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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic ovary syndrome is a syndrome and not a disease. It reflects multiple potential etiologies and variable clinical presentations that are reviewed in this article. In addition to menstrual dysfunction and hyperandrogenism, women with polycystic ovary syndrome also may have hypothalamic-pituitary abnormalities, polycystic ovaries on pelvic ultrasonography, infertility, obesity, and insulin resistance. A familial pattern occurs in some cases, suggesting a genetic component to the disorder. The three major pathophysiologic hypotheses that have been proposed to explain the clinical findings of the disorder as well as treatment options are reviewed in this article.
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PMID:Polycystic ovary syndrome. 992 12

Obesity is often associated with an impairment of the hypothalamic-pituitary-gonadal axis. The leptin-deficient ob/ob mouse model is characterized by a morbid obesity with a sterility in males and females that is corrected by continuous leptin treatment. Since ob/ob mice are maintained on the C57BL/6J inbred genetic background, we sought to determine whether their infertility can be corrected without leptin treatment but via the effect of modifier genes brought into the obese-sterile phenotype by a different genetic background. Thus, we generated via an F2 intercross ob/ob mice on a mixed C57BL/6J-BALB/cJ genetic background and assayed them for fertility by mating with wild-type C57BL/6J mice. Whereas genetically heterogeneous F2 obese females remained sterile like male and female C57BL/6J ob/ob mice, 41% of F2 C57BL/6J-BALB/cJ obese males were capable of reproducing despite a morbidly obese state. Therefore, the sterility of the original C57BL/6J ob/ob mouse model was genetically corrected independently of its obese state via the effects of modifier genes. Unlike testosterone levels, triglyceride levels, and testes weight-to-body weight ratios, which were all higher in fertile vs. sterile mice, glucose levels were similar in both groups, indicating that the underlying hyperglycemia of ob/ob mice was not an impediment to the onset of fertility. A genome-wide scan in F2 ob/ob males resulted in the localization of four modifier loci on chromosomes 1, 3, 5, and 14 with respective quantitative traits consisting of number of pregnancies, testes weights normalized to body weights, body weight at 8 weeks of age, and circulating testosterone. We conclude that the inheritance of modifier genes at the identified loci acts to promote fertility of otherwise sterile leptin-deficient obese male mice.
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PMID:Effect of the genetic background on the reproduction of leptin-deficient obese mice. 992

Galanin is a pleiotropic neuroendocrine signal produced in discrete subpopulations of neurons distributed in several sites in the hypothalamus. Neuropeptide Y and beta-endorphin also display pleiotropism, but they are produced by subpopulations of neurons located only in the arcuate nucleus of the hypothalamus. Each of these neuropeptides exerts a regulatory influence on reproduction and appetitive behavior. Experimental and morphologic evidence from our laboratory show direct contacts and interplay among these diverse signals. Seemingly, an interconnected network composed of these three neuropeptide-producing neurons provides precision and site specificity in the relay of information necessary to govern reproduction and appetite. Disruptions in this interplay are likely to manifest in untoward consequences such as infertility and obesity.
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PMID:Neuroendocrine interactions between galanin, opioids, and neuropeptide Y in the control of reproduction and appetite. 992 74

Women have a higher prevalence of obesity than men in most developed countries. Obesity affects many aspects of women's health by increasing risk for heart disease, diabetes, breast cancer, and infertility. One reason for the gender difference in obesity may be that fluctuations in reproductive hormone concentrations throughout women's lives uniquely predispose them to excess weight gain. Studies in experimental animals and women have shown that hormonal changes across the menstrual cycle affect calorie and macronutrient intake and alter 24-hour energy expenditure. Pregnancy is a significant factor in the development of obesity for many women. Various factors are associated with excess weight retention following pregnancy, including weight gain during pregnancy, ethnicity, dietary patterns, and interval between pregnancies. There is a need to tailor recommendations for energy intake during pregnancy to individual women, and recent evidence also suggests that the timing of weight gain during pregnancy is a critical factor. Menopause is also a high-risk time for weight gain in women. Although the average woman gains 2-5 pounds during menopausal transition, some women are at risk for greater weight gains. There is also a hormonally driven shift in body fat distribution from peripheral to abdominal at menopause, which may increase health risks in older women. Hormone therapies have varying impacts on body weight and fat distribution. In summary, hormonal fluctuations across the female life span may explain the increased risk for obesity in women. Awareness of these factors allows development of targets for prevention and early intervention.
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PMID:The influence of sex hormones on obesity across the female life span. 992 57

