Androgen Supplementation Research Articles

Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails.

On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, etal. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.

Mapping the Steroid Response to Major Trauma from Injury to Recovery: A Prospective Cohort Study

Background: Survival rates after severe injury are improving, but complication rates and outcomes are variable. This study addressed the lack of data on adrenal and gonadal steroid response during recovery from major trauma in relation to clinical outcomes, exploring potential targets for future intervention. Methods: We undertook a prospective, observational cohort study at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) >15) and at regular intervals for six months. We recorded clinical outcomes (ventilator days, length of hospital stay, organ dysfunction, sepsis), measured adrenal and gonadal steroids by tandem mass spectrometry, and assessed muscle loss by ultrasound and nitrogen excretion. Findings: We screened 996 multiply injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analysed all male survivors <50 years not treated with steroids (N=60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked one and six weeks post-injury, respectively. While glucocorticoid secretion remained within the reference range, serum testosterone, DHEA and DHEAS decreased sharply immediately after injury and took two, four, and more than six months, respectively, to recover; all three correlated with the sequential organ failure assessment (SOFA) score and probability of sepsis. Interpretation: The acute catabolic response to severe injury is accompanied by profound and sustained adrenal and gonadal androgen suppression. The impact of androgen supplementation on health outcomes after major trauma should be systematically explored. Funding: The Steroids and Immunity from injury through to Rehabilitation (SIR) Study was part of the Surgeon General’s Casualty Nutrition Study (SGCNS), supported by University Hospitals Birmingham NHS Foundation Trust (UHB) and the University of Birmingham. Additional funding was provided by the Drummond Trust Foundation. Declaration of Interest: There is no conflict of interests for any of the authors. JML and WA are supported by the National Institute for Health Research (NIHR) through the NIHR Birmingham Biomedical Research Centre. Ethical Approval: The protocol was approved by the NRES Committee South West – Frenchay 11/SW/0177 and MOD REC 116/Gen/10.

Beneficial Effects of Adrenal Androgen Supplement in Bleeding Cirrhotic Rats.

Critical illness is accompanied by hypothalamic-pituitary-adrenal axis activation, but adrenal insufficiency characterized by inadequate glucocorticoid synthesis is common in critically ill cirrhotic patients, the "hepato-adrenal syndrome." Adrenal cortex also synthesizes androgen (dehydroepiandrosterone, DHEA). DHEA maintains microcirculation by enhancing vascular endothelial nitric oxide synthase (eNOS) activity. In critical patients of other disease entities, a shift of adrenal steroidogenesis away from androgens toward glucocorticoid has been noted, arousing interests in androgen replacement in critical settings. Nevertheless, this has not been surveyed in cirrhosis with hemorrhage. In this study, liver cirrhosis was induced with common bile duct ligation (BDL) in Spraque-Dawley rats. Sham rats were controls. DHEA or vehicle was injected at the beginning of hemorrhage-transfused procedure, followed by terlipressin injection. Hemodynamic parameters were measured. Then abdominal aorta, superior mesenteric arteries (SMA) and splenorenal shunt (prominent portosystemic collateral vessel in rodents) eNOS and inducible NOS protein expressions were evaluated. In bleeding BDL groups without terlipressin injection, adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the DHEA response. The results showed that DHEA significantly elevated mean arterial pressure, cardiac output, and stroke volume of bleeding cirrhotic rats treated with terlipressin and reduced systemic vascular resistance without affecting SMA flow, resistance, and portal pressure. DHEA upregulated abdominal aorta and SMA eNOS expressions. ACTH did not stimulate DHEA synthesis in bleeding BDL rats. In conclusion, androgen deficiency exists in bleeding cirrhotic rats. DHEA augments terlipressin-induced amelioration of shock without influencing splanchnic hemodynamics, possibly rendering it a feasible adjunct to vasoconstrictors in variceal hemorrhage.

