Levels In Healthy Women Research Articles

The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

BACKGROUNDCombined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.METHODSA review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.RESULTSA total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18–40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) −0.49 nmol/l (−0.55, −0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20–25 µg EE had similar effects on total and free T compared with COCs with 30–35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20–25 µg EE) were found to have less impact on SHBG concentrations.CONCLUSIONSThe current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinical implications of suppressed androgen levels during COC use remain to be elucidated.

PP27 Pre-Gestational Diabetes and the Risks of Fetal and Infant Death: a Population-Based Study

BackgroundPre-gestational diabetes is associated with a range of adverse pregnancy outcomes, including an increased risk of major congenital anomalies. The impact on normally-formed offspring, however, is less well defined. This...

AB0074 The effect of physical exercise in the cytokines levels in patients with systemic lupus erythematosus

BackgroundThe literature shows that acute exercise increases IL-6 [1,2] and IL-10 [3,4] and TNF-a [5,6] serum levels in healthy subjects and can worse the inflammatory response in patients with diabetes...

Effect of the menstrual cycle on serum diamine oxidase levels in healthy women

ObjectivesSerum diamine oxidase (DAO) level is employed as a useful marker of intestinal mucosal integrity. As reported previously, the range of serum DAO levels in women is wider than that in men. We hypothesized that the menstrual cycle may affect DAO levels. Design and methodsThirty-six women of Japanese descent were recruited. All participants, aged 20–29years, were healthy. Food surveys utilized in this study were based on questionnaires validated by dietitians. Complete blood counts, biochemical parameters, female hormones, and serum DAO levels during the follicular and luteal phases were measured in each subject. ResultsBiochemical parameters, except for DAO levels, were comparable between the two phases. However, serum DAO levels during the luteal phase were significantly higher than those during the follicular phase. ConclusionsSerum DAO levels were influenced by the menstrual cycle. Furthermore, our findings suggest that serum DAO levels should be interpreted cautiously in premenopausal women.

Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study

Background This study investigated the effects of adding levomefolate calcium 0.451 mg (the calcium salt of L-5-methyltetrahydrofolate; Metafolin®) to an oral contraceptive containing ethinylestradiol (EE) 20 mcg/drospirenone (drsp) 3 mg on folate levels in healthy women seeking contraception. Study Design In this randomized, double-blind, multicenter US-based study, women (18–40 years) received 24 weeks (six cycles) of EE/drsp/levomefolate calcium or EE/drsp for 24 days followed by 4 days of levomefolate calcium alone or placebo, respectively. The primary efficacy variables were red blood cell (RBC) and plasma folate levels at 24 weeks. Results At week 24, increases from baseline in mean RBC (990 ± 390 nmol/L to 1406 ± 440 nmol/L) and plasma folate (45.0 ± 17.6 nmol/L to 60.8 ± 19.9 nmol/L) levels were observed in women who received EE/drsp/levomefolate calcium [per protocol set ( n=262); all values are displayed as mean ± standard deviation]. In contrast, marginal fluctuations were observed with EE/drsp (p<.0001 for between-treatment differences at week 24). Conclusion Clinically significant increases in folate status were observed with EE/drsp/levomefolate calcium compared with EE/drsp alone in US women of childbearing age.

Evaluation of the insulin-like growth factors (IGF) IGF-I and IGF binding protein 3 in patients at high risk for breast cancer

Our data suggest that serum concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 3 do not correlate with breast cancer development.

IL-17 Increased in the Third Trimester in Healthy Women with Term Labor

The function, peripheral blood expression, and physiologic importance of IL-17 is not well established. Detection of IL-17 in sera and plasma samples from patients with pre-eclampsia has been reported with inconsistent results. To establish the l levels of the IL-17 at peripheral level, we studied prospectively a cohort of 13 healthy pregnant women. To evaluate the changes in serum levels of IL-17 in healthy pregnant women in a prospective cohort. Thirteen healthy pregnant women were prospectively followed to evaluate serum levels of IL-17. Each patient was evaluated at each trimester. IL-17 levels were measured by ELISA. The statistical analysis was done using repeated measures anova and Bonferroni's multiple comparison test. IL-17 levels were significantly increased from first trimester with a mean of 14.61 up to 31.78 pg/mL at third trimester (P < 0.05), but when detectable, they were almost identical range in all trimesters. We propose that IL-17 levels in healthy women are present with very similar range levels during the whole pregnancy but the average is increased during the third trimester maybe as a part of the complex network of cytokines as a result of implantation, fetal development, and labor process itself.

Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study

Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABAA) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABAA receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63, p=0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABAA receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolon.

Urinary 2/16 estrogen metabolite ratio levels in healthy women: a review of the literature.

