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Weekly intramuscular injections of trenbolone-enanthate (TREN) elevate serum trenbolone in a sustainable manner. Intact male F344 rats were injected with 7.0 mg of TREN or vehicle under isoflurane anesthesia at baseline and 7 days later (as indicated by arrow). Blood samples were obtained by tail tip prior to injection and every 2 days thereafter for 10 days. Values are means SE; n 5. Some error bars are within the width of the symbol. 

Weekly intramuscular injections of trenbolone-enanthate (TREN) elevate serum trenbolone in a sustainable manner. Intact male F344 rats were injected with 7.0 mg of TREN or vehicle under isoflurane anesthesia at baseline and 7 days later (as indicated by arrow). Blood samples were obtained by tail tip prior to injection and every 2 days thereafter for 10 days. Values are means SE; n 5. Some error bars are within the width of the symbol. 

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Selective androgen receptor modulators (SARMs) now under development can protect against muscle and bone loss without causing prostate growth or polycythemia. 17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone), a potent testosterone analog, may have SARM-like actions because, unlike testosterone, trenbolone does not undergo tissue-specific 5α-reducti...

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... TREN administration elevated serum trenbo- lone concentrations throughout the 7 days following injection ( Fig. 1). On day 7, rats received an additional TREN injection, which resulted in peak trenbolone concentrations (46.0 5.6 ng/ml) occurring on day 9. Thus, once weekly TREN injections resulted in a sustained elevation of serum trenbolone, with peak concentrations occurring within 48 h. Within 10 days of administration, TREN also suppressed ...

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... The basic idea of the SARMs is that they modulate the transcriptional activity of the androgen receptor in a tissue-selective fashion. [8][9][10][11][12] Although the efficacy of SARMs for peripheral tissues such as muscle is well established, the extent to which SARMs exert protective androgen effects in the brain is unclear. 13,14 Several nonsteroidal selective androgen receptor agonists that are under preclinical or clinical development have been reported; several of these compounds have revealed potent and useful anabolic activity and acted as partial agonists in androgenic tissues in animal models. ...
Article
ACP‐105 is a novel non‐steroidal selective androgen receptor modulator (SARM) with a tissue‐specific agonist effect and does not have side effects associated with the use of common androgens. This research, reports a comprehensive study for the detection of ACP‐105 and its metabolites in racehorses after oral administration (in vivo) and postulating its structures using mass spectrometric techniques. To obtain the metabolic profile of ACP‐105, a selective and reliable LC‐MS/MS method was developed. The chemical structures of the metabolites were determined based on their fragmentation pattern, accurate mass, and retention time. Under the current experimental condition, a total of nineteen (19) metabolites were detected in ACP‐105 drug administered equine urine samples. The study results suggest the following: (1) ACP‐105 is prone to oxidation, which gives corresponding mono, di, and trihydroxylated metabolites, (2) along with oxidation, there is a possibility of elimination of water molecule (dehydration) from the 3rd position of the tropine moiety, resulting in the dehydrated analogs of corresponding mono, di, and trihydroxylated metabolites, (3) from the study on the metabolites using LC‐MS/MS, it is clear that the fragmentation pattern is identical and a great number of fragment ions are common in all the metabolites and the parent drug. (4) The ACP‐105 and its metabolites were detected for up to 72 hrs, thus the result is a valuable tool for evaluating its use and/or misuse in sport.
... The reduction of the intraprostatic TT levels decreases the conversion into DHT, and, thus, the hormone-receptor binding. [28][29][30][31][32][33] The impaired binding of androgens to their receptors prevents the translocation of AR from the cytoplasm to the nucleus of the prostate cells, making activation of specific pathways theoretically impossible. 34 In addition, patients with BPH present an extremely high DHT plasma concentration, compared to age-matched healthy subjects. ...
Article
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Benign prostatic hyperplasia (BPH) is a pathology that affects 50% of men over 50 years of age and 90% of men develop BPH in their eighth decade of life. In 2018, more than 1 billion men will be affected by this disease worldwide. However, the progression of BPH is highly complex and has been debated and studied for approximately four decades. Recent studies indicate that BPH can originate from the alteration of different hormone synthesis pathways, and that it is also linked to the function of hormone receptors. There is a close relationship between the progression of BPH and sexual hormones, such as progesterone, testosterone, dihydrotestosterone, and estrogen. The focus of this study was to characterize the interactions of these hormones and investigate the direct or indirect role of each sex hormone receptor in the progression of BPH. Although several studies have described the effects of these hormones on BPH, no conclusions have been drawn regarding their role in disease progression. Here, we present a literature review on the sexual receptors possibly involved in the progression of BPH.