Androgen treatment effects on hippocampus structure in boys with Klinefelter syndrome

Klinefelter syndrome (KS, 47,XXY) is the most common sex chromosome aneuploidy in males. A variety of complex clinical needs is associated with KS, including physical, cognitive and psychosocial impairments. Standard treatment for KS consists of androgen replacement therapy in adolescence to offset testosterone deficiency. Such treatment has a beneficial effect on the physical and behavioral manifestations of this syndrome. Whether androgen supplementation has a significant influence on the brain, however, is unknown. In the current study, we examined regional gray matter volume in boys with KS to assess whether treatment with oxandrolone, a synthetic hormone analog of testosterone, was associated with structural changes in the brain. Specifically, we focused our investigation on the hippocampus, given (1) its involvement in KS, and (2) the high concentration of androgen receptors found in this region. Structural magnetic resonance imaging data was acquired from a subsample of boys who completed a 2-year double-blind clinical trial in which patients were randomized to treatment with oxandrolone or to placebo, as well as from a sample of typically developing (TD) boys. Group differences in hippocampal volume were examined. A significant main effect of group was observed. Pairwise comparisons indicated smaller hippocampal volume in the placebo group relative to the oxandrolone group, as well as smaller volume in the placebo group relative to the TD control group. No difference in volume was observed between the treatment and TD groups. Moreover, across KS subgroups, a significant positive association was observed between hippocampus volume and performance on a spatial memory task, indicating treatment-based changes in brain structure may underlie cognitive change. These findings confirm prior reports implicating a role of the hippocampus in KS and are important in extending previous research by demonstrating a significant effect of androgens on brain structure.

AB011. The regulatory effects of androgen in wound healing of the prostatic urethra after thulium laser resection of the prostate

BackgroundThis research aims to determine the role of androgen in wound healing of the prostatic urethra after thulium laser resection of the prostate (TmLRP). Further, the change of basal cell proliferation and differentiation as well as macrophage polarization and the inflammatory response influenced by androgen were explored. Moreover, the macrophage cytokines effected by finasteride were detected in urine specimens from thulium laser prostatectomy patients, thus to reveal the mechanism of androgen in wound repair process after prostatectomy.Methods(I) Twenty-four 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; (II) immunohistochemical and immunofluorescence techniques were used to determine the basal cell proliferation and differentiation influenced by androgen; (III) the macrophage polarization and inflammatory response in the wound tissue and urine was also investigated; (IV) the macrophage cytokines effected by finasteride were detected in urine specimens from thulium laser prostatectomy patients by enzyme-linked immunosorbent assay (ELISA).Results(I) 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; (II) 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; (III) 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. TNF-α, IL-6 and IL-12 that secreted by M1 were higher than the other two groups, and IL-10 and TGF-1 that secreted by M2 were obviously postponed compared with the other two groups; (IV) in the urine specimens from thulium laser prostatectomy patients, the expression of TNF-α, IL-6 and IL-12 were lower while the expression of IL-10 and TGF-1 were higher under the influence of finasteride.Conclusions(I) Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP; (II) castration accelerates 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; (III) androgen inhibits the prostatic urethra wound healing by regulating the macrophage polarization; (IV) this research established foundation to reveal the mechanism and application of anti-androgen in the treatment of wound healing after prostatectomy.

Klinefelter Syndrome. The Effects of Early Androgen Therapy on Competence and Behavioral Phenotype.

Klinefelter syndrome (KS) is the result of sex chromosome aneuploidy most often characterized as 47,XXY. The typical features of KS include tall stature, gynecomastia, small firm testicles, hypergonadotropic hypogonadism, and infertility. However, abnormalities in neurodevelopment, cognition, and social and behavioral functioning also can be present. The abnormalities in neurodevelopment are believed to be due in part to androgen deficiency during early development and puberty. To discuss the role of androgens in normal adolescent development; discuss the cognitive, behavioral, and social functioning of children with KS; evaluate the evidence for early androgen therapy in men with KS; and discuss management strategies in the development of boys with KS. A systematic review of early androgen therapy and KS was performed using PubMed-Medline and Scopus databases. Relevant articles commenting on social, behavioral, cognitive, and physical outcomes among infants, children, and adolescents were included for reporting and discussion. Social and behavior functioning; cognitive outcomes; adverse effects associated with androgen therapy. 3 retrospective articles and 2 randomized controlled trials addressing early androgen therapy in boys with KS were reviewed. These studies showed an improvement in several aspects of social and cognitive functioning based on validated questionnaires. Treatment strategies, potential negative effects, and limitations of the literature on early androgen therapy in boys with KS are discussed. Our findings indicate that early androgen supplementation in children with KS combined with specific educational, family, and social support improves behavioral functioning. The optimal timing of hormonal therapy might require prospective studies, but based on our data and review of the literature, thebenefit of early hormonal and therapeutic intervention in KS is very encouraging. Flannigan R, Patel P, Paduch DA. Klinefelter Syndrome. The Effects of Early Androgen Therapy on Competence and Behavioral Phenotype. Sex Med Rev 2018;6:595-606.

