Increased levels of low-density lipoprotein oxidation in patients with familial hypercholesterolemia and in end-stage renal disease patients on hemodialysis

Patients with familial hypercholesterolemia (FH) and patients with end-stage renal disease (ESRD) undergoing dialysis suffer from accelerated atherosclerosis. Oxidation of low-density lipoprotein (LDL) cholesterol is crucial in atherogenesis. In the present study, we determined the LDL oxidation level and oxidizability of isolated LDL of 11 male patients with FH, 15 male ESRD patients on hemodialysis, and 15 age-matched male normolipidemic healthy controls. FH patients were without lipid-lowering medication for at least 4 weeks and were reassessed after 2 years of cholesterol-lowering therapy (statins). LDL oxidation level was measured by ELISA using monoclonal antibody 4E6 to oxidized LDL (oxLDL) as the capture antibody and anti-human apoB antibody for detection; results were expressed as percentage oxLDL. In FH patients and in ESRD patients on hemodialysis, both groups having a higher percentage of cardiovascular disease, mean plasma LDL oxidation levels were significantly elevated compared with controls (4.9 +/- 1.3; 3.7 +/- 2.0; 1.7 +/- 0.6%, respectively). Within each group of subjects, LDL oxidation level was not associated with history of cardiovascular disease. Furthermore, in neither group was a significant correlation found between plasma concentration of LDL cholesterol and LDL oxidation level. After cholesterol-lowering therapy, LDL oxidation level in FH patients had not changed significantly and remained elevated compared with controls, despite a reduction of LDL cholesterol by 55% on average. Also, absolute plasma oxLDL concentrations, obtained by multiplying LDL oxidation level with plasma LDL cholesterol concentration, were significantly higher in FH patients before and after cholesterol-lowering therapy and in ESRD patients on hemodialysis than in controls (489 +/- 145; 189 +/- 122; 100 +/- 65; and 59 +/- 27 micro moles/L, respectively). No correlation was found between plasma oxLDL concentration and parameters of LDL oxidizability, LDL fatty acids, and LDL alpha-tocopherol content. We conclude that cholesterol-lowering therapy does not normalize elevated LDL oxidation levels in FH patients and elevated LDL oxidation level in FH and in ESRD might mirror atherosclerosis.     

The effect of oral hormone replacement therapy on lipoprotein profile, resistance of LDL to oxidation and LDL particle size

Objectives: To disclose if oral estradiol (E₂), alone or in combination with natural progesterone (P) or medroxyprogesterone acetate (MPA), may modify the oxidizability of low density lipoprotein (LDL), and if the effect is achieved at physiological dosages. LDL oxidizability was assessed by the resistance to oxidation by copper and by the particle size profile, since small particles have increased oxidation susceptibility. Methods: Thirty-three women received two consecutive, two-month length doses of 1 and 2 mg/day of oral E₂. They were then randomly assigned to a fourteen-day treatment of 2 mg/day E₂ plus either 300 mg/day P or 5 mg/day MPA. A parallel group of experiments was performed on a pool of baseline plasma, where hormones were added at the desired concentration. Lipoprotein levels, resistance of LDL to oxidation, and LDL particle diameter, were measured at baseline and after each treatment. Results: Estradiol reduced LDL levels and increased high density lipoprotein (HDL) and triglycerides. P abolished these changes, whereas MPA only reversed the increase of HDL. Estradiol protected LDL from oxidation in a dose-dependent manner, although only at pharmacological concentrations (1 μM or higher). Both P and MPA were inert at either physiological or pharmacological concentrations. The size of the LDL particles remained unaffected except under MPA, in which it was reduced. Conclusions: Estradiol has a protective effect against LDL oxidation, although only at pharmacological dosages. P and MPA did not limit the E₂ action. The size of the LDL particles remained unaltered after each E₂ dose, but MPA, and not P, was associated with a diminution.     

