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Query: UMLS:C0497406 (overweight)
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The endocannabinoid system (ECS) is a lipid signalling system, comprising of the endogenous cannabis-like ligands (endocannabinoids) anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which derive from arachidonic acid. These bind to a family of G-protein-coupled receptors, called CB1 and CB2. The cannabinoid receptor 1 (CB1R) is distributed in brain areas associated with motor control, emotional responses, motivated behaviour and energy homeostasis. In the periphery, the same receptor is expressed in the adipose tissue, pancreas, liver, GI tract, skeletal muscles, heart and the reproduction system. The CB2R is mainly expressed in the immune system regulating its functions. Endocannabinoids are synthesized and released upon demand in a receptor-dependent way. They act as retrograde signalling messengers in GABAergic and glutamatergic synapses and as modulators of postsynaptic transmission, interacting with other neurotransmitters. Endocannabinoids are transported into cells by a specific uptake system and degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS is involved in various pathophysiological conditions in central and peripheral tissues. It is implicated in the hormonal regulation of food intake, cardiovascular, gastrointestinal, immune, behavioral, antiproliferative and mammalian reproduction functions. Recent advances have correlated the ECS with drug addiction and alcoholism. The growing number of preclinical and clinical data on ECS modulators is bound to result in novel therapeutic approaches for a number of diseases currently treated inadequately. The ECS dysregulation has been correlated to obesity and metabolic syndrome pathogenesis. Rimonabant is the first CB1 blocker launched to treat cardiometabolic risk factors in obese and overweight patients. Phase III clinical trials showed the drug's ability to regulate intra-abdominal fat tissue levels, lipidemic, glycemic and inflammatory parameters. However, safety conerns have led to its withrawal. The role of endocannabinoids in mammalian reproduction is an emerging research area given their implication in fertilization, preimplantation embryo and spermatogenesis. The relevant preclinical data on endocannabinoid signalling open up new perspectives as a target to improve infertility and reproductive health in humans.
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PMID:Endocannabinoid system: An overview of its potential in current medical practice. 1967 19

Polycystic Ovary Syndrome (PCOS) represents a common endocrinopathy, with anovulation and hyperandrogenism as cardinal symptoms. In recent years it has been recognized that insulin resistance is an intrinsec feature of the disorder and plays a central role in pathogenesis. PCOS is associated with important reproductive morbidity as shown by high prevalence of anovulatory infertility, spontaneous abortion, gestational diabetes and preeclampsia. The association of insulin resistance with this reproductive pathology has been well documented. Due to major implication of insulin resistance in PCOS pathogenesis, insulin reduction strategies were studied as a possible treatment for infertility in PCOS patients. Weight loss, even modest was proved to be a simple and efficient method to improve reproductive parameters in PCOS patients and should be recommended to all overweight and obese patients with infertility. Metformin was showed to induce ovulation, at least in a subset of patients with PCOS, but there are not unequivocal proves concerning its efficacy for pregnancies and live-birth rate, mainly because few trials studied this aspect. Therefore there are not enough evidences to recommend metformin for infertility treatment in PCOS. Few small studies with newer thiazolidindiones suggest their efficacy for ovulation induction, but further extensive studies are needed to confirm these results. In conclusion, reduction of insulin resistance was proved to ameliorate ovulation rate in PCOS patients, but strong evidences to sustain the utility of insulin-sensitizing drugs as a therapeutic option for infertility are lacking. Future studies are needed to elucidate these aspects and to characterize the particular subtype of patients with higher probability to respond to this treatment.
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PMID:Insulin resistance and fertility in polycystic ovary syndrome. 2010 21

The results of several studies point to an increased likelihood of abnormal semen parameters among overweight men, and an elevated risk for subfertility among couples in which the male partner is obese. Obesity is, therefore, associated with a higher incidence of male factor infertility. Several mechanisms might account for the effect of obesity on male infertility, both directly and indirectly, by inducing sleep apnea, alterations in hormonal profiles (reduced inhibin B and androgen levels accompanied by elevated estrogen levels) and increased scrotal temperatures, ultimately manifesting as impaired semen parameters (decreased total sperm count, concentration and motility; increased DNA fragmentation index). Neither the reversibility of obesity-associated male infertility with weight loss nor effective therapeutic interventions have been studied in-depth. The increasing prevalence of obesity calls for greater clinical awareness of its effects on fertility, better understanding of underlying mechanisms, and exploration into avenues of treatment.
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PMID:The effect of obesity on sperm disorders and male infertility. 2015 5

