output, enhanced arterial-venous oxygen difference, increased erythrocyte number, decreased body adiposity, and increased mitochondrial density (3). However, this great volume of exercise training can also place a tremendous amount of stress on the human body and can result in unwanted physiological responses and medical problems, which can potentially compromise the ability of an athlete to perform.
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Resistance exercise elicits an array of hormonal responses critical to acute muscular force and power production as well as subsequent tissue growth and remodeling. In general, the acute response is dependent upon the stimulus and may be the most critical element to tissue remodeling. Thus, modifications of training intensity, volume (or total work), muscle mass involvement, rest intervals, and frequency can impact the acute hormonal response. Long-term adaptations in neuroendocrine function seem minimal but may be related to the current intensity/volume of the training stimulus. The significance of these hormonal responses is not entirely known. For the sports nutritionist, the effect of various nutritional/supplemental strategies can indeed have an effect on the hormonal milieu. For instance, the timing of supplementation/feeding pre-and postexercise may affect the endocrine response to resistance exercise. Also, the consumption of various macronutrients can impact the basal concentration of various hormones.
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This chapter discusses the different types of doping agents that have been used since the pre-Christian era, such as hallucinogenic mushrooms and alcohol, up to those currently used by athletes today. Today, articles 2.1 through 2.8 of the World Anti-Doping Code, define doping as the violation of one or more of these articles through the use of prohibited substances or methods. In the present discussion on anabolic doping agents, the classes of banned substances covered include stimulants, anabolic agents, peptide hormones, and β2-adrenoceptor agonists, as well as masking and antiestrogenic agents. The pharmacokinetics, pharmacodynamics, and toxicology of these substances will be discussed along with some potential historical consequences of the use of certain doping agents by both axis and allied forces during World War II, and the terrible consequences that might be attributed to their use. Keywords Doping Anabolic Performance enhancement Athletics
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Complementary & Alternative Medicine for Prostate and Urologic Health is designed to capture and clinically review the comprehensive database of clinical research articles that support and do not support the utilization of a variety of dietary supplements and other complementary medicines that physicians are exposed to in their daily practice. This is a critical distinction between this book and any other Complementary & Alternative Medicine (CAM) books published to date. Each section of the book provides an easy to reference guide into the topic of interest for the individual that works in urology. The various sub-specialty groups in urology are adequately represented, which allows for a physician to rapidly and thoroughly investigate their topic of interest regardless of whether it is fertility, bladder cancer, or prostate disease. Rather than having to sort through the now thousands of articles published yearly on CAM in medicine, this volume focuses first on the specialty and secondarily how it compares to the overall CAM literature. Each chapter includes a summary page that will allow the physician a rapid review of the subject with a patient, colleague or student. The practical nature of this book in urology also cannot be overstated. Chapters include a general overview of the CAM agent, whether or not it has data in medicine and urology, and a list of potential drug interactions and specific clinical scenarios where it can be utilized or discouraged in the specialty. Complementary & Alternative Medicine for Prostate and Urologic Health represents a gold standard text for use in teaching, not only for the students interested in the urologic field but for all current urologic health providers.
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Abuse of hormones by adolescents and adults is increasing. Controversy exists about detection, factors that influence use, effects on athletic performance, and effectiveness of deterrence programs. The purpose of this study is to summarize data on hormone abuse, including prevalence, performance enhancement, adverse effects, and interventions. MEDLINE and LexisNexis databases searches between 1975 and June 2004 using the terms adolescent/adolescence or student or athlete combined with anabolic, steroid, dietary supplements, erythropoietin, or growth hormone, and prevalence, epidemiology, adverse effects, doping in sports, or substance abuse detection were performed. A total of 1174 citations were identified and 514 were retrieved for analysis based on relevance. National surveys since 1991 show anabolic steroid use increasing in high school students, particularly females. Use is highest among athletes and clusters with abuse of other drugs. Short-term use of low to moderate doses of anabolic steroids increases muscle strength in trained athletes; studies evaluating higher dose regimens have not been conducted. Low doses of anabolic steroid precursors, like androstenedione and dehydroepiandrosterone, variably alter testosterone levels in males but increase levels in women. Although erythropoietin clearly enhances aerobic performance, there is little research on human growth hormones' effects on strength or physical performance. Newer drug prevention programs appear promising in reducing performance enhancing substance use. Illicit anabolic-androgenic steroid use is increasing in adolescents and adults, and team-centered, peer-led interventions appear to be effective in deterrence. A successful nationwide approach will require focused educational efforts, additional research, and legislation to limit availability of anabolic steroid precursors.
