Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS: To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD: A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS: Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS: Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.     

Evidence for associations between common polymorphisms of estrogen receptor beta gene with homocysteine and nitric oxide.

BACKGROUND: Homocysteine and asymmetric dimethylarginine (ADMA) affect nitric oxide (NO) concentration, thereby contributing to cardiovascular disease (CVD). Both amino acids can be reduced in vivo by estrogen. Variation in the estrogen receptor (ER) may influence homocysteine and ADMA, yet no information is available on associations with single nucleotide polymorphisms in the estrogen receptor genes ERalpha (PvuII and XbaI) and ERbeta (1730G-->A and cx + 56 G-->A). OBJECTIVE: To find relationships between common polymorphisms associated with cardiovascular disease and cardiovascular risk factors homocysteine and ADMA. METHODS: In a cross-sectional study with healthy postmenopausal women (n = 89), homocysteine, ADMA, nitric oxide metabolites (NOx), plasma folate and ERalpha and beta polymorphisms ERalpha PvuII, ERalpha XbaI; ERbeta 1730G-->A (AluI), ERbeta cx + 56 G-->A (Tsp509I) were analyzed. RESULTS: Women who are homozygotic for ERbetacx + 56 G-->A A/A exhibited higher homocysteine (p = 0.012) and NOx (p = 0.056) levels than wildtype or heterozygotes. NOx concentration was also significantly affected by ERbeta 1730 G -->A polymorphism (p = 0.025). The ERbeta (p < 0.001) and ERalpha (p < 0.001) polymorphisms were in linkage disequilibrium. CONCLUSIONS: Women who are homozygotic for ERbetacx + 56 G-->A A/A may be at increased risk for cardiovascular disease due to higher homocysteine levels.     

The association of androgenic sex steroids with serum lipid levels in postmenopausal women

BACKGROUND: The aim of the present study was to examine the correlations between androgenic sex steroids and serum lipid levels in postmenopausal women. Methods. The study group included 72 postmenopausal women. Correlation analysis between serum hormone [dehydroepiandrosterone sulfate (DHEA-S), androstenedione, free testosterone and sex hormone binding globulin (SHBG)] and lipid [total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipoprotein (a) [Lp (a)], apolipoprotein A-1 (apo A-1) and apolipoprotein B (apo B)] levels was performed. RESULTS: DHEA-S was found to be positively correlated with HDL-C (r = 0.231, p = 0.049) and negatively correlated with Lp (a) (r = - 0.355, p = 0.002). These correlations were statistically significant even after adjustment for age and body mass index (BMI) (r = 0.332, p = 0.005 and r = -0.362, p = 0.002, respectively). SHBG was positively correlated with HDL-C (r = 0.352, p = 0.002). There was a significant but weaker correlation between SHBG and HDL-C levels after controlling for age and BMI (r = 0.243, p = 0.041). No other correlations were found between sex hormone and lipid levels. CONCLUSION: DHEA-S was found to be associated with a less atherogenic lipid profile in postmenopausal women.     

Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome.

AIM: This study was designed to examine the relationship between homocysteine (Hcy), lipoprotein levels and insulin resistance in obese and non-obese patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Eighty-five patients (38 obese, 47 non-obese) with PCOS and 50 healthy subjects (25 obese, 25 non-obese) were included in the study. PCOS was defined according to the Homburg criterion. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), insulin, 17-hydroxyprogesterone, free testosterone, androstenedione, vitamin B12 and folate were measured. Also, serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), apoprotein B (Apo B) and apoprotein A (Apo A) were determined. Plasma Hcy levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). RESULTS: Plasma Hcy levels were significantly higher in women with PCOS than in healthy women. HOMA-R (insulin resistance) was significantly higher in women with PCOS compared with healthy women. Serum fasting TC, LDL-C, TG, Apo B, vitamin B12 and folate levels were similar between PCOS and control groups. Lp(a) levels were higher in PCOS patients than in control subjects, whereas HDL-C and Apo A levels were lower. Compared with obese PCOS subjects, non-obese PCOS subjects had low HOMA-R, TC, LDL-C, TG, Apo B, Lp(a) and androgen levels. Plasma Hcy levels, serum HDL-C and Apo A levels were similar between obese and non-obese women with PCOS. Levels of HDL-C and Apo A were lower in both obese and non-obese PCOS patients than in obese and non-obese control subjects, whereas Lp(a) levels were higher. No correlation was observed between plasma Hcy, body mass index, HOMA-R, serum androgen levels, TC, LDL-C, HDL-C, Apo A, Apo B and Lp(a) levels. CONCLUSION: These results showed that elevated insulin resistance and plasma Hcy levels, and changes in serum lipid profile, which are possible risk factors for cardiovascular disorders, play important roles in the development of cardiovascular disease in both obese and non-obese patients with PCOS.     