This is a summary of the published literature on the urinary 2/16 estrogen metabolite ratio in human populations, and a report the observed range of normal values in healthy women. Original research studies that included the measurement of urinary estrogen metabolites in human subjects were identified through an extensive Medline search; 43 distinct studies were identified, including a total of 6802 healthy women. The range of mean values of the 2/16 ratio measured with the ELISA method varied from 0.98 to 1.74; in studies of pre-menopausal women the range of mean values was 1.5-2.74, in studies of post-menopausal women mean values ranged from 1.15 to 2.25. The heterogeneity across studies was highly significant (p-value Q-test: <0.0001). In multivariable analyses, only race confirmed its role as an independent predictor of 2/16 ratio (F-value: 7.95; p-value: 0.009), after adjustment for age and menopausal status. There appears to be a large body of data on the 2/16 urinary ratio in healthy women. However, summary estimates are difficult to perform due to the high variability of the published study-specific values. The data suggests that race may be a contributor to 2/16 urinary ratio levels.

Serum leptin levels during pregnancy in multiple sclerosis

Background Disease activity in patients with multiple sclerosis (MS) is suppressed during pregnancy, whereas attack frequency increases after delivery. It is yet unclear, which immuno – endocrinological processes mediate these disease fluctuations. Leptin has been identified as a hormone that can influence inflammatory activity. Objective The aim of this study was to investigate whether pregnancy-induced fluctuations of serum leptin levels differed between patients with MS and controls and whether serum leptin levels correlate with periods of enhanced and diminished disease activity. Methods Women with MS and healthy women were prospectively followed during and after pregnancy. The MS group could be studied already at a timepoint before pregnancy. Serum leptin and soluble leptin receptor (SLR) levels were measured using enzyme-linked immunosorbent assay. Results Pre-pregnancy serum leptin levels were (mean ± SD) 22.9 ± 12.8 ng/ml in the MS group. These levels increased in the third trimester to 28.5 ± 15.0 ng/ml (P = 0.007). The third trimester serum leptin levels in healthy women were comparable, 29.4 ± 19.0 ng/ml. Serum leptin levels after delivery dropped to 18.5 ± 12.8 ng/ml in women with MS (P < 0.001) and to a lesser extend (22.0 ± 17.5 ng/ml) in healthy women (P = 0.04). SLR levels showed the same pattern. Remarkably, women with the highest relative decrease in serum leptin levels after delivery had more often a postpartum relapse (P = 0.008). Conclusion In women with MS, leptin increased during late pregnancy. A postdelivery drop in leptin levels was observed in both the MS and control group. The postdelivery drop was associated with the occurrence of postpartum relapse.

Cancer risk factors associated with insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels in healthy women: effect modification by menopausal status

Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) appear to influence breast cancer risk and are hypothesized to mediate the effects of several cancer risk factors that depend on menopausal status. We investigated associations among cancer risk factors and plasma IGF-I and IGFBP-3 in 882 healthy control women (426 premenopausal, 456 postmenopausal) from two population-based breast cancer case–control studies. Interactions with menopausal status were statistically tested. We observed associations with non-modifiable (age, benign breast disease) and modifiable factors [body mass index (BMI), physical activity, smoking habits, alcohol consumption]. Furthermore, we demonstrated statistical interactions with menopausal status. Premenopausal IGFBP-3 levels increased and postmenopausal levels decreased with age (p-interaction = 0.001). Overweight postmenopausal women had higher IGF-I (p = 0.049) and IGFBP-3 (p = 0.005) levels than women with lower BMI. Postmenopausal IGF-I levels were positively associated with physical activity (p-trend = 0.012, p-interaction = 0.050). Postmenopausal current smokers had lower IGF-I (p = 0.014) and IGFBP-3 levels (p = 0.011). Increasing alcohol consumption was associated with lower premenopausal IGF-I (p-trend = 0.002, p-interaction = 0.004) and higher postmenopausal IGFBP-3 levels (p = 0.019). Benign breast disease was associated with higher premenopausal (p = 0.044) and postmenopausal (p = 0.002) IGF-I levels. IGF-I and/or IGFBP-3 potentially mediate changes in breast cancer risk associated with BMI, benign breast disease, and perhaps alcohol consumption. Other observed associations suggest that neither IGF-I nor IGFBP-3 alone acts as mediator. Consideration of menopausal status may help disentangle carcinogenic pathways involving IGF proteins.

