The effects of Pueraria mirifica extract, diadzein and genistein in testosterone-induced prostate hyperplasia in male Sprague Dawley rats.

Pueraria mirifica (PM) is a medicinal plant native to Thailand contained high amount of phytoestrogen and possesses anticancer activity. This study reports the effect of P. mirifica extract, phytoestrogen of diadzein and genistein for its benign prostate hyperplasia properties in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The P. mirifica extract was evaluated for its total phenols, flavonoid and antioxidant activity using DPPH, FRAP and metal chelating assay. The assessment of P. mirifica, diadzein and genistein against benign prostate hyperplasia was determined in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The total phenol was higher than flavonoid but showed low antioxidant activity of DPPH, FRAP and metal chelating. The aqueous PM extract at 1000 mg/kg significantly increased testosterone levels in testosterone-induced rats by 13% while diadzein and genistein increased it by 11% and 17% respectively. However, levels of FSH, LH, triglyceride and HDL are not affected by the oral administration of PM, diadzein and genistein to the rats. Similarly, total protein, albumin, globulin, total bilirubin, conjugated bilirubin, alkaline phosphatase, alanine aminotransferase, AST, and G-glutamyltransferase showed no significant difference as compared with negative control rats. The body weight of the rats, testis, kidney and liver showed no toxic effect. The zinc content increased significantly and the zinc transporter gen of ZnT4 and ZIP4 highly expressed suggesting that the PM, diadzein and genistein plays essential role in modulating prostate zinc homeostasis. Similarly, the expression of IL-6, AR and ER was significantly reduced indicating functioning in regulation of prostate growth and acts as anti-inflammatory role in preventing BPH. In conclusion, the results indicated that PM reduced BPH and contributed to the regulation in the zinc transport expression of the prostate cells in the benign prostate hyperplasia (BPH).

An exploration of the hypothesis that testosterone is implicated in the psychological functioning of women with polycystic ovary syndrome (PCOS).

One of the diagnostic features of polycystic ovary syndrome (PCOS) is elevation of the androgen, testosterone. It is known that women with PCOS are more likely to suffer from psychological problems, especially anxiety and depression, than other women. However, little is known of how much of this is due to testosterone, and if so, what the mechanism(s) might be. This study explores the hypothesis that testosterone impacts women with PCOS both directly and indirectly, via testosterone currently in the bloodstream and through prenatal exposure. It is hypothesised that direct effects occur when testosterone acts directly upon receptors; indirect effects occur where the impact of testosterone is mediated via another variable; activational effects are ephemeral and are caused by testosterone in the bloodstream; organizational effects occur prenatally and cause permanent changes. Four pathways are hypothesised in this paper: 1/ a direct and activational pathway which improves mental rotation ability; 2/ an indirect and activational pathway, whereby distress is caused when the physiological symptoms of testosterone are experienced as embarrassing or otherwise disturbing; 3/ an indirect and organizational effect on mood, where elevated prenatal testosterone predisposes women with PCOS to low blood sugar levels and thus low mood; 4/ and finally, it is suggested that the pathway from biology to psychology can be travelled in reverse, with a direct activational effect of relaxation training on the reduction of adrenal androgens. Testing these hypotheses has important implications for our understanding of PCOS, and our ability to treat this condition more effectively.

Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling.

OBJECTIVES: Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. MATERIALS AND METHODS: TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated. RESULTS: Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction. CONCLUSION: Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization.

Non-classical testosterone signaling in spermatogenic GC-2 cells is mediated through ZIP9 interacting with Gnα11.