... When examining the LABC muscle from TEST-E and TRENtreated rats, it was apparent that the 28-day androgen treatment increased Wnt5a protein expression in a manner that appears independent of the aromatization to estradiol, given the similar increase in Wnt5a among both androgen-treated groups. It is worth noting that certain rodent skeletal muscle tissues possess varying degrees of AR content (27,43). In this regard, the high AR-positive myonuclei that exist in LABC muscle as well as the gastrocnemius being an ambulatory muscle relative to the LABC (27) pose potential limitations in our mechanistic interpretation of LABC AR signaling and Wnt5a protein expression. ...
Article
We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum-free and total testosterone (TEST) and gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3, 6, 12, 18, and 24 mo (mo) old ( n = 9 per group). Free and total TEST was greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass ( r = 0.395, P = 0.007) as well as AR and Wnt5 protein levels (r = 0.670, P < 0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C 2 C 12 -derived myotubes with lower (75 ng/ml) and higher (150 ng/ml) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size ( P < 0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10-mo-old male Fischer 344 rats ( n = 10–11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E); trenbolone enanthate (TREN), a nonaromatizable synthetic testosterone analogue; or a vehicle (ORX only) for 4 wk. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus muscle compared with ORX only ( P < 0.05). To summarize, aromatizable and nonaromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss. NEW & NOTEWORTHY Results from this study demonstrate androgen and Wnt5 protein expression decrease with aging, and this may be a mechanism involved with age-related muscle loss.
... 11 We expand upon this observation by reporting that FIN did not inhibit the TE-induced preservation of LABC mass post-SCI, which supports the contention that type II 5α-reductase activity is not essential for androgen-mediated muscle maintenance. 19,43 This finding is provocative because the sublesional LABC muscle complex is non-weight-bearing, suggesting that TE produces myotrophic actions in a manner independent from loading. Similarly, testosterone has been shown to increase thigh muscle CSA 16 and basal metabolic rate in men with motor-complete SCI, 40,44 indicating that some functional benefit accompanies increased skeletal muscle mass in paralyzed limbs. ...
Article
We have reported that testosterone-enanthate (TE) prevents the musculoskeletal decline occurring acutely after spinal cord injury (SCI), but results in a near doubling of prostate mass. Our purpose was to test the hypothesis that administration of TE plus finasteride (FIN, type II 5α-reductase inhibitor) would prevent the chronic musculoskeletal deficits in our rodent severe contusion SCI model, without inducing prostate enlargement. Forty-three 16-week old male Sprague-Dawley rats received: (1) SHAM surgery (T9 laminectomy), (2) severe (250 kdyne) contusion SCI, (3) SCI+TE (7.0mg/week, i.m.) or (4) SCI+TE+FIN (5mg/kg/day, s.c.). At 8 weeks post-surgery, SCI animals exhibited reduced serum testosterone and levator ani/bulbocavernosus (LABC) muscle mass, effects that were prevented by TE. Cancellous and cortical (periosteal) bone turnover (assessed via histomorphometry) were elevated after SCI, resulting in reduced distal femur cancellous and cortical bone mass (assessed via microcomputed tomography). TE treatment normalized cancellous and cortical bone turnover and maintained cancellous bone mass at the level of SHAM animals, but produced prostate enlargement. FIN co-administration did not inhibit the TE-induced musculoskeletal effects, but prevented prostate growth. Neither drug regimen prevented SCI-induced cortical bone loss, although no differences in whole bone strength were present among groups. Our findings indicate that TE+FIN prevented the chronic cancellous bone deficits and LABC muscle loss in SCI animals without inducing prostate enlargement, which provides rationale for the inclusion of TE+FIN in multimodal therapeutic interventions intended to alleviate the musculoskeletal decline after SCI.
... A number of studies have investigated the endocrine disrupting effects of trenbolone in vertebrates and indications of interference with the HPG axis have been reported in several species (Hemmer et al., 2008;Schultz et al., 2013;Yarrow et al., 2011). Trenbolone interacts directly with ARs in peripheral tissues to initiate cellular responses similar to those stimulated by testosterone (T), but unlike T, it cannot be aromatized (Wilson et al., 2002). ...
