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Objective Menopausal status may increase cardiovascular disease (CVD) risk. Nitric oxide plays a role in the protection against CVD onset and progression but has not been studied around the time of menopause. We investigated associations between serum nitric-oxide metabolite (NOx) concentrations and menopausal status. Design Comparative case-control cross-sectional study. Setting Tehran Lipid and Glucose Study, university center. Sample Sub-groups from a cohort of 2137 women, of whom 213 met enrollment criteria. Methods We studied four sub-groups in a 1.2 ratio: (1) post-menopausal women (n = 29) with natural amenorrhea for 13–24 months, (2) age- and BMI-matched controls (n = 58) with regular menstrual cycles; (3) peri-menopausal women (n = 42) with natural amenorrhea for 1–12 months, and (4) age- and BMI-matched women as controls for the last group of women (n = 84). Main outcome measure Serum nitric oxide concentrations. Results Medians (inter-quartile ranges) of NOx in post-menopausal women and their controls were 31 (21.7–40.2) and 23.5 (17.2–31) μmol/L, respectively (p = 0.012). In peri-menopausal women and their controls the medians (inter-quartile ranges) were 28 μmol/L (18.5–50.5) and 25 (20–31.25) μmol/L, respectively (p = 0.035), but were not significantly different between peri- and postmenopausal women and were unchanged after adjustment for lipids. In a conditional fixed-effect logistic regression model, the risk of “transition to menopause” and “menopause” rose respectively 2.44- and 2.27-fold for a one-score increase in the NOx standard deviation. Conclusion Menopausal status, by itself and not as a consequence of aging, is associated with increased serum nitric oxide concentrations. Identification of variables associated with menopausal cardiovascular consequences may be used to improve women's health after menopause.

Objective. To characterize the physiological distribution of angiopoietins (Ang)-1 and Ang-2 and soluble endothelial cell-spesific tyrosine kinase receptor-2 (Tie-2) at term and following delivery. Design. A prospective, descriptive study. Setting. Helsinki University Central Hospital. Population. Twenty healthy term pregnant women undergoing elective cesarean delivery and their newborns. Methods. The concentrations were analysed by enzyme-linked immunosorbent assay in maternal antepartum and the first postpartum day sera, umbilical serum, amniotic fluid and maternal and newborn urine. Main outcome measures. Concentrations of Ang-1, Ang-1 and Tie-2. Results. Concentrations of maternal serum Ang-1 and Ang-2 decreased after delivery {[median (range)]: Ang-1, from 33 (25–51) to 30 (18–49) ng/mL, p= 0.017; and Ang-2, from 5.4 (1.8–18) to 1.4 (0.7–4.6) ng/mL, p < 0.0001}, whereas Tie-2 concentrations remained stable [23 (13–41) vs. 25 (14–29) ng/mL, p= 0.107]. Compared with maternal antepartum serum, umbilical serum concentrations of Ang-1 [46 (28–59) ng/mL, p < 0.0001] and Tie-2 [45 (21–71) ng/mL, p < 0.0001] were higher and those of Ang-2 similar [5.4 (1.8–18) vs. 4.2 (2.9–6.0) ng/mL; p= 0.067]. Low concentrations of Ang-1 [1.2 (0.1–2.2) ng/mL], Ang-2 [1.1 (0.3–4.1) ng/mL] and Tie-2 [0.4 (0.08–0.9) ng/mL] were observed in amniotic fluid, but they were undetectable in newborn urine and in most of the maternal urine samples. Conclusions. Maternal Ang-1 and Ang-2 concentrations decreased following delivery. Umbilical concentrations of Ang-1 and Tie-2 were higher than the maternal concentrations.

