Testosterone

This article presents an up-to-date review of the literature on hormone augmentation in the elderly to help primary care physicians better evaluate and utilize hormone replacement and optimization strategies to benefit their patients. The scientific literature suggests that hormone supplementation with estrogen, progesterone, testosterone, growth hormone, and thyroid hormone has the potential to improve quality of life and to prevent, or reverse, the many symptoms and conditions associated with aging, including fatigue, depression, weight gain,frailty, osteoporosis, loss of libido, and heart disease. Possible long-term side effects are also considered.

Introduction. It has been reported that lack of sexual activity due to erectile dysfunction (ED) may be associated with testosterone (T) decline. Aim. To investigate whether the known changes in sex hormones associated with resumption of sexual activity are sustained in the long term. Main Outcome Measures. Primary endpoints were variations from baseline of steroid hormones: total T, free T (f T), and estradiol (E). Secondary endpoints were variations of erectile function domain scores at International Index of Erectile Function-5 (IIEF-5).

This dissertation is based on a long-term ethnographic and sociophonetic study of 15 transgender people on the female-to-male (or transmasculine) identity spectrum. The focus of the study is the way these individuals’ voices change during the first 1-2 years of masculinizing hormone therapy, which brings about a drop in vocal pitch along with other salient physiological changes. Based on regular recordings of participants during a one year period, the analysis tracks changes in fundamental frequency as well as formant frequencies and the acoustic characteristics of [s], each of which has a different place in biology-driven theories of gender and the voice. In addition to ostensibly hormonally driven changes to speakers’ available fundamental frequency range, I present evidence that these speakers are engaged in various types of articulatory shifts as part of their gender role transition, which affect both formants and [s]. However, I argue that changes in all three of the phonetic domains examined here must be situated in both sociocultural and linguistic context, even where biology appears to play a significant role. The analyses presented, which include attention to both intra- and inter-speaker variation, draw on a multi-layered understanding of gender derived from transgender people’s own distinctions between gender assignment, gender role, gender identity, and gender presentation. My speakers’ metalinguistic commentary on gender and the voice further elucidates the constellations of phonetic features that combine to create their cohesive gendered speaking styles. Ultimately, I focus on the ways that changes in one phonetic variable, like pitch, can recontextualize other elements of a speaker’s linguistic style, like the acoustic spectrum of [s]. This connection drives home the necessity of considering the relationship between linguistic characteristics, rather than treating them as entirely separable variables. Attention to stylistic wholes, over individual variables, points us toward the notion that transmasculine individuals do not engage in across-the-board masculinization, but rather bring together acoustic characteristics acquired from disparate sources in order to construct phonetic styles that reflect their complex affiliations with manhood, maleness, and masculinity.

Introduction. Antiandrogen therapy has been used for 30 years to treat paraphilic patients and sexual offenders. Yet the therapeutic success of antiandrogens is uncertain. Furthermore, there is still a lack of comprehensive knowledge about the effects of androgen-lowering therapy in paraphilic patients. Aim. We discuss endocrinological, neurobiological, and therapeutic aspects of paraphilia with the aim of integrating these on the basis of the current neurobiological and clinical knowledge on testosterone that was set out in Part I of this review. Methods. Our review of the human literature comprises the current knowledge about the neurobiology of paraphilia and the known endocrinological, pathophysiological, and genetic aspects of this disorder. The role of testosterone is discussed. A survey of antiandrogen therapy and its outcome in paraphilic patients and sex offenders is provided.

In recent years, increased attention to women's sexual health has propelled basic scientific research and clinical trials investigating treatment paradigms for improving sexual well-being. As the prevalence of female sexual dysfunction has become manifest, knowledge of the intricate pathophysiological role of androgens in maintaining sexual function has fostered a clearer understanding of the effect of age on androgen status, the role of androgens in the postmenopausal ovary, and aetiological mechanisms of androgen insufficiency in premenopausal and postmenopausal women. Understanding the long-term safety and efficacy of physiological androgen replacement and the development of sensitive testosterone assays for specific use in women, will better characterise women who are most likely to respond to androgen therapy and, thereby, optimise their quality of life.