The prevalence of people who are overweight or obese has increased dramatically in high-income countries over the past 20 years. There is a strong association between obesity and infertility, and weight loss can result in increased fecundity in obese women. The aim of this study is to demonstrate the potential role of intragastric balloon in the treatment of obese-related infertility. This is a retrospective study. A chart review of 27 obese women seen between September 2003 and July 2008 was performed. They all presented with the diagnosis of infertility and had undergone endoscopic intragastric balloon positioning. Among these women who tried unsuccessfully to become pregnant before weight loss, 15 became pregnant afterward. The pregnancies proceeded without complications and ended with live births. An improvement in the fertility status after weight loss has been described, although data on fertility after weight loss following bariatric surgery are still limited. The results obtained in our experience are not different from data reported in literature for bariatric surgery. Therefore, balloon treatment might be effective in young infertile obese women who wish to become pregnant.
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PMID:The potential role of intragastric balloon in the treatment of obese-related infertility: personal experience. 2041 39

Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders of reproductive age women. The main signs of PCOS are as follows: androgen excess, menstrual dysfunction, infertility, obesity, and other numerous health problems. By different authors, the disorder affects 2-28% of reproductive age women. Polycystic ovary syndrome is characterized by presence of hyperandrogenism, anovulation, menstrual cycle disturbances, also by the other metabolic changes. The lack of well-defined and universally accepted diagnostic criteria makes identification of this syndrome confusing to many clinicians. There are only few studies concerning the correlations between phenotypic expression, body composition and PCOS, and relationship with the processes of growth and sexual maturation and various environmental factors (nutrition, physical activity, stress, and other factors). There is a lack of knowledge about further PCOS development and prognosis, considering the individual and environmental factors. Variation in human body composition and shape ranges considerably: many body size and shape indices (height, weight, body composition, and proportions) are the result of long evolution process and adaptation to environment. Obviously, the morphological body parameters, physiological and biochemical indices are complex and compound the interdependent system. By current literature, more than 50% of women are overweight or obese. If waist circumference and waist-to-hip ratio of women with PCOS increase, reproductive function and metabolic state of a woman is altered more than in cases when there are no changes in these parameters. The investigations of the strongest sexual dimorphism sign--the subcutaneous and visceral fat topography--showed that women with PCOS have greater adipose tissue mass in the areas of the abdomen, waist, and upper arms than control women. It is known that some indices of sexual dimorphism may be considered as the morphological signs of hyperandrogenism, for example handgrip, waist-to-hip ratio, hand and foot length, 2nd-to-4th digit (finger length) ratio (2D:4D), certain facial characteristics. Only 2D:4D ratio was investigated for the women with PCOS. The early changes of certain morphological and other indices of physical status could help to predict some metabolic characteristics, development of PCOS, and outcome of this syndrome.
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PMID:[Body composition and polycystic ovary syndrome]. 2044 89

Polycystic ovary syndrome (PCOS) is characterized by the presence of polycystic ovaries, menstrual dysfunction, infertility and biochemical and clinical hyperandrogenism and is associated with an increased prevalence of cardiometabolic risk factors and psychological problems. Despite the well-established benefits of exercise training and its recommendation as a cornerstone of PCOS management, few well-controlled randomized studies have been conducted evaluating the benefits of exercise training and specific exercise regimes in women with PCOS. From the limited studies there appears to be a beneficial effect of exercise either alone or in combination with energy restriction has shown to improve fitness, cardiovascular, hormonal, reproductive and psychological outcomes. While the addition of regular exercise to energy restriction appears to only have additional benefits for improving body composition, these greater improvements are likely to have long-term implications. While lifestyle modification including regular exercise appears to be an effective strategy for the management of overweight PCOS women, methodological limitations in the studies limit the generalizability of the findings. Future research with rigorous study designs is needed to determine specific exercise guidelines that will provide the greatest benefit for these women.
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PMID:Exercise for the treatment and management of overweight women with polycystic ovary syndrome: a review of the literature. 2054 40

The rising prevalence of obesity has had a profound impact on female reproductive health. Increased body mass index (BMI) is associated with ovulatory subfertility and anovulatory infertility. Overweight and obese women have poorer outcomes following fertility treatment. They respond poorly to clomiphene induction of ovulation and require higher doses of gonadotrophins for ovulation induction and superovulation. Ovarian stimulation for assisted reproduction produces fewer follicles resulting in the harvest of fewer oocytes. Fertilization rates are poorer and the embryo quality is impaired in younger women who are obese. Pregnancy rate in some studies is lower and there is an increased risk of early pregnancy loss. Weight loss regularizes menstrual cycles and increases the chance of spontaneous ovulation and conception in anovulatory overweight and obese women. Gradual sustained weight loss is beneficial whereas crash dieting is detrimental.
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PMID:The impact of female obesity on the outcome of fertility treatment. 2120 48

