The physiology of endocrine systems with ageing

During ageing, the secretory patterns of the hormones produced by the hypothalamic-pituitary axis change, as does the sensitivity of the axis to negative feedback by end hormones. Additionally, glucose homoeostasis tends towards disequilibrium with increasing age. Along with these endocrine alterations, a loss of bone and muscle mass and strength occurs, coupled with an increase in fat mass. In addition, ageing-induced effects are difficult to disentangle from the influence of other factors that are common in older people, such as chronic diseases, inflammation, and low nutritional status, all of which can also affect endocrine systems. Traditionally, the decrease in hormone activity during the ageing process has been considered to be detrimental because of the related decline in bodily functions. The concept of hormone replacement therapy was suggested as a therapeutic intervention to stop or reverse this decline. However, clearly some of these changes are a beneficial adaptation to ageing, whereas hormonal intervention often causes important adverse effects. In this paper, we discuss the effects of age on the different hypothalamic-pituitary-hormonal organ axes, as well as age-related changes in calcium and bone metabolism and glucose homoeostasis

Selenium status is positively associated with bone mineral density in healthy aging European men

Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Cortisol and Phosphate Homeostasis: Cushing’s Syndrome Is Associated With Reversible Hypophosphatemia

Objectives: The influence of hypercortisolism on phosphate homeostasis is relatively unknown. A few previous studies have reported on patients with Cushing’s syndrome (CS) with hypophosphatemia in whom serum phosphate normalized after initiation of treatment for CS. We aimed to investigate the prevalence of hypophosphatemia in CS, the association between the degree of hypercortisolism and serum phosphate and the change in serum phosphate after remission of CS. We compared the prevalence of hypophosphatemia in CS with the prevalence in the population-based Rotterdam Study (RS).  Methods: Patients diagnosed with CS and treated at the Department of Endocrinology of Erasmus MC in the period of 2002-2020 were included and data was collected on age at diagnosis, sex, serum phosphate, calcium and potassium levels, kidney function and BMI. Using multivariate linear regression, we analyzed the association between 24h urinary free cortisol excretion (UFC) and serum phosphate. Changes in serum phosphate and covariates were tested with a repeated measurement ANOVA, using mean levels of laboratory values for the periods before remission, and 0-14 days and 15-180 days after remission.  Results: Hypophosphatemia before treatment was present in 16% of the 99 CS patients with data on serum phosphate, 24h UFC and covariates. In comparison, the prevalence of hypophosphatemia in RS was 2.0-4.2%. Linear regression showed a negative association between the level of UFC and serum phosphate at diagnosis, which remained significant after adjusting for covariates [β -0.002 (95%CI -0.004; -0.0004), p=0.021]. A subset of 24 patients had additional phosphate measurements at 0-14 days and 15-180 days after remission. In this subgroup, serum phosphate significantly increased from 1.03 ± 0.17 mmol/L prior to remission to 1.22 ± 0.25 mmol/L 15-180 days after remission (p = 0.008). BMI decreased after remission [-1.1 kg/m2, (95%CI -2.09 to -0.07), p=0.037]. Other covariates did not show an equivalent change over time.  Conclusion: In this retrospective study, we found that 16% of patients with CS had hypophosphatemia. Moreover, serum phosphate was related to the level of cortisoluria and increased after remission of CS. Potential underlying mechanisms related to urinary phosphate excretion and possibly involving FGF23, BMI and parathyroid hormone levels should be further explored

Brief report: Effects of dehydroepiandrosterone and atamestane supplementation on frailty in elderly men

Background: It has been suggested that the age-related decline of androgens in men plays a distinct role in the development of several aspects of frailty. Therefore, hormone replacement might improve the course of frailty by increasing lean body mass and muscle strength, decreasing fat mass, and improving the subjective quality of life. Objective: The objective of the study was to assess whether hormone replacement with dehydroepiandrosterone (DHEA) and/or atamestane might improve the course of frailty. Design: This was a double-blind, randomized, controlled trial. Setting: The study was conducted in the general community. Participants: Participants included 100 nonhospitalized, nondiseased, independently living men, aged 70 yr and over with low scores on strength tests. Seventeen participants did not complete the trial. Intervention: Subjects were randomly assigned to one of four intervention arms: atamestane (100 mg/d) and placebo, DHEA (50 mg/d) and placebo, a combination of atamestane (100 mg/d) and DHEA (50 mg/d), or two placebo tablets for 36 wk. Main Outcome Measures: Physical frailty was measured by means of a specific test battery, including isometric grip strength, leg extensor power, and physical performance. Results: The randomization was successful, and 83 (83%) men completed the intervention. There were no differences between the treatment arms and placebo group in any of the outcome measurements after intervention. Conclusions: The results of this double-blind, randomized trial do not support the hypothesis that hormone replacement with DHEA and/or atamestane might improve the course of frailty

Sex hormones and cognitive decline in elderly men

Decline of cognitive function with age may be due, in part, to hormonal changes and it has been hypothesized that higher levels of endogenous sex hormones preserve brain function. The aim of this prospective cohort study was to determine the relative contribution of endogenous sex hormones to cognitive decline in a population-based sample of 242 elderly men aged 73-91 at baseline. Endogenous sex hormone levels were measured at baseline and participants underwent a cognitive assessment at baseline and at follow-up after 4 years. Higher estradiol (total and bioavailable) and estrone levels were associated with an increased risk of cognitive decline in elderly men independent of age, cardiovascular risk factors, atherosclerosis, and APOE genotype. These findings do not support the hypotheses that higher levels of endogenous sex hormones preserve brain function

Sex hormones and male health: Effects on components of the frailty syndrome

Physicians are seeing an increasing number of older male patients with chronic diseases and conditions. However, the potential relevance of low levels of circulating endogenous androgens in connection with these diseases and conditions is generally poorly understood. Research findings have suggested that androgens play a distinct role in bone metabolism, body composition such as muscle and fat mass and fat distribution, cognitive functioning, mood and well being. The aim of this paper is to summarize the currently available data on the association between endogenous androgens and the intermediate or clinically manifest indicators of chronic conditions in men that might contribute to the phenomenon 'frailty'. The evidence that reductions in endogenous androgens play a role in age-related health problems is circumstantial. Therefore, large-scale randomized trials are needed to establish whether aging males with low serum androgen levels benefit from androgen supplementation

Selenium status and association with bone mineral density.

<p>Selenium status and association with bone mineral density.</p