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Performance-enhancing substances (PESs) have unfortunately become ubiquitous in numerous sports, often tarnishing the spirit of competition. Reported rates of PES use among athletes are variable and range from 5 to 31 %. More importantly, some of these substances pose a serious threat to the health and well-being of athletes. Common PESs include anabolic-androgenic steroids, human growth hormone, creatine, erythropoietin and blood doping, amphetamines and stimulants, and beta-hydroxy-beta-methylbutyrate. With recent advances in technology, gene doping is also becoming more conceivable. Sports medicine physicians are often unfamiliar with these substances and thus do not routinely broach the topic of PESs with their patients. However, to effect positive change in the sports community, physicians must educate themselves about the physiology, performance benefits, adverse effects, and testing methods. In turn, physicians can then educate athletes at all levels and prevent the use of potentially dangerous PESs.
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Androstenedione is produced in the adrenal gland and gonads, has a weak intrinsic androgenic activity (~ 20% of testosterone), and is a prohormone for androgens (testosterone) and estrogens. 1 High levels of serum androstenedione may confer androgenic or estrogenic risk to women and men, respectively. 2,3 Children and adolescents are particularly vulnerable to the effects of androstenedione conversion to active sex steroids. The conversion of androstenedione to estrogens can cause feminisation of boys. In both boys and girls, the combined effects of excessive androgens and estrogens can induce premature puberty, and significantly compromise adult stature, by causing early closure of the growth plates of the long bones. 2,3 High-circulating androstenedione levels are indicated in virilising congenital adrenal hyperplasia, polycystic ovarian syndrome, and other causes of hirsutism in women. Specifically, high levels may cause disruption of normal sexual development, severe acne, excessive body hair, disruption of the menstrual cycle, and infertility in girls. 2,3 Elevated androstenedione levels may occur as a result of adrenal or ovarian tumours. 2,3 Increased androgen production, or a high androgenic activity, has also been shown to be associated with obesity or adiposity, metabolic disturbances, and development of metabolic syndrome in adult women. 4,5 Specifically, obese women with increased androgens are more prone to metabolic disturbances, such as hyperinsulinaemia, type 2 diabetes mellitus, lipid abnormalities, and hypertension. Therefore, they may be at particular risk of developing atherosclerotic complications. 6,7 Abstract Background: High androgenic activity in adolescent girls and adult women is associated with adiposity and metabolic disturbances. This study examined the relationship between salivary androstenedione levels, body composition, and physical activity levels in young girls.
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Objectives The present study aims to investigate the effects of resistance training on sex hormones and sperm parameters in male rats under X-ray. Methods In this experimental study, 24 Sprague Dawley rats (200–250 g) were randomly assigned into four groups: healthy control, irradiated control, healthy training and irradiated training. Irradiation was induced at a dose of 4 Gy on the whole body. The resistance training protocol was performed for 10 weeks. Finally, blood serum was used to assess FSH, LH and testosterone and sperm quality. Data were analyzed using ANOVA and Tukey’s post hoc test. Results The results showed that radiation significantly reduced serum levels of LH (p=0.42), FSH (p=0.001) and testosterone (p=0.28) between radiation control and healthy control groups. Also, no significant difference was observed between serum levels of LH (p=0.135) and testosterone (p=0.419) in radiation resistance training and the healthy control groups. In addition, significant differences were observed between radiation resistance training and radiation control groups in sperm parameters such as sperm count (p=0.02) and progressively motile sperm (p=0.031). Conclusions It seems that short-term resistance training can improve sperm parameters, including sperm count and sperm motility through increasing serum levels testosterone and LH in male rat under X-ray.
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The use and effects of selected performance-enhancing drugs and nutritional supplements are reviewed. Recent sports medicine studies are mostly double blind and placebo controlled but contain relatively small sample sizes. Their data appear reliable and are reported in reputable journals. Definitions and methods used in sports medicine are provided to enhance the understanding of this literature. The use of performance-enhancing substances is probably under-reported. Anabolic-androgenic steroids are reportedly used in 0% to 1% of women, 0.5% to 3% of high school girls, 1% to 5% of men, 1% to 12% of high school boys, and up to 67% of some groups of elite athletes. The use of combinations of performance-enhancing substances is common. Carbohydrate loading, adequate protein intake, creatine, blood doping, and erythropoietin (epoetin alfa) appear to enhance performance. Anabolic-androgenic steroids enhance performance, but health risks limit their use. Growth hormones and β2-selective adrenergic agonists may enhance performance, but additional studies are needed. Androstenedione, caffeine, amphetamines, and nonprescription sympathomimetics do not appear to enhance performance. Performance-enhancing drugs have shown some benefit in diseased patients with malnutrition and/or decreases in physical ability. Pharmacists and other health care providers have opportunities to improve the understanding, use, and monitoring of performance-enhancing substances.
