Blood pressure and contraceptive use

In a survey of 461 women routinely attending family planning clinics those taking oral contraceptives had significantly higher mean systolic and diastolic blood pressures than those using non-hormonal contraception. There appeared to be a dose-response relation of blood pressure to the progestogen component of two oral contraceptives with an identical 30 μg ethinyloestradiol component. This supports the idea that the progestogen as well as the oestrogen component has an aetiological role in the rise in blood pressure. There was a significant correlation of blood pressure with duration of current use of oral contraceptive but not with total duration of use. There was also a significant negative correlation of blood pressure with time since oral contraceptives were last taken, and women who had stopped using oral contraceptives over a month previously had similar blood pressures to those who had never taken them. In women taking oral contraceptives those who had either a history of hypertension in pregnancy or a family history of hypertension had significantly higher mean blood pressures than those who did not. Both systolic and diastolic blood pressures correlated independently with weight and body mass index, but controlling for the effect of this and age did not affect the above relations. No significant differences in mean blood pressures were found between different ethnic groups, and there was no relation of blood pressure to reported marital state, social class, parity, smoking, or alcohol use.Any oral contraceptive that has a less adverse effect on blood pressure has implications for general prescribing policy; thus even small differences in the progestogen contents of low-dose oestrogen pills may be important.     

Studies of Carbohydrate and Lipid Metabolism in Women Developing Hypertension on Oral Contraceptives

Metabolic studies in 100 women developing hypertension on combined oestrogen-progestogen oral contraceptives have been compared with similar studies in normotensive women on oral contraceptives, matched for age and duration of contraceptive use, and in women not taking contraceptives.The metabolic changes known to be induced by oral contraceptives—impaired glucose tolerance, elevated blood pyruvate levels, and raised serum lipid concentrations—were found to be exaggerated in the matched hypertensive group, largely due to pronounced abnormalities in 33 subjects with diastolic blood pressures over 110 mm Hg.Women developing severe hypertension were older, more obese, and of higher parity than those with mild hypertension and there was a high incidence of previous toxaemia of pregnancy in the hypertensive group.The results show that in women on oral contraceptives changes in blood pressure and in metabolic functions tend to be correlated with one another, and are consistent with the hypothesis that oral contraception induces a primary biochemical effect whose expression in the individual is determined by intrinsic factors including genetic constitution, age, weight, and parity.     

Effects of Obesity,Glucocorticoid, and Oral Contraceptive Therapy on Plasma Glucose and Blood Pyruvate Levels

The plasma glucose and blood pyruvate levels were determined after oral glucose tolerance test in six groups of women: non-obese and obese controls and in non-obese and obese women receiving glucocorticoid or oral contraceptive therapy. The mean fasting plasma glucose level was similar in all groups, but glucose tolerance was impaired in the obese controls, non-obese women on oral contraceptives or being treated with glucocorticoids, and appreciably impaired in the obese oral contraceptive and glucocorticoid groups compared with mean levels in non-obese subjects of the same groups. Obesity was associated with abnormally raised blood pyruvate levels in response to a glucose tolerance test in all groups. Striking similarities were observed between the responses of the plasma glucose and blood pyruvate levels to glucose tolerance tests in the obese control and non-obese oral contraceptive and non-obese glucocorticoid-treated groups. It is suggested that these abnormalities result from a common mechanism—namely, glucocorticoid excess.     

Myocardial Infarction and Carbohydrate Metabolism Relating to Diabetes Mellitus

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were “diabetic” or “probably diabetic” in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes.Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent).Patients with myocardial infarction have an increased incidence of diabetes mellitus.     