The purpose of this study was to determine normal values and evaluate clinical variables associated with postoperative C-reactive protein serum concentration after uncomplicated abdominal delivery.C-reactive protein serum concentrations were determined serially by a quantitative immunoturbidimetric assay in 479 clinically non-infected parturients undergoing uncomplicated Cesarean section, before operation and during the first week of puerperium. Associations between clinical variables and maximal postoperative C-reactive protein levels were examined by variance analysis.The preoperative values were significantly higher in parturients from whom samples were obtained after the onset of labor and/or rupture of the membranes (16 +/- 10 (s.d.) mg/l) compared with the preoperative values obtained from parturients operated with no labor and intact membranes (12 +/- 7 (s.d.) mg/l) (p0.0001). An overall significant increase was observed in C-reactive protein concentrations after delivery, peaking on the second postoperative day, compared with the preoperative values. In the parturients operated upon after the onset of labor or ruptured membranes, postoperative values were 24% higher up to the sixth postoperative day than in parturients operated upon with intact membranes and no labor. The onset of labor, duration of operation, the number of vaginal examinations and the duration of internal monitoring before operation were associated with the maximal postoperative C-reactive protein concentrations, but they explained only 9% of postoperative CRP level variation.The wide range of serum C-reactive protein concentrations during puerperium complicates its use as a simple marker in obstetric postoperative complications. However, after normal uncomplicated operative delivery, C-reactive protein concentrations rapidly decrease towards the baseline after the second to third postoperative day.

The role of progesterone levels during human labor is unclear.To investigate serum concentrations of progesterone and 5alpha-pregnane-3,20-dione in normal and abnormal deliveries.Venous and umbilical cord serum samples were collected from 108 parturient women. In a further 49 deliveries, arterial and venous umbilical cord sera were collected separately. The concentrations of progesterone and 5alpha-pregnane-3,20-dione were determined by radioimmunoassay. The delivery modes studied were: elective cesarean section; oxytocin-resistant dystocia; normal but induced delivery, and normal spontaneous delivery.Progesterone concentrations in maternal and umbilical serum were higher following normal labor than after dystocia (p0.005) and elective cesarean section (p0.005). The maternal and umbilical progesterone concentrations in dystocia and elective cesarean section were between 77-43% of those in normal labor. The concentrations did not vary between gestational weeks 37 and 42, within the different modes of delivery. The 5alpha-pregnane-3,20-dione serum concentration in the fetal compartment was twice that in the maternal compartment (p0.001); its concentration in venous umbilical serum was higher than in corresponding arterial samples (p0.001). No distinct differences in the 5alpha-pregnane-3,20-dione serum concentration were found with regard to parity or mode of delivery.High progesterone concentrations during parturition appear to be related to effective labor. The findings support results from in vitro experiments on human term myometrium.

Serum concentrations of follicle-stimulating hormone (FSH) were measured in a 33-year-old eurnenorrhoeic woman with primary infertility. Postmenopausal levels were obtained. Using an alternative assay, the patient was found to have normal levels of FSH. The probable cause of the misleading result is discussed.

Serum 5 alpha-pregnane-3,20-dione (5 alpha DHP) and progesterone (P) concentrations were studied in 11 women with uncomplicated pregnancies and deliveries during spontaneous labor and immediately after delivery. Blood samples were drawn 3-6 times during labor, as soon as possible post partum and 1, 3, 6 and 12 h post partum. P and 5 alpha DHP were analysed using RIA methods. There were no significant changes during labor in serum concentration of P and 5 alpha DHP, the values being 366 nmol/l +/- 25 SE and 128 nmol/l +/- 16 SE respectively. Whereas an earlier study has shown a significant decrease in 5 alpha DHP serum concentration between late pregnancy and spontaneous labor, this study showed no decrease during labor, indicating that the decrease occurred before the onset of labor. After parturition, the elimination of P from serum was faster and proportionally greater than for 5 alpha DHP, with a half-life of 38 min for P and 58 min for 5 alpha DHP. About 2-3 h post partum the serum concentrations stabilized just above luteal phase values. 12 h post partum, P and 5 alpha DHP were 12% and 23% respectively of pre-partum values.