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In general, nutritional sports ergogenics are designed to enhance energy production and/or improve body composition, promoting muscle growth and decreasing body fat. Many nutritional supplements and pharmacological substances have been used during resistance training without knowledge of the effects on human metabolism caused by their chronic administration. Before the utilization or prescription of any ergogenic aid, it is important to consider some questions about that substance: Is it effective? Is it safe? Is it legal and ethical? In this chapter we discuss the most widely utilized drugs and supplements among individuals engaged in resistance training-testosterone, creatine, beta-hydroxy beta-methylbutyrate (HMB) and caffeine-focusing on their effects on strength and body composition, the safety of their utilization, and their mechanisms of action.
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1. In a previous study of the effects of methandienone (Dianabol) on men undergoing athletic training, strength and performance increased, but not significantly more when the subjects were taking the drug than when they were taking placebo. The subjects did, however, gain more weight on the drug, with increases in total body potassium and muscle dimensions. It remained an open question whether the muscles had gained normal tissue or intracellular fluid. 2. In an attempt to distinguish between these possibilities the trial has been repeated, using as subjects seven male weight-lifters in regular training, and including measurements of total body nitrogen. As before, a dose of 100 mg of methandienone/day was given alternately with the placebo in a double-blind crossover experiment. The treatment periods lasted 6 weeks and were separated by an interval of 6 weeks. Body weight, potassium and nitrogen, muscle size, and leg performance and strength increased significantly during training on the drug, but not during the placebo period. 3. The finding of increased body nitrogen suggested that the weight gain was not only intracellular fluid. The increases in body potassium (436 ± sem 41 mmol) and nitrogen (255 ± 69 g) were too large in proportion to the weight gain (2.3 ± 0.4 kg) for this to be attributed to gain of normal muscle or other lean tissue, and imply gain of nitrogen-rich, phosphate-poor substance. Although this action of methandienone might be described as anabolic, the weight gain produced is not normal muscle.
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The hypothesis that serum concentrations of pituitary hormones, sex steroid hormones, or sex hormone-binding globulin (SHBG) affect the occurrence of prostatic cancer was tested in a consecutive sample of 93 patients with newly diagnosed, untreated cancer and in 98 population controls of similar ages without the disease. Cases did not differ significantly from controls regarding serum levels of luteinising hormone (LH) or follicle stimulating hormone (FSH). Remarkably close agreement was found for mean values of total testosterone (15.8 nmol l-1 in cases and 16.0 in controls), and free testosterone (0.295 and 0.293 nmol l-1, respectively), with corresponding odds ratios for the highest vs lowest tertile of 1.0 (95% confidence interval 0.5-1.9) for testosterone and 1.2 (95% confidence interval 0.6-2.4) for free testosterone. Similar close agreement between cases and controls was found for serum concentrations of estradiol, androstenedione and SHBG, although the mean estradiol level was non-significantly (P = 0.30) lower among cases. Changes secondary to the disease were unlikely to have affected the results materially, since only LH and FSH were associated with stage of disease and this relationship was weak. Our findings suggest that further analyses of serum hormone levels at the time of diagnosis are unlikely to improve our understanding of the etiology of prostatic cancer.