Influence of oral contraceptives on changes of the carbohydrate metabolism

Serum glucose and serum insulin levels were measured during oral glucose tolerance tests in 100 women, 20-39 years of age, who used the OC (oral contraceptive) preparation Stediril and in a control group of 96 women of the same age group. Significantly lower fasting serum glucose levels were observed after 6 months of OC use. Significant decreases in glucose tolerance were observed among OC users who had taken OCs for longer than 6 months. The blood glucose levels were elevated significantly in this group 60 and 120 minutes after the beginning of the test. No correlation could be found between age and changes in glucose tolerance. No significant differences in fasting serum insulin levels were found in either group. A significant increase in serum insulin levels was observed among women who had used OCs longer than 6 months; this increase was apparent only 120 minutes after the beginning of the test. These changes in glucose tolerance were found to be reversible. Glucose tolerance tests should be preformed once a year on OC users, more often if an abnormality in glucose metabolism, e.g. latent diabetes, is present.     

Beta-cell dysfunctions and insulin resistance in subjects with increased risk for type 2 diabetes mellitus

The aim of this study was to test if a beta-cell defect is associated to deterioration of glucose tolerance early during the natural history of the type 2 diabetes mellitus . In 41 overweight women, with macrosomic infants in their antecedent deliveries, measures of insulin response and insulin sensitivity were derived from a short (45 min) iv glucose test. The early (EIR) and the late (LIR) phase insulin responses and the insulin sensitivity index (Si) were calculated. According the response to 75 g oral glucose test the subjects were divided into two groups: Imparired glucose tolerance (IGT;n = 12), and normal glucose tolerance (NGT; n = 29). EIR was reduced in IGT group (14.9 ± 3.6 vs 37.0 ± 4.0; p< 0.002). Glucose tolerance during oral glucose tolerance test (OGTT), correlated inversly to EIR (r=-0.45; n=41; p< 0.01). A strong correlation of EIR to LIR (r=0.88; n = 41; p< 0.001) but no correlation between glucose tolerance and Si was found.     

A Comparison of the Oral and Intravenous Glucose Tolerance Tests in Non-Diabetic,Possible Diabetic and Diabetic Subjects

Results of standard three-hour oral glucose tolerance tests (OGTT) and intravenous glucose tolerance tests (IVGTT), performed on the same subjects, were compared in an attempt to determine their value in the diagnosis of borderline diabetes. A total of 83 such tests were carried out on 81 subjects. Applying the U.S. Public Health Service point count method to the results of the OGTT test, there were 38 normals, 23 possible diabetics and 22 diabetics. A constant (K) was calculated from the glucose disappearance rate in the IVGTT curves.K disagreed with the OGTT classification to a significant extent, especially in the possible diabetic and non-diabetic groups. Also, the correlation coefficients between K and the OGTT values were not impressive. This does not mean that one test is superior to the other, only that the accuracy of either test in diagnosing early diabetes is doubtful.Technically, the IVGTT was more difficult and time-consuming, and six of the 81 subjects suffered from thrombophlebitis at the site of glucose injection.     

Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis

ObjectiveTo compare the risk of idiopathic venous thromboembolism among women taking third generation oral contraceptives (with gestodene or desogestrel) with that among women taking oral contraceptives with levonorgestrel.DesignCohort and case-control analyses derived from the General Practice Research Database.SettingUK general practices, January 1993 to December 1999.ParticipantsWomen aged 15-39 taking third generation oral contraceptives or oral contraceptives with levonorgestrel.ResultsThe adjusted estimates of relative risk for venous thromboembolism associated with third generation oral contraceptives compared with oral contraceptives with levonorgestrel was 1.9 (95% confidence interval 1.3 to 2.8) in the cohort analysis and 2.3 (1.3 to 3.9) in the case-control study. The estimates for the two types of oral contraceptives were similar before and after the warning issued by the Committee on Safety of Medicines in October 1995. A shift away from the use of third generation oral contraceptives after the scare was more pronounced among younger women (who have a lower risk of venous thromboembolism) than among older women. Fewer cases of venous thromboembolism occurred in 1996 and later than would have been expected if the use of oral contraceptives had remained unchanged.ConclusionsThese findings are consistent with previously reported studies, which found that compared with oral contraceptives with levonorgestrel, third generation oral contraceptives are associated with around twice the risk of venous thromboembolism.     

