Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0028754 (
obesity
)
124,988
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have previously demonstrated that obese hyperandrogenic amenorrheic women are less likely to ovulate after clomiphene citrate (CC) medication. The present study was designed to identify whether additional endocrine screening characteristics, all potentially involved in ovarian dysfunction in 182 normogonadotropic oligoamenorrheic infertile women, are associated with ovarian response, which may improve overall prediction of CC-resistant anovulation. Standardized endocrine screening took place before initiation of CC medication (50 mg/day; increasing doses up to 150 mg/day if required) from cycle days 3-7. Screening included serum assays for fasting insulin and glucose, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, free IGF-I, inhibin B, leptin, and vascular endothelial growth factor. Forty-two women (22% of the total group) did not ovulate at the end of follow-up (a total number of 325 cycles were analyzed). Fasting serum insulin, insulin/glucose ratio, IGFBP-1, and leptin were all significantly different in univariate analyses (P < or = 0.02), comparing CC responders vs. nonresponders. Forward stepwise multivariate analyses in combination with factors reported earlier for prediction of patients remaining anovulatory after CC revealed a prediction model including 1) free androgen index (FAI = testosterone/
sex hormone-binding globulin
ratio), 2) cycle history (oligomenorrhea or amenorrhea), 3) leptin level, and 4) mean ovarian volume. These data suggest that decreased insulin sensitivity, hyperandrogenemia, and
obesity
, all associated with polycystic ovary syndrome, are prominent factors involved in ovarian dysfunction, preventing these ovaries from responding to stimulation by raised endogenous FSH levels due to CC medication. By using leptin instead of body mass index or waist to hip ratio, the previous model for prediction of patients remaining anovulatory after CC medication could be slightly improved (area under the curve from 0.82-0.85). This may indicate that leptin is more directly involved in ovarian dysfunction in these patients. The capability of insulin and IGFBP-1 to predict patients who remain anovulatory after CC disappears when FAI enters into the model due to a significant correlation between FAI and these endocrine parameters. This suggests that markers for insulin sensitivity (e.g. IGFBP-1 and insulin) are associated with abnormal ovarian function through its correlation with androgens, whereas leptin is directly involved in ovarian dysfunction.
...
PMID:Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. 1069 Aug 75
Obesity
has been associated with alterations in plasma steroid hormone concentrations in men. Older men present an altered steroid hormone profile compared to younger individuals, and an increase in body fatness and changes in adipose tissue (AT) distribution are noted with advancing age. Thus, there is a need to examine the relative importance of increased body fatness and changes in AT distribution with advancing age to plasma steroid hormone and
sex hormone-binding globulin
levels in men. We, therefore, investigated the relationships among age, body fatness, AT distribution, and the plasma steroid hormone profile in a group of 217 Caucasian men (mean age +/- SD, 36.2 +/- 14.9 yr) who covered a wide age range (17-64 yr). Compared to young adult men, older men were characterized by increased adiposity (P < 0.0001) expressed either as body mass index or total body fat mass assessed by underwater weighing. Differences in AT distribution were also noted with a preferential accumulation of abdominal fat as indicated by a larger waist girth (P < 0.0001) and higher visceral AT accumulation (P < 0.0001), measured by computed tomography, in older subjects. Age was associated with decreases (P < 0.0001) in C19 adrenal steroid levels, namely reduced dehydroepiandrosterone (DHEA), DHEA fatty acid ester, DHEA sulfate, as well as androstenedione levels. Androgens, i.e. dihydrotestosterone and testosterone, were also affected by age, with lower levels of both steroids being found in older individuals (P < 0.0005). When statistical adjustment for body fatness and AT distribution was performed, differences in C19 adrenal steroids between the age groups remained significant, whereas differences in androgens and
sex hormone-binding globulin
concentrations were no longer significant. The present study suggests that age-related differences in plasma steroid hormone levels, especially androgens, are partly mediated by concomitant variation in adiposity in men.
...