The antigonadotropic action of danazol is still a subject of controversy. Danazol does not cause a consistent and significant suppression of basal gonadotropin concentrations in premenopausal women. In order to investigate the possible effects of danazol on circulating gonadotropin levels in the absence of gonadal feedback, postmenopausal women were studied. Twelve healthy women, at least 3 years past the menopause, volunteered. Their mean age was 61.1 +/- 5.5 (SD) years. Danazol in daily doses of 400, 600 or 800 mg was given randomized, to 4 patients each, for 4 weeks. Venous samples were drawn at -1, 0, +1, +2, +4 weeks of medication. FSH and LH in serum were measured by means of double antibody radio-immunoassay. There was no significant difference between any of the pre-treatment means in the three dose groups. After 4 weeks of danazol treatment, FSH had decreased by 18%, 31%, and 32% in the 400, 600 and 800 mg groups, respectively. The corresponding decreases in LH were 14%, 24% and 21%. There was no significant dose response between any of the doses used. In the absence of significant differences between the pre-treatment means and of significant dose response, data for all 12 patients were pooled for statistical evaluation. The mean decrease in FSH was significant only after 4 weeks (-4.8 micrograms/l; p less than 0.001). The mean decrease in LH was significant after 1, 2 and 4 weeks of treatment (-1.0 to -1.13; p less than 0.01 or less).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum 5 alpha-pregnane-3,20-dione (5 alpha DHP) and progesterone (P) concentrations before spontaneous labor were studied in 13 women whose pregnancy and delivery were uncomplicated. Blood samples were drawn twice weekly from the 36th week of gestation up to the onset of spontaneous labor. P and 5 alpha DHP values were analysed by applying RIA methods. Mean serum 5 alpha DHP concentrations declined significantly during the last week of pregnancy, from 135 +/- 12 nmol/l 5 days prior to spontaneous labor, to 111 +/- 10 nmol/l on the day spontaneous labor started (p less than 0.005). No significant changes in progesterone concentration occurred during the observation period. These results suggest a change in 5 alpha DHP production preceding the onset of spontaneous labor.

An aqueous two-phase equilibrium partition system was used to assay SHBG-binding capacity. Sera from groups of postmenopausal women before and during unopposed estrogen replacement therapy were analyzed. The induction of SHBG showed considerable differences between different estrogens. Ethinyl-estradiol in a daily dose of 0.05 mg gave a 70% increase in the serum concentration of this liver derived protein. Estradiol-17 beta, 2 mg daily and estrone sulphate 1.25 mg gave moderate changes, whereas estriol in different doses had no effect. SHBG induction may reflect estrogen overtreatment.

Cytoplasmic progestin receptors in human myometrium and myomata of uteri, both with and without tumors, were determined. The same concentration was found in all tissues when expressed in terms of tissue weight or DNA content. However, tumors had slightly more receptors when calculated per mg of soluble protein. This was due to the fact that myomata contained considerably less soluble protein than the normal myometrium. The receptors present were dependent upon the serum concentration of estradiol. Increasing values were accompanied by an increase in the number of receptors. At estradiol levels exceeding 500 pmoles/l their number reached a plateau and became independent of the hormone concentration. Progesterone had no influence except at very high levels where it depressed the number of receptors significantly. The investigation did not reveal any difference in the number of or the hormonal regulation of cytoplasmic progesterone receptors present in the various tissues. However, it showed that tumors contained considerably less soluble protein than normal myometrium.

The serum melatonin concentration was measured in 11 runners before and after a long-distance race, and during one menstrual cycle of another 11 runners who were performing a strenuous training programme, and in their 12 control subjects. The concentration of melatonin was significantly increased (p less than 0.05) after the competition, whereas during one menstrual cycle of female runners it did not differ from the corresponding concentrations of non-athletes. Training did not cause any chronic changes in melatonin secretion, and the serum melatonin increases following the physical exercise remained clearly below the nocturnal level. Hence, the antigonadotropic effect of endurance running activity is very likely not a melatonin-associated phenomenon.