Transdermal estradiol reduces plasma myeloperoxidase levels without affecting the LDL resistance to oxidation or the LDL particle size

OBJECTIVE: This study was designed to investigate the effects of different therapeutic range doses of transdermal estradiol (E(2)), alone or in combination with progesterone (P) or medroxyprogesterone acetate (MPA), on plasma lipoprotein levels and on three parameters related with LDL oxidizability, the resistance of LDL to oxidation by copper, the LDL particle size, and the myeloperoxidase levels. DESIGN: Thirty-five healthy postmenopausal women who had been amenorrheic for at least 1 year received two consecutive, 2-month doses of transdermal estrogen (25-microg and 50-microg E(2) patch). Thereafter, they were randomly assigned to receive a 2-month treatment of either a 100-microg E(2) patch or a 50-microg E(2) patch combined with P (300 mg/day) or MPA (5 mg/day) during the last 14 days. RESULTS: Neither transdermal E(2) alone nor transdermal E(2) plus progestogen modified the lipoprotein profile, the LDL resistance to oxidation, or the LDL particle size. However, all treatments similarly reduced the myeloperoxidase protein levels. CONCLUSIONS: Different dosages of transdermal E(2) within the therapeutic range were equally effective in reducing myeloperoxidase protein levels. The effect remained after addition of P or MPA in a sequential regime.     

Influence of menstrual cycle on cardiac performance

OBJECTIVES: The purpose of this study was to investigate the relationship between endogen sex hormone levels and myocardial performance in two different phases of menstrual cycle. BACKGROUND: The relationships between cardiac performance and sex hormone levels in menstrual cycle have not yet been clearly identified. METHODS: Twenty-seven women at the age of 19-42 years (mean 24.11+/-6.02) with regular menstrual cycles (28-31 days) were enrolled in this study. Cardiac performance was evaluated by tissue Doppler imaging (TDI) derived myocardial performance index (MPI) in the menstrual and the luteal phases of the menstrual cycle. RESULTS: Left ventricular MPI were statistically significant between the menstrual phase and luteal phase of the menstrual cycle (Inferior 0.53+/-0.10 versus 0.44+/-0.09, P<0.001; Anterior 0.54+/-0.13 versus 0.45+/-0.10, P<0.008; Lateral 0.50+/-0.09 versus 0.44+/-0.12, P<0.03; Septum 0.54+/-0.07 versus 0.46+/-0.10, P<0.005; Global 0.52+/-0.06 versus 0.44+/-0.09, P<0.001). Right ventricle MPI between the two periods was also significantly different (0.49+/-0.10 versus 0.42+/-0.10, P<0.01). There was a moderate correlation between estrogen levels and global MPI (r=0.46, P=0.001), but no correlation was found between progesterone levels and global MPI (r=0.22, P=NS). CONCLUSION: We firstly demonstrated that endogen estrogen or progesterone improved the combined systolic and diastolic function in both left and right ventricle during luteal phases of menstrual cycle. Considering the previous studies and our results, estrogen may be responsible for this improvement.     

Effect of menopause on low-density lipoprotein oxidation: is oestrogen an important determinant?

Objectives: Significantly increased risk for developing cardiovascular disease in post-menopausal women is linked with the fall of oestrogen. Although supraphysiological levels of oestrogen may inhibit oxygen free radical mediated low-density lipoprotein (LDL) oxidation, the effect of physiological level of oestrogen on LDL oxidation is unknown. Methods: The present study compared oxidizability of LDL in healthy pre- and post-menopausal women by using a commonly employed copper ion-dependent method. Results: Pre-menopausal women (n=20, mean age 27) had significantly higher serum oestradiol level (576±109 pmol/l) in comparison to post-menopausal women (n=23, mean age 51, oestradiol 64±18 pmol/l, P<0.001). The oxidation of LDL in two groups was not different by measuring either the lag phase of conjugated dienes formation (54±12 vs. 55±14 min, P>0.05) or the generation of thiobarbituric acid reactive substances over 4 h of oxidation. The major lipid soluble antioxidant in LDL, vitamin E (determined as -tocopherol) is similar in two groups (2.34±0.48 vs. 2.40±0.56 nmol/mg LDL, pre- and post-menopausal subjects, respectively, P>0.05). Linear regression analysis found a weak but significant correlation between LDL vitamin E level and oxidizability of LDL in both groups but did not show effect of serum oestradiol levels. Conclusion: The results suggest that physiological levels of oestrogen may not be able to affect in vitro LDL oxidation.     

