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Unique efficiency of methionine metabolism in premenopausal women may protect against vascular disease in the reproductive years.

Premenopausal women develop occlusive artery disease less frequently than postmenopausal women. In coronary heart disease, higher blood levels of homocysteine-cysteine mixed disulphide have been reported. Therefore, in healthy subjects, we studied the role of menopausal status in the transsulphuration of methionine in 10 premenopausal and 10 postmenopausal women. To exclude the role of aging, we compared these results with those in 10 younger and 10 older men of comparable age groups. An oral methionine load (0.1 g/kg of body weight) was administered after overnight fasting. Before and during 8 h, thereafter, serum levels of methionine, homocystine, and homocysteine-cysteine mixed disulphide were measured. In the fasting state, serum methionine levels were similar in the premenopausal women and both groups of men. Postmenopausal women had significantly lower fasting levels. Peak levels and clearances of methionine after loading did not differ between the groups. In the fasting state, homocystine was never detectable; yet, after methionine loading, slight homocystinemia was present in 12 out of 20 men, and was more pronounced in all postmenopausal women. However, homocystinemia did not occur in any of the premenopausal women after loading. Fasting serum homocysteine-cysteine mixed disulphide levels did not differ between both groups of men and postmenopausal women. In premenopausal women, both fasting and postloading disulphide levels were significantly lower than in any other group. We conclude that premenopausal women have a unique efficiency of methionine handling, and thereby are preserved against the accumulation of homocysteine after methionine loading. We speculate that this phenomenon might account for the lower incidence of vascular disease in women in the reproductive life cycle.

Adult↗

Contraception guidance in women with pre-existing disturbances in carbohydrate metabolism.

OBJECTIVES: To review our studies on the clinical and metabolic impact of contraceptive methods in women with insulin dependent diabetes mellitus (IDDM) and women with previous gestational diabetes mellitus (GDM) in order to provide suggestions for the contraceptive counselling of these women. METHODS: The clinical events following first insertions of copper IUDs were studied in 103 women with IDDM and in 119 non-diabetic women. Moreover we studied the effects on glycometabolic control and lipid metabolism in women with well-controlled IDDM using low-dose oral contraceptives (OCs) containing ethinylestradiol combined with norethisterone (n = 10), levonorgestrel (n = 9) or gestodene (n = 11). Hemostatic and endothelial function was also studied in the women using the gestodene-containing preparation. Finally, we studied the impact of oral contraceptives on the insulin sensitivity in women with previous GDM. RESULTS: The continuation rates and indications for medical removal of the IUDs were similar in the diabetic and the non-diabetic women. There was no increased pregnancy rate or increased frequency of pelvic inflammatory disease in the diabetic women. The glycemic control was not changed by the OCs and none of the treatment regimens were associated with changes in plasma lipids linked to increased risk of atherosclerosis. Indications of increased fibrin formation, which seemed to be compensated by increased fibrinolytic activity, were noted with the gestodene-containing preparation. None of the women developed microalbuminuria during the study. Compared to normal women, we found reduced insulin sensitivity in the women with previous GDM using the pill. CONCLUSION: Intrauterine devices and barrier methods can be used by diabetic women with the same reservations as in the general population. Low-dose OCs do not influence the glycemic control and have no adverse impact on plasma lipids. The balance between fibrin formation and resolution was maintained during intake of the gestodene-containing pill. Our findings suggest that combined oral contraceptives can be used in women with uncomplicated IDDM and in women with previous GDM if clinical and metabolic monitoring can be ensured.

Case-Control Studies↗

The natural course of asymptomatic Chlamydia trachomatis infections: 45% clearance and no development of clinical PID after one-year follow-up.