A large number of micropropagated Euphorbia millii shoots from temporary immersion bioreactor showed thick broad leaves that were translucent, wrinkled and/or curled and brittle, symptoms of hyperhydricity. The environment inside bioreactor normally used in plant micropropagation is characterised by high relative humidity, poor gaseous exchange between the internal atmosphere of the bioreactor and its surrounding environment, and the accumulation of ethylene, conditions that may induce physiological disorders. A comparison of hyperhydric shoots (HS) with normal plants shows marked increase in malondialdehyde (MDA) content in HS plants. MDA, a decomposition product of polyunsaturated fatty acids hydroperoxides, has been utilized very often as a suitable biomarker for lipid peroxidation, which is an effect of oxidative damage. This hypothesis is also confirmed by the higher lipoxygenase (LOX) activity in HS plants. The potential role of antioxidant enzymes in protecting hyperhydric shoots from oxidative injury was examined by analyzing enzyme activities and isozyme profiles of hyperhydric and non-hyperhydric leaves of E. millii. Superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activity were significantly higher in hyperhydric tissue as compared to non-hyperhydric normal leaf tissue. After native polyacrylamide gel electrophoresis (PAGE) analysis, seven SOD isoenzymes were detected and the increase in SOD activity observed in hyperhydric tissue seemed to be mainly due to Mn-SOD and Cu/Zn-SOD. The activity of ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR) was proportionally increased in HS tissue compared to normal leaves indicating a crucial role in eliminating toxic H 2 O 2 from plant cells. The depletion of GSH and total glutathione in spite of higher GR activities observed in HS tissue indicates that mechanism of antioxidant defense was by enhanced oxidation of GSH to GSSG by DHAR yielding ascorbate (AA). The antioxidant metabolism has been shown to be important in determining the ability of plants to survive in hyperhydric stress and the up regulation of these enzymes would help to reduce the build up of ROS.

Introduction.  Controversy exists regarding testosterone replacement therapy (TRT) in men following radical prostatectomy (RP). Many clinicians are hesitant to offer patients TRT after an RP, out of concern that the increased androgen levels may promote tumor progression or recurrence from residual tumor. Recently, several small studies have demonstrated the use of TRT in men following an RP and have shown an improvement in serum testosterone levels with no increase in prostate-specific antigen (PSA) values.Aims.  The aim of this article is to assess changes in PSA and testosterone values in hypogonadal patients on TRT after RP and also to evaluate the impact of pathologic Gleason grade on ultimate PSA values.Methods.  All hypogonadal men who were treated with TRT by members of our department following RP were retrospectively reviewed. PSA values before RP, after RP, and after TRT were evaluated. Serum testosterone levels before and after TRT were also examined. Only patients with undetectable PSA values and negative surgical margins on pathologic specimen were offered TRT and included in the study.Main Outcome Measures.  Main outcome measures were changes in PSA and testosterone values after initiation of TRT.Results.  Fifty-seven men, ages 53–83 years (mean 64), were identified as having initiated TRT following RP. Men received TRT for an average of 36 months following RP (range 1–136 months). Patients were followed an average of 13 months after initiation of TRT (range 1–99 months). The mean testosterone values rose from 255 ng/dL before TRT to 459 ng/dL after TRT (P < 0.001). There was no increase in PSA values after initiation of TRT and thus no patient had a biochemical PSA recurrence.Conclusion.  TRT is effective in improving testosterone levels, without increasing PSA values, in hypogonadal men who have undergone RP. Khera M, Grober E, Najari B, Colen J, Mohamed O, Lamb D, and Lipshultz L. Testosterone replacement therapy following radical prostatectomy. J Sex Med **;**:**–**.

Objective: Previous studies of sex hormone concentrations in depression yielded inconsistent results. However, the activation of the hypothalamic-pituitary-adrenal system seen in depression may negatively affect gonadal function at every level of regulation. The objective of this study was to explore whether major depressive episodes are indeed associated with an alteration of gonadal function. Methods: Testosterone, pulsatile LH secretion, FSH, and cortisol were assessed using frequent sampling during a 24-hour period in 15 male inpatients with major depression of moderate to high severity and in 22 healthy comparison subjects (age range 22-85 years). Results: An analysis of covariance model showed that after adjustment for age only, daytime testosterone (p Ͻ .01), nighttime testosterone (p Ͻ .05), and 24-hour mean testosterone secretion (p Ͻ .01) were significantly lower in the depressed male inpatients. There was also a trend for a decreased LH pulse frequency in the depressed patients (p Ͻ .08). Conclusions: Gonadal function may be disturbed in men with a depressive episode of moderate to high severity. Key words: major depression, testosterone, LH, FSH, cortisol, men.