Low-density lipoprotein,its susceptibility to oxidation and the role of lipoprotein-associated phospholipase A2 and carboxyl ester lipase lipases in atherosclerotic plaque formation

An increased level of low-density lipoprotein (LDL) is a very well established risk factor of coronary artery disease (CAD). Unoxidized LDL is an inert transport vehicle of cholesterol and other lipids in the body and is thought to be atherogenic. Recently it has been appreciated that oxidized products of LDL are responsible for plaque formation properties previously attributed to the intact particle. The goal of this article is to review the recent understanding of the LDL oxidation pathway. The role of oxidized products and key enzymes (lipoprotein-associated phospholipase A₂ and carboxyl ester lipase) are also extensively discussed in the context of clinical conditions.     

T-lymphocyte reactivity during the menstrual cycle in women

Reactivity of blood lymphocytes to nonspecific mitogenic stimulation with phytohemagglutinin (PHA) was measured in nine healthy, regularly cycling women at three phases of their menstrual cycles corresponding to peak levels of estradiol (midfollicular phase), peak levels of progesterone (midluteal phase), and the lowest levels of both hormones (menstrual phase). Sampling points were verified by radioimmunoassay of estrogen, progesterone, luteinizing hormone, and follicle-stimulating hormone. There were significant increases in reactivity associated with an increasing concentration of PHA and with autologous plasma vs AB plasma. However, no differences were found in reactivity to PHA over the three menstrual cycle phases and correlational analyses indicated no relationship between counts and any of the hormones measured.     

Heart rate variability and endogenous sex hormones during the menstrual cycle in young women

To our knowledge, the relationship between all four endogenous female sex hormones and resting cardiac autonomic function has not been studied. The aim of the current study was to examine the association between the normal endogenous levels of oestrogen (17beta-oestradiol), progesterone, luteinising hormone and follicle-stimulating hormone and heart rate variability (HRV) during the menstrual cycle in young eumenorrheic women. Ten healthy, young, female subjects volunteered for this study. HRV and endogenous hormone levels were recorded at three phases of the menstrual cycle: menses (day 3.8 +/- 0.5), ovulation (day 15.8 +/- 0.7) and luteal (day 22.1 +/- 0.4) to ensure HRV recordings at times of low (menses) and high (ovulation and luteal) hormonal influence. Heart rate recordings were obtained from supine resting subjects and analysed on a Holter analysis system. Total power (TP, 0-1.0 Hz), low frequency (LF, 0.041-0.15 Hz), high frequency (HF, 0.15-0.80 Hz) and LF/HF components of HRV were examined. Despite a significantly greater HR at ovulation and normal cyclic variations in all endogenous sex hormone levels, no measure of HRV was significantly different between menstrual cycle phases. Significant correlations between oestrogen levels and absolute measures of HRV at ovulation were identified. The results of the current study demonstrated that the normal cyclic variations in endogenous sex hormone levels during the menstrual cycle were not significantly associated with changes in cardiac autonomic control as measured by HRV. Significant correlation between peak oestrogen levels and HRV measures at ovulation provided further support for the reported cardioprotective effects of oestrogen in healthy females.     

Changes in the biological:immunological ratio of basal and GnRH-releasable FSH during the follicular, pre-ovulatory and luteal phases of the human menstrual cycle

BACKGROUND: Significant changes in charge isoform distribution of serum FSH occur throughout the human menstrual cycle. In the present study, we analysed the impact of the changing endocrine milieu characteristic of the menstrual cycle on the capability of basal and gonadotrophin-releasing hormone (GnRH)-releasable FSH to trigger intracellular signal transduction via the human FSH receptor. METHODS: Seven normal women underwent blood sampling every 10 min for 10 h during the early follicular phase (FP), pre-ovulatory phase (PO) and mid- to late luteal phase (LP) of the menstrual cycle. Serum from successive samples collected across 2 h intervals containing FSH released under baseline and exogenous GnRH-stimulated conditions was tested for bioactivity employing a homologous in-vitro assay. RESULTS: The biological to immunological (B:I) ratio of basal and GnRH-releasable FSH was significantly (P < 0.05 ) higher at LP (range, 0.83 +/- 0.07 to 1.35 +/- 0.30) than during the FP (0.43 +/- 0.02 to 0.65 +/- 0.04) and PO (0.49 +/- 0.05 to 0.62 +/- 0.06). In all phases, the B:I FSH ratio in baseline samples was similar to those exhibited by samples collected after 10 and 90 microg GnRH administration. CONCLUSIONS: The selective increase in the capability of the admixture of FSH isoforms circulating during the LP to activate the FSH receptor, apparently represents an additional mechanism through which the anterior pituitary may regulate the maturation of those follicles destined to ovulate during the coming cycle.     

