High circulating oestrone and low testosterone correlate with adverse clinical outcomes in men with advanced liver disease.

Background & Aims: Circulating testosterone is usually reduced in men with cirrhosis, but there has not been a comprehensive analysis of androgen status or circulating oestrogens. Little is known about associations between circulating sex steroids with aspects of health in this population.

Methods: We report data from men with cirrhosis and low serum testosterone (<12 nmol/L or calculated free testosterone <230 pmol/L).

Low Hemoglobin Concentrations Are Associated With Sarcopenia, Physical Performance, and Disability in Older Australian Men in Cross-sectional and Longitudinal Analysis: The Concord Health and Ageing in Men Project.

Background: The objective of this study is to examine associations between Hb levels and sarcopenia, low muscle strength, functional measures, and activities of daily living (ADL) and instrumental ADL (IADL) disabilities in older Australian men.

Methods: Men aged 70 years and older (2005-2007) from the Concord Health and Ageing in Men Project were assessed at baseline (n = 1,705), 2 years (n = 1,367), and 5 years (n = 958). The main outcome measurements were walking speed, muscle strength, ADL and IADL disabilities, and sarcopenia using the Foundation for the National Institutes of Health criteria (low appendicular lean mass adjusted for body mass index < 0.

Glandular epithelial AR inactivation enhances PTEN deletion-induced uterine pathology.

Phosphatase and tensin homolog (PTEN) deletion induces uterine pathology, whereas androgen actions via androgen receptor (AR) support uterine growth and therefore may modify uterine cancer risk. We hypothesized that the androgen actions mediated via uterine glandular epithelial AR could modify PTEN deletion-induced uterine pathology. To test our hypothesis, we developed uterine glandular epithelium-specific PTEN and/or AR knockout mouse models comparing the uterine pathology among wild-type (WT), glandular epithelium-specific AR inactivation (ugeARKO), PTEN deletion (ugePTENKO), and the combined PTEN and AR knockout (ugePTENARKO) female mice.

Prevalence of the geriatric syndromes and frailty in older men living in the community: The Concord Health and Ageing in Men Project.

Aim: To describe the age at which the geriatric syndromes and frailty become common in community-dwelling men.

Methods: The Concord Health and Ageing in Men Project involves a population-based sample of 1705 community-dwelling men aged 70 and over from a defined geographic region in Sydney. Data were obtained by physical performance tests, clinical examinations, and questionnaire to determine the prevalence of the following conditions by five-year age group.

Temporal Changes in Androgens and Estrogens Are Associated With All-Cause and Cause-Specific Mortality in Older Men.

Context: The dynamic temporal relationship between changes in serum reproductive hormones and mortality in men has not been reported.

Objective: The objective of the study was to examine the relationship between progressive changes in circulating reproductive hormones over time with all-cause and cause-specific mortality in older men.

Design, Setting, And Participants: Community-dwelling men aged 70 years and older from the Concord Health and Ageing in Men Project study were assessed at baseline (2005-2007, n = 1705) and at 2-year (n = 1367) and 5-year follow-up (n = 958).

A simple, accurate and universal method for quantification of PCR.

Background: Research into gene expression enables scientists to decipher the complex regulatory networks that control fundamental biological processes. Quantitative real-time PCR (qPCR) is a powerful and ubiquitous method for interrogation of gene expression. Accurate quantification is essential for correct interpretation of qPCR data.

Temporal Trend in Androgen Status and Androgen-Sensitive Outcomes in Older Men.

Context: Although androgen status decreases with aging in unselected men, the contemporaneous relationship over time between circulating hormones and androgen-sensitive outcomes has not been reported.

Objective: To investigate the temporal relationships between age-specific androgen status and muscle (mass, strength), hemoglobin, and prostate-specific antigen (PSA).

Design, Setting And Participants: Men aged 70 years and older from the Concord Health and Ageing in Men Project study were assessed at baseline (2005–2007; n = 1705) and at 2-year (n = 1367) and 5-year follow-up (n = 958).

Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery.

The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR)-mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation.

Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency.

Objective: To review the doping status of dehydroepiandrosterone (DHEA) for female athletes with adrenal insufficiency within the framework of Therapeutic Use Exemption (TUE) applications for this proandrogen, which is included on the World Anti-Doping Agency (WADA)'s Prohibited List.