Could androgens protect middle-aged women from cardiovascular events? A population-based study of Swedish women: The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women. DESIGN: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208). RESULTS: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group. CONCLUSION: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors.     

Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women

OBJECTIVE(S): Raloxifene, a selective estrogen receptor modulator, has beneficial estrogen agonist effects on bone and cardiovascular risk factors and estrogen antagonist effects on the breast and uterus. Limited clinical data have shown a sustained decrease in total cholesterol, low-density lipoprotein cholesterol, and homocysteine levels; an elevated homocysteine level is an independent risk factor for atherosclerosis. All of these studies were conducted in relatively young populations of women (mean age, 52-54 years). Raloxifene does not affect hot flushes, a major immediate symptom of menopause. This drug may therefore be useful in older women to prevent osteoporosis and cardiovascular disease. The aim of this clinical study was to evaluate the effects of raloxifene on plasma lipids and homocysteine in older women. STUDY DESIGN: The subjects were 45 healthy postmenopausal women, aged 60 to 70 years. The women were randomly assigned to therapy with raloxifene or placebo, 60 mg/d for 1 year. Twenty-six women received raloxifene and 19 received placebo. Checkups were performed every 3 months. At baseline and after 3, 6, 9, and 12 months of treatment we measured homocysteine, total serum cholesterol, triglycerides, and both high-density lipoprotein and low-density lipoprotein cholesterol. RESULTS: An effect on lipids was evident by 3 months with no significant additional modification at 12 months. Mean low-density lipoprotein cholesterol levels were lowered by 15% and total cholesterol was lowered by 8.5%. No reduction in high-density lipoprotein cholesterol or triglycerides was observed. After 3 months of therapy, homocysteine was significantly lower than at baseline (9.9 +/- 1.6 vs 11 +/- 2.1 micromol/L; P < .05). The greatest reduction with respect to baseline was reached after 6 months of therapy (-19.5% +/- 3%; P < .05). CONCLUSION(S): The results of our study show that raloxifene at a dose of 60 mg/d reduces serum concentrations of low-density lipoprotein cholesterol and total cholesterol in healthy older women. Our study shows that in older women raloxifene leads to a 19.5% +/- 3% reduction in fasting homocysteine levels. Raloxifene may have a favorable effect on the incidence of cardiovascular disease in older women.     

Cardiovascular risk at age 53 years in relation to the menopause transition and use of hormone replacement therapy: a prospective British birth cohort study

OBJECTIVES: To investigate cardiovascular risk factors and changes in risk factor levels in relation to menopausal stage, hysterectomy status and hormone replacement therapy use in a cohort of women aged 53 years with prospective data on smoking, lifetime socio-economic circumstances, and blood pressure and obesity at age 43 years. DESIGN: A prospective study. SETTING: England, Scotland and Wales. POPULATION: A cohort of women from the Medical Research Council Survey of Health and Development. METHODS: A total of 1303 women, aged 53 years, from a UK birth cohort study with measures of cardiovascular risk factors were classified by five menopausal status groups (premenopause, perimenopause, postmenopause, hysterectomy and hormone replacement therapy user). Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol measurements were taken, and analysed within the groups taking confounding variables into account. Changes in body mass index and blood pressure measurement in the same women obtained when 43 years of age were also compared. MAIN OUTCOME MEASURES: Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol. RESULTS: At 53 years, body mass index, waist circumference, total and low density lipoprotein cholesterol, and glycosolated haemoglobin (HbA1c) varied by menopausal status group, but blood pressure did not. Levels of total cholesterol and HbA1c increased across the natural menopause transition, before and after adjustment for body mass index, smoking and lifetime socio-economic circumstances. After adjustment for confounders, levels of risk factors for hysterectomised women were similar to those of naturally postmenopausal women. Women on hormone replacement therapy had lower levels of total and low density lipoprotein cholesterol, HbA1c, and were less obese than postmenopausal women. The lower obesity levels were partly due to these women already being less obese at age 43 years. CONCLUSIONS: This study showed that naturally postmenopausal or hysterectomised women had higher levels of metabolic risk factors compared with premenopausal or perimenopausal women of the same age. The long term stability of these differences and their translation into variations in incidence of cardiovascular disease remain to be seen. The lower levels of metabolic risk factors for women on hormone replacement therapy may protect against future cardiovascular disease or may be overwhelmed by other adverse, and as yet unknown, effects of hormone replacement therapy.     

