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

To evaluate the effect of menopause and estrogen replacement therapy on leptin levels, 17 white postmenopausal women were recruited for the study. After an overnight fasting, blood samples were collected for LH, FSH, estradiol, testosterone, androstenedione, DHEA sulfate, insulin and leptin assays. Body mass index (BMI) and the waist-to-hip ratio were also evaluated. Patients were reanalyzed after a 12-week administration of transdermal estrogen patches delivering 50 microg 17beta-estradiol. The results were compared to those obtained from a group of 11 female volunteers in reproductive age, in whom basal blood was sampled during the early follicular phase of their cycle. Patients were divided into lean and obese according to their BMI. Obese postmenopausal women showed lower leptin levels when compared to premenopausal counterparts (25.1 +/- 5.9 vs. 37 +/- 11.3; p < 0.05), whereas no significant differences were found between the lean groups (14.5 +/- 3.8 vs. 14.4 +/- 4.9). Estrogen administration did not significantly change serum leptin concentrations in hypoestrogenized women (obese: 25.1 +/- 5.9 vs. 28. 6 +/- 9.2; lean: 14.4 +/- 4.9 vs. 17.6 +/- 7.2). A positive linear correlation was found between leptin plasma levels and BMI only in obese patients (r = 0.58; p < 0.01) both before and after estrogen treatment. Menopause is characterized by a decreased expression of the obese gene, even if estrogens do not seem to represent a main causal factor.
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PMID:Leptin levels in menopause: effect of estrogen replacement therapy. 1096 5

Estrogen regulates the amount of white adipose tissue (WAT) in females, but its role in males and whether WAT effects involve estrogen receptor-alpha (ERalpha) or ERbeta were unclear. We analyzed the role of ERalpha in WAT and brown adipose tissue by comparing these tissues in wild-type (WT) and ERalpha-knockout (alphaERKO) male and female mice. Brown adipose tissue weight was similar in alphaERKO and WT males at all ages. Progressive increases in WAT were seen in alphaERKO males with advancing age. Epididymal, perirenal, and inguinal WAT weighed 139-185% more in alphaERKO than in WT males by 270-360 days of age. Epididymal and perirenal adipocyte size was increased 20% in alphaERKO males. Adipocyte number was 82-168% greater in fat pads of alphaERKO vs. WT males. Compared with WT, 90-day-old alphaERKO females had increases in fat pad weights (54-103%), adipocyte size, and number. Both alphaERKO males and females had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase. Energy intake was equal in WT and alphaERKO males, indicating that obesity was not induced by hyperphagia. In contrast, energy expenditure was reduced by 11% in alphaERKO compared with WT males, indicating that altered energy expenditure may be important for the observed obesity. In summary, ERalpha absence causes adipocyte hyperplasia and hypertrophy, insulin resistance, and glucose intolerance in both sexes. These results are evidence that estrogen/ERalpha signaling is critical in female and male WAT; obesity in alphaERKO males involves a mechanism of reduced energy expenditure rather than increased energy intake.
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PMID:Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. 1107 86