An Indispensable Role of Androgen Receptor in Wnt Responsive Cells During Prostate Development, Maturation, and Regeneration

Androgen signaling is essential for prostate development, morphogenesis, and regeneration. Emerging evidence indicates that Wnt/β-catenin signaling also contributes to prostate development specifically through regulation of cell fate determination. Prostatic Axin2-expressing cells are able to respond to Wnt signals and possess the progenitor properties to regenerate prostatic epithelium. Despite critical roles of both signaling pathways, the biological significance of androgen receptor (AR) in Axin2-expressing/Wnt-responsive cells remains largely unexplored. In this study, we investigated this important question using a series of newly generated mouse models. Deletion of Ar in embryonic Axin2-expressing cells impaired early prostate development in both ex vivo and tissue implantation experiments. When Ar expression was deleted in prostatic Axin2-expressing cells at pre-puberty stages, it results in smaller and underdeveloped prostates. A subpopulation of Axin2 expressing cells in prostate epithelium is resistant to castration and, following androgen supplementation, is capable to expand to prostatic luminal cells. Deletion of Ar in these Axin2-expressing cells reduces their regenerative ability. These lines of evidence demonstrate an indispensable role for the Ar in Wnt-responsive cells during the course of prostate development, morphogenesis, and regeneration, which also imply an underlying interaction between the androgen and Wnt signaling pathways in the mouse prostate. Stem Cells 2018;36:891-902.

Eighteen-Year Effect of Androgen Therapy on Bone Mineral Density in Trans(gender) Men.

The study explores the influence of long-term androgen supplementation (18 years) on bone metabolism in trans(gender) men. Thirty five trans(gender) men aged (47±4) were treated with adequate dose of testosterone. BMD was measured by DEXA at lumbar spine and neck and T score was determined. Biochemical parameters of bone turnover were measured in all patients. As compared with female and male age matched controls they showed a not significantly different T-score at spine [1.213±0.15 in trans(gender) men vs. 1.192±0.19 in females and 1.203±0.06 g/cm2 in males (p<0.01)]. BMD in the hip skeleton in trans(gender) men (0.950±g/cm2) was statistically higher than females (0.822±0.09) but not statistically different from normal males 0.988±0.06). Circulating biochemical markers of bone formation, and resorption were not different between the trans(gender) men, and matched controls. We conclude that BMD at the hip (site rich in cortical bone) after adequate dose of testosterone therapy is higher while it is not different at the spine (trabecular bone) in trans(gender) men even after 18 years of testosterone administration.

Signs and symptoms, evaluation, and management of genitourinary tract consequences of premature ovarian insufficiency.

Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years old. Hypoestrogenism associated with this condition may result in vaginal atrophy and urine incontinence, called genitourinary syndrome. The symptoms include: vaginal dryness, irritation, dyspareunia, and dysuria. There is relative lack of studies on the occurrence and treatment of genitourinary problems in women with POI. Prevalence rates vary from 17 to 54% depending on cause, duration of oestrogen depletion, and the treatment used. Patients with POI gain lower scores in tests measuring vaginal health or sexual function in comparison to healthy peers. Hormonal treatment in premature ovarian insufficiency is recommended until the natural age of menopause. The vaginal route of oestrogen administration is supposed to be the criterion standard in treating genitourinary symptoms. Androgen supplementation is not routinely recommended.

Influence of androgen on myocardial apoptosis and expression of myocardial IR and IRS‑1 in chronic heart failure rat models.