Data Sources And Main Results: Current knowledge of adrenal pathophysiology with a focus on the physiological role and pharmacological effects of DHEA in female athletes including placebo-controlled clinical trials of DHEA and consensus clinical practice and prescribing guidelines.

Conclusions: Because there is no convincing clinical evidence to support the use of DHEA replacement therapy in women with adrenal failure, a TUE for DHEA is not justified by definite health benefit for either secondary or primary adrenal failure.

Epidemiological and Mendelian Randomization Studies of Dihydrotestosterone and Estradiol and Leukocyte Telomere Length in Men.

Context: Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is metabolized to DHT by 5α-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro.

Effects of Changes in Number of Medications and Drug Burden Index Exposure on Transitions Between Frailty States and Death: The Concord Health and Ageing in Men Project Cohort Study.

Objectives: To investigate the effects of number of medications and Drug Burden Index (DBI) on transitions between frailty stages and death in community-dwelling older men.

Design: Cohort study.

Setting: Sydney, Australia.

Natural history of non-neurogenic overactive bladder and urinary incontinence over 5 years in community-dwelling older men: The concord health and aging in men project.

Aims: To describe the natural history of non-neurogenic overactive bladder (OAB) and urgency incontinence in community-dwelling older men.

Methods: A representative sample of 1,705 community-dwelling men aged 70 and older in a defined geographic area of Sydney, Australia, had their urinary symptoms assessed using the International Prostate Symptom Scores (IPSS) and the International Consultation of Incontinence Questionnaire (ICIQ) at baseline, 2-year follow-up, and 5-year follow-up. Four hundred and eighty-eight men without neurological diseases or prostate cancer during follow-up, or history of urological treatment at baseline were included in the analysis.

Prospective longitudinal study of testosterone and incident depression in older men: The Health In Men Study.

Background: Depression in older men has been associated with low circulating testosterone concentration but data from prospective studies are limited.

Methods: We conducted a prospective longitudinal study in a community representative cohort of 3179 older men free of clinically significant depressive symptoms at baseline. The main objective of this study was to determine if low serum testosterone, dihydrotestosterone and estradiol concentrations are associated with the development of depressive symptoms.

Urinary Sex Steroids and Anthropometric Markers of Puberty - A Novel Approach to Characterising Within-Person Changes of Puberty Hormones.

Background/aims: The longitudinal relationships of within-individual hormone and anthropometric changes during puberty have not ever been fully described. The objectives of this study were to demonstrate that 3 monthly urine collection was feasible in young adolescents and to utilise liquid chromatography-tandem mass spectrometry assay methods for serum and urine testosterone (T), estradiol (E2) and luteinizing hormone (LH) in adolescents by relating temporal changes in urine and serum hormones over 12 months to standard measures of pubertal development.

Methods: A community sample of 104 adolescents (57 female) was studied over 12 months with annual anthropometric assessment, blood sampling and self-rated Tanner staging and urine collected every 3 months.

Association Rules Analysis of Comorbidity and Multimorbidity: The Concord Health and Aging in Men Project.

Background: Comorbidity and multimorbidity are common in older people. Here we used a novel analytic approach called Association Rules together with network analysis to evaluate multimorbidity (two or more disorders) and comorbidity in old age.

Methods: A population-based cross-sectional study was undertaken where 17 morbidities were analyzed using network analysis, cluster analysis, and Association Rules methodology.

Development and Characterization of Uterine Glandular Epithelium Specific Androgen Receptor Knockout Mouse Model.

While estrogen action is the major driver of uterine development, androgens acting via the androgen receptor (AR) may also promote uterine growth as suggested by uterine phenotypes in global AR knockout (ARKO) female mice. Because AR is expressed in uterine endometrial glands, we generated (Cre/loxP) uterine gland epithelium-specific ARKO (ugeARKO) to determine the role of endometrial gland-specific androgen actions. However, AR in uterine gland epithelium may not be required for normal uterine development and function because ugeARKO females had normal uterine development and fertility.

Estimating age-specific trends in circulating testosterone and sex hormone-binding globulin in males and females across the lifespan.

Background: Age-specific trends of serum testosterone and sex hormone-binding globulin across the full lifespan have not been reported.