Estrogen replacement therapy (ERT) increases a woman's risk of developing endometrial cancer approximately 120% for each 5 years of use. ERT increases a woman's risk of developing breast cancer approximately 10% for each 5 years of use. To reduce the greatly increased endometrial cancer risk, progestins have been added to ERT (estrogen-progestin replacement therapy; EPRT) for between 5 and 15 days (usually 7 or 10 days) per month in a sequential fashion (sequential EPRT; SEPRT) or with each dose of ERT (continuous-combined EPRT; CEPRT). We conducted two large case-control studies in postmenopausal women in Los Angeles to evaluate the effects of these changes on endometrial and breast cancer risks. As expected CEPRT was not associated with any increased risk of endometrial cancer. SEPRT with the progestin being given for 10 days per month also did not increase endometrial cancer risk. SEPRT with the progestin being given for 7 days per month did increase endometrial cancer risk with only a relatively slight reduction in risk compared to ERT effectively proportional to the reduction in the number of days of unopposed estrogen. The sharp contrast between the effects of 7 days and 10 days of progestin in SEPRT suggests that the extent of endometrial sloughing or of 'terminal' differentiation at the completion of the progestin phase may play a critical role in determining endometrial cancer risk. This may provide an explanation of why endometrial cancer risk increases so sharply with age in young women even in countries where obesity-associated anovulation is very uncommon; extended periods of unopposed estrogen is not an explanation but less than 10 days of an 'adequate' progesterone level may be. EPRT significantly increased the risk of breast cancer. EPRT was associated with an approximately 24% increase in risk for each 5 years of use; the effect was some 212-fold greater than the effect of ERT, which we had previously predicted on theoretical grounds. This effect could also be predicted from the results on mammographic densities seen in the PEPI randomized trial of different forms of hormone replacement therapy (HRT). In the PEPI trial EPRT increased mammographic densities to a much greater extent than ERT. Progestins need to be given to protect the endometrium. They need to be delivered to the endometrium in a manner that will have the least effect on the breast. This can be carried out by using a vaginal or direct endometrial route of administration. The vaginal route will provide adequate endometrial progestin levels with low blood levels so that the effects of the progestin on the breast should be small; with the direct endometrial route the blood progestin levels are even lower, and the effects of the progestin on the breast will be effectively zero. If this is unacceptable to a woman, then giving progestins by mouth (or transdermally) for 10 days every 3 to 4 months should provide satisfactory protection of the endometrium when used with standard-dose conjugated estrogen (CE). This regimen has much less effect on the breast than monthly SEPRT or CEPRT. Two clinical trials of 10 mg per day of MPA for 14 days every 3 months and 0.625 mg/day of CE have been published. Both studies suggest that this approach may be satisfactory in that the extent of hyperplasia was minimal. More studies of this approach are urgently needed.
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PMID:Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer. 1110 73

Despite evidence that supports the beneficial effects of postmenopausal hormone replacement therapy (HRT), concerns remain about its possible adverse effects. However, entry into the postmenopausal state is associated with many characteristics of the insulin resistance syndrome, including increased cardiovascular morbidity and mortality, accretion of generalised and visceral adiposity and insulin resistance. Studies carried out in postmenopausal women have revealed that an increase in visceral obesity is associated with an increase in androgenicity that, in turn, is associated with type 2 (non-insulin-dependent) diabetes mellitus. Short term studies of HRT containing conjugated estrogens (CEE) and medroxyprogesterone (MPA) have shown prevention of the accretion of visceral fat. However, longer term studies using other techniques suggest that these effects may be evanescent. A few trials suggest that oral estrogen therapy reduces postmenopausal insulin resistance, as suggested by reductions in fasting insulin and glucose levels and an increase in glucose metabolism rates, whereas most studies do not show an adverse effect upon carbohydrate metabolism. MPA may decrease these beneficial effects. Transdermal estrogen is essentially neutral with regard to insulin sensitivity and oral estradiol (17beta-estradiol) may also be neutral or enhance sensitivity. Different progestogens vary in their effects upon carbohydrate metabolism. The Postmenopausal Estrogen/Progestogen Intervention (PEPI) Study was a prospective, 3-year, randomised trial in 875 women that compared placebo, unopposed CEE, CEE plus continuous MPA, CEE plus cyclical MPA, and CEE plus cyclical micronised progesterone. Fasting insulin and glucose levels decreased significantly by 16.1% and 0.122 mmol/L, respectively, in all drug treatment groups. However, after a 75g glucose load, glucose levels at 2 hours increased by 0.33 mmol/L in the active treatment groups without a corresponding increase in insulin levels. No beneficial effects on waist/hip ratio could be demonstrated. Data from the PEPI trial also suggested that the maximum benefit regarding carbohydrate metabolism was achieved in patients who were the most hyperglycaemic and hyperinsulinaemic at the start of therapy. It can be concluded, therefore, that HRT has few, if any, harmful effects on carbohydrate metabolism and that it may be of benefit in women in modifying the long term complications of the postmenopausal state.
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PMID:Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study. 1120 Mar 6