The effect of 17beta-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of gamma-tocopherol and melatonin

OBJECTIVE: Estrogens have a potent antioxidant effect on low-density lipoprotein (LDL) cholesterol in vitro and in vivo. A variety of compounds with antioxidant properties, such as vitamins and other hormones, also have been recommended in clinical practice to prevent several diseases related to oxidation. The aim of this study was to compare the antioxidant potency of estradiol (E2), the liposoluble vitamin E (both, alpha- and gamma-tocopherol), and melatonin. DESIGN: LDL was isolated by ultracentrifugation from the plasma of 11 healthy, untreated postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with 15 microM of CuSO4 to induce oxidative stress and with one of the four compounds studied: E2, alpha-tocopherol, gamma-tocopherol, or melatonin in doses of 0, 5, 15, 50, and 500 microM and 1 and 2 mM. Malondialdehyde (MDA) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration (nmol/mg protein). MDA values were significantly different as compared with baseline at 5 microM of E2 (F = 47.17; p < 0.0001). Alpha-tocopherol, gamma-tocopherol, and melatonin also showed a significant decrease in MDA concentration but to a lesser degree. The reduction of MDA reached statistical significance at 50 microM with alpha-tocopherol, 500 microM with melatonin, and 1 mM with gamma-tocopherol. The antioxidant effect also reached a plateau at concentrations of 50 microM of E2 and 1 mM of alpha-tocopherol; gamma-tocopherol and melatonin did not reach a plateau at any dose tested. CONCLUSIONS: The antioxidant potency of E2 in vitro is at least 10-100 times greater than alpha- and gamma-tocopherol and melatonin. Whether this finding implies a better performance of E2 as a protective agent against oxidation-related diseases remains to be determined.     

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00±0.15, 5.36±0.17 (P<0.01), 5.63±0.13 (P<0.05) mmol/l, respectively for total cholesterol; 4.13±0.15, 3.64±0.15 (P<0.05), 3.82±0.12 (P<0.05) mmol/l, respectively for LDL-cholesterol; 48.19±9.90, 26.59±5.53 (P<0.03), 25.12±4.62 (P<0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r=−0.27, P<0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16±0.07 mmol/l) than in the premenopausal group (0.96±0.07) or postmenopausal group not using HRT (0.87±0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.     

Susceptibility to oxidation of plasma low-density lipoprotein in X-linked adrenoleukodystrophy: effects of simvastatin treatment

This paper shows for the first time the higher oxidizability of low-density lipoprotein (LDL) in plasma from adrenoleukodystrophy (ALD) patients compared to that of control subjects. LDL oxidation susceptibility was assessed by conjugate diene formation, hydroperoxide and lipoperoxide formation, and electrophoretic mobility. Simvastatin therapy, an HMG-CoA reductase inhibitor, seems to be a protective pharmacological agent against the higher oxidizability of LDL in plasma from ALD patients.     

