Effects of androgen on extracellular vesicles from endothelial cells in rat penile corpus cavernosum.

BACKGROUND: The explicit mechanism of erectile dysfunction caused by low androgen status is unknown. It was reported that eNOS was expressed in extracellular vesicles (EVs). Androgen may regulate erectile function by affect the release of EVs from endothelial cells. OBJECTIVES: To investigate whether androgen affects the production of EVs and nitric oxide (NO) in endothelial cells of rat penile corpus cavernosum. MATERIALS AND METHODS: Endothelial cells of rat penile corpus cavernosum were isolated and purified from 6-week-old healthy male Sprague Dawley (SD) rats. Endothelial cells were treated with different concentrations of dihydrotestosterone (DHT) in a cell culture medium as follows: no-androgen group (NA group, DHT 0 nmol/L), very-low androgen group (VLA group, DHT 0.1 nmol/L), low androgen group (LA group, DHT 1 nmol/L), and physiological concentrations androgen group (PA group, DHT 10 nmol/L). After 24 h, EVs of supernatant in each group were isolated and identified. The content of EVs and NO in the supernatant and the expression of CD9, CD63, TSG101, and eNOS in EVs were detected. RESULTS: Positive expression of CD9, CD63, TSG101, and eNOS was found in isolated EVs. The concentration of EVs was lower in the NA group compared with other groups (p < 0.01). The expression of eNOS and the concentration of NO was lower in the NA group than that in other groups (p < 0.05); it was lower in the VLA group than that in the LA group (p < 0.05) and lower in LA group than that in PA group (p < 0.05). When the concentration of DHT in endothelial cell culture medium ranged from 0 to 10 nmol/L, the concentration of DHT was positively correlated with the content of EVs and NO. CONCLUSION: Decrease in eNOS-expressing EVs is one mechanism of NO reduction in endothelial cells of rat corpus cavernosum caused by low androgen levels.

Testosterone Administration During Energy Deficit Suppresses Hepcidin and Increases Iron Availability for Erythropoiesis.

CONTEXT: Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis. OBJECTIVE: The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo. DESIGN: This was a 3-phase, randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at the Pennington Biomedical Research Center. PATIENTS OR OTHER PARTICIPANTS: Fifty healthy young males. INTERVENTION(S): Phase 1 was a 14-day free-living eucaloric controlled-feeding phase; phase 2 was a 28-day inpatient phase where participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-day free-living, ad libitum recovery period. MAIN OUTCOME MEASURE(S): Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined. RESULTS: Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did not differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism. CONCLUSION: These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit. This trial was registered at www.clinicaltrials.gov as #NCT02734238.

A secondary analysis of testosterone and electrically evoked resistance training versus testosterone only (TEREX-SCI) on untrained muscles after spinal cord injury: a pilot randomized clinical trial.

STUDY DESIGN: Secondary analysis of a clinical trial. OBJECTIVES: To perform a secondary analysis on the effects of neuromuscular electrical stimulation resistance training (RT) combined with testosterone replacement therapy (TRT) compared with TRT on the untrained muscles after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Twenty-two men with chronic motor complete SCI were randomized into TRT + RT group (n = 11) or TRT group (n = 11). Both groups received 16 weeks of TRT (2-6 mg/day) via testosterone patches. The TRT + RT group received twice weekly progressive RT of the knee extensor muscles using electrical stimulation and ankle weights. Magnetic resonance images were captured to measure cross-sectional areas (CSAs) of trunk, glutei, and leg muscles. RESULTS: Total and absolute gluteus maximus m. (14%, P = 0.003 and 16%, P = 0.001), gluteus medius m. (10%; P = 0.008 and 14%; P = 0.02), and total glutei m. (8%, P = 0.01 and 11%, P = 0.005) CSAs increased overtime for the TRT + RT group. Mean between-group differences of 2.86 (95% CI: 0.30, 5.4), 1.89 (95% CI: 0.23, 3.58) and 5.27 (95% CI: 0.90, 9.69) cm2 were noted for absolute gluteus maximus, total gluteus medius and total glutei CSAs, respectively (P < 0.05). Trunk muscle CSAs showed a trend towards an interaction between groups. CONCLUSIONS: RT combined with low-dose TRT results in significant hypertrophy compared with TRT only on the adjacent untrained glutei muscles. Trunk muscles may require direct stimulation to evoke hypertrophy. These exploratory findings may be of clinical relevance in the reduction of incidence and severity of pelvic pressure injuries.

