Changes In Testosterone Levels Research Articles

Mild Exercise Rescues Steroidogenesis and Spermatogenesis in Rats Submitted to Food Withdrawal.

The present investigation was undertaken to increase our insight into the molecular basis of the physiological changes in rat testis induced by food withdrawal, and to clarify whether reduced testicular function can be ameliorated by mild exercise. Male rats were selected for four separate experiments. The first of each group was chow-fed, the second was chow-fed and submitted to exercise (5 bouts in total for 30 min at 15 m/min, and 0° inclination), the third was submitted to food withdrawal (66 h) and the fourth was submitted to food withdrawal and to exercise. At the end of experiments, we investigated (i) serum and testicular sex hormone levels; (ii) protein levels of StAR, 3β-Hydroxysteroid dehydrogenase (3β-HSD) and P450 aromatase, which play a key role in steroid hormone biosynthesis; and (iii) protein levels of mitotic and meiotic markers of spermatogenesis in rats, in relation to testis morphology and morphometry. We found that mild exercise or food withdrawal alone induced a significant increase or decrease in both serum and testis testosterone levels, respectively. Interestingly, we found that these levels were brought back to basal levels when food withdrawal was combined with mild exercise. The changes in testosterone levels observed in our experimental groups correlated well with the expression of steroidogenic enzymes as well as with spermatogenic activity. With mild exercise the increased testosterone/17β-estradiol (T/E2) ratio in the testis correlated with an increased spermatogenic activity. The T/E2 ratio dropped in fasted rats and was significantly reversed when food withdrawal was combined with exercise. Histological and morphometric analyses confirmed that spermatogenic activity varied in concomitance with each experimental condition. Importantly, the testis and serum T/E2 ratios correlated, confirming that exercise rescues the decline in food withdrawal-induced spermatogenesis. In conclusion, this study highlights that mild exercise normalizes the reduced spermatogenic activity caused by food withdrawal through the modulation of the steroidogenic pathway and restoring the T/E2 ratio, underlining the beneficial effects of mild exercise on the prevention and/or amelioration of reduced testis function caused by restricted caloric intake.

Sex differences in the effects of gonadal hormones on white matter microstructure development in adolescence

Adolescence is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been few longitudinal investigations relating changes in gonadal hormones and WM development in adolescents. We acquired diffusion-weighted MRI to estimate mean fractional anisotropy (FA) from 10 WM tracts and salivary testosterone from 51 females and 29 males (ages 9–14 years) who were matched on pubertal stage and followed, on average, for 2 years. We tested whether interactions between sex and changes in testosterone levels significantly explained changes in FA. We found positive associations between changes in testosterone and changes in FA within the corpus callosum, cingulum cingulate, and corticospinal tract in females (all ps<0.05, corrected) and non-significant associations in males. We also collected salivary estradiol from females and found that increases in estradiol were associated with increases in FA in the left uncinate fasciculus (p = 0.04, uncorrected); however, this effect was no longer significant after accounting for changes in testosterone. Our findings indicate there are sex differences in how changes in testosterone relate to changes in WM microstructure of tracts that support impulse control and emotion regulation across the pubertal transition.

Impact and Outcomes of Pretreatment Total Serum Testosterone on Localized Prostate Cancer Patients.

Purpose To investigate how pretreatment testosterone levels correlate with progression-free survival, metastasis-free survival, and overall survival in a propensity-adjusted localized prostate cancer population. Methods Men diagnosed with clinical NCCN-risk stratified very-low, low, intermediate, high, and/or very-high risk prostate cancer who had a baseline total serum testosterone level≥100 ng/dl measured within the 100 days preceding the first definitive therapy were identified from our prospectively gathered institutional database. Cohorts below (100–239 ng/dl), within (240–593 ng/dl), or above (594 + ng/dl) one standard deviation from the mean testosterone level (416 ng/dl) were used for comparison. Progression-free, metastasis-free, and overall survival were evaluated. A separate cohort of men not receiving ADT was used to evaluate testosterone recovery after various treatment modalities (surgery, external beam radiation, brachytherapy, or combined EBRT + Brachy). Results There was no statistically significant difference between the low, average, and high testosterone cohorts for PFS, MFS, or OS. In men not using ADT, there were no statistically significant changes in testosterone levels 1 year after therapy, regardless of therapy type. Conclusion In men with serum testosterone levels >=100 ng/dl at diagnosis, baseline testosterone does not impact PFS, MFS, or OS. Recovery of testosterone back to baseline is expected for men undergoing either surgery, external beam or brachytherapy, or combined modality radiation when not using ADT.