Article
We investigated the effects of the androgenic growth promoter 17ß-trenbolone (17βTB) on adult Japanese quail (Coturnix japonica) exposed across three generations. The F0 generation was exposed after sexual maturity to 0, 1, 5, 10, 20, and 40 ppm through feed. The F1 generation was exposed in ovo by maternal transfer and through feed at the same doses as their parents. The F2 generation was exposed in ovo only. Levels of plasma sex steroids, gonadal Cytochrome P450 aromatase (CYP19A1) mRNA and select brain neuroendocrine peptide mRNAs were measured. In males, testosterone levels did not differ in any generation from those in controls. Estradiol was significantly elevated in 17βTB treated F0 and F1 males. In F0 and F1 females, testosterone was suppressed by 17βTB, whereas estradiol was significantly higher at 40 ppm in F0 and at 10 ppm in F1 females. CYP19A1expression in F1 males and females increased suggesting a compensatory response to the androgenic effects of 17βTB. Few significant effects were observed in the F2 birds indicating that in ovo exposure had limited effects on the monitored endpoints. Overall, our results confirmed endocrine disrupting effects of dietary 17βTB in Japanese quail but the response was dependent on sex, developmental stage at initiation of exposure, and dose.
... Previous explanations for reductions in fat mass after testosterone treatment include inhibition of adipocyte differentiation or a decrease in adipocyte size (51,52,54). Testosterone regulates adiposity via direct AR-mediated pathways, as evidenced by the AR knockout mouse, which exhibits reduced lipolysis (64) and elevated visceral adiposity (45), and by the ability of nonaromatizable androgens to prevent orchiectomy (ORX)-induced elevations in adiposity to a magnitude similar to that of testosterone (66). In addition, testosterone may indirectly regulate adiposity via estrogen receptor (ER) activation following the tissue-specific aromatization of testosterone, which occurs primarily in fat (5), with ϳ85% of total serum estradiol (E 2 ) being derived from peripheral aromatization and the remaining ϳ15% originating from gonadal aromatization (30,40). ...
... This administration regimen elevates circulating testosterone to the supraphysiological range for ϳ7 days in rats (67), which increases the likelihood of systemic aromatization. In addition, this dosing regimen has consistently been shown to prevent cancellous bone loss and produce potent myotrophic effects in young and skeletally mature rodents following ORX (35,66,67), while lower doses do not provide full musculoskeletal protection. AN was administered in a dose exceeding that which produced a marked reduction in circulating E 2 and dramatically elevated circulating testosterone (a hallmark characteristic of aromatase inhibition) in intact female rodents within 7 days of treatment (47). ...
... We previously reported that trenbolone enanthate (a nonaromatizeable synthetic testosterone analog) potently reduced visceral fat mass in young and older ORX animals, indicating that fat loss occurs in response to androgen administration, even in the absence of an androgenic substrate for aromatase (4,35,66). However, our previous work did not account for the possibility that androstendione (derived from dehydroepiandrosterone) can be aromatized to estrone and, subsequently, converted to E 2 by actions of 17␤-hydroxysteroid dehydrogenase in tissues, such as fat, expressing the required enzymes (50). ...
