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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.

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Cushing syndrome (CS), characterised by endogenous or exogenous glucocorticoid hormone excess, is associated with several systemic complications, including impaired glucose metabolism, which often becomes clinically manifest as diabetes mellitus (DM). In addition, CS can harm the arterial wall because of hyperglycaemia, dyslipidaemia, hepatic steatosis, and central obesity. These metabolic disorders promote atherosclerosis by synthesising adipokines, leptin, and proinflammatory cytokines. Lower limb arterial complications in CS are common and significantly impact morbidity and mortality. Furthermore, CS, in combination with DM, is likely to cause more diffuse vascular disease that predominantly affects distal arterial beds. In conclusion, CS promotes atherosclerosis, including peripheral artery disease, by causing functional and morphological deterioration of the arterial vessel wall and increasing the presence of classical risk factors of atherosclerosis.

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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/m2 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.

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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.

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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.

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AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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