There is increasing evidence that leptin is a physiological link between obesity and infertility. Although leptin receptors have been demonstrated in human ovaries, there is no information regarding the effects of leptin on cells from developing ovarian follicles. To test the direct effects of leptin on human ovarian cells, granulosa cells (GC) and theca cells were isolated from the ovaries of regularly cycling women. Serum was obtained at the time of surgery, and follicular fluid was aspirated from the follicles before isolation of the ovarian cells. Leptin concentrations were similar in follicular fluid and serum. RT-PCR analysis demonstrated that the long, signaling form of the leptin receptor was expressed in both theca and GC. In cultured GC, leptin had no effect on estradiol production, alone or in the presence of FSH, but caused a concentration-related inhibition of the insulin-like growth factor I (IGF-I) augmentation of FSH-stimulated estradiol production. The effect of leptin was specific, because there was no effect on progesterone production. In cultured theca cells, leptin did not alter androstenedione production, alone or in the presence of LH. Leptin caused a concentration-related inhibition of the IGF-I augmentation of LH-stimulated androstenedione production. These data demonstrate that leptin can directly inhibit IGF-I action in ovarian theca and GC at concentrations commonly present in obese women.
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PMID:Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. 1008 97

The diseases of the ovary which most frequently cause infertility are: anovulation from follicular atresia, the empty follicle syndrome, the luteinized unruptured follicle syndrome; chronic anovulation syndromes, within which polycystic ovarian syndrome plays a major role; ovarian endometriosis. Sonography and Color Doppler US are the first choice procedures in the monitoring of ovarian cycles, which combined with serum hormone values, are able to identify possible changes in the physiologic sequence of the cycle. In follicular atresia, ovaries with minute follicles (3mm or less) and early disappearance of primary follicle are observed on sonography. The empty follicle syndrome characterized by the lack of oocytes within the primary follicle, is of difficult sonographic diagnosis, a possible sign being the missed visualization of cumulus oophorus. The luteinized unruptured follicle syndrome consists in the absence of oocyte expulsion from primary follicle persisting more than 48 hours after LH blood peak. Doppler spectra of blood flow in perifollicular ovarian arteries maintain the features of the follicular phase, i.e. low diastolic velocities and high resistances. Among chronic anovulation syndromes, hyper-and hypogonadotropism cause ovarian amenorrhea where ovaries are similar to those of women in menopause: small size, very few or absent follicles. The polycystic ovarian syndrome is characterized by an abnormal pulsatile GnRH release which causes LH hypersecretion and FSH hyposecretion. The latter is not able to stimulate the growth and maturation of follicles, while the former causes hyperandrogenism with hirsutism and obesity and is responsible for hypertrophy and stromal hyperechogenicity. The sonographic diagnosis of polycystic ovarian syndrome is based on standardized morphostructural signs as increased volume of the ovaries (> 10 cm3), the presence of numerous (> or = 10) peripheral microfollicles (< or = 5 mm) with hyperechoic stroma. The endometrial cyst, usually present in ovarian endometriosis is visualized with sonography as a round neoformation with ill-defined walls, filled with a uniformly hypoechoic, corpuscular, partly hemorrhagic fluid; less frequently the appearance is that of a more complex structure posing differential diagnostic problems, mainly with the hemorrhagic corpus luteum; both pathological conditions appear poorly vascularized at Color Doppler, with tracings of high resistance arterial flow. Among the procedures of second choice, CT can show the high blood density common to the two conditions while on MRI the signal is mostly hyperintense in T1-weighted sequences with areas of lower signal intensity in T2-weighted sequences.
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PMID:Ovarian factor infertility. 1019 67

Weight reduction and exercise have been shown to help with menstrual disturbance and infertility in obese women with polycystic ovary syndrome. We studied the relationship between insulin sensitivity and ovulation patterns in 18 infertile anovulatory obese polycystic ovary syndrome (PCOS) women (NO) with normal glucose tolerance, aged between 22-39 yr with a body mass index of 27-45 kg/m2, before and after a 6-month diet and exercise program. This program promotes healthy lifestyle factors, but does not lead to rapid weight loss. The anthropometric, metabolic, and endocrine factors of these subjects were compared to those of 10 age- and weight-matched PCOS women with regular monthly ovulation (RO). Before lifestyle modification, the anovulatory subjects had greater central obesity than regular ovulators, as assessed by percent central fat (NO, 45.7 +/- 0.8%; RO, 42.2 +/- 1.6%; P < 0.05), higher glucose increment after glucose challenge (NO, 10.1 +/- 1.0 mmol/L; RO, 6.4 +/- 1.1 mmol/L; P < 0.02), lower insulin sensitivity index (NO, 1.2 +/- 0.2; RO, 2.8 +/- 0.6 micromol/kg x min/pmol/L; P < 0.005), higher plasma LH (NO, 8.9 +/- 0.9; RO, 4.6 +/- 0.9 IU/L; P < 0.005), and lower plasma sex hormone-binding globulin (NO, 18.0 +/- 2.5; RO, 27.8 +/- 5.7 nmol/L; P < 0.05]. Anovulatory subjects were classified as responders (R) to the intervention if they regained ovulation during the study. As a result of intervention, R showed an 11% reduction in central fat, a 71% improvement in insulin sensitivity index, a 33% fall in fasting insulin levels, and a 39% reduction in LH levels. None of these parameters changed significantly in nonresponders (NR). At the end of the study, R had lower fasting insulin (R, 13.6 +/- 1.7; NR, 23.0 +/- 3.5 mU/L) and LH levels (R, 5.0 +/- 1.7; NR, 7.4 +/- 1.4 IU/L), but similar androgen levels compared to NR. We conclude that lifestyle modification without rapid weight loss leads to a reduction of central fat and improved insulin sensitivity, which restores ovulation in overweight infertile women with PCOS. Lifestyle modification is the best initial management for obese women seeking to improve their reproductive function.
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PMID:Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. 1019 97