Chronic high-dose testosterone treatment: impact on rat cardiac contractile biology.

Androgen therapy provides cardiovascular benefits for hypogonadism. However, myocardial hypertrophy, fibrosis, and infarction have been reported in testosterone or androgenic anabolic steroid abuse. Therefore, better understanding of the factors leading to adverse results of androgen abuse is needed. The aim of the present study was to examine the impact of high dose of androgen treatment on cardiac biology, and whether exposure duration modulates this response. Male rats were treated with 10 mg/kg testosterone, three times a week, for either 4 or 12 weeks; vehicle injections served as controls. Four weeks of testosterone treatment induced an increase in ventricular wall thickness, indicative of concentric hypertrophy, as well as increased ejection fraction; in contrast, both parameters were blunted following 12 weeks of high-dose testosterone treatment. Cardiac myocyte contractile parameters were assessed in isolated electrically stimulated myocytes (sarcomere and intracellular calcium dynamics), and in chemically permeabilized isolated myocardium (myofilament force development and tension-cost). High-dose testosterone treatment for 4 weeks was associated with increased myocyte contractile parameters, while 12 weeks treatment induced significant depression of these parameters, mirroring the cardiac pump function results. In conclusion, chronic administration of high-dose testosterone initially induces increased cardiac function. However, this initial beneficial impact is followed by significant depression of cardiac pump function, myocyte contractility, and cardiac myofilament function. Our results indicate that chronic high-testosterone usage is of limited use and may, instead, induce significant cardiac dysfunction.

Gender, hyperandrogenism and vitamin D deficiency related functional and morphological alterations of rat cerebral arteries.

Hyperandrogenism is a risk factor of cerebrovascular diseases as androgens can alter markedly the regulation of cerebrovascular tone. We examined the combined impact of androgen excess and vitamin D deficiency (VDD), a common co-morbidity in hyperandrogenic disorders, on remodeling and testosterone-induced vascular responses of anterior cerebral arteries (ACA) in order to evaluate the interplay between androgens and VDD in the cerebral vasculature. Male and female Wistar rats were either fed with vitamin D deficient or vitamin D supplemented diet. Half of the female animals from both groups received transdermal testosterone treatment. After 8 weeks, vessel lumen, wall thickness and testosterone-induced vascular tone of isolated ACA were determined using pressure microangiometry and histological examination. Androgen receptor protein expression in the wall of cerebral arteries was examined using immunohistochemistry. In female rats only combined VDD and testosterone treatment decreased the lumen and increased the wall thickness of ACA. In males, however VDD by itself was able to decrease the lumen and increase the wall thickness. Vascular reactivity showed similar alterations: in females, testosterone constricted the ACA only after combined VDD and hyperandrogenism, whereas in males VDD resulted in increased testosterone-induced contractions in spite of decreased androgen receptor expression. In conclusion, a marked interplay between hyperandrogenism and VDD results in inward remodeling and enhanced testosterone-induced constrictions of cerebral arteries, which might compromise the cerebral circulation and thus, increase the risk of stroke in the long term. In addition, the early cerebrovascular manifestation of VDD appears to require androgen excess and thus, depends on gender.

Human in vivo metabolism study of LGD-4033.

Selective androgen receptor modulators (SARMs) are an emerging class of therapeutics targeted to cachexia, sarcopenia, and hypogonadism treatment. LGD-4033 is a SARM which has been included on the Prohibited List annually released by the World Anti-Doping Agency (WADA). The aim of the present work was the investigation of the metabolism of LGD-4033 in a human excretion study after administration of an LGD-4033 supplement, the determination of the metabolites' excretion profiles with special interest in the determination of its long-term metabolites, and the comparison of the excretion time of the phase I and phase II metabolites. The results were also compared to those derived from previous LGD-4033 studies concerning both in vitro and in vivo experiments. Supplement containing LGD-4033 was administered to one human male volunteer and urine samples were collected up to almost 21 days. Analysis of the hydrolyzed (with ß-glucuronidase) as well as of the non-hydrolyzed samples was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in negative ionization mode and revealed that, in both cases, the two isomers of the dihydroxylated metabolite (M5) were preferred target metabolites. The gluco-conjugated parent LGD-4033 and its gluco-conjugated metabolites M1 and M2 can be also considered as useful target analytes in non-hydrolyzed samples. The study also presents two trihydroxylated metabolites (M6) identified for the first time in human urine; one of them was recently reported in an LGD-4033 metabolism study in horse urine and plasma.