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Athletes often take androgenic steroids in an attempt to increase their strength. The efficacy of these substances for this purpose is unsubstantiated, however. We randomly assigned 43 normal men to one of four groups: placebo with no exercise; testosterone with no exercise; placebo plus exercise; and testosterone plus exercise. The men received injections of 600 mg of testosterone enanthate or placebo weekly for 10 weeks. The men in the exercise groups performed standardized weight-lifting exercises three times weekly. Before and after the treatment period, fat-free mass was determined by underwater weighing, muscle size was measured by magnetic resonance imaging, and the strength of the arms and legs was assessed by bench-press and squatting exercises, respectively. Among the men in the no-exercise groups, those given testosterone had greater increases than those given placebo in muscle size in their arms (mean [+/-SE] change in triceps area, 424 +/- 104 vs. -81 +/- 109 square millimeters; P < 0.05) and legs (change in quadriceps area, 607 +/- 123 vs. -131 +/- 111 square millimeters; P < 0.05) and greater increases in strength in the bench-press (9 +/- 4 vs. -1 +/- 1 kg, P < 0.05) and squatting exercises (16 +/- 4 vs. 3 +/- 1 kg, P < 0.05). The men assigned to testosterone and exercise had greater increases in fat-free mass (6.1 +/- 0.6 kg) and muscle size (triceps area, 501 +/- 104 square millimeters; quadriceps area, 1174 +/- 91 square millimeters) than those assigned to either no-exercise group, and greater increases in muscle strength (bench-press strength, 22 +/- 2 kg; squatting-exercise capacity, 38 +/- 4 kg) than either no-exercise group. Neither mood nor behavior was altered in any group. Supraphysiologic doses of testosterone, especially when combined with strength training, increase fat-free mass and muscle size and strength in normal men.
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The steroid hormone androstenedione profoundly influences the development and expression of sexual and aggressive behavior. The neural basis of these effects are, however, poorly understood. In this study we evaluated androstenedione's ability to maintain vasopressin peptide levels in the gonadal steroid-responsive vasopressin cells of the bed nucleus of the stria terminalis and the centromedial amygdala, and their projections. Adult male rats were castrated and given testosterone, androstenedione or no hormonal treatment for five weeks. Their brains were then processed for vasopressin immunoreactivity. Androstenedione and testosterone treatment were equally effective in preventing the reduction of vasopressin immunoreactivity associated with castration. Androstenedione may therefore be able to mimic the effects of testosterone on testosterone-responsive neural systems.
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In brief: High-density lipoprotein cholesterol (HDL-C) levels were measured in five elite weight-trained athletes who were intermittently taking anabolic-androgenic steroids and in 28 age- and sex-matched control subjects who had never taken anabolic-androgenic steroids Athletes had significantly lower levels of HDL C while taking steroids than while abstaining (p <.01). Athletes also had significantly lower HDL-C levels while using steroids than the control subjects (p <.001). Total cholesterol levels for the athletes remained unchanged throughout the study and were similar to control subject levels (p >.05).
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In brief: Despite warnings of possible risk to liver, prostate, and kidney function, the use of anabolic steroids has become widespread among athletes. This study examined the influence of oral and injected anabolic steroids on serum HDL-C levels in nine strength-trained men. The mean HDL-C concentration in these subjects was 17.0 ± 2.3 mg/100 ml, which was significantly lower (p ≤.05) than the means for untrained (46 ± 1.6 mg/100 ml) and strength-trained (44.6 ± 1.3 mg/100 ml) men who were not using these drugs. In light of the relationships reported between low levels of HDL-C and the incidence of coronary artery disease, the administration of these drugs to otherwise healthy men appears to be ethically and clinically inadvisable.
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The steroid hormone androstenedione profoundly influences the development and expression of sexual and aggressive behavior. The neural basis of these effects are, however, poorly understood. In this study we evaluated androstenedione’s ability to maintain vasopressin peptide levels in the gonadal steroid-responsive vasopressin cells of the bed nucleus of the stria terminalis and the centromedial amygdala, and their projections. Adult male rats were castrated and given testosterone, androstenedione or no hormonal treatment for five weeks. Their brains were then processed for vasopressin immunoreactivity. Androstenedione and testosterone treatment were equally effective in preventing the reduction of vasopressin immunoreactivity associated with castration. Androstenedione may therefore be able to mimic the effects of testosterone on testosterone-responsive neural systems.
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Background: The relation between endogenous steroid hormones and risk for breast cancer is uncertain. Measure-ment of sex hormone levels may identify women at high risk for breast cancer who should consider preventive ther-apies.