Although the mortality and incidence of cervical cancer have been decreasing, those of uterine-body, or endometrial, cancer have been increasing. The proportion of endometrial cancer was reported to have become 33.6% of primary uterine cancers in 1995. Infection with certain types of human papilloma virus (HPV) is considered to be etiologically important for the occurrence of cervical cancer. Because HPV is sexually transmitted, some risk factors for cervical cancer are associated with certain kinds of sexual behavior such as a young age at first intercourse, multiple partners, and infrequent use of barrier-type contraceptives such as condoms. Frequent conceptions and deliveries and histories of sexually transmitted diseases like infection with herpes simplex virus type 2 or chlamydia also have been suggested to be associated with the risk of cervical cancer. Smoking habits and infrequent intake of vegetables and fruits may be related to the increased risk of cervical cancer by supporting persistent infection of HPV through impaired immunological function. Although host factors such as a variant of a tumor suppressor gene like p53 have been assessed in terms of the risk of cervical cancer, these are not yet clearly elucidated. Estrogen stimulation of the endometrium unopposed by progesterone stimulation, namely, unopposed estrogen stimulation, is thought to be involved in the etiology of endometrial cancer. Frequent intake of animal fat, obesity or being overweight, infertility, and histories of diabetes mellitus, hypertension, and polycystic ovary syndrome have been reported to be risk factors for endometrial cancer, and they are thought to increase unopposed estrogen stimulation. Estrogen replacement therapy for postmenopausal symptoms, tamoxifen therapy for breast cancer, and taking sequential-type oral contraceptives have been shown to be exogenous risk factors for endometrial cancer in that they increase unopposed estrogen stimulation to endometrium.
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PMID:[Recent progress in epidemiologic research of uterine cancer]. 1124 42

Hypertension, central obesity and dyslipidemia are associated with high cardiovascular risk. Estrogen therapy in women has beneficial effects on some of these metabolic cardiovascular risk factors. It is not known whether dietary estrogens have similar effects, especially in Western populations. We studied the association between dietary phytoestrogen intake and metabolic cardiovascular risk factors in postmenopausal women. For this purpose, 939 postmenopausal women participating in the Framingham Offspring Study were included in this cross-sectional study. Mean blood pressure, waist-hip ratio (WHR) and lipoprotein levels were determined in quartile categories of dietary phytoestrogen (isoflavones and lignans) intake, determined by a food-frequency questionnaire. In addition, a metabolic syndrome score was defined according to WHO criteria (range 0-6). The WHR was lower in women in the highest quartile of intake of lignans compared with the lowest [-0.017; 95% confidence interval (CI) -0.030 to -0.0016]. In the highest quartile of intake of isoflavones, plasma triglyceride levels were 0.16 mmol/L lower (95% CI, -0.30 to -0.02) compared with the lowest quartile of isoflavones; for lignan intake, this difference was 0.23 mmol/L (95% CI, -0.37 to -0.09). In the highest quartile of isoflavone intake, the mean cardiovascular risk factor metabolic score was 0.43 points lower (95% CI, -0.70 to -0.16) than the lowest quartile. The difference in this score between the extreme quartiles of intake of lignans was -0.55 points (95% CI, -0.82 to -0.28). In conclusion, high intake of phytoestrogens in postmenopausal women appears to be associated with a favorable metabolic cardiovascular risk profile.
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PMID:Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal U.S.women: the Framingham study. 1182 90