Retinol-binding protein levels are increased in association with gonadotropin levels in healthy women

Recent studies have demonstrated an association between retinol-binding protein (RBP4) and insulin resistance. Retinol-binding protein is decreased in women and elevated in polycystic ovary syndrome. However, prior studies have not investigated the relationship between RBP4, gonadal steroids, and gonadotropins in healthy women. The aim of this study was to determine the RBP4 levels in a cohort of healthy women with a range of body mass indices and glucose tolerances to investigate the relationship between RBP4, gonadotropin levels, and menopausal status. Serum RBP4 levels were measured by enzyme-linked immunosorbent assay and quantitative Western blot in 88 healthy women (aged 24-59 years) from the general community in a cross-sectional study. Retinol-binding protein was higher in postmenopausal compared with premenopausal women (26.1 ± 2.1 vs 19.3 ± 0.5 μg/mL, P = .001). In univariate analysis, RBP4 was associated with follicle-stimulating hormone ( r = 0.37, P = .0004), luteinizing hormone ( r = 0.3, P = .005), and sex hormone–binding globulin ( r = −0.24, P = .03) and trended to significance with estradiol ( P = .09) but not with free testosterone or dehydroepiandrosterone sulfate. Retinol-binding protein was also associated with insulin at 2 hours during an oral glucose tolerance test ( r = 0.24, P = .03) and the area under the curve for insulin during the oral glucose tolerance test ( r = 0.26, P = .02). In multivariate regression modeling, both follicle-stimulating hormone ( P = .03) and luteinizing hormone ( P = .04) remained significantly associated with RBP4 after controlling for estradiol, sex hormone–binding globulin, insulin area under the curve, cholesterol, triglycerides, waist-to-hip ratio, and tumor necrosis factor α. Retinol-binding protein was not associated with inflammatory markers or with carotid intima-media thickness. Therefore, RBP4 is higher in postmenopausal women and is associated with gonadotropin concentrations in healthy women.

MUC1 568 A/G genotype-dependent Cancer Antigen 15-3 levels in breast cancer patients

Objectives CA 15-3 is a widely used tumor marker for breast cancer. We have investigated whether the MUC1 568 A/G polymorphism can influence CA 15-3 levels in healthy women and patients with breast tumors. Design and methods CA 15-3 was measured in 208 healthy women, in 67 with benign disease, and in 162 women with breast cancer. All subjects were genotyped for the MUC1 568 A/G polymorphism. Results Significant differences were observed between mean CA 15-3 levels of control subjects grouped according to the MUC1 568 genotype (mean ± SD): AA (10.3 ± 3.8), AG (15.9 ± 5.0) and GG (19.0 ± 5.6) U/mL, p < 0.0001. Similar (median) results were observed in women with benign breast disease: AA (10.2), AG (14.2) and GG (16.6) U/mL, p < 0.0001, and those with breast cancer: AA (10.4), AG (17.1) and GG (23.9) U/mL, p < 0.0001. Conclusions The MUC1 568 A/G polymorphism strongly influences CA 15-3 levels in healthy women and women with either benign or malignant breast tumors.

Intravenous Lipid and Heparin Infusion-Induced Elevation in Free Fatty Acids and Triglycerides Modifies Circulating Androgen Levels in Women: A Randomized, Controlled Trial

The polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism and associated with obesity and impaired glucose metabolism. Despite the high prevalence of PCOS and the considerable clinical impact, the precise interplay between metabolism and hyperandrogenemia is not entirely clear. The objective of the study was to analyze the effects of iv lipid and heparin infusion on circulating androgen levels in healthy women. This was a randomized, controlled, crossover trial. The study was conducted at an endocrinology center. Patients included 12 healthy young women during the early follicular phase of two subsequent cycles. After an overnight fast, a 20% lipid/heparin or a saline/heparin infusion was administered in random order for 330 min. A detailed characterization of androgen metabolism was performed. Elevations in free fatty acids and triglycerides, induced by lipid/heparin infusion, elevates the levels of androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone, 5alpha-dihydrotestosterone, estrone, and 17beta-estradiol. Urinary excretion of DHEA, DHEAS, 5-androstene-3beta,17beta-diol, and the sum of urinary excreted DHEA and its 16-hydroxylated downstream metabolites, 16alpha-hydroxy-DHEA and 5-androstene-3beta,16alpha,17beta-triol, were reduced. The mechanism of iv lipid and heparin infusion-induced elevation of circulating androgens described here might contribute to the development of hyperandrogenism in women with PCOS and suggests that lowering of hyperlipidemia might be a potential therapeutic target in patients with PCOS to treat hyperandrogenemia.

Leptin and cardiovascular disease: response to therapeutic interventions.

Leptin and cardiovascular disease: response to therapeutic interventions.