PMID:Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study. 1072 34
The majority of obese persons have hyperinsulinemia and disturbances in the secretion of melatonin, catecholamines and pituitary, thyroid, adrenal and gonadal hormones. These hormones play an important role in the regulation of collagen metabolism either by acting directly or by influencing IGF-I production. This study aimed at ascertaining whether, and to what degree, the changes in the concentration of hormones listed above as well as in the concentration of
sex hormone-binding globulin
(
SHBG
) and insulin-like growth factor-I (IGF-I) affect the metabolism of collagen as evaluated indirectly from the measurement of propeptides of type I (PICP) and type III procollagen (PIIINP) in blood serum and hydroxyproline in urine. The study compared 30 women with extreme
obesity
before and three to five years after jejunoileostomy with 20 healthy women of reproductive age. All non-operated obese women showed significantly increased concentration of serum insulin, IGF-I, melatonin, norepinephrine, free triiodothyronine, estradiol, total and free testosterone, PICP, PIIINP and urinary excretion of hydroxyproline, while the levels of epinephrine, progesterone and
SHBG
were significantly decreased. Changes in the level of the examined markers of collagen metabolism correlated positively with the concentration of insulin, IGF-I and sex hormones, while the correlation with epinephrine, cortisol and thyroid hormones was negative. All women who were treated previously by jejunoileostomy showed a decreased of body mass to regular values, normalization of hormonal disturbances and normal collagen metabolism. The obtained results show that the increased collagen metabolism observed in extremely obese women is caused indirectly by altered endocrine activity.
...
PMID:Assessment of the relationship between collagen metabolism and selected hormonal factors in extremely obese women before and after jejunoileostomy. 1093 49
We explored the relationship between insulin-like growth factor-1 (IGF-1) concentrations and breast cancer risk. Also, we examined whether
obesity
,
sex hormone-binding globulin
(
SHBG
), and estradiol influenced IGF-1 concentrations. A pilot study of 60 postmenopausal African-American women (30 cases and 30 controls) was used. Plasma concentrations of IGF-1 were higher among the cases, as compared to the controls. A negative trend was seen for plasma concentrations of IGF-1 and TNM (tumor-node-metastasis) stage and IGF-1 and body mass index. IGF-1 was found to be associated negatively with
SHBG
. After adjustment, plasma concentrations of IGF-1 remained significantly and positively associated with breast cancer risk (odds ratio, 1.183; 95% confidence interval, 1.167-1.201). No significant associations for breast cancer risk were observed for estradiol,
SHBG
, and body mass index. Further research with a larger sample is needed to clarify the relationships between
obesity
and IGF-1 concentrations to breast cancer risk in this population.
...
PMID:Insulin-like growth factor-1 and breast cancer risk in postmenopausal African-American women. 1097 80
Many clinical manifestations shown by obese women point to the disturbances of secretory activity of hypothalamus-pituitary-ovary axis (h-p-o). Because of antigonadotropic activity of melatonin (MEL) it is essential to define this hormone participation in inducing the disturbances of the h-p-o axis. We evaluated the relationship between MEL secretion and circadian concentrations of LH, FSH, E[_2], P, TT, FT,
SHBG
as measured at 3 h intervals, in 9 obese women showing android type of adipose tissue distribution (BMI > 30 kg/m[^2]; WHR > 0.8) and in 6 women showing gynoid type of adipose tissue distribution (BMI > 30 kg/m[^2]; WHR < 0.8). All patients were between 55 and 62 years of age. A considerable increase of circadian MEL secretion was observed in all obese patients. Suppression of MEL rhythmicity was observed in all patients, while nocturnal phase shift of MEL occurred only in women showing android type of adipose tissue distribution. Significant decrease of circadian LH, P and
SHBG
values which was accompanied by the elevation of E[_2], TT and FT levels was observed in women with a disturbed rhythmicity of MEL secretion (particularly in case of androidal-type
obesity
). Based on these results it is suggested that MEL participates in inducing h-p-o axis disturbances in obese women of post-menopausal age.