The relationship between menstrual cycle phases and suicide attempts

OBJECTIVE: The validity of prior studies on the menstrual cycle and suicide attempts assumes that suicidal women accurately describe their cycles. The three objectives of this study were 1) to explore whether prior inconsistencies are due to the effects of sample selection and method of assessment of the menstrual cycle, 2) to assess the relationship between the menstrual cycle phase and suicide attempts, and 3) to establish the role of sexual hormones in suicide attempts. METHODS: The original sample included 134 women who came to the emergency room of a general hospital after a suicide attempt. One hundred eight female blood donors were recruited as control subjects. The menstrual cycle was divided into follicular, midcycle, and luteal phases using two clinical methods and serum hormonal assessment. Dividing the follicular phase into menstrual and nonmenstrual phases was also considered. RESULTS: Two of 11 previously used sampling methods produced a sample size similar to that of the hormonal assessment. kappa values between the two clinical and the endocrinological methods were low (0.40-0.50). The number of suicide attempts during the follicular phase (particularly during the menstrual phase) was significantly higher than expected. CONCLUSIONS: Despite the inability to control for other variables and limitations, the results of this study suggest that sample selection could introduce biases and that studies relating psychiatric symptomatology and menstrual cycle phases need to use hormonal determinations. New studies are needed to verify that suicide attempts are more frequent during the follicular phase (particularly during the menstrual phase).     

Immunohistochemical localization of cyclooxygenase and prostaglandin I2 synthase in human female reproductive organs

The localization of cyclooxygenase and prostaglandin I₂ synthase in human female reproductive organs was examined by immunohistochemistry. Cyclooxygenase was localized in the cytoplasm of various cell types. The extent of cyclooxygenase expression in endometrial epithelial cells varied with the menstrual cycle, showing a peak at the secretory phase. Cyclooxygenase was also detected in the secretory cells, but not in the ciliated cells, of the fallopian tubes. Prostaglandin I₂ synthase was detected in the cytoplasm of myometrial cells throughout the menstrual cycle and during pregnancy. The results suggest that cyclooxygenase expression in endometrial epithelial cells may be regulated by ovarian hormones, and that the localization of cyclooxygenase in secretory cells—but not ciliated cells—in the fallopian tube may reflect the different functions of these two cell types.     

Pulsatile secretion of human chorionic gonadotropin in normal adults

We used very sensitive and specific monoclonal-antibody sandwich assays for human chorionic gonadotropin (hCG) and human luteinizing hormone (hLH) to measure both hormones in serum samples from normal men and women. When single serum samples from 92 men were studied, 73 percent had detectable hCG. In normal men, the amount of detectable hCG averaged 8.9 pg per milliliter, with a range of less than 3.0 to 160 pg per milliliter (biologic potency = 13,450 IU per milligram). In postmenopausal women the hCG level averaged 111 pg per milliliter and ranged from 32 to 510. In women of reproductive age the hCG level varied with the menstrual cycle. Gonadotropin-releasing hormone administered to 10 normal men increased both hCG and hLH. When daily serum samples were studied throughout a normal menstrual cycle, hCG concentrations paralleled those of hLH; follicular-phase concentrations were higher than those of the luteal phase, and there was a midcycle ovulatory peak of hCG coincident with the hLH peak. When hCG was measured every 10 minutes for six hours in eight postmenopausal women, distinct pulses were detected in parallel with those of hLH: hLH pulsed at a mean (+/- SEM) frequency of 0.56 +/- 0.08 pulses per hour; hCG pulsed at 0.54 +/- 0.07 pulses per hour. The mean pulse durations were 89 +/- 22 and 56 +/- 20 minutes for hLH and hCG, respectively. We conclude that hCG is produced in a pulsatile fashion, probably by the pituitary, in all normal adults.     

Effect of menstrual phase on the acetate correction factor used in metabolic tracer studies.

The acetate correction factor is used to account for retention of carbon label in exchange reactions of the tricarboxylic acid cycle in studies estimating free fatty acid oxidation with carbon-labeled tracers. Previous evidence indicates that substrate utilisation and metabolic rate vary across the menstrual cycle, which may alter the correction factor. We therefore derived the acetate correction factor for each of three menstrual phases (early follicular [EF], late follicular [LF], and midluteal [ML] phase) from the fractional recovery of 13CO2 from a constant infusion of sodium-[1-13C] acetate during 90 min of submaximal exercise (60% VO2-max) in sedentary eumenorrhoeic women. There was no difference in the correction factor between the EF and LF or the LF and ML phases, but the correction factor derived in the ML phase was significantly lower than in the EF phase (p < 0.05). Neither energy expenditure nor whole body substrate utilisation during exercise varied significantly between menstrual phases and therefore cannot explain the observed difference in the correction factor. The lower correction factor in the ML phase, compared to the EF phase, would result in only a small increase of -6% in the calculated plasma free fatty acid oxidation rate.     