Although classical and non-classical signaling of testosterone has been documented in several investigations, the nature of the receptor involved in the non-classical pathway remains a source of controversy. While some investigators favor the exclusive participation of the cytosolic/nuclear androgen receptor (AR) in both pathways, others propose a membrane-bound receptor as the mediator of the non-classical testosterone signaling. Evidence is provided here that in the spermatogenic cell line GC-2 the non-classical signaling pathway of testosterone, characterized through the activation of Erk1/2 and transcription factors like CREB or ATF-1, is not mediated through the classical nuclear androgen receptor (AR) but rather by a membrane-associated receptor. This receptor is ZIP9, a Zn(2+) transporter from the family of the ZRT, IRT-like proteins (ZRT=zinc-regulated transporter; IRT=iron-regulated transporter), which directly interacts with the G-protein Gnα11. siRNA-induced abrogation of the expression of either of these two proteins, whose close contacts are demonstrated by an in situ proximity assay, completely prevents all non-classical signaling effects of testosterone addressed. In contrast, silencing of AR expression does not influence the same signaling events. The identification of ZIP9/Gnα11 interactions as the mediators of the non-classical testosterone signaling cascade in spermatogenic GC-2 cells might help to supplement our knowledge concerning the role of testosterone in male fertility and reproduction.

Seasonal modulation of immunity by melatonin and gonadal steroids in a short day breeder goat Capra hircus.

Role of melatonin in regulation of immunity and reproduction has never been studied in detail in goats. The aim of the present study was to explore hormonal regulation of immunity in goats with special reference to melatonin. Plasma of male and female goats (n = 18 per sex per season) was processed for hormonal (estrogen, testostrone, and melatonin) and cytokine (interleukin [IL-2], IL-6, and tumor necrosis factor α) measurements during three seasons, i.e., summer, monsoon, and winter. To assess cell-mediated immune response, percent stimulation ratio of thymocytes was recorded during three seasons. To support and establish the modulation by hormones, Western blot analysis for expressions of melatonin receptors (MT1, MT2), androgen receptor, and estrogen receptor α and estimations of marker enzymes, arylalkylamine N-acetyltransferase for melatonin and 3ß-hydroxysteroid dehydrogenase activities for steroidogenesis were performed in thymus. All the hormones and cytokines were estimated by commercial kits. Biochemical, immunologic, and Western blot analyses were done by standardized protocols. We noted a significant increase in estrogen and testosterone levels (P < 0.05) in circulation during monsoon along with melatonin (P < 0.05) presenting a parallel relationship. Expressions of melatonin receptors (MT1 and MT2) in thymus of both the sexes were significantly high (P < 0.01) during winter. Estrogen receptor α expression in female thymus was significantly high during monsoon (P < 0.05). However, androgen receptor showed almost static expression pattern in male thymus during three seasons. Further, both arylalkylamineN-acetyltransferase and 3ß-hydroxysteroid dehydrogenase enzyme activities were significantly high (P < 0.05; P < 0.01, respectively) during monsoon. These results suggest that there may be a functional parallelism between gonadal steroids and melatonin as melatonin is progonadotrophic in goats. Cell-mediated immune parameters (percent stimulation ratio of thymocytes) and circulatory levels of cytokines (IL-2, IL-6, and tumor necrosis factor α) were significantly high (P < 0.01) during monsoon. In vitro supplementation of gonadal steroids to T-cell culture suppressed immunity but cosupplementation with melatonin restored it. Further, we may also suggest that reproductive and immune seasonality are maintained by variations in circulatory hormones and local synthesis of melatonin and gonadal steroids. These functional interactions between melatonin and gonadal steroid might be of great importance in regulating the goat immunity by developing some hormonal microcircuit (gonadal steroid and melatonin) in lymphatic organs.

Do fat supplements increase physical performance?

Fish oil and conjugated linoleic acid (CLA) belong to a popular class of food supplements known as "fat supplements", which are claimed to reduce muscle glycogen breakdown, reduce body mass, as well as reduce muscle damage and inflammatory responses. Sport athletes consume fish oil and CLA mainly to increase lean body mass and reduce body fat. Recent evidence indicates that this kind of supplementation may have other side-effects and a new role has been identified in steroidogenensis. Preliminary findings demonstrate that fish oil and CLA may induce a physiological increase in testosterone synthesis. The aim of this review is to describe the effects of fish oil and CLA on physical performance (endurance and resistance exercise), and highlight the new results on the effects on testosterone biosynthesis. In view of these new data, we can hypothesize that fat supplements may improve the anabolic effect of exercise.

Testosterone alters genomic responses to song and monoaminergic innervation of auditory areas in a seasonally breeding songbird.