...
PMID:Circadian oscillation of melatonin, gonadotropins, sex hormones and SHBG in post-menopausal women showing android and gynoid type obesity. 1097 44
Obesity
is a major feature in women with polycystic ovary syndrome (PCOS), and evidence suggests that
obesity
contributes to the pathogenesis of PCOS by aggravating the intrinsic insulin resistance of these women. Hyperinsulinemia appears to increase circulating androgens in PCOS by stimulating ovarian androgen production and suppressing serum
SHBG
, and also appears to play a pathogenic role in the anovulation of the disorder. The use of insulin sensitizing drugs has been shown to decrease serum insulin in both obese and nonobese women with PCOS, and to simultaneously reduce circulating ovarian androgens and to improve ovulation.
...
PMID:Obesity, insulin, sex steroids and ovulation. 1099 13
Controversial effects of weight reduction on gonadotropin secretion in
obesity
have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum
sex hormone-binding globulin
concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum
sex hormone-binding globulin
(r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.
...
PMID:The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. 1099 21
Increased total and intraabdominal fat (IAF)
obesity
as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of
sex hormone-binding globulin
(
SHBG
) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of
obesity
and IRS despite low IAF, would have higher levels of circulating
SHBG
compared with CAU women, and whether there would be negative relationships between indexes of
obesity
and risk factors associated with IRS and
SHBG
levels. We measured body composition,
SHBG
, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable
obesity
(48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar
SHBG
(117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women
SHBG
correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and
SHBG
in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and
SHBG
persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional
obesity
, glucose, and lipid metabolism with
SHBG
in CAU women are different from those in postmenopausal obese AA women.
...
PMID:Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women. 1123 84
A Western lifestyle has been implicated in the pathogenesis of prostate cancer. However, no clear association between
obesity
and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin are present in the prostate. Leptin may, thus, be associated with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in Northern Sweden. Blood pressure, body mass index, and use of tobacco were recorded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and
sex hormone-binding globulin
were analyzed in stored samples. Their influences on prostate cancer were estimated by conditional logistic regression analysis. Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables, testosterone, and IGF-I and its binding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium. Moderately elevated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic intraepithelial neoplasia lesions, or to indirect actions through other mechanisms. A critical fat mass related to an interior milieu favorable for prostate cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.
...
PMID:Leptin is associated with increased prostate cancer risk: a nested case-referent study. 1123 30
Sex steroid hormones in both males and females have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Evidence also suggests a direct relationship between sex hormones and risk factors for cardiovascular disease. In the present review article, we will discuss recent studies that have examined the complex interrelationships between sex hormones,
SHBG
,
obesity
and risk factors for cardiovascular disease. Male
obesity
and excess abdominal adipose tissue accumulation is associated with reductions in gonadal androgen and low adrenal C19 steroid concentrations. Reduced C19 steroids are also related to an altered metabolic risk factor profile including glucose intolerance and an atherogenic dyslipidemic state. However, the concomitant visceral obese state appears as a major correlate in these associations. In women, menopause-induced estrogen deficiency and increased androgenicity are associated with increased abdominal obesity and with the concomitant alterations in the metabolic risk profile. The accelerated accretion of adipose tissue in the intra-abdominal region coincident with the onset of menopause may explain part of the increased risk of cardiovascular disease in postmenopausal women. In both men and women, plasma levels of
sex hormone-binding globulin
are strong correlates of
obesity
and risk factors for cardiovascular disease, and more importantly, the relationships between low
SHBG
and altered plasma lipid levels appear to be independent from the concomitant increased levels of visceral adipose tissue.
SHBG
concentration may, therefore, represent the most important and reliable marker of the sex hormone profile in the examination of the complex interrelation of sex steroid hormones,
obesity
, and cardiovascular disease risk.
...
PMID:Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women. 1124 20
<< Previous
1
2
3
4
5
6
7
8
9
10
Next >>