The natural course of asymptomatic Chlamydia trachomatis infections in women was studied during one year in a cohort based nested case-control study. Healthy women (n = 744, from four company health services in Amsterdam) with a medical check-up prior to job engagement were included. C. trachomatis-positive women (n = 30, cases) and a randomly selected control group of C. trachomatis-negative women (n = 186, controls) were followed for one year. Urine specimens (at one, six and 12 months) were analysed for the presence of C. trachomatis-DNA and the C. trachomatis-serovars, and questionnaires were filled in. The C. trachomatis prevalence and natural course in relation to demographic and sexual characteristics after one, six and 12 months were studied. The main outcome measures were 1) the prevalence of C. trachomatis using urine specimens; 2) self-reported complaints; 3) clinical symptoms reported to the coordinating physicians. The prevalence of asymptomatic C. trachomatis infections was 4% and there was no correlation with demographic and sexual characteristics. The person/year clearance rate was 44.7% per year. None of the C. trachomatis-positive women developed clinical symptoms or used C. trachomatis specific antibiotic treatment. Women with or without an asymptomatic infection had the same number of self-reported urogenital complaints during follow-up. In persisting infections twice as many C. trachomatis-serovar E infections were detected as compared to clearing infections. Our findings showed that almost half of the asymptomatic C. trachomatis infections in women cleared during one year of follow-up and none developed clinical pelvic inflammatory disease (PID), which is a much lower figure than previously suggested. Therefore these data are important for cost effectiveness calculations in screening programmes for asymptomatic C. trachomatis infections.

Case-Control Studies↗

Progesterone in gestational diabetes mellitus: guilty or not guilty?

Insulin resistance is one of the metabolic changes in pregnancy, but only a fraction of women develop overt impaired glucose tolerance or frank diabetes. Most women are able to compensate this altered metabolic state by increasing the amount of insulin produced by the pancreatic beta cells. Progesterone might well be the key to the development of gestational diabetes. Previously high progesterone levels have already been shown to be correlated with the development of glucose abnormalities in pregnancy and now, in a new paper, progesterone receptor-knockout mice are found to have improved glucose tolerance. These mice showed increased insulin secretion, which is probably linked to the presence of increased numbers of beta cells in their pancreas. Is progesterone therefore the 'ultimate bad guy', prohibiting normal adaptation of the pancreatic beta-cell reserve during pregnancy?

Animals↗

Serum inhibin B correlates with successful ovulation in infertile women.

PURPOSE: To investigate whether inhibin B and activin A serum and follicular fluid levels in infertile women undergoing induction of superovulation correlate with successful ovulation. METHODS: Infertile women (n = 16) (30-43 years of age) undergoing induction of superovulation for assisted reproduction were studied. A blood sample was collected before and days 3, 8, and 12 during the induction of superovulation. A follicular fluid sample at the time of ovarian pick up was also collected. Serum and follicular fluid were assayed for inhibin B, activin A, and estradiol. RESULTS: According to the successful follicular development women were divided in two groups: (A) responders (n = 10) and (B) poor responders (n = 6). Women of group A showed mean follicular fluid inhibin B levels higher than in group B (P = 0.001), while no significant difference for activin A levels was found. During induction of superovulation serum activin A levels did not change in both groups of women, while inhibin B and estradiol levels significantly increase only in responder women (P < 0.001). Serum inhibin B and estradiol levels correlated with follicles developed > or = 10 mm (P = 0.000). CONCLUSIONS: Serum inhibin B is an effective marker of follicular development in infertile women undergoing induction of superovulation, and may represent a further marker for ovarian follicular capacity.

Activins↗

Risk stratification of obesity as a coronary risk factor.

