Lifestyle measures (LSMs) should be the first-line approach offered for obesity-related functional hypogonadism (FH). When LSMs fail, the role of testosterone replacement treatment (TRT) is unclear. ...GLP1 receptor agonist liraglutide is linked to progressive and sustained weight loss. A potential direct impact of GLP1 on hypothalamus-pituitary-testicular (HPT) axis was reported in animal models. We aimed to compare the effects of liraglutide and TRT on FH in obese men that had been poor responders to LSM, by means of reversal of FH and weight reduction. We designed a 16-week prospective randomized open-label study with 30 men (aged 46.5 ± 10.9 years, BMI 41.2 ± 8.4 kg/m2, mean ± s.d.) that were randomized to liraglutide 3.0 mg QD (LIRA) or 50 mg of 1% transdermal gel QD (TRT). Sexual function and anthropometric measures were assessed. Fasting blood was drawn for determination of endocrine and metabolic parameters followed by OGTT. Model-derived parameters including HOMAIR and calculated free testosterone (cFT) were calculated. Total testosterone significantly increased in both arms (+5.9 ± 7.2 in TRT vs +2.6 ± 3.5 nmol/L in LIRA) and led to improved sexual function. LIRA resulted in a significant increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P < 0.001 for between-treatment effect). Subjects treated with LIRA lost on average 7.9 ± 3.8 kg compared with a 0.9 ± 4.5 kg loss in TRT (P < 0.001). Metabolic syndrome was resolved in two patients in LIRA and in no subjects in TRT. Liraglutide was superior to TRT in improving an overall health benefit in men with obesity-associated FH after LSM failed.
Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are increasingly recognised for their role in cardiovascular (CV) physiology. The GH-IGF-1 axis plays an essential role in the development ...of the CV system as well as in the complex molecular network that regulates cardiac and endothelial structure and function. A considerable correlation between GH levels and CV mortality exists even among individuals in the general population without a notable deviation in the GHIGF- 1 axis functioning. In addition, over the last decades, evidence has demonstrated that pathologic conditions involving the GH-IGF-1 axis, as seen in GH excess to GH deficiency, are associated with an increased risk for CV morbidity and mortality. A significant part of that risk can be attributed to several accompanying comorbidities. In both conditions, disease control is associated with a consistent improvement of CV risk factors, reduction of CV mortality, and achievement of standardised mortality ratio similar to that of the general population. Data on the prevalence of peripheral arterial disease in patients with acromegaly or growth hormone deficiency and the effects of GH and IGF-1 levels on the disease progression is limited. In this review, we will consider the pivotal role of the GH-IGF-1 axis on CV system function, as well as the far-reaching consequences that arise when disorders within this axis occur, particularly in relation to the atherosclerosis process.
Polycystic ovary syndrome (PCOS) is a polyendocrine disorder and the most common endocrinopathy in women of reproductive age. Affected women have an elevated prevalence of being overweight and obese. ...Our study sought to determine how weight loss associated with lifestyle changes affects the endometrium specific proteome, endocrine-metabolic characteristics, and motor capabilities of obese women with PCOS and infertility. A group of 12 infertile women under the age of 38 with PCOS and BMI ≥30 kg/m
2
were included in the study. An evaluation was performed by a gynecologist and an endocrinologist. The weight-loss program lasted 8 weeks under the guidance of a professional trainer. Endometrial sampling during a period of implantation window for proteome determination was performed before and after weight loss. In endometrial samples at the end of the study increased protein abundance was recorded for Legumain, Insulin-like growth factor-binding protein 7, Hepatocyte growth factor receptor, Keratin, type II cytoskeletal 7, and Cystatin-B, while the B-lymphocyte antigen CD20 protein abundance decreased. Our results also indicate significantly lowered fasting blood glucose level and free testosterone concentration and significant improvements in body composition and physical capacity. This study may open up the venues for investigating important biomarkers that may affect endometrial receptivity.
Clinical Trial Registration
https://clinicaltrials.gov/ct2/show/NCT04989244?term=NCT04989244&draw=2&rank=1
, identifier: NCT04989244.
Context
: The presence of several cardiovascular risk factors is observed in women with polycystic ovary syndrome (PCOS). On the other hand, the QTc interval duration, which is related to cardiac ...arrhythmia and sudden death, has not been investigated thoroughly in PCOS population.
Objective
: To investigate QTc interval duration and its relation to testosterone in women with PCOS.
Design
: Cross sectional case-control study.
Setting
: Outpatient setting, tertiary university medical centre.
Patients
: We enrolled 119 consecutive patients in whom PCOS was diagnosed based on oligomenorrhea, infertility (>2 yr), ineffective ovarian stimulation, and ultrasonographic criteria. The control group (controls) included 64 age-matched healthy women without clinical or laboratory evidence of PCOS.
Interventions
: In all participants we measured QTc interval duration on a standard electrocardiogram and determined plasma levels of high sensitivity C-reactive protein (hsCRP), endothelin-1 (ET-1), insulin, and testosterone.
Main outcome measure
: Shorter QTc interval duration in PCOS patients.
Results
: When compared to controls, PCOS patients displayed higher values of hsCRP (2.35±2.14 mg/l
vs
1.18±1.24 mg/l;
p
=0.01), ET-1 (23.6±10.3 ng/l
vs
12.9±20.7 ng/l;
p
=0.03), insulin (18.5±7.8 mIU/l
vs
10.7±9.1 mIU/l;
p
=0.02), and testosterone (2.7±2.1 nmol/l
vs
1.4±1.7 nmol/l;
p
=0.01). QTc interval in PCOS patients was significantly shorter than in controls (401±61 msec
vs
467±61 msec;
p
=0.007), and inversely related to the plasma levels of testosterone (Spearman −0.45,
p
=0.005).