and aggression during the breeding season. However, the role of T in year-round territorial birds is still enigmatic, especially in tropical birds. Spotted antbirds (Hylophylax n. naevioides) defend territories in the Panamanian rainforest year-round but have low plasma T levels (0.1-0.2 ng/ml), except during brief periods of social challenges. We manipulated T action in captive male Spotted antbirds to test whether this hormone is involved in the regulation of song and aggression. Timplants increased plasma androgen levels (T and dihydrotestosterone) and enhanced song in nonbreeding males. During a staged male-male encounter, T-implanted males sang more and were more aggressive than controls. In a second experiment, we blocked the two known T actions: its binding to androgen receptors and its conversion into estradiol by the enzyme aromatase. For this, we administered the androgen receptor antagonist flutamide (Flut) in combination with the aromatase inhibitor 1-4-6 androstatrien-3,17-dione (ATD) to birds in breeding condition. ATD ؉ Flut treatment significantly elevated plasma levels of luteinizing hormone, presumably via the lack of T feedback from its receptors. ATD ؉ Flut-treated birds gave fewer spontaneous songs than control-implanted males. During staged male-male encounters, ATD ؉ Flut-treated males did not sing at all and showed reduced aggressive behavior. Our data indicate that T can regulate aggressive behavior in these tropical birds. Although plasma T levels can be low year-round, Spotted antbirds may use T either by secreting it briefly during social challenges, by having a high sensitivity to T action, or by enzymatically converting circulating T precursors directly at the site of action. We hypothesize that plasma T levels are kept low in these year-round territorial birds to avoid potentially detrimental effects of tonically elevated T. Future treatment of nonbreeding birds with ATD ؉ Flut will reveal whether T is indeed involved year-round in regulating aggressive behavior.

Learning is ubiquitous in the animal kingdom but has been studied extensively in only a handful of species. Moreover, learning studied under laboratory conditions is typically unrelated to the animal's natural environment or life history. Here, we designed a task relevant to the natural behavior of male African cichlid fish (Astatotilapia burtoni), to determine if they could be trained on a spatial task to gain access to females and shelter. We measured both how successfully animals completed this task over time and whether and how immediate early gene and hormone expression profiles were related to success. While training fish in a maze, we measured time to task completion, circulating levels of three key hormones (cortisol, 11-ketotestosterone, and testosterone) and mRNA abundance of seven target genes including three immediate early genes (that served proxies for brain activity) in nine brain regions. Data from our subjects fell naturally into three phenotypes: fish that could be trained (learners), fish that could not be trained (non-learners) and fish that never attempted the task (non-attempters). Learners and nonlearners had lower levels of circulating cortisol compared to fish that never attempted the task. Learners had the highest immediate early gene mRNA levels in the homologue of the hippocampus (dorsolateral telencephalon; Dl), lower cortisol (stress) levels and were more motivated to accomplish the task as measured by behavioral observations. Fish that never attempted the task showed the lowest activity within the Dl, high stress levels and little to no apparent motivation. Data from non-learners fell between these two extremes in behavior, stress, and motivation.

Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5e-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5~-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5~-reduction of the steroids does not occur in the muscle. 7e-methyl-19nortestosterone (MENT) does not get 5~-reduced due to steric hindrance from the 7~-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7~-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.

There is little doubt that family factors can influence involvement in delinquency, although the full nature and extent of their influences remain unclear. In recent decades, testosterone has been increasingly implicated as a contributor to adolescent offending. The present study sought to determine whether two important types of familial factors--parental socioeconomic status and amicable parent-child relationships--are interacting with testosterone (and possibly other androgens) to affect delinquency. A large sample of North American college students self-reported their involvement in eight categories of delinquency along with self-ratings of various androgen-promoted traits (e.g., muscularity and low-deep voice), parental social status, and the quality of the relationships they had with parents. In both sexes, parent-child relationships and androgens were significantly associated with delinquency but parental social status was not. Factor analysis revealed that the authors&#39; m...