The effect of hormone replacement therapy on the levels of serum lipids, apolipoprotein AI, apolipoprotein B and lipoprotein (a) in Turkish postmenopausal women

Objectives Estrogen replacement therapy alters the lipid profiles favorably for delaying atherosclerosis in postmenopausal women. The effects of estrogen plus progesterone combination therapy on lipids are controversial. This study was designed to evaluate the effect of female sex hormones on lipids and lipoproteins and to clarify the influence of progesterone on the effect of estrogen in postmenopausal women.Methods Of the 60 postmenopausal women admitted to our menopause clinic, 40 had intact uterus and received continuous 0.625 mg conjugated equine estrogen (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA), whereas the remaining 20 were hysterectomized and received 0.625 mg CEE daily. To assess the alterations in lipids and lipoproteins during menopause, 45 healthy premenopausal women were investigated. Lipid and lipoprotein levels were assessed in each subject at baseline and at the 6th and 18th months of therapy.Results In menopause, a shift towards more atherogenic lipid and lipoprotein profiles than those of the premenopausal state was found. Following 18 months of treatment, both regimens reduced total cholesterol (TC) levels as compared with the baseline (6.4 vs. 6.9% in the CEE/MPA and CEE groups, respectively). The CEE group had a more pronounced increase in high-density lipoprotein (HDL) cholesterol than the CEE/MPA group (10.3 vs. 8.8%, respectively). Both groups displayed reduced TC, low-density lipoprotein (LDL) cholesterol and apolipoprotein-B (ApoB) concentrations, whereas triglycerides increased, with a greater tendency to increase in the CEE/MPA group at the end of the trial. Also, the lipoprotein (a) [Lp(a)] levels decreased significantly (27.6 vs. 24.5% in the CEE/MPA and CEE groups, respectively). This decrease was more pronounced in subjects with a relatively higher basal Lp(a) concentration.Conclusion Both treatment regimens caused positive alterations in the lipid and lipoprotein profiles. This association might play a pivotal role in the postmenopausal increases in atherosclerotic diseases and cardioprotective effect of estrogen in postmenopausal women.     

连续服用低剂量复方炔诺酮与复方18-甲基炔诺酮对妇女脂质代谢的远期影响

目的 评价连续服用国产低剂量复方炔诺酮（复方炔诺酮）和低剂量复方１８－甲基炔诺酮（复方１８－甲）,对妇女脂质代谢的远期影响。方法 对连续服用复方炔诺酮（复方炔诺酮组,１６７例）和复方１８－甲（复方１８－甲组,１５０例）５～２５年及同期放置宫内节育器（ＩＵＤ）的健康妇女（对照组,１３１例）进行血清甘油三酯（ＴＧ）、总胆固醇（ＴＣ）、高密度脂蛋白（ＨＤＬ－Ｃ）、低密度脂蛋白（ＬＤＬ－Ｃ）、载脂蛋白Ａｌ（ＡｐｏＡｌ）、载脂蛋白Ｂ（ＡｐｏＢ）、脂蛋白ａ「Ｌｐ（ａ）」的测定。３组妇女的年龄、避孕药服用时间、体重指数、经济状况等,差异均无显著性。结果 与对照组比较,服用复方炔诺酮和复方１８－甲５～２５年妇女血清各项脂质水平均有不同程度的变化,两类口服避孕药使ＴＧ、ＨＤＬ－Ｃ显著升高;使ＡｐｏＡ１极显著升高。按不同避孕时间分     

Distinct lipid/lipoprotein profiles and hormonal responsiveness in nine ethnic groups of postmenopausal Asian women: the Pan-Asia Menopause (PAM) study.