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Dietary indoles in cruciferous vegetables induce cytochrome P450 enzymes and have prevented tumors in various animal models. Because estradiol metabolism is also cytochrome P450 mediated and linked to breast cancer risk, indoles may similarly reduce estrogen-responsive tumors in humans. We examined several indoles in female Sprague-Dawley rats for induction of hepatic estradiol 2-hydroxylation. The most potent inducer, indole-3-carbinol, was administered to humans (500 mg daily for 1 wk). It significantly increased the extent (mean ± SEM) of estradiol 2-hydroxylation from 29.3% ± 2.1% to 45.6% ± 2.1% ( P <.001). These results indicate that indole-3-carbinol strongly influences estradiol metabolism in humans and may provide a new chemopreventive approach to estrogen-dependent diseases. [J Natl Cancer Inst 82:947–949, 1990]
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Endogenous androgens have been suggested as determinants of risk of prostatic cancer. To examine this possibility, baseline sex hormone levels were measured in 1008 men ages 40-79 years who had been followed for 14 years. There were 31 incident cases of prostatic cancer and 26 identified from death certificates with unknowndates of diagnosis. In this study, total testosterone, estrone, estradici, and sex hormone-binding globulin were not related to prostate cancer, but plasma androstenedione showed a positive dose-response gradient. Age-adjusted relative risks of prostatic cancer for low (0-2.2 IIMI, middle (2.3-3.1 im ). and high (3.2+ UM)fertiles of androstenedione were 1.00, 1.34, and 1.98, respectively (/' trend < 0.05). The linear gradient of risk persisted after adjustment for age and body mass index. If confirmed, these data suggest that andro stenedione might increase the occurrence of clinically manifest prostatic cancer.
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To the Editor:— Orally given methyltestosterone has been used in clinical practice since its introduction by Foss in 1939 (Brit. M. J.2:11, 1939) both for its anabolic and for its androgen effects. It was not until 1947 that Werner (Am. J. Med.3:52, 1947) suggested that its use might rarely be associated with jaundice. Other reports followed (Kinsell, L. W.: Gastroenterology11:672, 1948; Werner, S. C.; Hanger, F. M.; and Kritzler, R. A.: Am. J. Med.8:325, 1950; Wood, J. C.: J. A. M. A.150:1484-1486 [Dec. 13] 1952; Van Dommelen, C. K. V., and Van der Steur, J. C.: Nederl. tijdschr. geneesk.99:2732, 1955; Brick, I. B., and Kyle, L. H.: New England J. Med.246:176, 1952). According to Werner and co-workers (ibid.) the whole picture of jaundice associated with methyltestosterone seems to be due to bile stasis. Biopsy showed dilated
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The utilization of plasma dehydroisoandrosterone for estrogen production was studied in 4 normal young nonpregnant women and in one young surgical castrate woman. The mean transfer constant for total conversion to estrogen, [σ]DEBU’ was 0.0016 of which about one third (0.0005) could be accounted for by conversion of dehydroisoandrosterone first to plasma androstenedione which in turn was converted to estrone. The remaining fractional conversion appeared to result principally in estradiol formation via a pathway probably not involving plasma androstenedione. The conversion of plasma dehydroisoandrosterone to estrogen was similar in the surgical castrate to that observed in the ovulating women. It is concluded that plasma dehydroisoandrosterone is converted to estrogen at extraglandular site(s) but this contribution represents only a minor fraction of total estrogen production in normal young women.
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Serum androstenedione and testosterone levels were measured in 39 male patients with pancreatic cancer, and compared with the values obtained from 37 male patients with chronic pancreatitis or benign obstructive jaundice, and with those from 36 male patients with other gastrointestinal malignancies. Mean androstenedione values were significantly higher in the pancreatic cancer patients when compared to both control groups, and mean testosterone levels were significantly lower. The testosterone/androstenedione ratio was calculated and was also found to be significantly lower in the patients with pancreatic cancer. There was no difference in this ratio or in the androstenedione or testosterone levels when comparing both control groups. In two patients with stage I pancreatic cancer, serum androstenedione and testosterone levels were significantly altered, and returned to normal values after successful resection. These results confirm previous findings indicating that there is signifcant derangement in the androgen profile of patients with pancreatic cancer. (C) Lippincott-Raven Publishers.
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Thirteen experienced male weightlifters taking high-protein diets and regular exercise took part in a double-blind crossover trial of methandienone 10 or 25 mg/day to seeif the drug improved athletic performance. Their improvemments were significantly greater on methandienone than on placebo; their body weights rose (though this seemed to be associated with water retention); and systolic blood pressure rose significantly. Methandienone caused many side effects, and three men had to withdraw because of them. All side effects disappeared after the drug was stopped. Anabolic steroids are effective only when given combination with exercise and high-protein diet. We deprecate their use in athletics but can suggest no way of stopping it.
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[7-3HA1Androstenedione and [4-14C]estrone or [7-3H]testosterone and [14C]estradiol were infused at constant rates into brachial arm veins of 15 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle, and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In seven men the mean +/- SE value for the fractional conversion of androstene tissue. In eight men the mean +/- SE value for the fractional conversion of testosterone to estradiol was 0.0007 +/- 0.0001 for muscle and 0.0012 +/- 0.0002 for adipose tissue. Both of these values were significantly (P less than 0.01) less than the respective values of androstenedione aromatization to estrone. If constancy of tissue aromatization throughout the body is assumed, the muscle accounts for 25-30% and adipose tissue for 10-15% of the total extragonadal aromatization of androgens to estrogens.