The serum concentrations of the vitamin D metabolites 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D and 25,26-(OH)2D, and of vitamin D binding protein (DBP), were determined longitudinally in 22 vitamin D supplemented pregnant women, and in 17 age-matched non-pregnant women studied during the summer. The pregnant women had higher 25-OHD and 1,25-(OH)2D, similar 24,25-(OH)2D, and lower 25,26-(OH)2D concentrations than the non-pregnant group. The relative concentrations of 24,25-(OH)2D and 25,26-(OH)2D (expressed as the molar ratio of these metabolites to 25-OHD) were lower during pregnancy. The DBP levels were increased in pregnancy, but the calculated free fraction (i.e. not bound to DBP) of the hormonal form of vitamin D, 1,25-(OH)2D, was still persistently higher in the pregnant than in the non-pregnant women. The study suggests that a daily vitamin D supplement of 400 IU satisfies the vitamin D requirement of pregnant women living in a cool climate with limited sun exposure. The increased absolute and relative concentration of 1,25-(OH)2D and decreased relative levels of 24,25-(OH)2D and 25,26-(OH)2D further suggest that the increased intestinal calcium and phosphate absorption, which is known to occur during pregnancy, is at least partially mediated by the vitamin D endocrine system.

The 24-hour variation in total and unconjugated serum estradiol-17 beta as well as the daily variation in one-hour serum concentration values of FSH and LH have been examined in 9 post-menopausal women given 2 mg tablets of estradiol-17 beta daily for 14 days. The tablets were manufactured according to a new dispersion method aiming at producing essentially smaller crystals, thereby enhancing the bioavailability of the estradiol-17 beta. In comparison with other preparations, this one provides a more rapid absorption, reaching peak effect after only 1 or 2 hours and presenting a higher peak than has been found with any of the others. The elimination from serum combines a rapid initial phase followed by a very slow one. Thus serum levels of estradiol-17 beta 24 hours after administration are significantly higher than the levels measured before administration of the first tablet. A rather small but significant reduction in serum LH and FSH was observed on the third and subsequent treatment days.

The endometrial response in 10 postmenopausal women receiving estrogen replacement therapy was evaluated morphologically and quantified by morphometric analysis. During 6 months of cyclic treatment with percutaneous estradiol-17 beta, 3 mg daily, the mean relative endometrial gland volume increased from 10% to 40%. In each individual woman this morphometric parameter was significantly correlated to the serum concentration of estradiol-17 beta. The decline in FSH level during treatment showed no significant correlation to the endometrial response or the estrogen level. In some endometrial samples from women during treatment, glands with incomplete epithelial lining and rows of glandular epithelial cells were observed. It is suggested that these phenomena represent early forms of glandular development.

Immunoglobulins A, G and M and the complement components C3, C4 and CI-INH were quantified in sera from 59 women using an intra-uterine contraceptive device (IUCD). Most of the women were using a Cu IUCD, and the mean duration of use was 7.3 years. No differences in the concentrations were detected compared with control subjects. Our data, however, do not exclude a possible temporary change in the concentrations of immunoglobulins and complement components.The serum concentrations of immunoglobulins (Ig) A, G, and M and the complement components C3, C4, and C1-INH were quantified in 59 IUD users. The majority of study subjects were using a copper-containing device, and the mean duration of use was 7.3 years. No significant differences were found between study subjects and 49 controls who were not using an IUD or oral contraceptives in terms of the mean concentrations and standard deviations of the immunoglobulins and complement components. The mean concentrations of these factors in IUD users versus controls, respectively, were as follows: IgG, 10.95 gm/1 vs 10.07 gm/1; IgA, 2.04 gm/1 vs 1.91 gm/1; IgM, 1.61 gm/1 vs 1.50 gm/1; C3, 0.68 gm/1 vs 0.65 sgm/1; C4, 0.32 gm/1 vs 0.29 gm/1; and C1-INH, 0.32 gm/1 vs 0.32 gm/1. These findings pertain to long-term IUD use, and do not exclude the possibility that temporary increases in serum concentrations of immunoglobulins and complement components occur. Recommended for further research are longitudinal studies that compare concentrations of these factors before and at intervals after IUD insertion.

HPL concentration was determined by an immunochemical method from 48 serum samples of 41 women with a complication of pregnancy. While no correlation was found between HPL and pregnancy week, a statistically significant correlation was observed between HPL and oestriol. Placental and infant birth weights had a highly significant correlation with HPL. No significant deviation from the standard was observed in the serum HPL of toxaemia patients, or in HPL of those with prolonged pregnancies or variations in foetal heart rate. Because of great individual variation no general limits could be calculated for maternal serum HPL concentration at 30–42 weeks of pregnancy.