Many adolescents present with hirsutism and irregular menses. The challenge for the clinician is to distinguish physiologic anovulatory cycles from true menstrual disorders such as PCOS, and to differentiate PCOS from other causes of hyperandrogenism in hirsute adolescents. Common clinical features seen in adolescents with PCOS include hirsutism, acne, menstrual irregularity, and obesity. Biochemical abnormalities include hyperandrogenism, acyclic estrogen production, LH hypersecretion, decreased levels of SHBG, and hyperinsulinemia. Management strategies for a patient with PCOS include treatment of features which may cause distress to the adolescent, such as hirsutism, acne, and irregular menses, and prevention of long-term sequelae. Oral contraceptive pills, antiandrogens, and cosmetic treatments are used to treat hirsutism, acne, and menstrual irregularity. Oral contraceptive pills or medroxyprogesterone acetate are given to prevent endometrial hyperplasia and carcinoma. Counseling about weight loss and nutrition are essential, as weight loss may improve signs of hyperandrogenism and menstrual irregularity and may prevent NIDDM and cardiovascular disease. Insulin-sensitizing agents show promise in terms of decreasing hyperandrogenism, restoring ovulatory cycles, treating infertility, and preventing long-term sequelae. Finally, it is important to recognize that adolescents with PCOS may experience psychological distress because of the clinical manifestations of hyperandrogenism or when confronted with the information that they have a chronic illness. Psychological support should be available for these young women. Future research is likely to further elucidate the pathophysiology of PCOS, identify candidate genes, and clarify which adolescents are at risk for long-term sequelae. Prospective studies are needed to identify which therapies could potentially reduce the risk of infertility, diabetes, cardiovascular disease, and endometrial carcinoma in young women with PCOS.
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PMID:Polycystic ovary syndrome. 1037 Jul 13

The frequency of endocrine abnormalities during the follicular phase in non-pregnant women with a history of recurrent abortion was investigated in a case-control study. A total of 42 consecutive women with recurrent spontaneous abortion (three or more consecutive abortions, mean +/- SD: 3.9 +/- 1.1 range 3-8) with no parental chromosome rearrangement or uterine abnormality were studied during the early follicular phase under standardized conditions. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, androstenedione, testosterone, dehydroepiandro-stenedione, 17-OH-progesterone, oestradiol, progesterone and thyroid stimulating hormone (TSH) were measured by commercially available radioimmunoassays. Controls were 42 nulligravid females with tubal or male factor infertility without miscarriage. Mean (SD) concentrations of prolactin and androstenedione were 14.2 +/- 6.7 ng/ml versus 10.5 +/- 3.5 ng/ml (95% CI 0.8-6.1) and 2.3 +/- 0.9 ng/ml versus 1.7 +/- 0.6 ng/ml (95% CI 0.2-0.9) in the study and control groups respectively. The other endocrine parameters were comparable in both groups. Obesity [BMI weight (kg)/height (m2) > or = 25] was more prevalent (23 versus 5 women, P = 0.0001) in the study than the control group. Recurrent spontaneous abortion is associated with abnormalities in prolactin and androgen secretion during the follicular phase, suggesting an endocrine aetiology in this disorder. Reduction of body weight and correction of hyperprolactinaemia and of hyperandrogenism may reduce the rate of miscarriage in a subsequent pregnancy in these women.
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PMID:Endocrine abnormalities during the follicular phase in women with recurrent spontaneous abortion. 1037 87

The importance of genetic factors in obesity is under investigation. During the last few years, our understanding of the regulation of body weight in mammals has broadened to include several new proteins based on the cloning of genes from rodent mutants and characterization of their effects on energy stores and metabolism. Since its discovery in 1994, leptin has been acknowledged as an adipocyte-derived signal molecule, able to limit food intake and increase energy expenditure by interacting with specific leptin receptors located in the central nervous system and in peripheral tissues. Leptin is also important for growth, reproduction and neuroendocrine signalling. Although leptin is mainly synthesized in adipocytes, it is also expressed in the placenta, epithelium of the stomach and breast glands and, under certain conditions, in skeletal muscles. The importance of leptin is demonstrated by the discovery of mutations in the genes encoding leptin and its receptor among some subjects with morbid obesity and infertility. Plasma concentration of leptin should be measured in obese infertile adolescents since replacement could be curative among individuals with leptin deficiency.
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PMID:[Leptin--a fatty tissue hormone with many functions]. 1039 77


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