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Serum 5alpha-dihydrotestosterone (DHT) and testosterone (T) were measured in 98 normal adult men aged between 20-80 years, separating T and DHT by thin layer chromatography and using a sensitive and reliable radio-immunoassay. In three age groups between 20-40, 40-60 and 60-80, the means +/- SEM for serum DHT were 84 +/- 4, 79 +/- 3 and 67 +/- 3 (ng/100 ml) respectively. The corresponding values for testosterone were 559 +/- 25, 491 +/- 25 and 475 +/- 28 (ng/100 ml). A significant decrease was observed in the DHT level of the 60-80 years age group compared to either the 20-40 (P less than 0.01) or the 40-60 (P less than 0.02) age groups. There was a moderate decline in the testosterone level of the 60-80 years age group compared to 20-40 years (P less than 0.05) but there were no significant changes in the testosterone levels between other groups.
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The effects of anabolic steroids on body composition, blood pressure, lipid profile and liver functions were studied in male body builders who received a weekly i. m. injection of nandrolone-decanoate (100 mg) or placebo for 8 weeks in a double blind way. In addition, 5 body builders received the same dosage of nandrolone-decanoate or placebo, in a double blind cross-over design during two 8-week periods, interspersed by 12 weeks. Anabolic steroids induced a 25-27% decrease in HDL-cholesterol, which was virtually reversed 6 weeks after cessation of drug use. In the SAD group an increase in diastolic blood pressure was observed, which returned to pre-anabolic values approximately 6 weeks after cessation of drug administration. No deleterious effects of anabolic drugs on plasma activity of liver enzymes were found. Increases in lean body mass were found in all groups, though the increase in the subjects who received anabolic steroids was superior to that in the placebo-treated subjects. The increase in lean body mass suggests increases in muscle mass.
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The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.
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The effects of self-administered anabolic steroids (AS) on lipoproteins, liver function, and blood pressure were studied in male amateur body builders. Twenty body builders were studied at the end of a course of AS (group 1) and 42 body builders were studied after discontinuation of the AS for a mean of 5 months (group 2). Sixteen body builders were studied after discontinuation of AS for at least 2 months and at the end of a 9-week course of AS (group 3). A group of 13 body builders who never used AS served as a control group. Both groups 1 and 2 showed higher levels of transaminas and a higher systolic blood pressure than the controls (P less than 0.05). Group 3 showed an increase of the transaminases an a slight but significant increase of systolic blood pressure (+3 mm Hg) and heart rate (+7 bts/min) after one course of AS (P less than 0.05). Group 1 showed a considerably lower high-density lipoprotein cholesterol (HDLC) (P less than 0.001), a higher low-density lipoprotein cholesterol (LDLC) (P less than 0.05), and a lower apoprotein A-l/B ratio (Apo A-l/ApoB) (P less than 0.001) than the controls and group 2. The ratio of LDLC/HDLC in group 1 was fourfold higher than in the controls (P less than 0.01). In group 3 HDLC decreased from 1.18 +/- 0.05 to 0.60 +/- 0.08 mmol/l (P less than 0.001) and LDLC increased from 3.97 +/- 0.39 to 5.74 +/- 0.71 mmol/l (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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1. Plasma glucose and insulin concentrations were measured during oral (OGTT) and intravenous (IVGTT) glucose tolerance tests in nine patients off- and on-treatment with the anabolic steroid, methandienone (Dianabol). 2. On-treatment, the tolerance tests showed a markedly increased insulin response accompanied by impairment of glucose tolerance, characteristics normally attributed to insulin resistance. However, fasting plasma glucose (FPG) and insulin (FPI) concentrations were significantly reduced, whereas the pattern normally associated with insulin resistance is for both to be raised. 3. IVGTT glucose and insulin profiles were analysed using an algorithm derived from the minimal models of glucose and insulin dynamics originally proposed by R. Bergman and co-workers. Measures for the following parameters were thus obtained: Si, the sensitivity of glucose disposal to insulin; Sg, net insulin independent glucose disposal; ϕ1, the integral concentration of insulin delivered during the first phase of insulin secretion relative to the initial increase in glucose concentration above a model-derived threshold; ϕ2 the sensitivity of the rate of rise of insulin concentration in the second phase of insulin secretion to the concentration of glucose above a model-derived threshold; κ, the fractional clearance rate of insulin; and tl/2, the insulin half-life. 4. Si was significantly reduced on treatment by a factor of 4. Sg, ϕ1, ϕ2 and t1/2 were all significantly increased, and κ was significantly reduced. The increases in Sg and ϕ1 both showed significant correlations with the increase in weight on-treatment. 5. The reduction in FPG and FPI can be explained by the combined effects of the increase in Sg and Dianabol-induced resistance to glucagon. 6. Application of the Bergman models proved to be of value in identifying and quantifying Dianabol-induced insulin resistance. Model-derived parameters of insulin clearance and net insulin independent glucose uptake were also of use in interpreting the changes in glucose and insulin concentrations observed. However, model-derived parameters of pancreatic insulin secretion were likely to have been confounded by reduced hepatic insulin uptake associated with a state of relative insulin resistance.
