https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)62167-9.pdf

Frailty in elderly people

The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI 5 the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index of bioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG. (J Clin Endocrinol Metab 84: 3666 ‐3672, 1999)

/pdf/a-critical-evaluation-of-simple-methods-for-the-estimation-3di58nh2sy.pdf

A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum

The Standards of Care (SOC) for the Health of Transsexual, Transgender, and Gender Nonconforming People is a publication of the World Professional Association for Transgender Health (WPATH). The overall goal of the SOC is to provide clinical guidance for health professionals to assist transsexual, transgender, and gender nonconforming people with safe and effective pathways to achieving lasting personal comfort with their gendered selves, in order to maximize their overall health, psychological well-being, and self-fulfillment. This assistance may include primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services (e.g., assessment, counseling, psychotherapy), and hormonal and surgical treatments. The SOC are based on the best available science and expert professional consensus. Because most of the research and experience in this field comes from a North American and Western European perspective, adaptations of the SOC to other parts ...

Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7

Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

Pathophysiology of Human Visceral Obesity: An Update

Objective: Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testos...

/pdf/testosterone-therapy-in-men-with-androgen-deficiency-5gq7m38esq.pdf

Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline.

Background Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied. Methods Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group. Results A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load. Conclusions In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.)

https://www.hormonebalance.org/images/documents/Basari%2010%20TRT%20men%20Cardiac%20events%20NEJM.pdf

Adverse Events Associated with Testosterone Administration

Background The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. Methods Seventy-five women, 31 to 56 years old, who had undergone oophorectomy and hysterectomy received conjugated equine estrogens (at least 0.625 mg per day orally) and, in random order, placebo, 150 μg of testosterone, and 300 μg of testosterone per day transdermally for 12 weeks each. Outcome measures included scores on the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and a sexual-function diary completed over the telephone. Results The mean (±SD) serum free testosterone concentration increased from 1.2±0.8 pg per milliliter (4.2±2.8 pmol per liter) during placebo treatment to 3.9±2.4 pg per milliliter (13.5±8.3 pmol per li...

Transdermal testosterone treatment in women with impaired sexual function after oophorectomy

An investigation of the micellar phase of sodium dodecyl sulfate in aqueous sodium chloride solutions using quasielastic light scattering spectroscopy

From measurements of the autocorrelation function and time-averaged intensity of light scattered from aqueous bile salt-lecithin solutions, we deduced the mean hydrodynamic radius (Rh), shape, and polydispersity of bile salt-lecithin mixed micelles as functions of bile salt species, lecithin to bile salt (L/BS) molar ratio, total lipid concentration (0.625-10 g/dL), temperature (20-60 degrees C), and NaCl concentration (0.15-0.6 M). Our data suggest that at low L/BS ratios (0 to approximately 0.6) simple bile salt micelles coexist in varying proportions with minimum-sized mixed micelles (Rh, 18-35 A). These solutions are highly polydisperse and display features dependent upon the particular bile salt species. At high L/BS ratios (greater than 0.6), only mixed micelles are present, and their sizes increase markedly (Rh, 20 leads to 300 A) with increases in L/BS ratio and appear to diverge as the lecithin-bile salt phase limit is approached. The shape of the mixed micelles as deduced from light-scattering measurements and confirmed by transmission electron microscopy is disklike. The radii of the disks, however, are not compatible with Small's model of mixed micellar structure [Small, D.M. (1967a) Gastroenterology 52, 607-a1 but are consistent with a new model proposed here in which bile salts and lecithin interact to form a mixed bilayer disk which is surrounded on its perimeter by bile salts. The inclusion of bile salts in a fixed stoichiometry within the interior of the bilayers is shown to provide a quantitative explanation for the divergence of the mixed micellar sizes, their temperature dependence, and the origin of the lecithin-bile salt phase limit. The influence of total lipid concentration on both mixed micellar size and the lecithin-bile salt phase limit is explained by the "mixed disk" model by taking account of the equilibrium between mixed micelles and bile salt monomers in the intermicellar solution. By use of this concept, deductions of the intermicellar bile salt concentration in taurocholate-lecithin solutions are made and are shown to vary as a function of mixed micellar size and temperature. The range of values obtained, 3-6 mM, is comparable in magnitude to the critical micellar concentration of the pure bile salt.

Quasielastic light-scattering studies of aqueous biliary lipid systems. Mixed micelle formation in bile salt-lecithin solutions.

A strong increase has been measured in the size and polydispersity of sodium dodecyl sulfate (SDS) micelles on increasing the detergent concentration in solutions containing high salt (NaCl) concentration. The mean hydrodynamic radius and the polydispersity of the micelles were measured. A thermodynamic theory of micelle formation and growth is presented. This theory makes use of the experimentally established result that the micelles have the shape of prolate spherocylinders. The micellar size and polydispersity is determined at each temperature and salt concentration by 2 chemical potentials. These are the chemical potential changes associated with transferring a detergent monomer from the solvent to either the cylindrical or spherical region of the micelle. Using only these 2 chemical potentials as parameters, one can predict accurately the hydrodynamic radius, the polydispersity, and the scattered light intensity over the entire experimental range of detergent concentration, temperature, and salt concentration. 43 references.

Norman A. Mazer

Papers

Adverse Events Associated with Testosterone Administration

Transdermal testosterone treatment in women with impaired sexual function after oophorectomy

An investigation of the micellar phase of sodium dodecyl sulfate in aqueous sodium chloride solutions using quasielastic light scattering spectroscopy

Quasielastic light-scattering studies of aqueous biliary lipid systems. Mixed micelle formation in bile salt-lecithin solutions.

Thermodynamic analysis of the growth of sodium dodecyl sulfate micelles