Neuronal nitric oxide synthase (nNOS) in the medial preoptic area (MPOA) has been implicated in various physiological functions, including male rat copulation. Based on their apparent sensitivity to gonadal steroid manipulation, we hypothesized that nNOS cells contain steroid receptors, and the testosterone-induced restoration of nNOS-immunoreactivity in castrates should accompany the restoration of copulation. In Experiment 1, we investigated co-localization of nNOS with the androgen receptor (AR) and the estrogen receptor alpha (ERa) using immunocytochemistry. We found regionally specific co-localizations of nNOS-AR and nNOS-ERa. In Experiment 2, we investigated the relationship between MPOA nNOS-immunoreactivity (ir) and copulatory measures in the testosterone-induced restoration paradigm in castrates. The restoration of various copulatory measures was accompanied by an increase in optical density of nNOS-ir, but not in the number of nNOS-ir cells. These data provide additional evidence supporting the role of MPOA nitric oxide in male rat copulation. D 2005 Elsevier B.V. All rights reserved.

To investigate whether autonomic nervous system (ANS) hyperactivity may be a potential cause for the relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). Twenty-four patients were recruited for this study. Complete physical examinations, urine analysis, uroflowmetry, and postvoid residual urine volume (PVRU) analysis were performed. The potential impact of some factors such as hyperglycemia, obesity, and hyperlipidemia were analyzed. These values were correlated with the various symptom scores. We performed an electromyographic and an electrocardiographic evaluation. The alterations after treatment with 2 different alpha-blockers were also analyzed. The electromyographic and electrocardiographic assessments revealed a minimal increase in ANS activity and it did not change significantly after treatment (P &gt; 0.05). After treatment, maximum flow rate increased and PVRU decreased significantly (P &lt; 0.001 and P &lt; 0.001, respectively); total and...

Steroid hormone measurement, first developed with radioimmunoassay, is now becoming easier with the use of automated platforms of immunoassay. However, some hormones remain uneasily detectable because of their low blood concentration, their structural homology or the presence of interferences. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be considered as an alternative to immunoassays. This approach allows the simultaneous determination of several parameters thanks to its selectivity led by the detector mass spectrometer and the separate dimension of chromatography liquid. In addition, recourse to UHPLC (ultra high performance liquid chromatography) allows improving selectivity and sensitivity while limiting the samples volumes. The &quot;ready-to-use&quot; kits are now available and added to the &quot;homemade&quot; techniques developed by laboratories, thus giving opportunity for measurement of a wide steroid panel with only one sample. Finally, mass spectrometry ...

Twenty males participated in a 2-month study examining the relationship between 8 a.m. plasma testosterone levels and orgasmic frequency. Within subjects, higher levels of testosterone are associated with periods of sexual activity. Over subjects, however, the direction of the relationship is reversed. Mean testosterone levels were higher for sexually less active individuals.

Cyproterone acetate is a powerful antiandrogen used in the treatment of the paraphilias for at least a decade. Studies have reported it effective in reducing the recidivism rates of sexual crimes perpetrated by men. It acts through competitive inhibition of the androgen receptors blocking the effects of testosterone and dihydrotestosterone. Systematic clinical study of its effectiveness and its clinical effects on sexual behavior is lacking, however. In the current study 19 paraphilic men who had also recidivated in a variety of sexual crimes were treated with cyproterone acetate and placebo in a double-blind crossover design. The use of active drug was associated with a significant reduction of some aspects of sexual behavior, particularly sexual fantasies. There were also significant effects on levels of circulating sex hormones and some effects on physiological measurements and self-reports of sexual arousal.

The aim of this study was to see whether or not physiological hormonal fluctuations during the menstrual cycle modulate normal aggressiveness in psychophysically healthy women. In 15 probands estrogens (E), progesterone (PROG) and free testosterone (FT) plasma levels were measured by immunochemiluminescence and levels of global aggressiveness and its subitems "verbal aggressiveness", "suspiciousness" and "resentments" were measured by the Buss-Durkee Rating Scale in the early follicular, midluteal and premenstrual phases of the cycle. E and PROG levels varied significantly along the menstrual cycle, while those of FT, of global aggressiveness (GA) and of its subitems did not change. Values of global aggressiveness did not correlate with any of the hormonal parameters studied. However, E values correlated positively with "verbal aggression" scores in the follicular phase and positively with "resentment" in the premenstruum, while PROG levels correlated negatively with "suspiciousness" and "resentment" in the premenstrual phase of the cycle. Hormonal and psychological changes from one phase to the next (Δ) revealed that Δ E in the second half of the cycle correlated negatively with "verbal aggressiveness", while Δ PROG from follicular to luteal and from luteal to premenstrual phases correlated negatively with "resentment". Thus, although aggressiveness did not seem to vary along the menstrual cycle, nor to correlate with hormonal changes, hormone secretions and fluctuations might possibly modulate some of the physiological aspects of the behavioral parameter.