We examined the extent of coronary heart disease (CHD) risk factor clustering in overweight persons with a body mass index (BMI) of 25 to 29 and an obesity BMI of >/=30 and the influence of this on the hazard of myocardial infarction and coronary mortality. A total of 1,309 men and 739 women aged 30 to 74 years, initially free of cardiovascular disease, comprised the overweight subject group, and 375 men and 356 women comprised the obese subject group at risk. The sample was derived from the original Framingham Study cohort at the 11th biennial examination, and their offspring at initial examination. During 16 years of follow-up of overweight subjects, 188 men and 44 women had CHD events, indicating an age-adjusted rate that was not much different from the slim subjects. In the obese subject group, 72 men and 37 women developed CHD, corresponding to age-adjusted risk ratios 1.48 times that of lean men, and 2.09 times that of lean women. Risk factors were categorized as systolic blood pressure >/=140 mm Hg, total cholesterol >/=240 mg/dl, high-density lipoprotein (HDL) cholesterol <35 mg/dl for men and <40 mg/dl for women, heart rate >80 beats/min, history of smoking, history of type 2 diabetes, and electrocardiographic left ventricular hypertrophy. Being overweight occurred in isolation of CHD risk factors in 22% of men and in 16.4% of women. Being obese occurred in isolation in only 12.8% of men and 9% of women. Clusters of >/=2 risk factors occurred in 56% of obese men and in 62.4% of obese women, a frequency substantially exceeding that in slim subjects. Compared with obese men without risk factors, those with >/=3 factors had a 2.07 age-adjusted relative risk of developing CHD, and obese women had a 10.9 relative risk (p <0.05). Being overweight and obese promotes clusters of CHD risk factors that greatly influence their impact. Global risk assessment can identify high-risk overweight candidates for CHD who most urgently need correction of associated risk factors, as well as sustained weight reduction.

Adult↗

Cerebrovascular hemodynamics in chronic hypertensive pregnant women who later develop superimposed preeclampsia.

OBJECTIVE: We have previously shown that normotensive pregnant women who later develop preeclampsia demonstrate lower baseline pulsatility index (PI) and resistance index (RI) but normal vasodilatory responses to stimulation tests. In the current study, we tested the hypothesis that women with chronic hypertension who later developed superimposed preeclampsia behave similarly. METHODS: Transcranial Doppler ultrasound was performed on 17 women with chronic hypertension during the second trimester of pregnancy to measure middle cerebral artery (MCA) velocities. Superimposed preeclampsia developed in seven patients (SUPER group) while the rest did not develop preeclampsia (CHT group). Measurements were performed in the left lateral position at baseline on room air, during 5% CO2 inhalation, and during a 2-minute isometric handgrip test. Blood pressure, heart rate, O2 saturation, and end-tidal PCO2 were recorded with each Doppler measurement. Mean PI, RI, and cerebral perfusion pressure (CPP) at each time were compared using two-way repeated measures analysis of variance. Statistical significance was set at P < .05. RESULTS: The women who developed superimposed preeclampsia did this an average of 8.7 +/- 1.3 weeks after the study. MCA PI and RI were lower, and CPP higher, in the SUPER group compared to the CHT group (0.64, 0.46, and 80.7 vs 0.74, 0.51, and 63.6, respectively; P < .05). Both maneuvers caused reduction in MCA PI and RI in both groups, whereas CPP increased only in the SUPER group. CONCLUSIONS: These findings suggest that women destined to develop preeclampsia have cerebral hemodynamic changes that predate the development of overt preeclampsia.

Adult↗

Mid-trimester uterine artery Doppler screening as a predictor of adverse pregnancy outcome in high-risk women.