Obesity and overweight are not only problem of developed nations but also increasing problem in developing countries with health consequence. Studies have highlighted the link between obesity, infertility and adverse reproductive health outcome. Obesity contribute majorly to two most common medical risks in pregnancy: diabetes and hypertension. Is is associated with increasesd risk of large-for-gestational age and hypertensive disorders, including pre-eclampsia, which may be associated with low birth weight. Combination of factors viz individual lifestyle, environmental and genetic play role in obesity. Weight loss has demonstrated to improve fertility in obese women through recovery of spontaneous ovulation, and improved response to ovarian stimulation in infertility treatment. Therefore, weight management intervention, should be considered for overweight and obese infertile women.
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PMID:Obesity and reproductive performance in women. 2149 6

Hypogonadotropic hypogonadism (HH) is characterised by delayed puberty and infertility. Congenital HH comprises Kallmann syndrome with hypo-/anosmia and idiopathic HH (IHH). The genetic origin remains unknown in most cases, but the defective GnRH receptor gene (GNRHR) accounts for a considerable proportion of IHH. Here we describe a pair of siblings diagnosed with IHH. Aged 17 years, the boy was referred because of short stature (162 cm) and overweight (62.5 kg). He presented no signs of puberty, bone age of 14.5 years and insulin resistance. His sister, aged 16 years, also displayed delayed puberty. She was 166 cm tall and weighed 52 kg; her bone age was 12.5 years. Pelvic ultrasonography showed an infantile uterus and fibrous ovaries. In both siblings, serum gonadotropins were extremely low, and non-responsive to GnRH. Testosterone (1.38 nmol/l) and IGF1 (273 ng/ml) were decreased in the boy, although the girl did not present IFG1 deficiency. Her serum oestradiol was 10 pg/ml. MRIs of the hypothalamo-pituitary region and olfactory bulbs revealed them to be normal. The patients' sense of smell was unaltered. Their parents appeared to be first degree cousins. Considering the clinical data and potentially autosomal recessive HH transmission, the GNRHR gene was screened. The siblings turned out to be homozygous for the G416A transition, which had previously been identified in other HH individuals. The parents were heterozygous mutation carriers. The proband, moderately responding to LH, was started on low dose testosterone replacement, and his sister on transdermal oestradiol. Molecular data indicative of GnRH resistance could guide their future therapy should they desire fertility restoration. Further observations of the male patient may provide insights into androgen's influence on body mass, growth and insulin sensitivity.
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PMID:Hypogonadotropic hypogonadism due to GnRH receptor mutation in a sibling. 2171 11

Thyroid hormones, which influence body metabolism and development, could be affected by persistent organic pollutants. We sought to examine the relationship between polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) and thyroid disease. We employed incidence density sampling to perform a nested case control analysis of the Michigan Long-Term PBB Cohort. Cohort members (n=3333) were exposed to PBBs through contaminated cattle feed in 1973-1974 and to PCBs through daily life. Those with detectable serum PBB and PCB concentrations at enrollment were categorized into tertiles of PBB and PCB exposure. Case-patients were cohort members answering "Yes" to "Has a healthcare provider ever told you that you had a thyroid problem?" during follow-up interviews; control-patients were cohort members answering "No". We used odds ratios (OR) with 95% confidence intervals (CI) to compare odds of thyroid disease by PBB and PCB exposure and by various risk factors. Total cumulative thyroid disease incidence after 33 years was 13.9% among women and 2.6% among men. After adjusting for body mass index, we found no statistically significant differences in odds of any type of thyroid disease among women or men with elevated PBB or PCB exposure. Compared to control-patients, women with thyroid disease had increased odds of being overweight/obese (OR=2.82, 95% CI: 1.94-4.11) and developing infertility (OR=1.71, 95% CI: 1.08-2.69), diabetes (OR=1.61, 95% CI: 1.04-2.51), or arthritis (OR=1.71, 95% CI: 1.18-2.50) during follow-up. Additional research should explore potential associations between PBBs/PCBs and thyroid disease among children exposed in utero.
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PMID:Incidence of thyroid disease following exposure to polybrominated biphenyls and polychlorinated biphenyls, Michigan, 1974-2006. 2173 18


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