BACKGROUND: Lipid/lipoprotein profiles, among other factors, are associated with risk of cardiovascular disease. Because cardiovascular disease varies in Asian countries, we hypothesized that lipid profiles differ in ethnic groups of postmenopausal Asian women. To add to the limited body of information currently available, we also investigated the effects of estrogen/progestin therapy on lipid/lipoprotein profiles in postmenopausal Asian women. METHODS: The Pan-Asia Menopause (PAM) study was a prospective, randomized, double-blind clinical trial evaluating 1028 postmenopausal women at 22 investigational centers in 11 Asian countries/territories. Subjects were randomly assigned to one of three doses of continuous combined conjugated estrogens (CE)/medroxyprogesterone acetate (MPA): CE/MPA (in mg/day) = 0.625/2.5, 0.45/1.5 or 0.3/1.5. The treatment period, following baseline evaluations, consisted of six continuous 28-day cycles. Analysis of lipid profiles was a secondary objective of the PAM study. Total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density cholesterol (VLDC-C), triglycerides and lipoprotein(a) were analyzed at a central laboratory by state-of-the-art methods. RESULTS: Mean concentrations of total cholesterol, LDL-C, VLDL-C and triglycerides differed significantly among the nine ethnic groups of postmenopausal women. This difference was independent of body mass index and age, two factors that also influenced lipid/lipoprotein profiles. Mean HDL-C concentrations also differed, but this difference was influenced by body mass index in a weak interaction. All three doses of CE/MPA significantly lowered total cholesterol. Treatment with the high and middle doses significantly lowered LDL-C, and increased HDL-C, VLDL-C and triglycerides. The high dose produced a significant decrease in lipoprotein(a). CONCLUSIONS: The different lipid/lipoprotein profiles in the nine ethnic groups of postmenopausal Asian women evaluated here suggest a relationship to differences in the prevalence of cardiovascular disease reported for different regions in Asia. However, the reported prevalence data on cardiovascular disease morbidity and mortality in the regions corresponding to the nine ethnic groups are insufficient to allow qualitative comparisons with the lipid profiles shown in our study. The lipid/lipoprotein changes in response to estrogen/progestin therapy observed here are consistent with those reported for Western women.     

Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome

Aim.?This study was designed to examine the relationship between homocysteine (Hcy), lipoprotein levels and insulin resistance in obese and non-obese patients with polycystic ovary syndrome (PCOS).

Materials and methods.?Eighty-five patients (38 obese, 47 non-obese) with PCOS and 50 healthy subjects (25 obese, 25 non-obese) were included in the study. PCOS was defined according to the Homburg criterion. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), insulin, 17-hydroxyprogesterone, free testosterone, androstenedione, vitamin B₁₂ and folate were measured. Also, serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), apoprotein B (Apo B) and apoprotein A (Apo A) were determined. Plasma Hcy levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA).

Results.?Plasma Hcy levels were significantly higher in women with PCOS than in healthy women. HOMA-R (insulin resistance) was significantly higher in women with PCOS compared with healthy women. Serum fasting TC, LDL-C, TG, Apo B, vitamin B₁₂ and folate levels were similar between PCOS and control groups. Lp(a) levels were higher in PCOS patients than in control subjects, whereas HDL-C and Apo A levels were lower. Compared with obese PCOS subjects, non-obese PCOS subjects had low HOMA-R, TC, LDL-C, TG, Apo B, Lp(a) and androgen levels. Plasma Hcy levels, serum HDL-C and Apo A levels were similar between obese and non-obese women with PCOS. Levels of HDL-C and Apo A were lower in both obese and non-obese PCOS patients than in obese and non-obese control subjects, whereas Lp(a) levels were higher. No correlation was observed between plasma Hcy, body mass index, HOMA-R, serum androgen levels, TC, LDL-C, HDL-C, Apo A, Apo B and Lp(a) levels.