Article
The influence of the aromatase enzyme on the chronic fat-sparing effects of testosterone requires further elucidation. Our purpose was to determine whether chronic anastrozole (AN; aromatase inhibitor) treatment alters testosterone-mediated lipolytic/lipogenic gene expression in visceral fat. 10 month old F344 rats (n=6/group) received SHAM surgery, orchiectomy(ORX), ORX+testosterone-enanthate(TEST; 7.0mg/week), or ORX+TEST+AN(0.5mg/day), with drug treatment beginning 14 days post-surgery. At day 42, ORX animals exhibited nearly undetectable serum testosterone and 29% higher retroperitoneal fat mass versus SHAM (p<0.001). Testosterone treatment produced a ~380-415% higher serum testosterone versus SHAM (p<0.001) and completely prevented ORX-induced visceral fat gain (p<0.001). Retroperitoneal fat was 21% and 16% lower in ORX+TEST versus SHAM (p<0.001) and ORX+TEST+AN (p=0.007), while serum estradiol was 62% (p=0.024) and 87% (p=0.010) higher, respectively. ORX stimulated lipogenic-related gene expression in visceral fat, demonstrated by ~84-154% higher SREBP-1 (p=0.023), FASN (p=0.01), and LPL mRNA (p<0.001) versus SHAM, effects that were completely prevented in ORX+TEST animals (p<0.01 versus ORX for all). FASN (p=0.061, trend) and LPL mRNA (p=0.043) were lower in ORX+TEST+AN versus ORX and not different than SHAM, but remained higher than ORX+TEST (p<0.05). In contrast, the ORX-induced elevation in SREBP-1 mRNA was not prevented by TEST+AN, with SREBP-1 expression remaining ~117-171% higher than SHAM and ORX+TEST (p<0.01). Across groups, visceral fat mass and lipogenic-related gene expressions were negatively associated with serum testosterone, but not estradiol. Aromatase inhibition constrains testosterone-induced visceral fat loss and the down-regulation of key lipogenic genes at the mRNA level, indicating that estradiol influences the visceral fat-sparing effects of testosterone.
... Saitoh et al. revealed that injection of ND into young and old mice clearly induced an increase in erythroid colonyforming units (CFU-E); erythroid burst-forming units (BFU- E); and granulocytic-macrophage committed progenitor cells (CFU-GM) in bone marrow in both groups [3] . Moreover , low-dose administration of a considerable number of androgens alters hemoglobin concentrations, while producing potent hypertrophy actions in skeletal muscle [4] . The investigation showed that the use of anabolicandrogenic steroids (AAS) could also be a risk factor to toxicant-associated with fatty liver disease [5] . ...
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Background Nandrolone decanoate (ND) is a doping agent and it is used by athletes. Objectives This study was carried out to evaluate the chronic, high doses of ND administration on Blood cell, lipid profile, and Liver enzymes in male rats. Materials and Methods This experiment was executed on 30 wistar- Albino male rats divided, after weighing, in control, placebo, and test groups (n = 10). Test group received 15 mg/kg intramuscular (IM) ND for duration of 8 weeks. Group placebo received the same volume of placebo although control group did not receive any agent during the trial period. At the end, animals were anesthetized by diethyl ether, scarified, and then blood samples were collected from cervical vessels immediately. Blood cell, lipoprotein profile, and liver enzymes were measured by ordinary methods. Obtained data were analyzed by SPSS V. 15, via ANOVA and Tukey test. Results were expressed as mean ± SD. Statistical difference was significantly recognized by P ≤ 0.05. Results Results showed that AST, ALT, cell blood count, hemoglobin, hematocrite, and cholesterol values in group test were increased significantly compared to those of other groups; however, HDL value in this group decreased noticeably compared to control and Placebo groups. Conclusions Present study revealed that chronic high doses of ND administration alter the liver enzymes, lipid profile, and blood parameter in male rats.
... Furthermore, recent evidence suggests that trenbolone administration may be cardioprotective against ischaemia reperfusion injury (Donner et al., 2016). Yarrow et al. (2011) demonstrated that testosterone and trenbolone treatments equally increased mass of the highly androgensensitive levator ani bulbocavernosus (LABC) muscle in rats, although specific mechanisms were not delineated. Interestingly, in the previous investigation, low, moderate and high doses of trenbolone produced similar increases in LABC mass when compared to testosterone (Yarrow et al., 2011). ...
... Yarrow et al. (2011) demonstrated that testosterone and trenbolone treatments equally increased mass of the highly androgensensitive levator ani bulbocavernosus (LABC) muscle in rats, although specific mechanisms were not delineated. Interestingly, in the previous investigation, low, moderate and high doses of trenbolone produced similar increases in LABC mass when compared to testosterone (Yarrow et al., 2011). Ye et al. (2014) later demonstrated that testosterone and low-dose trenbolone treatments equally reduced the expression of muscle proteolysis-related genes and enhanced insulin-like growth factor signalling in the LABC, albeit by somewhat different mechanisms. ...