PURPOSE,PATIENTS,ANDMETHODS: Theclassic agent for cutaneous leishmaniasis is pentavalent antimony. However, there are no reports of the efficacy of antimony versus placebo or of the efficacy of any alternative therapy versus either antimony or placebo. In the present report, the oral antifungal agent ketoconazole (600 n&day for 28 days) was compared to a recommended regimen of intramuscular Pentostam (20 mg antimony/kg, with a maximum of 850 mg antimony/day, for 20 days) in a randomized study of the treatment of Panama&n cutaneous leishmaniasis due to L&IImauia bradiensis paname& A separate group of patients with this disease was administered placebo.

Multiple studies report relationships between circulating androgens and performance on sexually differentiated spatial cognitive tasks in human adults, yet other studies find no such relationships. Relatively small sample sizes are a likely source of some of these discrepancies. The present study thus tests for activational effects of testosterone (T) using a within-participants design by examining relationships between diurnal fluctuations in salivary T and performance on a male-biased spatial cognitive task (Mental Rotation Task) in the largest sample yet collected: 160 women and 177 men. T concentrations were unrelated to within-sex variation in mental rotation performance in both sexes. Further, between-session learning-related changes in performance were unrelated to T levels, and circadian changes in T were unrelated to changes in spatial performance in either sex. These results suggest that circulating T does not contribute substantially to sex differences in spatial ability in young men and women. By elimination, the contribution of androgens to sex differences in human performance on these tasks may be limited to earlier, organizational periods.

We evaluated the eects of smoking on testicular function and fertilizing potential in rats. Twenty rats (group A) were exposed to the smoke of 20 cigarettes for 1 h per day. Ten rats (group B) were exposed to the smoke of 40 incense sticks for 1 h per day, and an additional 10 rats served as a control group (group C). After 10 weeks of daily exposure, serum levels of nicotine and cotinine were assessed, and a mating test was conducted. Five days later, serum concentrations of testosterone before and after human chorionic gonadotropin (hCG) stimulation, gonadotropins, and epididymal sperm content and motility were evaluated. In addition, in vitro fertilization was carried out. Nicotine and cotinine were detected in group A, but not in groups B and C. Basal serum testosterone and gonadotropin concentrations did not dier signi®cantly among the three groups, but the testosterone response to hCG stimulation was signi®cantly lower in group A than in groups B and C. Group A showed signi®cant reductions in epididymal sperm content and motility, and in fertility in vivo and in vitro. These ®ndings suggest that smoking leads to a secretory dysfunction of the Leydig cells, and also a de®ciency in sperm maturation and spermatogenesis. In addition, smoking has a detrimental eect on sperm fertilizing potentials in vivo and in vitro.

The objective was to characterize testicular development in Blackbelly sheep, focusing primarily on Sertoli cell number. Lambs (n = 43) were allotted into eight groups, and surgically castrated at 0, 3, 6, 9, 12, 15,18 or 21 weeks of age (n = 4-6 lambs per group). Testes were fixed and paraffin-embedded, cross-sections (5 mm) were stained and evaluated with quantitative morphometry techniques. Testis weight increased at a greater rate between 9 and 15 weeks of age, which was associated with remarkable changes in testicular histology, including increases in tubular tissue volume, and tubule diameter and length. Spermatogenesis started in a period between 9 and 12 weeks, lumen and elongated spermatids were observed for the first time at 12 weeks (78% of the tubules) and 15 weeks (37% of the tubules), respectively. Total number of Sertoli cells (mean AE S.E.M.) increased steadily from birth (531 AE 76 Â 10 6 ) to 15 weeks (12,008 AE 1722 Â 10 6 ), with no changes afterwards. Sertoli cell number per gram of testicular tissue decreased as lambs were older, with the most remarkable change occurring between Weeks 9 and 12. An early increase in serum LH was observed at 6 weeks of age, with testosterone (T) increasing at Weeks 12 and 21. In conclusion, Sertoli cells maintained the capacity of proliferating from birth to 15 weeks of age in Blackbelly sheep; furthermore, the period of accelerated testis growth was associated with increased serum T concentration and with important changes in testicular morphology, as a consequence of the beginning and establishment of spermatogenesis and Sertoli cell maturation. #