Conclusion.?These results showed that elevated insulin resistance and plasma Hcy levels, and changes in serum lipid profile, which are possible risk factors for cardiovascular disorders, play important roles in the development of cardiovascular disease in both obese and non-obese patients with PCOS.     

Effect of hormone replacement therapy, tibolone and raloxifene on serum lipids, apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women.

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxffene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, dimacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n = 34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n = 80), continuous combined 17beta-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n = 58), tibolone 2.5 mg (n = 83) and raloxifene HCl 60 mg (n = 50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (-11.2%, -11.9% and -11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA1 were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA1, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, -13.6%; and ApoA1, -9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (-13.2 to -29.0%). In conclusion, each therapy regimen had a diferent effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

Platelet activation status decreases after menopause.

OBJECTIVE: The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation. BACKGROUND: Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women. METHODS: By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb-IIIa complex (GPIIb-IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets x mean fluorescence of positive platelets). Also, thromboxane A2 was quantified by means of its main plasma metabolite, thromboxane B2, by enzyme immunoassay. RESULTS: P-selectin and GPIIb-IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin+ platelets and of GPIIb-IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3 +/- 3, n = 10) and Group B (6.2 +/- 2.9, n = 27; mean +/- standard deviation (SD), p < 0.001). GPIIb-IIIa binding index also differed significantly between both groups (Group A: 18.8 +/- 2.3, n = 10 vs. Group B: 16.2 +/- 3.1, n = 27; mean +/- SD, p < 0.0018). Plasma concentration of thromboxane B2 was 1.07 +/- 0.5 pg/well before menopause (Group A, n = 10) and 1.9 +/- 4.1 pg/well after menopause (Group B, n = 27), not significantly different (mean +/- SD, baseline x therapy, p = 0.85). CONCLUSIONS: After the menopause, climacteric women--whose estradiol status is low--have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.     

Levels of lipoprotein(a) in normal and compromised pregnancy

OBJECTIVE: To study maternal lipoprotein(a) levels in normal pregnancy and in pregnancy with evidence of vascular disease in the maternal uteroplacental circulation defined by Doppler ultrasound study. SAMPLES: Maternal venous blood was collected from 75 normal pregnant women and 68 pregnant women with evidence of potential uteroplacental vascular disease identified by Doppler ultrasound study. METHODS: Plasma lipoprotein(a) levels in maternal blood were measured using an enzyme-liked immunosorbent assay method. MAIN OUTCOME MEASURES: Plasma lipoprotein(a) levels and pregnancy outcome were examined. RESULTS: None of the normal group had lipoprotein(a) levels greater than 30 mg/dl, a cutoff level which has been associated with increased risk of atherosclerosis. 28 of the 68 women with uteroplacental insufficiency had lipoprotein(a) levels greater than this cutoff level. In this group there was a statistically significant higher prevalence of preeclampsia in comparison with women with a normal lipoprotein(a) level (p < 0.001). The lipoprotein(a) level was significantly higher in severe (n = 13, median 60.5 mg/dl, P < 0.001] than in mild preeclampsia (n = 5, median 34 mg/dl). Those with high levels (> 30 mg/dl) exhibited significantly more adverse indices of fetal outcome. CONCLUSION: This study has demonstrated that high levels of lipoprotein(a) interfere with uteroplacental circulation and play a role in the pathophysiology of preeclampsia. Lipoprotein(a) concentrations are associated with the severity of the disease. We suggest that high levels of lipoprotein(a) might affect the placenta and fetus.     