Mating-induced increase in &lt;i&gt;Kiss1&lt;/i&gt; mRNA expression in the anteroventral periventricular nucleus prior to an increase in LH and testosterone release in male rats

Kisspeptin has an indispensable role in gonadotropin-releasing hormone/gonadotropin secretion in mammals. In rodents, kisspeptin neurons are located in distinct brain regions, namely the anteroventral periventricular nucleus-periventricular nucleus continuum (AVPV/PeN), arcuate nucleus (ARC), and medial amygdala (MeA). Among them, the physiological role of AVPV/PeN kisspeptin neurons in males has not been clarified yet. The present study aims to investigate the acute effects of the olfactory and/or mating stimulus with a female rat on hypothalamic and MeA Kiss1 mRNA expression, plasma luteinizing hormone (LH) and testosterone levels in male rats. Intact male rats were exposed to the following stimuli: exposure to clean bedding; exposure to female-soiled bedding as a female-olfactory stimulus; exposure to female-soiled bedding and mating stimulus with a female rat. The mating stimulus significantly increased the number of the AVPV/PeN Kiss1 mRNA-expressing cells in males within 5 minutes after the exposure, and significantly increased LH and testosterone levels, followed by an increase in male sexual behavior. Whereas, the males exposed to female-soiled bedding showed a moderate increase in LH levels and no significant change in testosterone levels and the number of the AVPV/PeN Kiss1 mRNA-expressing cells. Importantly, none of the stimuli affected the number of Kiss1 mRNA-expressing cells in the ARC and MeA. These results suggest that the mating-induced increase in AVPV/PeN Kiss1 mRNA expression may be, at least partly, involved in stimulating LH and testosterone release, and might consequently ensure male mating behavior. This study would be the first report suggesting that the AVPV/PeN kisspeptin neurons in males may play a physiological role in ensuring male reproductive performance.

EFFECT OF A COMBINATION OF DUTASTERIDE AND PARENTERAL TESTOSTERONE UNDECANOATE ON TESTOSTERONE DEFICIENCY SYMPTOMS AND PROSTATE IN PATIENTS WITH TESTOSTERONE DEFICIENCY AND BENIGN PROSTATIC HYPERPLASIA

Background and objective The effect of a combination of testosterone and 5-Alpha reductase inhibitors (5-ARIs) on serum tes-tosterone levels, TD symptoms, and the prostate are not sufficiently established. Therefore, we examined the effects of long-acting parenteral testosterone undecanoate (TU) and dutasteride used in combination for the treatment of BPH patients with TD.&nbsp; Subjects and methods We selected 130 patients with a prostate volume (PV) &gt; 30 g from those diagnosed with TD and had received parenteral TU for 1 year. These patients were assigned to the following two groups: Group I, which comprised patients who received TU injections along with dutasteride, and Group II, which included patients with TU-only treatment. Statistical analyses were performed between the two groups to compare the results of serological tests, symptom questionnaire scores, and PV.&nbsp; Results No significant differences were observed in the baseline characteristics such as mean age, comorbidities, testosterone levels, symptom questionnaire scores between the two groups. There were no significant differences in the testosterone levels or the change in testosterone levels after treatment between the two groups. The PV was significantly increased in Group II and significantly decreased in Group I. Both groups showed a significant increase in the total scores and all subscale scores of the IIEF and AMS after treatment. Group II had a significantly higher total IIEF score than Group I and a significantly lower score in the sexual function subscale of the AMS after treatment. Conclusions The combination of TU and dutasteride considerably improved serum testosterone levels, alleviated TD symptoms, and effectively reduced PV in patients with TD and BPH. However, compared with the TU-only treatment, the combination was less effective in improving symptoms related to sexual function. Therefore, dutasteride should be used with caution when treating BPH patients with TD, who mainly complain of sexual dysfunction.