Serum anti-Mullerian hormone throughout the human menstrual cycle

BACKGROUND: The anti-Mullerian hormone (AMH) is a member of the transforming growth factor (TGF) superfamily. In women, AMH serum levels can be almost undetectable at birth, with a subtle increase noted after puberty. Data are lacking with regard to menstrual cycle day-to-day fluctuations. This longitudinal study was designed to investigate the pattern of secretion of AMH throughout the menstrual cycle in regularly cycling women. METHODS: Twelve healthy female subjects aged 18-24 years participated in this study. Blood samples were taken every other day throughout one menstrual cycle. Serum FSH, LH, estradiol (E(2)), progesterone, inhibin B and AMH levels were assayed by double-antibody radioimmunoassay using commercial kits. RESULTS: Serum AMH in the first days of the menstrual cycle (days -14 to -12) was 3.8 +/- 1.2 ng/ml (mean +/- SD). No significant changes were observed in serum AMH levels throughout the menstrual cycle. The highest value was 3.9 +/- 1.3 ng/ml at day -12 and the lowest value was 3.4 +/- 1.1 ng/ml at day 14, and the difference was not significant. CONCLUSION: In this study, we demonstrated that serum AMH levels do not change significantly throughout the menstrual cycle. Hence, AMH exhibits a relatively stable expression during the menstrual cycle, making it an attractive determinant of ovarian activity.     

Cognitive function effects of suppressing ovarian hormones in young women

OBJECTIVE: To evaluate the effect of a pharmacologically induced, temporary suppression of ovarian hormones on healthy young women's cognitive functioning. DESIGN: Sixteen healthy women with normal menstrual cycles completed the California Verbal Learning Test, a digit span test, and a verbal fluency test in the follicular phase of a normal menstrual cycle and a second time after four monthly injections of the gonadotropin-releasing hormone (GnRH) agonist. Women were randomly assigned to complete a third testing either after resuming cycles in the follicular phase or after three more injections of the GnRH agonist and while wearing an estradiol patch. The control group consisted of 10 women who were tested three times in the follicular phase of their menstrual cycles. RESULTS: Results showed no change in cognitive functioning across sessions or groups in women with suppressed ovarian function. Women who had the highest levels of menopausal symptoms when taking the GnRH agonist did not have significantly lower cognitive functioning. CONCLUSIONS: This study did not find any effect of suppression in ovarian hormones on cognitive performance of young women.     

Menstrual cycle dependent variability for serum tumor markers CEA, AFP, CA 19-9, CA 125 and CA 15-3 in healthy women

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19-9, CA 125, CA 15-3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase-dependent difference was observed for CA 15-3, midluteal concentrations (mean +/- SEM; 26.33 +/- 1.56 U/ml) higher than the midfollicular (mean +/- SEM; 19.27 +/- 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively). CA 15-3 antigen is a product of the MUC-1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15-3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15-3 appears indicated in interpretation of individual results.     

Comparison of VO2max and disease risk factors between perimenopausal and postmenopausal women

OBJECTIVE: This study determines whether maximal oxygen consumption (VO2 max) is higher in perimenopausal women compared with similarly aged postmenopausal women and whether the lower VO2 max in postmenopausal women is associated with a higher total and visceral fat mass, less favorable lipid and glucose metabolism, and lower bone mineral density (BMD). DESIGN: Participants were 18 perimenopausal women (mean +/- SD; irregular menstrual cycle in the past 6 months) aged 49 +/- 4 years and 18 postmenopausal women (no menstrual cycle in the past year) aged 52 +/- 2 years who were matched for body mass index and race. Women were sedentary, and none were on hormone replacement therapy. Body composition (dual-energy x-ray absorptiometry and CT), VO2 max, fasting concentrations of sex steroid hormones, lipoproteins, insulin, and glucose were determined. RESULTS: VO2 max was 17% lower (22 +/- 3 v 27 +/- 7 mL.kg.min; P 相似文献