Effect of hormone replacement therapy,tibolone and raloxifene on serum lipids,apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxifene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, climacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n=34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n=80), continuous combined 17β-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n=58), tibolone 2.5 mg (n=83) and raloxifene HCl 60 mg (n=50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA₁), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (?11.2%, ?11.9% and ?11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA₁ were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA₁, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, ?13.6%; and ApoA₁, ?9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (?13.2 to ?29.0%). In conclusion, each therapy regimen had a different effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

Effects of third-generation oral contraceptives on high-sensitivity C-reactive protein and homocysteine in young women

OBJECTIVE: To evaluate the effect of third-generation oral contraceptives on high-sensitivity C-reactive protein (CRP), homocysteine, and lipids levels in a population of young, fertile, nonobese women. METHODS: Blood markers were evaluated in 277 healthy white women (mean age 23 years and mean body-mass index 21 kg/m(2)). Seventy-seven oral contraceptive users were compared with 200 non-oral contraceptive users. Progressive cutoffs of high-sensitivity CRP and homocysteine levels were examined. RESULTS: Levels of high-sensitivity CRP posing a high risk of cardiovascular disease (3.0 to less than 10.0 mg/L) were found in 27.3% of oral contraceptive users and in 8.5% of non-oral contraceptive users (odds ratio 4.04; 95% confidence interval [CI] 1.99-8.18). Levels of high-sensitivity CRP at intermediate risk (1.0 to less than 3.0 mg/L) were found in 32.5% of oral contraceptive users and in 11.0% of non-oral contraceptive users (odds ratio 3.89; 95% CI 2.03-7.46). Notably, non-oral contraceptive users were 8.65 (95% CI 4.39-17.1) times as likely to demonstrate a protective level of high-sensitivity CRP (less than 0.5 mg/L) compared with oral contraceptive users. Oral contraceptive use increased serum triglycerides (P<.001) and total cholesterol P=.001); however, high-density lipoprotein, not low-density lipoprotein, contributed to this increase. A decreased ratio of low-density lipoprotein to high-density lipoprotein cholesterol was observed in oral contraceptive users compared with nonusers (P=.016). Oral contraceptive use did not affect homocysteine levels. CONCLUSION: Third-generation oral contraceptive use increases low-grade inflammatory status measured by high-sensitivity CRP concentrations. Alteration of inflammatory status in oral contraceptive users could affect the risk of venous thromboembolism, cardiovascular disease, and other oral contraceptive-associated adverse conditions in young women.     

An in vivo system in man for quantitation of estrogenicity. I. Physiologic changes in binding capacity of serum corticosteroid-binding globulin

A modified method of measuring the binding capacity of corticosteroid-binding globulin (CBG-BC) in serum using 3H-cortisol saturation-charcoal adsorption is described. Forty serum samples per day can be assayed in duplicate, each sample with a heated nonspecific binding blank (60 degrees C.). The interassay coefficient of variation is less than 6 per cent. All age groups of men and women had similar levels of CBG-BC, except postmenopausal women, whose levels were higher (15.9 +/- 0.2 vs. 18.7 +/- 0.8 microgram per 100 ml., mean +/- standard error of the mean, respectively; z = -3.51, p less than 0.001). The variance of serum levels of CBG-BC throughout the menstrual cycle in five women was small (coefficient of variation = 13 per cent) and showed no relationship to the marked and cyclic changes in estradiol levels (coefficient of variation = 73 per cent). In pregnancy the levels of CBG-BC increased linearly after estradiol levels exceeded 1,300 pg. per milliliter and after estrone levels exceeded 500 pg. per milliliter (r = 0.88, p less than 0.001; and r = 0.85, p less than 0.001, logarithmic regression analysis). The findings of this study indicate that serum levels of CBG-BC are relatively constant in men and menstruating women. In pregnancy after a high threshold of endogenous estrogen is reached, CBG-BC increases in a direct dose-response manner as levels of estradiol increase further.     

A marathon: the immediate effect on female runners' luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, and cortisol levels

This study was designed to measure the changes that occur in luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, and cortisol levels in women at the immediate conclusion of a marathon and to compare the results with those in women on the United States Women's Water Polo Team at the conclusion of a strenuous practice session. Thirty-one women runners were included in this study, and each woman served as her own control. Thirteen women were studied from the United States Women's Water Polo Team. In the postmarathon group, cortisol levels showed a mean increase of 211% (p = less than 0.005), FSH levels were unchanged; LH levels, contrary to other published reports, were reduced by 36% (p = less than 0.005); and prolactin levels showed a mean increase of 327% (p = less than 0.005). These results were analyzed in the age groups 20 to 30, 30 to 40, and 41 +. All age groups had similar changes. In members of the United States Women's Water Polo Team, there were no significant changes in cortisol, FSH, LH, or testosterone levels. Prolactin levels showed an average increase of 70% (p = less than 0.002). These data indicate that acute exercise by running a marathon does alter the immediate hormonal profile. The data also indicate that acute exercise in an aquatic program results in a different response.     

Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women

Serum lipids and lipoproteins were examined in a group of 45 healthy postmenopausal women who were treated for 2 years with either 3 mg of percutaneous estradiol (n = 20) or placebo (n = 25). Percutaneous estradiol was given alone during the first year of treatment and in combination with oral micronized progesterone (200 mg) for 12 days of each cycle during the second year. The women were examined every 3 months throughout the 2 years. Percutaneous estrogen therapy significantly reduced total serum cholesterol and low-density lipoprotein cholesterol, whereas no significant differences were observed in serum triglycerides and high-density lipoprotein cholesterol. Addition of oral progesterone during the second year of treatment did not produce any significant alterations in serum total cholesterol or low-density lipoprotein cholesterol, both of which remained significantly reduced. Serum triglycerides remained virtually unchanged, whereas a slight but significant increase (p less than 0.05) was observed in high-density lipoprotein cholesterol levels at the end of the study period. We conclude that percutaneous estrogen administration produces changes in total serum cholesterol and low-density lipoprotein cholesterol levels similar to those observed after oral estrogen administration. However, the magnitude and time course of the response seem to be modulated by the route of administration. Addition of oral micronized progesterone does not influence the beneficial estrogenic actions on serum lipids and lipoproteins and seems to be a proper "progestogen" in percutaneous estrogen therapy.     

Exercise Improves Self-Reported Sexual Function Among Physically Active Adults

BackgroundSexual dysfunction is common among adults and takes a toll on quality of life for both men and women.AimTo determine whether higher levels of weekly cardiovascular exercise are protective against self-reported sexual dysfunction among men and women.MethodsWe conducted an international online, cross-sectional survey of physically active men and women between April and December 2016, assessing exercise activity categorized into sextiles of weekly metabolic equivalent-hours. Odds ratios (ORs) of sexual dysfunction for each activity sextile compared with the lowest sextile were calculated using multivariable logistic regression, controlling for age, body mass index, diabetes mellitus, tobacco/alcohol use, sport, and marital status.Main Outcome MeasuresFemale sexual dysfunction was defined as a score ≤26.55 on the Female Sexual Function Inventory and erectile dysfunction (ED) was defined as a score ≤21 on the Sexual Health Inventory for Men.Results3,906 men and 2,264 women (median age 41–45 and 31–35 years, respectively) met the inclusion criteria for the study. Men in sextiles 2–6 had reduced odds of ED compared with the reference sextile in adjusted analysis (P_trend = .03), with an OR of 0.77 (95% CI = 0.61–0.97) for sextile 4 and 0.78 (95% CI = 0.62–0.99) for sextile 6, both statistically significant. Women in higher sextiles had a reduced adjusted OR of female sexual dysfunction (P_trend = .02), which was significant in sextile 4 (OR = 0.70; 95% CI = 0.51–0.96). A similar pattern held true for orgasm dissatisfaction (P_trend < .01) and arousal difficulty (P_trend < .01) among women, with sextiles 4–6 reaching statistical significance in both.Clinical ImplicationsMen and women at risk for sexual dysfunction regardless of physical activity level may benefit by exercising more rigorously.Strengths & LimitationsStrengths include using a large international sample of participants with a wide range of physical activity levels. Limitations include the cross-sectional design, and results should be interpreted in context of the study population of physically active adults.ConclusionHigher cardiovascular exercise levels in physically active adults are inversely associated with ED by self-report in men and protective against female sexual dysfunction in women.Fergus KB, Gaither TW, Baradaran N, et al. Exercise Improves Self-Reported Sexual Function Among Physically Active Adults. J Sex Med 2019;16:1236–1245.