OBJECTIVE: To assess the value of uterine artery Doppler ultrasound screening, when performed in a clinical setting, to predict complications of impaired uteroplacental blood flow in high-risk women. DESIGN: A prospective audit. SUBJECTS: A total of 116 pregnancies in 114 women at high risk of pre-eclampsia and/or small-for-gestational-age (SGA) babies attending a maternal-fetal medicine clinic at National Women's Hospital, a tertiary referral hospital, Auckland, New Zealand. METHODS: Uterine artery Doppler screening was performed as part of clinical practice between 22 and 24 weeks' gestation. A resistance index (RI) was calculated from each uterine artery and the presence or absence of a notch was determined. An RI of > 0.58 was defined as abnormal and an RI of > or = 0.7 was defined as very abnormal. The main outcome measures were: pre-eclampsia, SGA baby (birth weight < 10th centile), placental abruption, intrauterine death, 'all' and 'severe' outcomes. RESULTS: Thirty-two (27.5%) women developed pre-eclampsia, 31 (26.7%) had SGA babies, 23 (20%) were delivered at < 34 weeks because of pregnancy complications, and there were three (2.6%) placental abruptions and three (2.6%) perinatal deaths. The sensitivity of any RI of > 0.58 for pre-eclampsia, SGA, 'all' outcomes and 'severe' outcome was 91%, 84%, 83% and 90%, respectively. The specificity of any RI of > 0.58 for these outcomes was 42%, 39%, 47% and 38%, respectively. The positive predictive value of any RI of > 0.58 for the same outcomes was 37%, 33%, 58% and 24%, respectively. Among women with both RI values of > or = 0.7, 58%, 67%, 85% and 58% developed pre-eclampsia, SGA, 'all' and 'severe' outcomes, respectively. In women with bilateral notches, 47%, 53%, 76% and 65% developed the respective outcomes. Women with both RI values of > or = 0.7 and women with bilateral notches had relative risks of 11.1 (95% CI 2.6-46.4) and 12.7 (95% CI 4.0-40.4) for developing severe outcome, respectively. Only 5% of women with both RI values of < 0.58 developed a severe outcome. CONCLUSION: In high-risk women, uterine artery Doppler waveform analysis performed best in the prediction of severe adverse outcome and was better than clinical risk assessment in the prediction of pre-eclampsia and SGA babies. Further studies are necessary to determine how information from uterine artery Doppler studies should modify current practice in high-risk women.

Adult↗

Effect of repeated whole blood donations on serum immunoreactive erythropoietin levels in autologous donors.

The effect of repeated phlebotomy on serum immunoreactive erythropoietin levels was studied prospectively in 69 autologous blood donors. At the time of the initial phlebotomy, 11 men (33%) and two women (6%) were anemic; during the course of blood donations, anemia (defined as a hematocrit less than 0.41 for men and less than 0.36 for women) developed in an additional 17 men (71%) and 14 women (45%). Although there was an increase in the level of serum immunoreactive erythropoietin with successive phlebotomies, the increase was not substantially out of the normal range. The lack of an erythropoietic response to repeated phlebotomies in association with the small increment in the serum erythropoietin level was not due to iron deficiency, since the level of red-cell free protoporphyrin did not increase in these patients. We conclude that within the hematocrit range permissible for autologous blood donation, the degree of anemia experienced is insufficient to initiate an adequate increase in erythropoietin production; as a consequence, mild anemia develops in a majority of donors, and the volume of blood donated is inadequate to meet their operative needs.

Adolescent↗

Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women.

OBJECTIVE: To estimate the rate of congenital varicella zoster virus syndrome in neonates born to women developing varicella zoster virus infections during pregnancy. METHODS: Pregnant women with clinical varicella zoster virus infection were enrolled at ten perinatal centers. Maternal and fetal immunoglobulin (Ig) G and IgM by fluorescent antibody confirmed 74.3% of cases. Specialists examined neonates at 0-6 months, 7-18 months, and 19-30 months after delivery to detect abnormalities of their eyes, hearing, and physical and developmental features. A hierarchical set of criteria was used to define congenital varicella syndrome. A jury of four investigators assigned the classification of all findings. RESULTS: In 362 women enrolled from 1993 to 1996, 15 had herpes zoster, and 347 had primary varicella zoster virus infection. Varicella zoster virus affected 140 women (38.7%) in the first trimester, 122 (33.7%) in the second trimester, and 100 (27.6%) in the third trimester. Five twin pairs were included. Only one case (0.4%) of definite congenital varicella syndrome was found, a 3360-g female infant having a left retinal macular lesion with typical skin scars after maternal varicella at 24 weeks. The maternal blood sample at birth was negative for IgG antibodies to toxoplasmosis and cytomegalovirus. Two cases involved fetal death at 20 weeks and fetal hydrops at 17 weeks after maternal varicella at 11 and 5 weeks, respectively. We found no cases of limb hypoplasia, microcephalus, or cataract. CONCLUSION: The frequency of congenital varicella syndrome is very low (0.4%) in a prospectively studied cohort. Eye examinations of exposed infants had a low yield.