Behavioral responses to social stimuli often vary according to endocrine state. Our previous work has suggested that such changes in behavior may be due in part to hormone-dependent sensory processing. In the auditory forebrain of female white-throated sparrows, expression of the immediate early gene ZENK (egr-1) is higher in response to conspecific song than to a control sound only when plasma estradiol reaches breeding-typical levels. Estradiol also increases the number of detectable noradrenergic neurons in the locus coeruleus and the density of noradrenergic and serotonergic fibers innervating auditory areas. We hypothesize, therefore, that reproductive hormones alter auditory responses by acting on monoaminergic systems. This possibility has not been examined in males. Here, we treated non-breeding male white-throated sparrows with testosterone to mimic breeding-typical levels and then exposed them to conspecific male song or frequency-matched tones. We observed selective ZENK responses in the caudomedial nidopallium only in the testosterone-treated males. Responses in another auditory area, the caudomedial mesopallium, were selective regardless of hormone treatment. Testosterone treatment reduced serotonergic fiber density in the auditory forebrain, thalamus, and midbrain, and although it increased the number of noradrenergic neurons detected in the locus coeruleus, it reduced noradrenergic fiber density in the auditory midbrain. Thus, whereas we previously reported that estradiol enhances monoaminergic innervation of the auditory pathway in females, we show here that testosterone decreases it in males. Mechanisms underlying testosterone-dependent selectivity of the ZENK response may differ from estradiol-dependent ones

Endogenous testosterone and cortisol modulate neural responses during induced anger control.

Research with violent offenders and delinquent adolescents suggests that endogenous testosterone concentrations have the strongest positive correlations with violence among men who have low concentrations of cortisol. The present study tested the hypothesis that testosterone and cortisol would similarly interact to determine neural activation in regions supporting self-regulation in response to anger provocation. Nineteen healthy Asian male participants were insulted and asked to control their anger during functional magnetic resonance imaging (fMRI). When cortisol levels were low, testosterone positively correlated with activation in the dorsolateral prefrontal cortex (dlPFC) and thalamus, but not when cortisol levels were high. During induced anger control, functional connectivity was increased between the amygdala and a top-down prefrontal cortical control network. Moreover, the amygdala-PFC connectivity was strongest among those high in testosterone and low in cortisol. This research highlights a possible neural mechanism by which testosterone and cortisol may influence anger control.

Salivary hormones, IgA, and performance during intense training and tapering in judo athletes.

The aims of this study were to identify the time course of change of salivary testosterone (sT), cortisol (sC), and IgA (SIgA); mood state; and performance capacity during a 2-week taper in judo athletes and to examine the diurnal variation in these salivary markers. Eleven male judo athletes completed 5 weeks of training: 1 week of normal training (NORM), 2 weeks of intensified training (INT), and 2 weeks of exponential tapering (TAPER). Once per week subjects completed vertical and horizontal countermovement jump tests, a grip strength test, a Special Judo Fitness Test, a multistage aerobic fitness test, a 3 × 300-m run test, and anthropometric measurement. Subjects also completed questionnaires to assess mood state and muscle soreness. Two daily saliva samples (at 0700 and 1900) were collected at the end of each week during NORM and INT and every day during TAPER. Increased morning sT, decreased evening sC, lower muscle soreness, and enhanced mood state (p < 0.05) were evident by the early phases of TAPER. A significant 7.0% improvement in 3 × 300-m performance time, a 6.9% improvement in the vertical jump (p < 0.05), and increased morning and evening SIgA secretion rate (p < 0.01) were observed during the middle-late phases of TAPER. The higher values of salivary variables were observed in the morning. This study indicates that salivary hormones display diurnal variation. Furthermore, changes in hormonal responses, mood state, and muscle soreness precede enhancements in performance and mucosal immunity, suggesting that judo athletes taper for at least a week before competition.

Testosterone regulates cardiac contractile activation by modulating SERCA but not NCX activity.