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Endocrine responses in seven power athletes were investigated during a 12 week strength training period, when the athletes were taking high doses of androgenic-anabolic steroids, and during the 13 weeks following drug withdrawal. During the use of steroids significant decreases (P less than 0.05 to 0.001) in the serum concentrations of thyroid stimulating hormone, thyroxine, triidothyronine, free thyroxine, and thyroid hormone-binding globulin (TBG) were found, whereas the value of triidothyronine uptake increased (P less than 0.001). In relation to the changes in the thyroid function parameters measured, we suggest that the primary target of androgen action was TBG biosynthesis. In five of the seven subjects, serum concentrations of growth hormone increased at some point of the study 5 to 60-fold. Because of the use of exogenous testosterone, serum testosterone concentration tended to increase. This increase was associated with a corresponding increase (P less than 0.001) in serum estradiol. Furthermore, there were major decreases in serum LH (P less than 0.01) and FSH (P less than 0.01) concentrations, and testicular testosterone production was therefore decreased. This was characterized by a very low serum testosterone concentration (5.1 +/- 1.8 nmol/l) 4 weeks following drug withdrawal. Cessation of drug use resulted in return of all the variables measured to the initial values, except for serum testosterone, which was at a low level (14.6 +/- 8.8 nmol/l) 9 weeks after drug withdrawal, indicating prolonged impairment of testicular endocrine function. No consistent changes were found in the eight control athletes.
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Because peripheral aromatization is the major source of circulating estrogens in men and postmenopausal women, we studied the aromatase activity in muscle tissue from both men and postmenopausal women. To do so, the in vitro conversion of tritiated androstenedione to estrogen in homogenates of skeletal muscles obtained at autopsy was studied. Samples from lower limb muscles of both men and postmenopausal women produced estrogen, ranging from 8.5-39.8 pg/g wet wt. The conversion was almost the same as that reported for human adipose tissue, suggesting that the contributions of muscle and fat to the extraglandular production of estrogens in these subjects might be similar. This is the first direct confirmation of muscle aromatase activity and indicates the possible importance of muscle as an extragonadal source of estrogen in both men and postmenopausal women.
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The purpose of the present investigation was to study the effects of testosterone and anabolic steroids on serum lipids in power athletes. Altogether 11 national top-level adult athletes completed the study. Five of them volunteered for the study group and the rest for controls. The follow-up consisted of 9 months of a strength training period. During the first 6 months, the subjects in the study group self-administered androgenic steroids on an average of 57+24.9 mg/day. The most interesting observation was the extremely low high-density lipoprotein (HDL) and HDL2 cholesterol concentrations of the androgen users. After 8 weeks of training, the study group had significantly (P < 0.05) lower HDL cholesterol concentrations than the control group (0.53±0.11 and 1.14±0.19 mmol/l, respectively). This difference remained significant from 8 to 32 weeks of training. No systematic changes were observed in the control group. The HDL2 cholesterol concentration decreased by about 80% (P < 0.01) and HDL3 cholesterol by about 55% (P < 0.01) from the onset values in the study group. A substantial decrease in HDL cholesterol to total cholesterol and in HDL2 cholesterol to HDL3 cholesterol ratios were also noticed under the influence of exogenous androgens. The results of this study suggest that the sustained use of testosterone and anabolic steroids have a marked unfavorable effect on the pattern of HDL cholesterol in the serum of male power athletes.