Comparsion the changes in hormonal levels of testosterone and cortisol following resistance training with and without blood flow restriction in female athletes

Background: There is a great deal of variability in the response of cortisol and testosterone to different methods of exercise training. One of the methods of exercise that is considered today is the exercises with blood flow restriction. Therefore, this study aimed to compare the changes in hormonal levels of testosterone and cortisol following resistance training with and without blood flow restriction in female athletes. Methods: 30 active females aged 23-30 years were randomly divided into three groups: traditional resistance training, resistance training with blood flow restriction and control. Training started with one set of 30 reps and ended with two sets repeated until exhaustion. Blood sampling prior to and immediately after exercise training took place to measure levels of testosterone and cortisol. T-test for comparison within group and one-way ANOVA was used to compare between groups comparison. Results: Results showed no significant increase for testosterone levels in within and between groups comparison. (P=0/724). Also, cortisol levels were significantly increased only in group without blood flow restriction compared to the pre-test (P=0/001). But in between groups comparison, there was a significant increase in serum levels of cortisol in two training groups compared to the control group (P=0/002). Conclusion: It seems that athletes who are in the rehabilitation phase and are not capable of lifting heavy weights, low intensity exercises with blood flow restriction can be replaced with without blood flow restriction exercises with high intensity.

Enhancement of paraben-fungicidal activity by sulforaphane, a cruciferous vegetable-derived isothiocyanate, via membrane structural damage in Saccharomyces cerevisiae.

Parabens have been widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, foods and beverages. Commonly, methyl-, ethyl-, propyl- and butylparaben are used independently or in combination to maintain the quality of industrial products, and they are considered to have low toxicity. However, recent evidence has suggested that parabens are toxic in mammalian cells, and parabens have been associated with allergic-contact dermatitis, breast cancer and changes in testosterone levels. Sulforaphane, a cruciferous vegetable-derived isothiocyanate, was effective in decreasing the growth inhibitory concentrations of ethyl-, propyl-, butyl- and methylparaben in the yeast Saccharomyces cerevisiae. The sulforaphane-enhanced fungicidal effects of methylparaben were deemed to be caused by drastic cell membrane damage and the leakage of internal substances, such as nucleotides, from S. cerevisiae cells. Moreover sulforaphane markedly decreased the minimum concentration of methyl- and ethylparaben required to inhibit the growth of various microbes, such as the pathogenic yeast that causes severe mycosis, Candida albicans; the filamentous fungi Aspergillus niger; and the Gram-negative bacterium Escherichia coli. Enhanced antimicrobial activity from the beneficial components of edible plants may increase paraben efficacy at low concentrations and minimize preservative-induced side effects in consumers. SIGNIFICANCE AND IMPACT OF THE STUDY: Sulforaphane, a natural and beneficial cruciferous vegetable-derived isothiocyanate, increased the ability of parabens to disrupt fungal cell membranes. Paraben-containing products have been reported to cause allergic contact dermatitis and drug hypersensitivity; therefore, methods to preserve organic products that may reduce the concentrations of parabens are both timely and necessary. In this study, we found that the combined antimicrobial effects of sulforaphane and parabens had the potential to reduce the paraben concentration needed to preserve organic products, thereby indicating that paraben toxicity may be reduced without affecting its activity as a preservative.