Alterations in intracellular Ca(2+) transients of cardiomyocytes in orchidectomized (ORX) rats could be a cause of cardiac dysfunction in the hypogonadal condition. To investigate the role of male sex hormones in intracellular Ca(2+) homeostasis during relaxation, Ca(2+)-handling activities by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and the Na(+)/Ca(2+) exchanger (NCX) were evaluated in the ventricular muscle of 10-wk-old ORX rats with and without testosterone supplementation (2.5 mg/kg testosterone propionate, 2 times/wk). ORX induced a 50% decrease in contraction force accompanied by a prolonged time to achieve 50% relaxation (T(50)) in isolated intact ventricular trabeculae, which was partially corrected by testosterone administration. Maximum active tension was also suppressed in ORX rats without changes in myofilament Ca(2+) sensitivity and passive stiffness of the heart. Using a sarcoplasmic reticulum-enriched membrane preparation, the maximum thapsigargin-sensitive SERCA activity of the ORX rat was 27% lower with an increased Ca(2+) sensitivity, which was prevented by testosterone treatment. However, neither changes in SERCA content nor its modulating components, sarcolipin and heat shock protein 20, were detected in the ORX rat, but there was a significant decrease in the phosphorylated Thr(17) form of phospholamban. Despite a lower level of NCX protein in the heart of ORX rats, prolonged T(50) disappeared after an incubation with thapsigargin (10 µM), implying a lack of effect of male sex hormone deficiency on NCX function. These findings indicate that male sex hormones can regulate cardiac relaxation by acting mainly through SERCA. However, a detailed mechanism of SERCA modulation under male sex hormone deficiency status remains to be explored.

Effect of threonine on immunity and reproductive performance of male mice infected with pseudorabies virus.

The experiment was conducted to evaluate the effects of dietary threonine (Thr) supplement on reproductive performance and immune function of the male mice challenged with pseudorabies virus (PRV). Kun-Ming male mice were assigned randomly to four groups with different Thr levels (0.70%, 0.88%, 1.10% and 1.30%). Half of the mice in each group were injected with PRV or phosphate-buffered saline (PBS) after 5 weeks' adaptation to diets. The second experiment examined the effects of dietary Thr level on copulation rate, pregnancy rate and average number per litter of PRV- or PBS-challenged male mice that copulated with adult female mice on the 9th day post PRV challenge. Sperm quality and testosterone of mice were decreased after PRV infection, but this effect was attenuated by increasing Thr levels. Copulation and conception rates were increased with increasing Thr levels (P = 0.14), but litter size was not affected (P > 0.05). In the PBS and PRV groups, mice fed higher levels of Thr had increased immunoglobulin (Ig)G, IgA and IgM concentrations. The PRV-specific antibody level, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α concentration in PRV groups enhanced with increasing Thr levels; however, there was no difference in PBS groups. Furthermore, higher toll-like receptor (TLR)2 and TLR9 expressions in testis were observed by PRV challenge compared with PBS groups, and higher Thr supplement attenuated PRV-challenged induced the upregulation effect of TLR2 and TLR9 mRNA expression in testis (P < 0.05). These data suggest that higher Thr consumption was recommended in order to counteract the deleterious effects of virus invasion, possibly through the downregulated expression of TLRs, and thus to improve immunity and reproduction performance of male mice challenged with PRV.

Sarcopenia in the elderly.

Sarcopenia is the age-related loss of muscle. It leads to loss of muscle power, which in the end results in frailty and disability. There are numerous causes of sarcopenia. Treatment consists of resistance exercise and a leucine-enriched essential amino acid protein supplement. There is an emerging role for testosterone and other anabolic steroids. An activin II receptor soluble fusion protein is showing great potential to increase muscle mass and bone mineral density.

Androgen rather than estrogen up-regulates brain-type cytochrome P450 aromatase (cyp19a1b) gene via tissue-specific promoters in the hermaphrodite teleost ricefield eel Monopterus albus.