Adult↗

Pregnancy experience in women who later developed oestrogen-related cancers (Denmark).

OBJECTIVES: There has been speculation that women with oestrogen-related cancers have been exposed to high levels of oestrogen in earlier life and therefore also during their pregnancies prior to the disease. For this reason we examined signs of reproductive outcome related to oestrogen exposure such as twinning, sex ratio, birth weight and congenital malformation in women who later were diagnosed with breast cancer, endometrial or ovarian cancer. METHODS: For 5213 children born to women who later developed breast cancer, 557 children born to women who later developed ovarian cancer and 173 children born to mothers with endometrial cancers we selected as a control four times as many newborns of mothers without these cancers after matching for mothers' parity, age, date of birth and hospital attended. All data were extracted from existing nationwide files. Most of the women's reproductive lives fell within the period of the birth registry from 1973 to 1993. RESULTS: No differences in sex ratio, birth weight or malformation were found between the newborns to cancer or control mothers in any of the cancer groups studied. The only significant findings were less than expected births of twins to mothers who later developed cancer of the ovaries and a higher proportion of newborns with a birth weight over 4000 g in the cancer corpus uterus group. CONCLUSION: Although the amount of information is limited for endometrial and ovarian cancers, we found no strong indication of elevated oestrogen levels during pregnancy.

Adult↗

Is conservative management of preterm rupture of membranes justified?

The management of preterm rupture of membranes (ROM) is controversial. Some advise immediate delivery and others advocate conservative approach in the hope of decreasing morbidity and mortality rates associated with prematurity. A retrospective review of 75 pregnancies with preterm ROM treated conservatively was performed to delineate the relative risk factors. All patients with preterm ROM were placed at bed rest until either labor or chorioamnionitis prompted delivery. Chorioamnionitis developed in 25% of the cases. The percentage of women developing chorioamnionitis increased with duration of ROM. Fetal morbidity and mortality was not increased in the group with chorioamnionitis. Hyaline membrane disease (HMD) and intra ventricular hemorrhage (IVH) were the major causes of neonatal death in the entire group of preterm ROM. There was a significant relationship between neonatal mortality and birth weight. The smaller the birth weight, the greater the risk of neonatal death. Our data support the conservative approach to preterm ROM especially in the very low birth weight group where extreme caution must be taken before a decision is made to terminate pregnancy.

Adult↗

Generalization effects of coping-skills training: influence of self-defense training on women's efficacy beliefs, assertiveness, and aggression.

Concern for personal safety is a pervasive stressor for many women. Developing competencies in physical self-defense may empower women to engage more freely in daily activities with less fear. This study assessed the effects of physical self-defense training on multiple aspects of women's perceived self-efficacy and other self-reported personality characteristics. Training powerfully increased task-specific (self-defense) efficacy beliefs as well as physical and global efficacy beliefs. Training increased self-reported assertiveness, and posttraining decreases in hostility and aggression were found on several of the subscales of The Aggression Questionnaire (A. H. Buss & M. Perry, 1992), indicating that training did not have an aggression-disinhibiting effect. In the experimental condition, most of the effects were maintained (and some delayed effects appeared at follow-up.

Adaptation, Psychological↗

Effect of HIV infection on atypical squamous cells of undetermined significance.