This article reviews the published literature on the relationship between combined OCs (oral contraceptives) administration and metabolic and cerebro- and cardiovascular effects. All retrospective studies show an increase in the risk of thromboembolic accidents, while only a few of the prospective studies do. A study of the Royal College of General Practitioners (RCGP) states that the risk of myocardial infarction is multiplied by 5.22 in OCs users, and that smoking, but not age, greatly increases the risk. All studies document an increase in risk of cerebrovascular effects; high arterial pressure and smoking increase the risk, but obesity does not. Synthetic estrogens increase triglyceride levels according to dosage, but progesterone does not. Estrogen increases cholesterol level, estroprogestational agents increase it slightly, while progesterone does not cause any increase. Synthetic estrogens tend to increase low density lipoprotein cholesterol and derivates of progesterone do not; high density lipoprotein levels are increased by estrogens but decreased by progesterone. Age, smoking and diabetes increase the risk. Recent studies of the RCGP eliminate the responsibility of estroprogestins in causing diabetes, while other authors think the opposite. In general, the literature does not agree on the metabolic side effects of combined OC use, and conclusions are often opposite between retrospective and prospective studies. There still are not any epidemiological studies on the metabolic side effects of the mini-pill.
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PMID:[True and false regarding metabolic risk in contraception]. 1226 91

Epilepsy in women raises special reproductive and general health concerns. Seizure frequency and severity may change at puberty, over the menstrual cycle, with pregnancy, and at menopause. Estrogen is known to increase the risk of seizures, while progesterone has an inhibitory effect. Many antiepileptic drugs induce liver enzymes and decrease oral contraceptive efficacy. Women with epilepsy also have lower fertility rates and are more likely to have anovulatory menstrual cycles, polycystic ovaries, and sexual dysfunction. Irregular menstrual cycles, hirsutism, acne, and obesity should prompt an evaluation for reproductive dysfunction. Children who are born to women with epilepsy are at greater risk of birth defects, in part related to maternal use of antiepileptic drugs. This risk is reduced by using a single antiepileptic drug at the lowest effective dose and by providing preconceptional folic acid supplementation. Breastfeeding is generally thought to be safe for women using antiepileptic medications.
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PMID:Epilepsy in women. 1240 23

Elderly women with the lowest serum estrogen levels are at the greatest risk of bone loss and fractures, but it is controversial whether the ovaries contribute to estrogen production after menopause, and therefore, whether bilateral oophorectomy in postmenopausal women might have adverse skeletal effects. To address this potential problem, we estimated long-term fracture risk among 340 postmenopausal Olmsted County, MN, women who underwent bilateral oophorectomy for a benign ovarian condition in 1950-1987. In over 5632 person-years of follow-up (median, 16 years per subject), 194 women experienced 516 fractures (72% from moderate trauma). Compared with expected rates, there was a significant increase in the risk of any osteoporotic fracture (moderate trauma fractures of the hip, spine, or distal forearm; standardized incidence ratio [SIR], 1.54; 95% CI, 1.29-1.82) but almost as large an increase in fractures at other sites (SIR, 1.35; 95% CI, 1.13-1.59). In multivariate analyses, the independent predictors of overall fracture risk were age, anticonvulsant or anticoagulant use for > or = 6 months, and a history of alcoholism or prior osteoporotic fracture; obesity was protective. Estrogen replacement therapy was associated with a 10% reduction in overall fracture risk (hazard ratio [HR], 0.90; 95% CI, 0.64-1.28) and a 20% reduction in osteoporotic fractures (HR, 0.80; 95% CI, 0.52-1.23), but neither was statistically significant. The increase in fracture risk among women who underwent bilateral oophorectomy after natural menopause is consistent with the hypothesis that androgens produced by the postmenopausal ovary are important for endogenous estrogen production that protects against fractures.
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PMID:Fracture risk after bilateral oophorectomy in elderly women. 3026 33

We studied the role of estrogen in the gender differences in insulin resistance observed in the apoB/BATless mouse, a model of obesity, insulin resistance, and hyperlipidemia. Ovariectomized apoB/BATless mice were more obese and more insulin-resistant than sham ovariectomized apoB/BATless mice. Estrogen replacement by subcutaneous pellet reversed the obesity, lowered plasma insulin levels, and normalized both glucose tolerance and insulin sensitivity associated with ovariectomy. The apoB/BATless mouse should be a good model to delineate the molecular mechanisms whereby estrogen protects against insulin resistance.
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PMID:Ovariectomy leads to increased insulin resistance in human apolipoprotein B transgenic mice lacking brown adipose tissue. 1280 87


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