Background: Hereditary hemochromatosis resulting either from homozygosity for the C282Y polymorphism of the HFE gene, or compound heterozygosity for C282Y and H63D, manifests with liver disease and hypogonadism. However, it is unclear whether men who are heterozygotes for C282Y or H63D exhibit subtle abnormalities of sex hormone status. Aims: To evaluate whether heterozygosity for either of the HFE gene polymorphisms C282Y or H63D is associated with circulating testosterone and SHBG in men. Subjects and methods: We performed a cross-sectional analysis of 388 community-dwelling men. Men were genotyped for C282Y and H63D. Sera were analysed for testosterone and SHBG, and insulin resistance was estimated using a homeostatic model (HOMA2-IR). Results: Mean age of men in the cohort was 56.9 yr. Men who were heterozygous for the C282Y polymorphism in the HFE gene had higher SHBG levels than men who did not carry this polymorphism (mean±SE, 38.2±1.64 vs 32.8±0.71 nmol/l, p=0.006). Total and free testosterone levels did not differ in the two groups. In multivariate analysis adjusting for potential confounders including age, waist circumference, testosterone, and HOMA2-IR, C282Y heterozygosity remained associated with SHBG levels (p<0.001). Conclusion: The C282Y polymorphism is associated with SHBG levels in men who do not manifest iron overload. Further studies are needed to clarify potential mechanisms and determine the clinical relevance of this finding. (J. Endocrinol. Invest. 33: 544-548, 2010)

Twenty-three parotid and twelve submandibular human salivary glands were used for analyzing in vitro metabolism of progesterone (P) and/or testosterone (T), in order to find out their possible contribution to the concentrations of salivary P or T. Glands were excised from 21 women and 14 men because of a stone, tumor or sialoadenitis, and the healthy tissue was used for incubation. The tissues were homogenized and incubated with 5 to 7 nmol/I of [14C]P or [t4C]T for 2 h, extracted with methylacetate and subjected to two dimensional thin-layer chromatography. The thin-layer plates were autoradiographed, and the radioactivity of the different metabolites were counted to assess the amounts of metabolites formed. No lipoidal or conjugated steroids were formed. All of the radioactivity was associated with the free fraction of steroids. Both P and T were metabolized significantly more actively in male submandibular gland compared to male parotid gland (P <0.05-0.01). No significant differences were found between female and male parotid glands, nor between the parotid glands of hormonally medicated (oral contraceptives or postmenopausal estrogen treatment) and non-medicated women. The submandibular glands more actively metabolized the steroids studied than the parotids (P < 0.01). The main metabolites were 20~t-hydroxy-4 pregnen-3-one for P, and androstenedione for T. In conclusion, the present results bring further evidence that the P or T levels in saliva may not be identical with the unbound steroid fraction in circulation, but a part of the steroids are metabolized in salivary glands. However, due to the rapid passage of steroids from blood to saliva, the metabolism demonstrated probably does not form an important source of error in salivary P and T measurements.

To examine acute responses and recovery of force and serum hormones to combined endurance and strength loadings utilizing different orders of exercises before and after training. Methods: Physically active men were matched to an order sequence of endurance+strength (E+S, n=12) or strength+endurance (S+E, n=17). The subjects performed one experimental loading consisting of steady-state cycling and a leg press protocol before and after 24 weeks of order-specific combined training. Results: No between-group difference in acute reductions of force was observed at week 0 (E+S-23%, p<0.001; S+E-22%, p<0.01) and 24 (E+S-25%, p<0.001; S+E-27%, p<0.001) and recovery in force was completed after 24h in both groups. Concentrations of growth hormone (22-kDa) increased post-acute loading at week 0 (E+S, +57 fold, p<0.05; S+E, +300 fold, p<0.001; between-groups p<0.001) and 24 (E+S, +80 fold, p<0.01; S+E, +340 fold, p<0.05; between-groups p<0.05). No significant acute responses in concentrations of testosterone were observed at week 0 or 24. However, at week 0 testosterone was reduced during recovery following the E+S loading only (24h-23%, p<0.01; 48h-21%, p<0.001; between-groups at 24h and 48h, p<0.05), but was no longer observed after training. 1RM strength improved similarly in E+S (13%, p<0.001) and S+E (17%, p<0.001). Conclusions: This study showed an order effect (E+S vs. S+E) in concentrations of testosterone during 2 days of recovery at week 0, which was diminished after training at week 24. This initial difference in testosterone concentrations during recovery did not seem to be associated with strength development.