CYP19A1 in the brain and pituitary of vertebrates is important for reproductive and non-reproductive processes. In teleosts, it is broadly accepted that estradiol (E(2)) up-regulates cyp19a1b gene via a positive autoregulatory loop. Our present study, however, showed that E(2) did not up-regulate ricefield eel cyp19a1b in the hypothalamus and pituitary, whereas dihydrotestosterone (DHT) or testosterone (T) stimulated cyp19a1b expression only in the pituitary. Two tissue-specific promoters, namely promoter I and II directing the expression in the brain and pituitary respectively, were identified. Promoter I contained a non-consensus estrogen response element (ERE), and consequently did not respond to E(2). Promoter II contained an androgen response element (ARE) and consequently responded to DHT. Taken together, these results demonstrated a novel steroidal regulation of cyp19a1b gene expression and an alternative usage of tissue-specific cyp19a1b promoters in the brain and pituitary of a teleost species, the ricefield eel.

Premotor synaptic plasticity limited to the critical period for song learning.

Synaptic plasticity has been hypothesized to underlie learning and memory. Understanding of how such plasticity might produce motor learning is limited, in part because of the paucity of model systems with a tractable learned behavior under control of a discrete neural circuit. Songbirds possess both of these traits, thereby providing an excellent model for studying vertebrate motor learning. We report unique evidence of long-term depression (LTD) in the juvenile songbird premotor robust nucleus of the arcopallium (RA). LTD induction at RA recurrent collateral synapses requires NMDA receptors, postsynaptic depolarization, and postsynaptic calcium, and can be reversed by high-frequency stimulation. In adult birds, which have exited the critical period for sensorimotor learning and cannot modify their song, we were no longer able to induce LTD at RA collateral synapses. Furthermore, testosterone-induced premature maturation of song in juveniles abolishes LTD. LTD in nucleus RA therefore makes an excellent candidate mechanism to mediate song learning during development and is well-suited to provide insight into other forms of vertebrate motor learning.

Combining behavioral endocrinology and experimental economics: testosterone and social decision making.

Behavioral endocrinological research in humans as well as in animals suggests that testosterone plays a key role in social interactions. Studies in rodents have shown a direct link between testosterone and aggressive behavior(1) and folk wisdom adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic or even aggressive behavior(2). However, many researchers doubt a direct testosterone-aggression link in humans, arguing instead that testosterone is primarily involved in status-related behavior(3,4). As a high status can also be achieved by aggressive and antisocial means it can be difficult to distinguish between anti-social and status seeking behavior. We therefore set up an experimental environment, in which status can only be achieved by prosocial means. In a double-blind and placebo-controlled experiment, we administered a single sublingual dose of 0.5 mg of testosterone (with a hydroxypropyl-ß-cyclodextrin carrier) to 121 women and investigated their social interaction behavior in an economic bargaining paradigm. Real monetary incentives are at stake in this paradigm; every player A receives a certain amount of money and has to make an offer to another player B on how to share the money. If B accepts, she gets what was offered and player A keeps the rest. If B refuses the offer, nobody gets anything. A status seeking player A is expected to avoid being rejected by behaving in a prosocial way, i.e. by making higher offers. The results show that if expectations about the hormone are controlled for, testosterone administration leads to a significant increase in fair bargaining offers compared to placebo. The role of expectations is reflected in the fact that subjects who report that they believe to have received testosterone make lower offers than those who say they believe that they were treated with a placebo. These findings suggest that the experimental economics approach is sensitive for detecting neurobiological effects as subtle as those achieved by administration of hormones. Moreover, the findings point towards the importance of both psychosocial as well as neuroendocrine factors in determining the influence of testosterone on human social behavior.

Association of the infusion of Heteropterys aphrodisiaca and endurance training brings spermatogenetic advantages.

The species Heteropterys aphrodisiaca is commonly used as a stimulant by popular medicine in the Cerrado, a savanna-like biome, Brazil. Recent studies have proved its protective effects on testes of animals submitted to treatment using Cyclosporine A, as well as its stimulus effect in increasing testosterone secretion. Therefore, the present study was designed to analyze whether the association of the plant infusion and endurance exercise could potentiate the stimulating effect. The animals were separated into 4 groups: two control (sedentary and trained) receiving water and two treated (sedentary and trained) receiving the plant infusion daily (104 mg/day). The proportion of the seminiferous tubule compartment and interstitium was analyzed. Within the seminiferous epithelium, the number of Sertoli and germ cells were counted in order to evaluate whether the treatment would alter the spermatogenic dynamics, analyzing: the spermatogenic yield, the mitotic and meiotic indexes, the total number of germ cells and the Sertoli cell support capacity. Trained and treated animals showed increased spermatogenic yield and spermatogonia mitosis, and no significant differences in apoptotic indexes. Despite the results showing the same pattern regarding yield and mitotic index, the meiotic index was higher in the sedentary/treated group. Therefore, the H. aphrodisiaca infusion increased both the testosterone production and the spermatogonia mitosis, thus increasing the spermatogenic yield.