Low intrasexual competitiveness and decreasing testosterone in human males (Homo sapiens): the adaptive meaning

Abstract The development of indirect mechanisms of intrasexual competition (e.g., visual identification of possible rivals) could be related to personality traits such as aggressiveness and self-esteem. However, the study of endocrine changes associated to indirect mechanisms of intrasexual competition is scarce. The aim of this study was to investigate the changes in testosterone levels after a rival choice test in men and how intrasexual competitiveness, aggressiveness, and self-esteem modulate these changes. A group of 160 healthy men answered four personality questionnaires, participated in a rival choice test, and donated saliva samples to measure the changes in their testosterone levels. We found a significant decrease in testosterone levels of men with lower intrasexual competitiveness, but testosterone levels remained stables in competitive men. Non-significant results were found for aggressiveness and self-esteem. These decreases in testosterone levels could be interpreted as an adaptation aimed to reduce costs in male-male contests in Western modern societies.

Association of Serum Testosterone at 12 Years with a Subsequent Increase in Bone Mineral Apparent Density at 18 Years: A Longitudinal Study of Boys in Puberty

Background: Cross-sectional studies have associated serum testosterone with bone mineral density (BMD). However, there is a shortage of prospective longitudinal studies in this domain, leaving it unclear whether changes in testosterone level precede changes in BMD. Objectives: To examine the association between serum testosterone concentration at the age of 12 years and a subsequent increase in BMD by the age of 18 years. Methods: Eighty-eight boys with a mean age of 12.1 ± 0.7 (time point 1 [T1]) and 18.0 ± 0.7 (T2) were investigated. For both time points, serum testosterone was measured from venous blood samples. Total body (TB) and lumbar spine (LS) BMD and bone mineral apparent density (BMAD) were measured. As different brands of DEXA machines were used at T1 and T2, we calculated SD scores (SDS) from samples at T1 and T2 and their change (Δ). As covariates, bone age at T1 and physical activity (PA) by accelerometer at T1 and T2 were measured. Results: Serum testosterone at T1 was positively correlated with TB BMD at T2 (r = 0.28; p < 0.01), Δ TB BMAD SDS (r = 0.47; p < 0.0001) and Δ LS BMAD SDS (r = 0.23; p < 0.05). When additionally controlling for bone age and total PA at T1, the correlation between testosterone at T1 and Δ TB BMAD SDS remained significant (r = 0.32; p < 0.05). Conclusions: Serum testosterone concentration at the age of 12 years is associated with a subsequent increase in TB BMAD by the age of 18 years. This supports the inference that testosterone levels in early puberty may influence subsequent bone mineral accrual.

Castration Induces Down-Regulation of A-Type K+ Channel in Rat Vas Deferens Smooth Muscle

A-type K+ channels contribute to regulating the propagation and frequency of action potentials in smooth muscle cells (SMCs). The present study (i) identified the molecular components of A-type K+ channels in rat vas deferens SMs (VDSMs) and (ii) showed the long-term, genomic effects of testosterone on their expression in VDSMs. Transcripts of the A-type K+ channel α subunit, Kv4.3L and its regulatory β subunits, KChIP3, NCS1, and DPP6-S were predominantly expressed in rat VDSMs over the other related subtypes (Kv4.2, KChIP1, KChIP2, KChIP4, and DPP10). A-type K+ current (IA) density in VDSM cells (VDSMCs) was decreased by castration without changes in IA kinetics, and decreased IA density was compensated for by an oral treatment with 17α-methyltestosterone (MET). Correspondingly, in the VDSMs of castrated rats, Kv4.3L and KChIP3 were down-regulated at both the transcript and protein expression levels. Changes in Kv4.3L and KChIP3 expression levels were compensated for by the treatment with MET. These results suggest that testosterone level changes in testosterone disorders and growth processes control the functional expression of A-type K+ channels in VDSMCs.