T raumatic brain injury (TBI) remains a major public health problem in developed countries because of its high incidence and high mortality rates. 1-3 TBI patients represent the largest proportion of patients, approximately 20%, who require enteral or parenteral nutrition support. 4

The objective of the study was to evaluate, through quantitative methods, the structural alterations in the corpora cavernosa of rats submitted to orchiectomy as well as the role of late hormone replacement in overturning the possible structural alterations. Twenty-five male rats were assigned into 5 groups with 5 animals each and treated as follows: ORCHIEC-1 5 submitted to orchiectomy and sacrificed after 1 month; C-1 5 control group sacrificed after 1 month; ORCHIEC-2 5 submitted to orchiectomy and sacrificed after 2 months; C-2 5 control group sacrificed after 2 months; and T 5 submitted to orchiectomy, underwent testosterone replacement with testosterone undecanoate (100 mg/kg) after 1 month, and sacrificed after 1 month of hormonal replacement. Smooth muscle, collagen, and elastic system fibers of penile corpora cavernosa were quantified. There was a significant decrease in the absolute values of smooth muscle, sinusoidal space, and total area of corpora cavernosa after 2 months in the castrated group when compared with controls. Overall, regarding density, no significant differences were observed among the groups. The hormonal replacement with testosterone was able to reverse the alterations observed. The method used for this research allowed demonstrating that absolute values are reliable to quantify the structural alterations of corpora cavernosa structures. The results suggest that hormonal replacement, even when instituted at a late stage, is effective in reversing the corpora cavernosa's structural alterations produced by castration.

Maynei Hayeshua medical center Bnei Brak, Israel (1941), no causal relation between serum testosterone and PCa has been established. While testosterone declines with age, the prevalence of PCa increases with age. The lack of casual relationship between testosterone and PCa is Keywords Prostate cancer mechanism-varicocelevenous drainage of reproductive system Possible cause for the evolution of prostate cancer Y. Gat et al.

In this study, we investigated the role of hormones in the pathogenesis of calcifications in ovary and in endometrium and their neoplasms of the gynecologic tract and assessed the anatomic location and incidence of these calcifications. The study consists of three parts designed to investigate the pathogenesis, the location, and the incidence of calcifications in ovary and endometrium and their neoplasms. In the first part, 79 female guinea pigs were divided into 10 groups, and different hormones, given weekly for 12 months, were administered to the guinea pigs by group. A control group of 7 guinea pigs received sterile water. Calcifications developed in 5 of 7 guinea pigs treated with prolactin, 10 of 20 treated with human chorionic gonadotropin, 5 of 11 treated with estradiol, 3 of 7 treated with estrone, 1 of 6 treated with growth hormone, and 1 of 10 treated with testosterone; in 20 of the guinea pigs, the calcifications developed in the stroma of the endometrium, and in 5 guinea pigs, they developed in the ovary. The second part of the study consisted of an evaluation of the specific location of calcifications in 43 consecutive human surgical ovaries and endometria. Calcifications were seen only in the stroma in 100% of the ovarian serous adenofibroma specimens; in ovarian serous borderline neoplasms, the stroma contained 70 to 100% of the calcifications, and the epithelium had 0 to 30% of the calcifications. In ovarian serous carcinoma specimens, the calcifications were seen in the stroma in 50 to 60% of the cases, in the epithelium in 40% of the cases, and in areas of necrosis in 10% of the cases.

The steroidal hormonal proWles of two sympatric species of desert snails, Sphincterochila zonata and Sphincterochila prophetarium were determined at three ecophysiological-behavior stages, i.e., aestivation, cryptobiosis, and active-feeding phases. Live snails were collected in their natural habitat every month for 13 months, the corpi removed and extracted with organic solvents and the progesterone, testosterone, and estrogen concentrations determined by radioimmunoassay. In both these hermaphroditic species during aestivation, a peak of testosterone followed by a peak of estrogen was observed. During the brief active intervals, minor peaks of estrogen were also observed but these were much lower than seen during aestivation. Although the two species have diVerent microhabitats during aestivation, there was little diVerence in the hormonal proWle, although S. prophetarum had about two fold higher progesterone concentration than S. zonata.