Conclusions
: QTc interval in PCOS patients is short, and inversely associated with increased levels of testosterone. QTc interval duration is not part of an adverse cardiac risk profile in PCOS.
Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal ...(HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.
•A new platform for the integrated assessment of waste heat recovery is presented.•The platform assesses physical, techno-economic, market and business dimensions.•The platform achieves robust ...results within a short time-frame.•The new platform aims to help untapping the large waste heat potential.
At a time when European countries try to cope with escalating energy prices while decarbonizing their economies, waste heat recovery and reuse arises as part of the solution for sustainable energy transitions. The lack of appropriate assessment tools has been pointed out as one of the main barriers to the wider deployment of waste heat recovery projects and as a reason why its potential remains largely untapped.
The EMB3Rs platform emerges as an online, open-source, comprehensive and novel tool that provides an integrated assessment of different types of waste heat recovery solutions, (e.g. internal or external) and comprises several analysis dimensions (e.g. physical, geographical, technical, market, and business models). It has been developed together with stakeholders, and tested in a number of representative contexts, covering both industrial and heat network applications. This has demonstrated the enormous potential of the tool in dealing with complex simulations, while delivering accurate results within a significantly lower time-frame than traditional analysis.
The EMB3Rs tool removes important barriers such as analysis costs, time and complexity for the user, and aims at supporting a wider investment in waste heat recovery and reuse by providing an integrated estimation of the costs and benefits of such projects. This paper describes the tool and illustrates how it can be applied to help unlock the potential of waste heat recovery across European countries.
Atherosclerosis is considered a systemic disease. Therefore, in patients with atherosclerotic disease effects on various sections of the arterial system are expected. The aim of our study was to ...determine whether patients with evident peripheral arterial occlusive disease (PAOD) of the lower limbs have any subclinical functional or structural arterial wall changes in other sections of the arterial system.
The study included 54 patients with PAOD, Fontaine stage II and a claudication distance from 50 to 500 m (average 250+/-170 m). Their mean age was 64. None of them had any symptoms or signs of coronary or cerebrovascular atherosclerosis (CVD). The control group consisted of 50 healthy volunteers with a mean age of 64 years without any risk factors of atherosclerosis. In all subjects the carotid intima-media thickness (IMT), was measured, the presence of atherosclerotic plaques in the carotid artery (CA) was registered and the endothelium-dependent dilation capability of the brachial artery (BA) during reactive hyperemia was measured using the B-mode ultrasound technique.
The average IMT was significantly greater in PAOD patients than in controls (0.8+/-0.2 mm vs 0.6+/-0.1 mm, p<0.001). In patients atherosclerotic plaques in the CA were also more numerous than in controls (38 vs 4, p<0.001). The IMT of patients was related to body mass index (BMI), ankle-brachial pressure index (ABI), LDL cholesterol and to the number of atherosclerotic plaques. In PAOD patients flow-mediated dilation of the BA was significantly lower than in controls (7.2+/-4.9% vs 12.3+/-2.1%, p<0.001). The dilation capability of the BA was linearly related to the BMI, ABI and IMT.
The results of our study show that PAOD patients without clinical evidence of CVD have morphological changes of the CA, increased IMT and numerous atherosclerotic plaques. Furthermore, in PAOD patients flow-mediated endothelium-dependent dilation of the peripheral arteries is decreased. These results support the hypothesis that atherosclerosis is a generalized disease, leading to functional and structural changes in several segments of the arterial system.
Abstract A focused surgical approach based on pre-operative localization replaced the classical four-gland exploration in patients with primary hyperparathyroidism (PHP). Sestamibi scanning and ...ultrasound are most often used localization modalities with reported sensitivity of 54–100% for identification of single gland disease. The aim of this study was to analyze the results of pre-operative localization with1 ⁸F-Fluorocholine PET/CT (FCh-PET) in patients with PHP.A retrospective review of 151 patients with PHP who underwent surgery after pre-operative localization with FCh-PET was performed. Only a focused parathyroidectomy without ioPTH testing had been done in patients with single adenoma on FCh-PET. Primary outcome was operative failure, defined as persistent PHP. According to pre-operative FCh-PET 126 (83,4%) patients had single adenoma, 22 (14,5%) multiglandular disease and the test was negative in only two patients. Intraoperative failure experienced 4/126 patients (3,3%) with single adenoma. Removed parathyroid glands were normal in three and hyperplastic in one patient with intraoperative failure. A limited bilateral neck exploration with ioPTH testing was used in 14/22 patients with double adenoma according to pre-operative FCh-PET. In 6/14 patients surgery confirmed double adenoma while 8 patients had only a single adenoma and all 14 patients were cured. A classical four-gland exploration without ioPTH testing was used in 8/22 patients with more than two pathological glands according to pre-operative FCh-PET. All 8 patients had hyperplasia and two experienced intraoperative failure. In two patients with negative FCh-PET a classical four-gland exploration without ioPTH testing was used. One patient had a single adenoma and was cured and only normal parathyroid glands were found in the other patient with intraoperative failure.A preoperative localization with FCh-PET is a reliable test in patients with PHP. Patients with a single adenoma on FCh-PET can safely undergo a focused parathyroidectomy without ioPTH testing.
PDF
