Cardiovascular Disease and Metabolic Syndrome in Infertility

Dyslipidemia and hypertension are frequent symptoms in infertile couples. These symptoms in compilation with other as central obesity and insulin resistance are part of the well-known metabolic syndrome (MS). Initially MS was used to predict cardiovascular disease, it is now clear that the molecular and physiologic abnormalities seen in metabolic syndrome extend well beyond the cardiovascular system. Growing evidence has linked MS and its individual symptoms to the increasing prevalence of infertility [1]. Hypertension and dyslipidemia increase the risk of long-term cardiovascular disease in type 2 diabetes [2], which are disproportionally more harmful in lowand middle-income countries than in high-income countries [3].


Introduction
Dyslipidemia and hypertension are frequent symptoms in infertile couples. These symptoms in compilation with other as central obesity and insulin resistance are part of the well-known metabolic syndrome (MS). Initially MS was used to predict cardiovascular disease, it is now clear that the molecular and physiologic abnormalities seen in metabolic syndrome extend well beyond the cardiovascular system. Growing evidence has linked MS and its individual symptoms to the increasing prevalence of infertility [1]. Hypertension and dyslipidemia increase the risk of long-term cardiovascular disease in type 2 diabetes [2], which are disproportionally more harmful in low-and middle-income countries than in high-income countries [3].
The relationship between androgen deficiency and atherosclerosis is controversial. Studies suggest that androgen deficiency is associated with increased triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in infertile men. The androgen therapy has been associated with increased levels of high-density lipoprotein cholesterol HDL-C and may improve reverse cholesterol transport [4]. The incidence of obesity (18%), overweight (30.2%), diabetes mellitus (4.7%), glucose intolerance (15%), hypertension (26%) and dysplipidemia (65%) was observed en infertile men. The dyslipidemia was isolated hypercholesterolemia, isolated triglyceridemia or both. In them a positive correlation between estradiol (E2) and follicle-stimulating hormone (FSH) was observed when estradiol levels exceed 50pg/mL [5]. In men with coronary artery disease Gensini score (to reflect the extent and severity of coronary atherosclerosis) didn´t show correlation neither with the number of involved segments nor with the androgen levels. TGs, TC and LDL-C levels also had no correlation with testosterone (T), free-testosterone (FT) nor dehydroepiandrosterone-sulphate (DHEA-S). However, FT showed negative correlation with lipoprotein (a) and C-reactive protein [6].
Another heart disease recently associated with hormonal changes is atrial fibrillation, which is the most common serious abnormal heart rhythm, and a frequent cause of ischaemic stroke. Increase T serum levels were associated with lower risk in men and

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Wings to the Research with higher risk in women. So that low testosterone levels are associated with increased risk of future atrial fibrillation and/or ischaemic stroke in men, while they are protective in women [7].
Low T serum levels are observed among men with Type 2 Diabetes Mellitus and are inversely related to insulin resistance. T in diabetic men has been inversely related to body mass index (BMI), waist circumference, and glucose tolerance, pre and post insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) [8]. BMI has positive relation with the value of systolic blood pressure, ratio LH/FSH and T, and negative correlation with FSH and PRL in infertile woman with polycystic ovary (PCO). Last patients with BMI >24kg/m 2 showed higher systolic pressure and DHEA-S and post insulinemia levels in comparison with a <24kg/ m 2 group [9]. Other associations have been observed in males with hypertension, the link between insulin sensitivity and hypothalamic-pituitary-gonadal axis is maintained along the entire spectrum of glucose tolerance [8]. Obesity can be related to cardiovascular, metabolic problems, prostate dysfunction, and declining on sperm parameters in morbid obesity. Oxidative stress, hormonal and metabolic changes increase as adiposity progresses in an individual, so we may expect infertility, prostate pathologies could be avoided if hyperadiposity in infertile men is controlled opportunely [10].
It is necessary to keep in mind that cardiovascular diseases can be influenced by sex hormones, such as other types of hormones. T is a pleiotropic hormone that plays an important role in the human body. Through its conversion to E2, T affects bone health, including bone density. There has been a renewed interest in the systemic role of T in pain, well-being, and cardiovascular function in women and men alike. It´s necessary to revisit the clinical role of T given its potential for applications to treat mood, cognitive health, and other illnesses, and its anabolic role in bone and muscle; it must also be treated carefully when taking into account the risks of its excessive use [11]. In native men from high altitudes it has been observed that higher serum T levels are associated with excessive erythrocytosis and with lower sperm motility [12]. Endocrine regulation in cardio-vascular system (CVS) may occur in many ways. Apart from hormones usually connected with CVS regulation, other more can act on it. A few of these act directly through specific receptors in heart or vessel wall cells, whereas some act indirectly -stimulating other neuroendocrine factors. Additionally, novel mechanisms of signal transduction have been discovered for steroid and thyroid hormones, which are independent of gene transcription regulation and are -known as "nongenomic". It´s difficult to exclude other type of hormones such as urotensin II, endothelins, angiotensin II, catecholamines, aldosterone, antidiuretic hormone, glucocorticosteroids, thyroid hormones, growth hormone and leptin that increase blood pressure. Also the decrease of hypotensive substances as natriuretic peptides, the calcitonin gene-related peptide (CGRP) family, angiotensin 1-7, substance P, neurokinin A, ghrelin, Parathyroid hormone-related protein (PTHrP) and oxytocin which could be too involved. But the particular effect of mediator depends on many circumstances i.e., hormone concentration and the receptor type. It may also undergo contraregulation. The majority of these hor-mones play an important role in the pathogenesis of CVS diseases', which can result in the development of new medicines [13].

Conclusion
Metabolic syndrome may be the main or associated cause of reproductive failure and cardiovascular disorders, but the possible interactions that exist between the systems must be focused on each patient individually.