The present study aimed to investigate the effect of androgens on chronic heart failure (CHF) in a rat model. A total of 120 Sprague Dawley male rats were randomly divided into the following groups: (A) sham operation group, (B) castrated group, (C) heart failure (HF) group, (D) castrated+HF group, and (E) castrated+HF + testosterone (T) replacement therapy group. There were 20 rats in groupA, and 25 rats in the other groups. Surgical castration was performed on groupsB, D and E, and T replacement therapy was administered to groupE. GroupsC, D and E were treated with doxorubicin hydrochloride to prepare the CHF animal model. The insulin sensitivity index (ISI) was calculated from fasting blood glucose and fasting insulin levels. Echocardiography was performed. Venous blood was collected for plasma T level test. Myocardial tissue was used for apoptosis index analysis. The expression levels of myocardial insulin receptor (IR) and insulin receptor substrate‑1 (IRS‑1) were measured by reverse transcription semi‑quantitative polymerase chain reaction. Compared with groupA, the T level and ISI decreased, whereas the expression level of IR and IRS‑1 were increased in the CHF group(P<0.05). Following castration, the T level and ISI were significantly decreased, and the expression of IR and IRS‑1 were increased compared with the uncastrated CHF rats (P<0.01). Following androgen administration, the ISI increased, expression of IR and IRS‑1 decreased, and the myocardial apoptosis index decreased (P<0.05). Taken together, these results demonstrated that androgen supplementation could improve insulin resistance and affect the expression of IR and IRS‑1 in CHF, thereby reducing myocardial apoptosis and improving cardiac function.

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.

AB029. The regulatory effects of androgen in wound healing of the prostatic urethra after thulium laser resection of the prostate

BackgroundThis research aims to determine the role of androgen in wound healing of the prostatic urethra after thulium laser resection of the prostate (TmLRP). Further, the change of basal cell proliferation and differentiation as well as macrophage polarization and the inflammatory response influenced by androgen were explored. Moreover, the macrophage cytokines effected by finasteride were detected in urine specimens from thulium laser prostatectomy patients, thus to reveal the mechanism of androgen in wound repair process after prostatectomy.Methods(I) Twenty-four 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; (II) immunohistochemical and immunofluorescence techniques were used to determine the basal cell proliferation and differentiation influenced by androgen; (III) the macrophage polarization and inflammatory response in the wound tissue and urine was also investigated; (IV) the macrophage cytokines effected by finasteride were detected in urine specimens from thulium laser prostatectomy patients by ELISA.Results(I) 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; (II) 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; (III) 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. TNF-α, IL-6 and IL-12 that secreted by M1 were higher than the other two groups, and IL-10 and TGF-β1 that secreted by M2 were obviously postponed compared with the other two groups. 4. In the urine specimens from thulium laser prostatectomy patients, the expression of TNF-α, IL-6 and IL-12 were lower while the expression of IL-10 and TGF-β1 were higher under the influence of finasteride.Conclusions(I) Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP; (II) castration accelerates 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; (III) androgen inhibits the prostatic urethra wound healing by regulating the macrophage polarization; (IV) this research established foundation to reveal the mechanism and application of anti-androgen in the treatment of wound healing after prostatectomy.

Testosterone Replacement in a Man with Intermediate-risk Prostate Cancer

In brief, a hypogonadal man with successfully treated localized prostate cancer deserves testosterone therapy (TTh) regardless of grade. The evidence is not conclusive but compelling. The story is different for those with intermediate-risk disease who, for a variety of reasons, need TTh but cannot or elect not to have treatment of their primary malignancy, but still desire androgen supplementation.

Androgen supplementation improves some but not all aspects of immune senescence in aged male macaques.