Article
We quantified serum lipids and postheparin plasma lipolytic activities in 5 weightlifters presently self-administering androgenic steroids (users) and an equal number not currently using these drugs (non-users). Mean (+/- SD) age (23 +/- 2 vs 25 +/- 4 yr), body weight (102.7 +/- 11.4 vs 86.8 +/- 13.6 kg), and percent body fat (8.6 +/- 2.5 vs 7.8 +/- 6.0%) were not different in users and non-users, respectively. Similarly, there were no differences in total cholesterol (183 +/- 27 vs 176 +/- 32 mg.dl-1) low-density lipoprotein-cholesterol (138 +/- 25 vs 108 +/- 32 mg.dl-1), or triglyceride (93 +/- 26 vs 93 +/- 41 mg.dl-1) levels in the two groups. High-density lipoprotein (HDL)-cholesterol concentrations, however, were significantly lower in the users (26 +/- 10 vs 50 +/- 13 mg.dl-1; P less than 0.05), and most of the difference was due to lower HDL2-cholesterol concentrations (6 +/- 4 vs 22 +/- 9 mg.dl-1; P less than 0.05). Postheparin plasma lipoprotein lipase activity was only slightly lower in the users (3.49 +/- 2.23 vs 5.36 +/- 1.73 mumol FFA.ml-hr-1; P= NS). but hepatic triglyceride lipase activity was significantly higher in this group (27.99 +/- 6.89 vs 11.15 +/- 2.76, mumol FFA.ml-hr-1: P less than 0.001) and correlated inversely with HDL2-cholesterol concentrations (r = -0.81; P less than 0.01). We conclude that androgenic hormones reduce HDL-cholesterol concentrations and the HDL2-cholesterol subfraction, possibly by enhancing hepatic triglyceride lipase activity.
Article
Twenty four experienced weight trainers were divided into 4 matched groups according to bodyweight and bench pressing power. Each subject trained 3 days per week for a total of 8 wk. During the initial 4 wk, no ergogenic aids were administered. Group treatments were implemented as follows during the final 4 wk of training: Group I members received 20 mg of methandrostenolone and 30 gr of 90% dietary high protein supplementation daily; Group II members received equivalent placebo dosages of methandrostenolone and similar dietary high protein supplementation; Group III members received only dietary high protein supplementation, and members of Group IV received no treatment. Strength and body build evaluations were conducted 3 times; prior to commencement of training, following the initial 4 wk and following the final 4 wk. Results of the strength and body build evaluations revealed significantly accelerated gains during the final 4 wk of training for Group I members as compared to members of Groups II, III and IV. Similarly, Group II outgained Groups III and IV and Group III outgained Group IV. Results of the subjective evaluations by participating subjects indicated that Group I members perceived more of an effect from the drug than members of Group II; however, Group II reported more side effects. It was concluded that 20 mg of methandrostenolone can effectively accelerate strength and muscularity gains in experienced weight trainers over a 4 wk period. It was also concluded that the manipulation of psychological motivational factors can enhance strength development; however, somewhat less effectively than actual anabolic steroid administration.
Article
Continuous infusions of Delta(4)-androstenedione-7-(3)H and testosterone-7-(3)H have been used to demonstrate that these androgens are converted to estrone and 17beta-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [chi(-PRO)] and free precursor steroid [chi(-PRE)], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [rho](BB) (AE1), for androstenedione conversion to estrone ([rho](BB) (AE1) = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [rho](BB) (TE2), for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [rho](BB) value are greater in males than females. For the androgen interconversions, [rho](BB) (AT) is 4.5% in males and 2.2% in females; [rho](BB) (TA) is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03.
Article
The interconversion and extraction of testosterone and androstenedione across and within different tissues or areas have been studied by the constant infusion technique. The results were calculated using the (3)H/(14)C ratios and radioactive concentrations of testosterone and androstenedione obtained from afferent and efferent blood and tissues at equilibrium. In each tissue studied, the interconversion between testosterone and androstenedione inside the tissue was significantly higher than the corresponding interconversion across the tissue. The pulmonary contribution to the total interconversion between testosterone and androstenedione was far more important than that of any of the other tissues studied. The hepatic metabolic clearance rates of testosterone and androstenedione were not different from their metabolic clearance rates in the mesenteric area. The extraction of each of these compounds, although not negligible, was lower in the kidney and the femoral bed compared with the extraction in the liver and the mesenteric area. Finally, with the possible exception of the liver, testosterone and androstenedione were more completely metabolized when they originated from the cells than from afferent blood. The evaluation of these different tissue transfer constants provides more precise information concerning the relative importance of different sites in the metabolism of these interconverting hormones.