BACKGROUND: Detection of atypical squamous cells of undetermined significance (ASCUS) is a cervical cytologic finding that is suggestive but not definitive of squamous intraepithelial lesions (SILs). METHODS: We examined the risk, characteristics, and progression of ASCUS in women with and without human immunodeficiency virus (HIV) infection. Cervical Papanicolou (Pap) test and colposcopy data were obtained at the first 10 semiannual visits for the HIV Epidemiology Research study of 774 HIV-infected and 480 demographically similar, HIV-uninfected women in the United States. Multiple logistic regression models and Cox proportional hazards models were utilized. RESULTS: ASCUS was more common among HIV-infected women (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0] to 2.6 [95% CI, 1.9-3.6]) after adjustment for human papillomavirus (HPV) infection and other risk factors (e.g., race, condyloma, and prior Pap test result). Among women with normal Pap test results at enrollment, the cumulative incidence of ASCUS was 78% among HIV-infected women and 38% among HIV-uninfected women. HIV-infected and HIV-uninfected women with ASCUS did not differ by prevalence of indices of inflammation (inflammation on Pap test and leukocytes on cervical gram stain). HPV infection, including high risk types, was more common among HIV-infected women with ASCUS. Among women with ASCUS, 60% of HIV-infected and 25% of HIV-uninfected women developed SILs (P < .01). Compared with HIV-infected women with higher CD4+ lymphocyte counts, HIV-infected women with CD4+ lymphocyte counts < 200 cells/microL were more likely to present subsequently with a SIL detected by Pap test (OR, 1.7; 95% CI, 0.8-3.6). CONCLUSIONS: Higher risk of SIL following the appearance of ASCUS among HIV-infected women, especially women with low CD4+ lymphocyte counts, supports the need for follow up with colposcopy and histologic examination, as indicated, to allow early detection and treatment of SIL.

CD4 Lymphocyte Count↗

Pulmonary function in young smokers: male-female differences.

To delineate the pattern of pulmonary function abnormalities and associated pathophysiologic mechanisms in young smokers, 205 volunteers between the ages of 18 and 25 were studied with a variety of pulmonary function tests. Differences between male and female smokers were observed. Pulmonary function abnormalities consistent with small airway dysfunction were noted in male smokers, but not in female smokers. Decreased forced expiratory flows at high lung volumes suggesting large airway dysfunction were noted in both male and female smokers. Decreases in diffusing capacity for CO consistent with abnormalities of the pulmonary vascular system were seen in smokers of both sexes, but were more prominent in females. Because men develop chronic obstruction pulmonary disease more frequently than do women even when adjustments for smoking are made, and because women develop primary pulmonary hypertension more frequently than do men, these chronic diseases may reflect distinct pathophysiologic response of the 2 sexes to agents such as cigarettes.

Adolescent↗

Postpartum thyroiditis is associated with fluctuations in transforming growth factor-beta1 serum levels.

Postpartum thyroiditis (PPT) is characterized by a rapid evolution and recovery of euthyroidism. Therefore, it can represent a good model to study early cytokine fluctuations in autoimmune thyroid diseases. TGFbeta1 is an immunosuppressive cytokine, as it inhibits T and B cell proliferation, natural killer cell cytotoxic activity, and the generation of T cell cytotoxicity. The aim of this study was to assess serum concentrations of TGFbeta1 during pregnancy and to study possible serum fluctuations of this cytokine during the different phases of PPT. Thyroid biochemical pattern, antithyroid autoantibodies (ATA), and total and active TGFbeta1 (aTGFbeta1) serum concentrations were evaluated in 63 pregnant women. Thirty-four of them were ATA(+), and 29 were ATA(-). Twenty of the 34 ATA(+) women were followed in the postpartum year. Nine of these 20 women developed PPT; 11 remained euthyroid. All of the PPT women became euthyroid during the follow-up. Our results showed 1) detectable serum levels of aTGFbeta1 in 50% of ATA(+) pregnant women, suggesting that the presence of autoantibodies may characterize a favorable condition for TGFbeta1 activation; and 2) decreased total TGFbeta1 and increased aTGFbeta1 serum levels during the active phase of PPT in ATA(+) women. This seems to suggest that inflammation may be responsible for TGFbeta1 activation and autoantibody increase because of antigen release. Although further studies of women with persistent hypothyroidism after the postpartum year are needed, the possibility that the enhanced activation of TGFbeta1 may contribute to resolution of thyroid inflammation postpartum cannot be excluded.

Adult↗