Aging leads to a progressive decline in immune function commonly referred to as immune senescence, which results in increased incidence and severity of infection. In addition, older males experience a significant disruption in their levels of circulating androgens, notably testosterone and dehydroepiandrosterone (DHEA), which has been linked to sarcopenia, osteoporosis, cardiovascular disease, and diabetes. Since sex steroid levels modulate immune function, it is possible that the age-related decline in androgen levels can also affect immune senescence. Therefore, in this study, we evaluated the pleiotropic effects of physiological androgen supplementation in aged male rhesus macaques (n=7/group) on immune cell subset frequency and response to vaccination. As expected, frequency of naïve CD4 and CD8 T cells declined in aged non-treated macaques, while that of memory T cells increased. In contrast, frequency of naïve and memory T cells remained stable in androgen-supplemented males. In addition, levels of inflammatory cytokines increased less steeply in supplemented aged males compared to the aged controls. Despite these changes, androgen-supplemented animals only showed modest improvement in antibody responses following vaccination compared to age non-treated controls. These data indicate that short-term physiological androgen supplementation can improve some but not all aspects of immune senescence.

Salvage Strategies for Management of Testicular Tumors.

Testicular germ cell tumors (GCTs) comprise 2% of all human male malignancies and are the most common solid tumors in men between ages 15 and 35 years. Risk of contralateral testicular GCT is between 1 and 5%. Partial orchidectomy (PO) was originally described in 1984 by Richie. The evolving indications include metachronous tumors and tumor in solitary testicles. Also, small non-palpable lesions detected only by ultrasonography (USG) in asymptomatic patients is another indication. Salvagability is only chosen for tumors less than 2 cm in size. The key feature of PO is an inguinal approach with early vascular control using a rubber tourniquet before testicular mobilization into the field to avoid systemic tumor seeding. After, mass excision with a margin mandatory frozen section is done to assess adequacy of resection. Intra-op USG may be beneficial in small non-palpable lesions. Post op tumor markers are assessed and patients are taught self-examination of testis. Recent series shows that PO is safe and gives adequate oncological control. Carcinoma in situ (CIS) in the affected testis at PO or after testicular sparing surgery remains a challenge. At most centers, 20 Gy is recommended when adjuvant local radiation treatment is chosen to treat CIS. But this dose may hamper Androgen production. Radical orchiectomy remains the gold standard and should be discussed as part of informed consent. It is mandatory to highlight the risks of local recurrence and CIS, and treatment (observation, radiation, or completion orchiectomy) as well as the need for androgen supplementation and fertility risks before choosing testicular salvage procedures.

Effect of Methyltrienolone on the Metabolic Disorders in Rat Model of Alloxan-Induced Diabetes

Aim: The aim of the study was to investigate the restoration of metabolic imbalance related with deficiency of insulin by the exogenous androgen supplementation in the experimental model of alloxan-induced diabetes in Wistar male rats. Methods: The experimental diabetes was induced by a single intraperitoneal administration of alloxan. The concentrations of glucose, immunereactive insulin, corticosterone, testosterone and estradiol were examined in blood, the intensity of DNA and RNA synthesis and androgen receptor expression were studied in the liver tissue – at 15th, 30th and 45th days of alloxan-induced diabetes. The synthetic androgen methyltrienolone was administered to rats with 30-days diabetes during 15 days. All data were compared to control group received solvent. Results: The induction of diabetes increased the concentrations of glucose, corticosterone and estradiol while decreases insulin and testosterone concentration in blood as well as DNA/RNA synthesis and androgen receptors expression in hepatocytes. The administration of exogenous androgen significantly restored the metabolic imbalance and the expression of androgen receptors and increased DNA/RNA synthesis in liver cells maintained close to control level. Conclusion: The administration of methyltrienolone reduced the effect of “diabetic stress” and restored the hormonal dysfunction induced by alloxan.

Androgen supplementation for hypoactive sexual desire disorder in postmenopausal women: A systematic review and meta-analysis

Androgen supplementation for hypoactive sexual desire disorder in postmenopausal women: A systematic review and meta-analysis

Effect of androgen supplementation on activity-rest patterns in old males

Effect of androgen supplementation on activity-rest patterns in old males

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study.