Efficacy of Dehydroepiandrosterone (DHEA) to overcome the effect of ovarian ageing (DITTO): A proof of principle double blinded randomized placebo controlled trial.

OBJECTIVE: To evaluate the effect of DHEA supplementation on In-Vitro Fertilisation (IVF) outcome as assessed by ovarian response, oocyte developmental competence and live birth rates in women predicted to have poor ovarian reserve (OR). The feasibility of conducting a large trial is also assessed by evaluating the recruitment rates and compliance of the recruited participants with DHEA/placebo intake and follow-up rates. STUDY DESIGN: A single centre, double blinded, placebo controlled, randomized trial was performed over two years with 60 women undergoing in-vitro fertilisation (IVF). Subjects were randomized, based on a computer-generated pseudo-random code to receive either DHEA or placebo with both capsules having similar colour, size and appearance. 60 women with poor OR based on antral follicle count or anti-Mullerian hormone thresholds undergoing IVF were recruited. They were randomised to receive DHEA 75mg/day or placebo for at-least 12 weeks before starting ovarian stimulation. They had long protocol using hMG 300 IU/day. Data analysed by "intention to treat". Ovarian response, live birth rates and molecular markers of oocyte quality were compared between the study and control groups. RESULTS: The recruitment rate was 39% (60/154). A total of 52 participants (27 versus 25 in the study and placebo groups) were included in the final analysis after excluding eight. While the mean (standard deviation) DHEA levels were similar at recruitment (9.4 (5) versus 7.5 (2.4) ng/ml; P=0.1), the DHEA levels at pre-stimulation were higher in the study group than in the controls (16.3 (5.8) versus 11.1 (4.5) ng/ml; P<0.01). The number (median, range) of oocytes retrieved (4, 0-18 versus 4, 0-15 respectively; P=0.54) and live birth rates (7/27, 26% versus 8/25, 32% respectively; RR (95% CI): 0.74 (0.22-2.48) and mRNA expression of developmental biomarkers in granulosa and cumulus cells were similar between the groups. CONCLUSION: Pre-treatment DHEA supplementation, albeit statistical power in this study is low, did not improve the response to controlled ovarian hyperstimulation or oocyte quality or live birth rates during IVF treatment with long protocol in women predicted to have poor OR.

Serum and follicular fluid testosterone concentrations do not correlate, questioning the impact of androgen supplementation on the follicular endocrine milieu.

Basic research into a possible link between serum and follicular fluid androgen concentrations to detemine whether androgen supplementation in low responders affects follicular endocrine milieu is still lacking. Ninety-seven women (aged 28-43 years) undergoing one natural IVF cycle without any hormone stimulation were analysed. Serum and follicular fluid were collected at the time of follicle aspiration, and the concentrations of LH, total testosterone, oestradiol, dehydroepiandrosterone and anti-Mullerian hormone (AMH) were determined. Serum LH (P = 0.003) and AMH (P = 0.026) concentrations, and follicular fluid AMH (P = 0.015) decreased with increasing age. Within follicular fluid, total testosterone was correlated with oestradiol (P < 0.001) and AMH (P = 0.010); LH correlated with AMH (P = 0.005). Correlation analysis of serum and follicular fluid hormone concentrations revealed that LH, oestradiol and AMH correlated (P < 0.001), whereas testosterone did not. Testosterone serum concentrations did not correlate with other follicular fluid hormones, such as dehydroepiandrosterone, oestradiol and AMH, whereas serum LH correlated with follicular flulid AMH (P < 0.008). Follicular fluid hormone concentrations seem to be independent from serum testosterone. Therefore, it is questionable whether an increase in serum testosterone concentration by androgen supplementation could improve the follicular endocrine milieu.

Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency.

Importance: Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events. Objective: To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. Design, Setting, and Participants: A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012. Exposures: Any prescribed TRT given by injection, orally, or topically. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. Results: The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72). Conclusions and Relevance: Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.

[Oral Testosterone Undecanoate Capsules combined with Qilin Pills for late-onset hypogonadism in males].