Sleep restriction and testosterone concentrations in young healthy males: randomized controlled studies of acute and chronic short sleep

Low testosterone in men increases the risk for various disorders. Severe sleep restriction (SR) may reduce testosterone, but the effects of long-term short sleep are unknown. This study tested the effects of SR on circulating testosterone in healthy young men. Randomized controlled studies of SR vs habitual sleep (HS) in inpatient (study 1, n=14) and outpatient (study 2, n=13) settings. Study 1 involved severe, acute SR (4 hours time in bed [TIB]) vs HS (9 hours TIB) for 5 nights; study 2 consisted of mild, long-term SR (HS 1.5 hours of sleep/night) vs HS for 6 weeks. Plasma testosterone levels were measured at baseline and end point (study 1) or baseline, week 3, and week 6 (study 2) of each phase. Linear model analyses to assess the effects of SR on testosterone were performed separately for each study. Study 1: There were no significant sleep-time interaction on testosterone concentrations (change in testosterone levels during HS = 22.86 ± 163.79 ng/dL; SR = 43.73 ± 159.96 ng/dL, P = .41) and no main effect of sleep duration (P = .13). Study 2: There were a trend for a sleep-time interaction (P = .067) and a main effect of sleep on testosterone concentrations from 6 weeks of SR (P = .0046). Testosterone concentrations were slightly lower but increased over time with SR relative to HS. Sleep restriction does not adversely affect plasma testosterone levels in healthy young men. Given prior contradicting evidence, confirmatory studies should be done to ascertain the influence of sleep duration and quality on testosterone concentrations in men throughout life.

Switching from a gonadotropin-releasing hormone (GnRH) agonist to a GnRH antagonist in prostate cancer patients: A systematic review and meta-analysis.

We sought to address whether there are clinical responses when patients who are failing gonadotropin-releasing hormone (GnRH) agonist therapy are switched to degarelix. Androgen-deprivation therapy remains the backbone of treatment for disseminated prostate cancer and may be achieved with orchiectomy, GnRH agonists, or degarelix, a GnRH antagonist. We conducted a systematic review and meta-analysis with a search of the BIOSIS Previews, Embase, International Pharmaceutical Abstracts, MEDLINE, and Google Scholar databases using key terms. Quantitative meta-analysis was performed to provide a pooled estimate of prostate specific antigen (PSA) response at three months. Thirteen studies were identified, eight of which were included in the qualitative and quantitative analyses. Patient characteristics were broadly similar between the studies. Out of 155 patients across all included studies, 20 had stable PSA after the switch (12.9%), 14 had a 10-30% decrease in PSA (9.0%), three had a 30-50% decrease (1.9%), and 13 had a more than 50% decrease (8.4%). Random effects meta-analysis of these data demonstrated a pooled response rate of 27.75% (95% confidence interval 18.9-36.5%; I2=7.9%). Changes in testosterone levels following the switch could not be quantitatively assessed due to lack of sufficient data. Our results suggest that a switch to GnRH antagonist following progression on a GnRH agonist may result in a stable or decreased PSA at three months in about 30% of patients. This information should be considered among the potential options to discuss with patients with a rising PSA on GnRH agonist therapy.

Neuroendocrine Whiplash: Slamming the Breaks on Anabolic-Androgenic Steroids Following Repetitive Mild Traumatic Brain Injury in Rats May Worsen Outcomes

Sport-related concussion is an increasingly common injury among adolescents, with repetitive mild traumatic brain injuries (RmTBI) being a significant risk factor for long-term neurobiological and psychological consequences. It is not uncommon for younger professional athletes to consume anabolic-androgenic steroids (AAS) in an attempt to enhance their performance, subjecting their hormonally sensitive brains to potential impairment during neurodevelopment. Furthermore, RmTBI produces acute neuroendocrine dysfunction, specifically in the anterior pituitary, disrupting the hypothalamic-pituitary adrenal axis, lowering cortisol secretion that is needed to appropriately respond to injury. Some AAS users exhibit worse symptoms post-RmTBI if they quit their steroid regime. We sought to examine the pathophysiological outcomes associated with the abrupt cessation of the commonly abused AAS, Metandienone (Met) on RmTBI outcomes in rats. Prior to injury, adolescent male rats received either Met or placebo, and exercise. Rats were then administered RmTBIs or sham injuries, followed by steroid and exercise cessation (SEC) or continued treatment. A behavioral battery was conducted to measure outcomes consistent with clinical representations of post-concussion syndrome and chronic AAS exposure, followed by analysis of serum hormone levels, and qRT-PCR for mRNA expression and telomere length. RmTBI increased loss of consciousness and anxiety-like behavior, while also impairing balance and short-term working memory. SEC induced hyperactivity while Met treatment alone increased depressive-like behavior. There were cumulative effects whereby RmTBI and SEC exacerbated anxiety and short-term memory outcomes. mRNA expression in the prefrontal cortex, amygdala, hippocampus, and pituitary were modified in response to Met and SEC. Analysis of telomere length revealed the negative impact of SEC while Met and SEC produced changes in serum levels of testosterone and corticosterone. We identified robust changes in mRNA to serotonergic circuitry, neuroinflammation, and an enhanced stress response. Interestingly, Met treatment promoted glucocorticoid secretion after injury, suggesting that maintained AAS may be more beneficial than abstaining after mTBI.

Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).

Background:Multiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS.Methods:Data from 1,050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors.Results:Median baseline values for T, A, and, DHEA were 1.0, 13.5 and 8.1, ng/dL respectively while 6 week levels were 0.64, 7.0 and 6.8, ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI=1.01–1.03, p=0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ≥50% decline in PSA with an odds ratio of 0.93 (95% CI=0.85–0.98, p-value=0.039).Conclusions:Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

Skeletal Muscle Hypertrophy, Insulin-like Growth Factor 1, Myostatin and Follistatin in Healthy and Sarcopenic Elderly Men: The Effect of Whole-body Resistance Training.

Background:Sarcopenia describes the inevitable deterioration in muscle mass and strength that accompanies biological aging. The purpose of this study was to investigate the effects of resistance training (RT) on quadriceps hypertrophy and related biochemistry in sarcopenic and healthy elderly men.Methods:A total of 31 elderly men (55–70 years old) were classified as sarcopenic and nonsarcopenic and were divided into two groups. Both groups participated in a progressive RT program for 8 weeks.Results:Data indicated that the strength in the sarcopenic group increased more than the healthy group (P < 0.05). Quadriceps cross-sectional area also increased more in the healthy group (P < 0.05). Myostatin concentration decreased in both groups after training (P < 0.05). Follistatin and testosterone increased in the healthy group; in contrast, only testosterone increased in the sarcopenic group after training (P < 0.05).Conclusions:The findings from this study suggest that RT improves muscle cross-sectional area and biomarker-related muscle loss in both healthy and sarcopenic elderly men. The findings also demonstrate that growth factor profiles at baseline and changes in testosterone levels play an important role in muscle hypertrophy observed in both groups.

Effect of atorvastatin on testosterone levels

Background Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial. Objectives Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work. Selection criteria RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females. Data collection and analysis Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence. Main results We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 μmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels. Authors' conclusions We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.

Experimental manipulation of a signal trait reveals complex phenotype-behaviour coordination

Animals use morphological signals such as ornamental traits or weaponry to mediate social interactions, and the extent of signal trait elaboration is often positively associated with reproductive success. By demonstrating relationships between signal traits and fitness, researchers often make inferences about how behaviour operates to shape those outcomes. However, detailed information about fine-scale individual behaviour, and its physiological basis, can be difficult to obtain. Here we show that experimental manipulations to exaggerate a signal trait (plumage colour) and concomitant changes in testosterone and stress-induced corticosterone levels altered social interactivity between manipulated males and their social mates. On average, darkened males did not have higher levels of interactivity than unmanipulated males; however, males who experienced a greater shift in colour (pale to dark), a larger, positive change in testosterone levels, and a dampened stress-induced corticosterone response had a larger increase in the number of interactions with their social mate post-manipulation compared to pre-manipulation. This work provides new insights into the integration and real-time flexibility of multivariate phenotypes and direct evidence for the role of social interactions in pair bond maintenance.

Bisphenol A-Induced Endocrine Toxicity and Male Reprotoxicopathy are Modulated by the Dietary Iron Deficiency.