... Doses and the enanthate forms of testosterone and trenbolone were chosen given that (i) enanthate esters of testosterone and trenbolone allow for elevated circulating testosterone (Yarrow et al., 2008) and trenbolone (Yarrow et al., 2011) for ~7 days and (ii) 1.0 mg week −1 trenbolone increases LABC mass equally to 7.0 mg week −1 TEST without increasing prostate mass (Yarrow et al., 2011). The LABC muscle was chosen for examination because the administered doses of testosterone and trenbolone have consistently been shown to produce potent myotrophic effects in the LABC muscle of young and mature rodents following ORX Yarrow et al., 2008Yarrow et al., , 2011Ye et al., 2014), a result of the high androgen receptor-positive myonuclei expression in this muscle (Rand & Breedlove, 1992;Ye et al., 2014). ...
Article
The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week(-1) ) or ORX + trenbolone (TREN; 1.0 mg week(-1) ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.
... Recent investigations have examined the effects of TEST therapy on various musculoskeletal parameters in orchiectomised (ORX) rats; ORX is a procedure that drastically reduces circulating androgens, although low levels can circulate due to the adrenal glands being intact. For instance, Yarrow et al. (2011) demonstrated that ORX+TEST treat-ments increased rat levator ani/bulbocavernosus (LABC) muscle mass in young ORX animals, and McCoy et al. (Yarrow et al., 2008) reported similar effects in mature ORX animals, although specific anabolic mechanisms were not delineated. ...
Article
Full-text available
The effects of testosterone (TEST) treatment on markers of skeletal muscle ribosome biogenesis in vitro and in vivo were examined. C2 C12 myotubes were treated with 100 nm TEST for short-term (24-h) and longer-term (96-h) treatments. Moreover, male 10-month-old Fischer 344 rats were housed for 4 weeks, and the following groups were included in this study: (i) Sham-operated (Sham) rats, (ii) orchiectomised rats (ORX) and (iii) ORX+TEST-treated rats (7.0 mg week(-1) ). For in vitro data, TEST treatment increased c-Myc mRNA expression by 38% (P = 0.004) after 96 h, but did not affect total RNA, 47S pre-rRNA, Raptor mRNA, Nop56 mRNA, Bop1 mRNA, Ncl mRNA at 24 h or 96 h following the treatment. For in vivo data, ORX decreased levator ani/bulbocavernosus (LABC) myofibril protein versus Sham (P = 0.006), whereas ORX+TEST (P = 0.015) rescued this atrophic effect. ORX also decreased muscle ribosome content (total RNA) compared to Sham (P = 0.046), whereas ORX+TEST tended to rescue this effect (P = 0.057). However, other markers of ribosome biogenesis including c-Myc mRNA, Nop56 mRNA, Bop1 mRNA, Ncl mRNA decreased with ORX independently of TEST treatments (P < 0.05). Finally, lower phospho-(Ser235/236)-to-total rps6 protein and lower rpl5 protein levels existed in ORX+TEST rats versus other treatments, suggesting that chronic TEST treatment may lower translational capacity.
... Unlike TEST, 17␤-hydroxyestra-4,9,11-trien-3-one (trenbolone, TREN) is a selective AR modulator and does not undergo 5␣-reduction or aromatisation (32,33). Additionally, TREN causes a more potent reduction in retroperitoneal/visceral fat pad mass than TEST in hypogonadic male rats (34,35). More recently, we have shown that TREN improves multiple components of the MetS and improves myocardial tolerance to I-R in normogonadic rats (36). ...
... Unlike TEST, TREN treatment additionally reduced visceral fat mass and protected animals against lean mass (muscle) loss. These results support previous findings which highlight TREN's ability to more effectively reduce retroperitoneal and visceral adiposity in male rats (36) than TEST (34). The antiobesity effects of androgens are directly mediated press.endocrine.org/journal/endo 9 by the AR which is more densely expressed in visceral than subcutaneous adipocytes (54,55). ...
Article
The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone deficiency (TD) and potentially impairs the therapeutic efficacy of classical testosterone replacement therapy (TRT). We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose diet (HF/HS). Following 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet mini-osmotic pumps containing either vehicle, 2 mg/kg/day testosterone (TEST) or 2 mg/kg/day trenbolone (TREN) were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage following in vivo ischaemia-reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased subcutaneous and visceral adiposity; circulating triglycerides, cholesterol and insulin; and myocardial damage, with low circulating testosterone compared to CTRLs. Both TEST and TREN protected HF/HS+ORX animals against subcutaneous fat accumulation, hypercholesterolaemia and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia and hyperinsulinaemia; and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TRT may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.