Serum Selenium Levels in Healthy Women in Tabriz, Iran

Selenium is of fundamental importance to human health, and selenium deficiency is associated with disease conditions. The objective of this study was to investigate the serum level of selenium in women of childbearing age and postmenopausal women living in Tabriz, Iran. In this cross-sectional study, 60 healthy women of childbearing age and 60 healthy postmenopausal women were studied with the use of biochemical methods (measurement of serum selenium by graphite furnace atomic absorption spectrometry), anthropometric measurements (weight and height), and interviews. The average serum selenium was 76.67 +/- 17.98 microg/L (range, 42.00 to 166.61 microg/L). This level was lower than those reported in other provinces of Iran and some other countries. Sixty-nine women (57.5%) had serum selenium concentrations under 80 microg/L. There was no significant difference in selenium level between the two groups of women. Serum selenium level did not vary with age and body mass index. Some Iranian women are of borderline selenium status and as a consequence are more susceptible to selenium-deficiency diseases. There is a need for community-based programs to encourage people to increase consumption of selenium-rich sources, such as marine foods.

A dietary pattern characterized by high consumption of whole-grain cereals and low-fat dairy products and low consumption of refined cereals is positively associated with plasma adiponectin levels in healthy women

In light of the potential beneficial effects of adiponectin on insulin resistance, metabolic syndrome, and cardiovascular risk, it is becoming increasingly important to identify all modifiable factors, including dietary patterns, that may affect circulating adiponectin concentrations. The aim of the present study was to explore potential associations between dietary patterns and plasma adiponectin levels using principal component analysis (PCA) in a sample of apparently healthy adult Mediterranean women. Two hundred twenty women were enrolled in this study. Anthropometric and body composition measurements were performed in all subjects. Blood samples were taken, and adiponectin concentrations were measured. Food intake was evaluated by 3-day food diaries, and PCA was used for the identification of the participants' dietary patterns. The PCA identified 10 dietary components explaining 82% of the total variance in food intake. Bivariate correlation between circulating adiponectin levels and dietary components revealed a positive significant association only with the first component that was characterized by high intake of whole-grain cereals and low-fat dairy products as well as low intake of refined cereals ( P = .04). This association remained unchanged after controlling for potential confounders (standardized β coefficient = 0.18, P = .03). A dietary pattern characteristic of consumption of alcoholic beverages was found to be marginally related to adiponectin levels in the multivariate model (standardized β coefficient = 0.14, P = .10). Our data indicate that a dietary pattern characterized by a high consumption of whole-grain cereals and low-fat dairy products is modestly positively associated with adiponectin concentrations.

Effect of a proprietary Magnolia and Phellodendronextract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial

BackgroundRecent research has established correlations between stress, anxiety, insomnia and excess body weight and these correlations have significant implications for health. This study measured the effects of a proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense (Relora®) on anxiety, stress and sleep in healthy premenopausal women.MethodsThis randomized, parallel, placebo controlled clinical study was conducted with healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scores above the national mean for women on self-reporting anxiety. The intervention was Relora (250 mg capsules) or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety. The study was conducted by Miami Research Associates, a clinical research organization in Miami, FL.ResultsThe intent-to-treat population consisted of 40 subjects with 26 participants completing the study. There were no significant adverse events. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments conducted in this study including salivary cortisol and amylase levels, appetite, body morphology and sleep quality/latency were not significantly changed by Relora in comparison to placebo.ConclusionThis pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.

Exercise and cardiovascular risk reduction: time to update the rationale for exercise?

although it is generally accepted that the promotion of exercise accords with clinical best practice, the anecdotal experience of many primary care physicians, cardiologists, and exercise physiologists is that, even when exercise prescriptions are adhered to, risk factors often fail to demonstrate

The effect of different preparations of hormone therapy on tumor necrosis factor-α levels in women with surgical menopause

The aim of the present prospective controlled study was to examine the influence of 17β-estradiol and tibolone on tumor necrosis factor-α (TNF-α) levels in healthy women with surgical menopause. Forty-five surgically menopausal women were included in the study. Thirty women were randomized to receive tibolone 2.5 mg or 17β-estradiol 2 mg daily for 16 weeks. Fifteen surgically menopausal women who refused hormone therapy served as controls. Serum was collected from the subjects at baseline and at the end of the study for TNF-α assay. Neither tibolone nor 17β-estradiol showed a significant influence on TNF-α level at the end of 16 weeks in comparison with baseline. Although tibolone induced a trend toward decreased level of TNF-α (3.30 ± 0.42 vs. 2.56 ± 1.94 μg/dl), this was non-significant. The slight increase observed in TNF-α level in the control group was also insignificant (3.60 ± 1.20 vs. 4.10 ± 0.70 μg/dl). Overall, these results demonstrate no significant effects of either tibolone or 17β-estradiol on circulating TNF-α level in surgically menopausal women. However, the significant difference achieved between the tibolone and control group after treatment is promising and needs to be investigated in trials with longer treatment periods.