OBJECTIVE: To investigate the clinical effects of oral Testosterone Undecanoate Capsules (TUC) combined with Qilin Pills (QLP) on late-onset hypogonadism (LOH) in men. METHODS: Sixty-three LOH patients meeting the inclusion criteria were randomly divided into a control group (aged ï¼»48.4 ± 6.2ï¼½ yr, n = 32) and an experimental group (aged ï¼»47.2 ± 5.6ï¼½ yr, n = 31) to be treated with oral TUC (80 mg, qd) and TUC + QLP (6g, tid), respectively, both for 3 months. Comparisons were made between the two groups of patients in the IIEF-5 scores, total testosterone (TT) levels, and scores in the Aging Males' Symptoms (AMS) scale before and after treatment. RESULTS: After treatment, the patients of the experimental group, as compared with the controls, showed a significantly increased IIEF-5 score (21.7 ± 5.8 vs 15.9 ± 4.7, P <0.05) and TT level (ï¼»16.7 ± 2.2ï¼½ vs ï¼»13.1 ± 2.8ï¼½ nmol/L, P <0.05), but a decreased AMS score (20.7 ± 5.7 vs 31.3±6.5, P <0.05). CONCLUSIONS: TUC combined with Qilin Pills has a better effect and a lower rate of adverse reactions than TUC used alone in the treatment of late-onset hypogonadism in males.

The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency.

Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content (p < 0.05) but it did not affect femoral biomechanical strength (p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength.

Biphasic effect of Syzygium aromaticum flower bud on reproductive physiology of male mice.

The flower buds of Syzygium aromaticum (clove) have been used for the treatment of male sexual disorders in indigenous medicines of Indian subcontinent. Therefore to evaluate the efficacy of Syzygium aromaticum on the male reproductive health, chronic oral exposure of aqueous extract of flower buds of Syzygium in three doses (15 mg, 30 mg and 60 mg kg-1 BW) were studied for a single spermatogenic cycle (35 days) in Parkes (P) strain mice. Lower dose (15 mg) of Syzygium aromaticum flower buds increased serum testosterone level and testicular hydroxysteroid dehydrogenase (HSD) activities and improved sperm motility, sperm morphology, secretory activity of epididymis and seminal vesicle, and number of litters per female. On the other hand, higher doses (30 and 60 mg) of the treatment adversely affected above parameters. Further, higher doses of the extract also had adverse effects on daily sperm production, 1C cell population and on histology of testis. In conclusion, Syzygium aromaticum flower buds extract exhibits biphasic effect on reproductive physiology of male mice. Lower dose of Syzygium aromaticum flower bud extract is androgenic in nature and may have a viable future as an indigenous sexual rejuvenator, while higher doses adversely affected functional physiology of reproductive organs.

High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats: Assessment of echocardiographic, morphologic, and oxidative stress parameters.

The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats.

Sex differences and endocrine regulation of auditory-evoked, neural responses in African clawed frogs (Xenopus).

Mating depends on the accurate detection of signals that convey species identity and reproductive state. In African clawed frogs, Xenopus, this information is conveyed by vocal signals that differ in temporal patterns and spectral features between sexes and across species. We characterized spectral sensitivity using auditory-evoked potentials (AEPs), commonly known as the auditory brainstem response, in males and females of four Xenopus species. In female X. amieti, X. petersii, and X. laevis, peripheral auditory sensitivity to their species own dyad-two, species-specific dominant frequencies in the male advertisement call-is enhanced relative to males. Males were most sensitive to lower frequencies including those in the male-directed release calls. Frequency sensitivity was influenced by endocrine state; ovariectomized females had male-like auditory tuning while dihydrotestosterone-treated, ovariectomized females maintained female-like tuning. Thus, adult, female Xenopus demonstrate an endocrine-dependent sensitivity to the spectral features of conspecific male advertisement calls that could facilitate mating. Xenopus AEPs resemble those of other species in stimulus and level dependence, and in sensitivity to anesthetic (MS222). AEPs were correlated with body size and sex within some species. A frequency following response, probably encoded by the amphibian papilla, might facilitate dyad source localization via interaural time differences.

Fundamental understanding of drug absorption from a parenteral oil depot.

Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter.

Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization.

Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in the circulation and has potent multifunctional activity. Epidemiological evidence suggests that levels of serum DHEA decrease with advancing age, and this has been associated with onset or progression of various age-related ailments, including cognitive decline and dementia, cardiovascular disease, and obesity. Consequently, these findings have sparked intense research interest in DHEA supplementation as an "antiaging" therapy. Currently, DHEA is being used by 25% of in vitro fertilization (IVF) clinicians as an adjuvant in assisted reproductive programs, yet the therapeutic benefit of DHEA is unclear. Here, we examined the use of novel DHEA-containing oral troches in patients undertaking IVF and investigated the impact of these troches on their serum androgen profile. This retrospective study determined the androgen profile of 31 IVF patients before (baseline) and after DHEA supplementation (with DHEA). Baseline serum measurements of testosterone (total and free), DHEA sulfate (DHEAS), sex hormone-binding globulin (SHBG), and androstenedione were made before and after supplementation. Each patient received DHEA troches containing 25 mg of micronized DHEA, and troches were administered sublingually twice daily for a period of no greater than 4 months. Adjuvant treatment with DHEA boosted the serum concentration of a number of androgen-related analytes, including total and free testosterone, androstenedione, and DHEAS, while serum SHBG remained unchanged. Supplementation also significantly increased the free-androgen index in IVF patients. Interestingly, the increase in serum analyte concentration following DHEA supplementation was found to be dependent on body mass index (BMI), but not individual age. Patients with the lowest BMI (<20.0 kg/m(2)) tended to have lower testosterone and DHEAS, but higher SHBG and androstenedione levels in comparison with other BMI groups postsupplementation. However, patients in the highest BMI group (>30.0 kg/m(2)) tended to have lower androgen responses following DHEA supplementation, but these were not statistically different from the corresponding baseline level. This method of DHEA administration results in a similar enhancement of testosterone, DHEAS, and androstenedione levels in comparison with other methods of administration. Furthermore, we showed that BMI significantly influences DHEA uptake and metabolism, and that BMI should be carefully considered during dosage calculation to ensure a significant and robust androgen-profile boost.

Recruiting older people at nutritional risk for clinical trials: what have we learned?

BACKGROUND: The difficulty of recruiting older people to clinical trials is well described, but there is limited information about effective ways to screen and recruit older people into trials, and the reasons for their reluctance to enrol. This paper examines recruitment efforts for a community-based health intervention study that targeted older adults. METHODS: One year randomized control trial. Undernourished men and women, aged ≥ 65 years and living independently in the community were recruited in three Australian states. Participants were allocated to either oral testosterone undecanoate and high calorie oral nutritional supplement or placebo medication and low calorie oral nutritional supplementation. Hospital admissions, functional status, nutritional health, muscle strength, and other variables were assessed. RESULTS: 4023 potential participants were identified and 767 were screened by a variety of methods: hospital note screening, referrals from geriatric health services, advertising and media segments/appearances. 53 participants (7% of total screened) were recruited. The majority of potentially eligible participants declined participation in the trial after reading the information sheet. Media was the more successful method of recruiting, whereas contacting people identified by screening a large number of hospital records was not successful in recruiting any participants. CONCLUSION: Recruitment of frail and older participants is difficult and multiple strategies are required to facilitate participation. TRIAL REGISTRATION: Australian Clinical Trial Registry: ACTRN 12610000356066 date registered 4/5/2010.

[Hormonal deficiencies in the elderly: is there a role for replacement therapy?]. / Déficiences hormonales du sujet âgé: faut-il les traiter?

Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to differentiate: 1) the physiological functional loss, which is a natural phenomenon without clear deleterious consequences on health and should not be compensated by the administration of hormones only to restore plasma levels similar to those measured in young people and 2) a pathological defect that deserves a replacement therapy to correct the endocrine deficiency and improve the health status of older individuals. This article considers the deficiencies in insulin, thyroid hormones, growth hormone, dehydroepiandrosterone (DHEA) and testosterone. For each hormone, a benefit/risk ratio of a so-called replacement therapy will be analyzed.

Anabolic-androgenic steroid use among Brazilian bodybuilders.

This cross-sectional, quantitative, exploratory study investigated the prevalence and profile of anabolic-androgenic steroids (AAS) users amongst a convenience sample of 510 bodybuilders from 52 gyms, in João Pessoa, Brazil, with a structured questionnaire containing selected questions about socioeconomic and training variables on the use of AAS. Data were analyzed using frequency and chi-square tests. AAS prevalence use was 20.6%; mostly young men (98.1%), of a low education level (46.7%), who trained for more than 4 years (49.5%). The use of AAS was related to the use of dietary supplements. About 81% of consumed AAS consisted of Deca-Durabolin, Winstrol, and Sustanon. Study's limitations are noted.