Bisphenol A (BPA) is suspected to cause hormonal imbalance in humans. Dietary factors are known to bring changes in hormonal profile. In order to study chemico-biological interaction of iron deficiency on toxicity outcome of BPA exposure, we studied the modulatory effects of iron deficiency on the hormone levels in rats chronically-exposed to BPA. Weanling rats maintained on normal and iron-deficient diets were exposed to low level of BPA at 0, 1, 5 and 10 ppm for six months through drinking water. The serum levels of thyroidstimulating hormone (TSH), testosterone, progesterone and estradiol were measured in the animals by enzyme-linked immunosorbent assay kit. Histopathology was performed to check the pathological changes in gonads. No significant change was observed in TSH, progesterone and estradiol levels at 1 and 5 ppm BPA. However, at 10 ppm BPA a significant increase in TSH level was observed in the animals maintained on an iron-deficient diet of either sex. BPA caused a significant change in testosterone level even at 5 and 10 ppm doses in animals of either sex. However, in male rats 1 ppm dose also showed a significant effect in the animals maintained on iron deficient diet. Changes in the histoarchitecture of the testes at high dose of BPA (10 ppm) were more remarkable in anemic rats. These results suggest that iron deficiency has no generalized effect on hormonal levels in BPA-treated animals and trends indicate a more remarkable effect in male animals at hormonal and tissue levels.

Genetic Variation in the Androgen Receptor and Measures of Plasma Testosterone Levels Suggest Androgen Dysfunction in Alzheimer's Disease.

Alzheimer’s disease (AD) prevalence varies by sex, suggesting that sex chromosomes, sex hormones and/or their signaling could potentially modulate AD risk and progression. Low testosterone levels are reported in men with AD. Further, variation in the androgen receptor (AR) gene has been associated with AD risk and cognitive impairment. We assessed measures of plasma testosterone levels as a biomarker of AD in male participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Baseline testosterone levels were significantly different between clinical diagnosis groups [cognitively normal controls, mild cognitive impairment (MCI), or AD], with the lowest testosterone levels in men with AD. Lower baseline testosterone levels were associated with higher baseline clinical severity. Change in testosterone levels between baseline and 1-year follow-up varied by diagnosis; MCI had the greatest decreases in testosterone levels between baseline and 1-year follow-up. Despite differences by clinical diagnosis, there was no association between plasma testosterone and CSF biomarkers of AD pathology. We also tested single nucleotide polymorphisms (SNPs) in AR for association with AD risk in a separate cohort from ADNI and found 26 SNPs associated with risk for AD. The top associated SNP is predicted to be an expression quantitative trait locus for AR in multiple tissues, including brain, with the AD-associated risk allele predicted to confer lower AR expression. Our findings suggest a link between the androgen pathway and AD through Aβ/tau independent pathways. These effects may be most pronounced during conversion from MCI to dementia.

603 Clinical trial with natural extracts from Lycium chinense for eugonadal men with late-onset hypogonadism-related symptoms: placebo-control, double-blind, randomized study

The purpose of this study was to evaluate the efficacy and safety of natural extracts from Lycium chinense on eugonadal men with late-onset hypogonadism(LOH)-related symptoms. Seventy-eight eugonadal men over 40 years of age with LOH-related symptoms were included in this study, and divided into two groups: treatment group and placebo-control group. Treatment was given orally to these patients three times daily for two months. Laboratory and endocrinological profiles were reviewed, and LOH symptoms were judged by means of several health assessment instruments such as the Aging Males’ Symptoms (AMS) scale. All patients represented no significant differences in vital sign, liver and kidney profile, urinalysis. In total score of AMS scale, placebo group had no significant change in mean score after treatment, but treatment group had decreased their score about 2.63 at 4 weeks and 2.69 at 8 weeks. (p=0.019, 0.038). In AMS subscale analysis, there were no significant differences in psychological and somatic subscale but significant decreased about 1.07 score at sexual subscale in treatment group. Lipid profiles were no definite changes between two groups and also in pre-treatment and post-treatment. PSA and serum testosterone level changes shows no significant difference between two groups.