Effect of Citrullus colocynthis Schrad fruits on testosterone-induced alopecia.

Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA) is the most common form of alopecia, which affects millions of men and women worldwide, and is an androgen driven disorder. Here, the Citrullus colocynthis Schrad fruit is evaluated for hair growth activity in androgen-induced alopecia. Petroleum ether extract of C. colocynthis was applied topically for its hair growth-promoting activity. Alopecia was induced in albino mice by testosterone administration intramuscularly for 21 days. Its inhibition by simultaneous administration of extract was evaluated using follicular density, anagen/telogen (A/T) ratio and microscopic observation of skin sections. Finasteride (5α-reductase inhibitor) solution was applied topically and served as positive control. Petroleum ether extract of C. colocynthis exhibited promising hair growth-promoting activity, as reflected from follicular density, A/T ratio and skin sections. The treatment was also successful in bringing a greater number of hair follicles in anagenic phase than the standard finasteride. The result of treatment with 2 and 5% petroleum ether extracts were comparable to the positive control finasteride. The petroleum ether extract of C. colocynthis and its isolate is useful in the treatment of androgen-induced alopecia.

Association of the infusion of Heteropterys aphrodisiaca and endurance training brings spermatogenetic advantages

The species Heteropterys aphrodisiaca is commonly used as a stimulant by popular medicine in the Cerrado, a savanna-like biome, Brazil. Recent studies have proved its protective effects on testes of animals submitted to treatment using Cyclosporine A, as well as its stimulus effect in increasing testosterone secretion. Therefore, the present study was designed to analyze whether the association of the plant infusion and endurance exercise could potentiate the stimulating effect. The animals were separated into 4 groups: two control (sedentary and trained) receiving water and two treated (sedentary and trained) receiving the plant infusion daily (104mg/day). The proportion of the seminiferous tubule compartment and interstitium was analyzed. Within the seminiferous epithelium, the number of Sertoli and germ cells were counted in order to evaluate whether the treatment would alter the spermatogenic dynamics, analyzing: the spermatogenic yield, the mitotic and meiotic indexes, the total number of germ cells and the Sertoli cell support capacity. Trained and treated animals showed increased spermatogenic yield and spermatogonia mitosis, and no significant differences in apoptotic indexes. Despite the results showing the same pattern regarding yield and mitotic index, the meiotic index was higher in the sedentary/treated group. Therefore, the H. aphrodisiaca infusion increased both the testosterone production and the spermatogonia mitosis, thus increasing the spermatogenic yield.

Sports-related issues and biochemistry of natural and synthetic anabolic substances.

Testosterone is the principal male sex hormone. As with all natural steroids, it is biosynthesized from cholesterol. Phase I metabolism employs some very specific enzymes and pathways. Phase II metabolism and excretion follow more general patterns. The effects of testosterone are twofold: anabolic and androgenic. Because of its anabolic effects, testosterone is frequently abused in sports. Because of its endogenous nature, testosterone doping is difficult to detect. The standard procedure is based on the evaluation of the urinary steroid profile. Conspicuous samples then are submitted to compound-specific (13)C/(12)C analysis. Synthetic and endogenous steroids differ in this measure. Numerous xenobiotic compounds have been derived from testosterone. The modifications typically aim at a reduction of the androgenic properties while maintaining the anabolic potential. Most of these compounds have been withdrawn from the legal market. However, they are found to be illicitly added to otherwise inefficient nutritional supplements. These products represent a major problem to doping control. Recently, clinical trials with selective androgen receptor modulators have been started.