Methods: We deduced age-specific trends in serum testosterone and sex hormone-binding globulin in males and females between ages 10 and 90 from a large sample of consecutive results from a single large pathology laboratory. Coded results of 110,712 consecutive blood samples requesting serum testosterone over seven years (2007-2013) comprising blood testosterone, sex hormone-binding globulin and calculated free testosterone together with gender and age were analysed create smoothed age-specific centiles (2.

Testicular function in a birth cohort of young men.

Study Question: By investigating a birth cohort with a high ongoing participation rate to derive an unbiased population, what are the parameters and influences upon testicular function for a population not selected with regard to fertility?

Summary Answer: While varicocele, cryptorchidism and obesity may impact on human testicular function, most common drug exposures and the presence of epididymal cysts appear to have no or minimal adverse impact.

What Is Known Already: The majority of previous attempts to develop valid reference populations for spermatogenesis have relied on potentially biased sources such as recruits from infertility clinics, self-selected volunteer sperm donors for research or artificial insemination or once-fertile men seeking vasectomy. It is well known that studies requiring semen analysis have low recruitment rates which consequently question their validity.

Prenatal testosterone exposure is related to sexually dimorphic facial morphology in adulthood.

Prenatal testosterone may have a powerful masculinizing effect on postnatal physical characteristics. However, no study has directly tested this hypothesis. Here, we report a 20-year follow-up study that measured testosterone concentrations from the umbilical cord blood of 97 male and 86 female newborns, and procured three-dimensional facial images on these participants in adulthood (range: 21-24 years).

Age-specific population centiles for androgen status in men.

Aim: The age-specific population profiles in men of circulating testosterone and its two bioactive metabolites dihydrotestosterone (DHT) and estradiol (E2) across the adult lifespan and its determinants are not well described.

Objective: Our objective was to deduce smoothed age-specific centiles of circulating testosterone, DHT, and E2 in men using pooled data from population-based studies in three Australian cities from liquid chromatography-mass spectrometry steroid measurements in a single laboratory.

Design, Setting, And Participants: We pooled data of 10 904 serum samples (serum testosterone, DHT, E2, age, height, and weight) from observational population-based studies in three major cities across Australia.

Androgen receptor splice variants and polycystic ovary syndrome: cause or effect?

Androgen receptor (AR)-mediated androgen action provides not only a classical pivotal role in male development and functions but also a recently proven role in female reproductive physiology. Splice variants of AR are reported to occur in various androgen-sensitive cancers and now, a recent study by Wang . proposed that AR splice variants have an etiological role in polycystic ovary syndrome (PCOS).

Androgen actions via androgen receptor promote PTEN inactivation induced uterine cancer.

Haploinsufficient inactivating phosphatase and tensin homolog (Pten) mutations cause Cowden syndrome, an autosomal dominant risk genotype for hormone dependent reproductive cancers. As androgen actions mediated via the androgen receptor (AR) supports uterine growth and may modify uterine cancer risk, we hypothesized that a functional AR may increase PTEN inactivation induced uterine cancer. To test the hypothesis, we compared the PTEN knockout (PTENKO) induced uterine pathology in heterozygous PTENKO and combined heterozygous PTEN and complete AR knockout (PTENARKO) female mice.

Measurement of Estradiol in Human Serum by LC-MS/MS Using a Novel Estrogen-Specific Derivatization Reagent.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described that employs a novel derivatization reagent for the measurement of serum estradiol (E2), with simultaneous analysis of underivatized testosterone (T) and dihydrotestosterone (DHT). The main advantage of the new derivatization reagent 1,2-dimethylimidazole-5-sulfonyl chloride is its analyte-specific fragmentation that enables monitoring of confirmatory mass transitions with high sensitivity. The reaction mixture can be analyzed without additional purification steps using a 9.

Adolescent testosterone influences BDNF and TrkB mRNA and neurotrophin-interneuron marker relationships in mammalian frontal cortex.

Late adolescence in males is a period of increased susceptibility for the onset of schizophrenia, coinciding with increased circulating testosterone. The cognitive deficits prevalent in schizophrenia may be related to unhealthy cortical interneurons, which are trophically dependent on brain derived neurotrophic factor. We investigated, under conditions of depleted (monkey and rat) and replaced (rat) testosterone over adolescence, changes in gene expression of cortical BDNF and TrkB transcripts and interneuron markers and the relationships between these mRNAs and circulating testosterone.