African American men have the highest incidence of prostate cancer among ethnic groups, and racial disparity is highest in younger men. Prostate cancer prevalence is rising in HIV-infected men due to improved survival on antiretroviral therapies, yet little is known about racial differences in prostate cancer risk by HIV-infection status and age. This is a prospective cohort study of prostate cancer risk in 2,800 HIV-infected and -uninfected men who have sex with men (MSM) aged 40-70 years (22% African American) who were enrolled in the multicenter AIDS cohort study from 1996 to 2010. Poisson regression models were used to examine associations between race and HIV-infection status and prostate cancer risk among men aged 40-70, 40-55, and 56-70 years. Among men aged 40-70 years, incidence rates (IR) per 100,000 person-years were 169 among all men and 276 among African American HIV-infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0, 95% CI 0.55-1.82), but nearly threefold higher in African Americans compared to non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36-5.18 and 1.27-8.16 for all or HIV-infected men, respectively). Racial disparity in prostate cancer risk was greatest in African American men aged 40-55 years (adjusted IRR 3.31, 95% CI 1.19-9.22). Prostate cancer risk showed associations with family history of prostate cancer (p=0.001), but not heavy smoking, androgen supplement use, or HIV-related factors. Among MSM, African American HIV-positive and HIV-negative men aged 40-55 years have threefold increased risk of young-onset prostate cancer compared to non-African American men, highlighting the need to make informed decisions about screening in this population.

MP87-12 ADRENAL ANDROGENS FACILITATE PROSTATE CANCER CELL RESISTANCE TO ANDROGEN DEPRIVATION THERAPY

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2017MP87-12 ADRENAL ANDROGENS FACILITATE PROSTATE CANCER CELL RESISTANCE TO ANDROGEN DEPRIVATION THERAPY Michael Fiandalo, John Stocking, Elena Pop, Krystin Mantione, John Wilton, and James Mohler Michael FiandaloMichael Fiandalo More articles by this author , John StockingJohn Stocking More articles by this author , Elena PopElena Pop More articles by this author , Krystin MantioneKrystin Mantione More articles by this author , John WiltonJohn Wilton More articles by this author , and James MohlerJames Mohler More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2716AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate Cancer (CaP) growth and survival is dependent on the interaction of androgen receptor (AR) and testicular androgens, testosterone and dihydrotestosterone (DHT). Men that fail potential curative treatment are treated with androgen deprivation therapy (ADT). ADT is palliative and CaP recurs as the lethal phenotype. One mechanism that contributes to CaP recurrence is intratumoral intracrine androgen metabolism, which is the conversion of weak adrenal androgens (androstenedione [ASD] or dehydroepiandrosterone [DHEA]) to T or DHT. Mice lack adrenal androgens and therefore adrenal androgen contribute to CaP xenograft recurrence is overlooked. The hypothesis for these studies is adrenal androgen supplementation will facilitate androgen dependent human CaP CWR22 xenograft resistance to ADT. METHODS Mice were castrated, implanted with CWR22 and silastic tubes that contained T and empty silastic tubes that contained ASD or DHEA. T silastic tubes were removed after CWR22 tumor volumes reached 0.5 cc to simulate ADT. Digital calipers were used to measure changes in CWR22 tumor volume. Mouse serum, prostate and CWR22 were harvested at designated time points and liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to measure androgen levels. RESULTS CWR22 xenografts treated with no adrenal androgen regressed and began to grow 120 days after T silastic tube removal. ASD treated CWR22 tumors did not regress; CWR22 tumor growth increased and mice were euthanized because tumors grew beyond veterinary limits. DHEA treated CWR22 did not regress and did not grow like ASD treated CWR22. However, CWR22 xenografts recurred faster than control CWR22 xenografts. Serum PSA levels correlated with tumor volume. CWR22 androgen levels decreased in all treatment groups, but T levels remained sufficient to activate AR in ASD treated CWR22, but not control or DHEA treated CWR22 xenografts. CONCLUSIONS DHEA and ASD supplementation facilitated CWR22 resistance to ADT. However, CWR22 xenografts responded differently to DHEA and ASD, which suggests that adrenal androgens may play different roles when CaP cells undergo ADT. These studies show that adrenal androgen contributes should be taken into account when in vivo studies are performed to test CaP responses to ADT or therapeutic agents. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1170 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Michael Fiandalo More articles by this author John Stocking More articles by this author Elena Pop More articles by this author Krystin Mantione More articles by this author John Wilton More articles by this author James Mohler More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...