Obesity, increased visceral fat and disturbed glucose metabolism have been found in borderline personality disorder (BPD) patients. These conditions are often associated with disturbed androgen metabolism. Elevated androgens in women are related to polycystic ovaries (PCO) and might have an impact on psychopathology. Thus, higher prevalence of PCO and elevated androgen levels are suspected in BPD. In the study, we examined 31 BPD patients and 30 healthy controls ultrasonographically for PCO and measured their serum levels of androgens and interacting hormones. Furthermore, influence on psychopathology of free testosterone (FT) serum level was assessed. PCO was significantly more prevalent in BPD patients (30.4%) compared to healthy controls (6.9%). Testosterone, FT, androstenedione (A), and 17a-hydroxyprogesterone (17-OHP) were significantly elevated in the BPD group independently of BMI. FT serum level significantly correlated with depressive symptoms. In summary, our data suggest a disturbed androgen metabolism in BPD patients.

Background: In animals, fetal testosterone (fT) plays a central role in organizing the brain and in later social behavior. In humans, exposure to atypical levels of prenatal androgens may result in masculine behavior and ability patterns. Normal inter-individual variation in fT levels has also been correlated with later sex-typed behavior.

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0152 in human plasma to support clinical development. The method consisted of a solid-phase extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray TM for analysis. d 7 -GDC-0152 was used as the internal standard. A linear regression (weighted 1/concentration 2 ) was used to fit calibration curves over the concentration range of 0.02-10.0 ng/mL for GDC-0152. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 99.3% with a precision (%CV) of 13.9%. For quality control samples at 0.0600, 2.00 and 8.00 ng/mL, the between-run %CV was ≤8.64. Between-run percentage accuracy ranged from 98.2 to 99.6%. GDC-0152 was stable in human plasma for 363 days at À20 C and for 659 days at À70 C storage. GDC-0152 was stable in human plasma at room temperature for up to 25 h and through three freeze-thaw cycles. In whole blood, GDC-0152 was stable for 12 h at 4 C and at ambient temperature. This validated LC-MS/MS method for determination of GDC-0152 was used to support clinical studies.

Co-occurrence of cyclopiazonic acid (CPA) and aflatoxin B 1 (AFB 1 ) has been reported in different food commodities. Recently, we have shown that CPA reduces AFB 1 mutagenicity in the standard Salmonella -Microsome-Assay using rat S9-mix for metabolic activation (Environ. Toxicol. Pharmacol. 11 (2002) 207). When using S9-mix prepared from individual liver fractions of human patients, CPA was found to be non-mutagenic, but exerted a significant reduction of the mutagenicity of AFB 1 . Moreover, CPA was shown to inhibit testosterone hydroxylation, but not methoxyresorufin dealkylation (MROD), in human S9. Thus, the reduction of the AFB 1 mutagenicity by CPA may be attributed to the inhibitory effect of CPA on cytochrome P450 (CYP450) 3A4 activity. These findings might be of relevance to the epidemiology of food-borne mycotoxicosis as similar molar ratios to those investigated here have been reported in food commodities. #

Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetration of caffeine (log P À0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. Results: The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56-1.36 mm). Conclusions: A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.

The effects of nutrition on the testis were investigated in groups of five mature Merino rams that were fed either a sub-maintenance (low) diet or a supra-maintenance (high) diet for 69 days. Testosterone, oestradiol and inhibin were measured in blood plasma sampled simultaneously from jugular and testicular veins after an i.v. injection of 200 ng ovine LH kg \m=-\1.Plasma concentrations of testosterone, inhibin and oestradiol were higher in testicular than in jugular vein plasma for both diets (P< 0.01). After the LH injection, jugular plasma testosterone increased more rapidly (P < 0.01) in rams fed the high diet than in rams fed the low diet. This was not seen in the testicular vein. Oestradiol concentrations were higher in rams on the high diet than in those on the low diet, in both the testicular (P< 0.0001) and the jugular vein (P < 0.02). Diet did not affect inhibin concentrations. Testes were surgically removed and processed for light microscopy. Testicular mass and seminiferous tubule length and diameter were higher with the high diet than the low diet (P < 0.01). The number of Sertoli cell nuclei per testis was also affected (high diet: 120 \m=+-\6\m=x\108; low diet: 77 \ m=+-\7 \m=x\10 8; P < 0.001), whereas the proportion of testis occupied by Sertoli cell nuclei was not affected. The number of Leydig cells per testis was not affected by diet, but Leydig cells occupied a greater volume of testis in rams on the high diet than in those on the low diet (P < 0.001). The effects of nutrition on Leydig and Sertoli cells are consistent with changes in the endocrine and exocrine functions of the testis. The finding that Sertoli cell population was altered in adult rams may be explained by the GnRH-independent effects of nutrition.