Pregnancy induced hypertension: evidence for increased cell membrane permeability to sodium.

In a cross sectional study of 137 women of childbearing age (16-40) the effects of normal pregnancy, hypertensive pregnancy, and oral contraceptives on red cell electrolyte content and sodium efflux rates were examined and the results compared with values in a control group of normotensive, non-pregnant women. Efflux rate constants were significantly increased in normotensive pregnancy and in women taking oral contraceptives. This was associated with a significant increase in sodium permeability in the contraceptive group. A much larger increase in sodium permeability and efflux rate constant was seen in the hypertensive group. The results permit a hypothesis that the hormonal changes induced by pregnancy and oral contraceptives increase membrane permeability to sodium and stimulate sodium efflux. The rise in blood pressure associated with use of oral contraceptives may have a similar aetiology to that occurring in pregnancy induced hypertension.     

Evaluation of Serum Selenium Levels in Turkish Women with Gestational Diabetes Mellitus, Glucose Intolerants, and Normal Controls

The aim of the study was to investigate the association between serum selenium levels in patients with gestational diabetes mellitus (GDM) and glucose intolerants and compare them with those of glucose-tolerant pregnant women. This cross-sectional study was prospectively performed in a total of 178 pregnant women undergoing a 50-g oral glucose tolerance test between 24 and 28 weeks of gestation who were grouped according to their status of glucose tolerance as with gestational diabetes (group A, abnormal 1- and 3-h glucose tolerance test; n = 30), glucose intolerant (group B, abnormal 1-h but normal 3-h glucose tolerance test; n = 47), or normal controls (group C, normal 1-h glucose test; n = 101). Serum selenium levels were measured with a graphite furnace atomic absorption spectrophotometer using a matrix modifier. Median maternal age and gestational age at the time of diagnosis in group A (gestational age = 24.8 [24-27]), group B (gestational age = 24.7 [24-27]), and group C (gestational age = 25 [24-28]) did not differ. Patients with gestational diabetes mellitus and those with glucose intolerants had lower selenium level than that of the normal pregnant women (P < 0.001). There was a significant inverse correlation between selenium and blood glucose level, and also selenium supplementation might prove beneficial on patients with GDM and prevent or retard them from secondary complications of diabetes.     

Haemostasis and oral contraceptives

Selected hemostasis parameters were assayed in 131 women ingesting different kinds of oral contraceptives and 36 control women. No differences were noted in the plasma levels of fibrinogen, antithrombin III, prekallikrein, alpha 2 antiplasmin, fibrinopeptide A, platelet factor 4 and beta-thromboglobulin. Protein C and plasminogen levels were significantly higher in pill users (p less than 0.001, p less than 0.01) and fibronectin levels were lower (p less than 0.05). Canonical correlation, performed between clinical parameters and hemostasis data, revealed a negative correlation between antithrombin III levels and family history for thromboembolic diseases. A positive correlation was noted between fibrinogen and fibronectin levels in obese OC users. The data suggest that women taking OCs are not in a state of "hypercoagulability."     

Circadian changes in salivary constituents and conductivity in women and men.

Circadian rhythms in salivary [glucose], [Na+], [K+] and conductivity were measured in 2 age groups of men (men A, 20-45 years and men B, 46-60 years) and 8 different states of fertility in women (normally menstruating, taking oral contraceptives, pregnant, lactational amenorrhea, lactational amenorrhea and taking oral contraceptives, lactating and menstruating, menopausal, and post-menopausal). Unstimulated whole saliva (2-3 ml) was collected every 3 h over a 48 h span. Analysis of Spearman Rank Correlations indicated significant circadian rhythms (significant positive coefficients) for all groups of [Na+] (mean = 0.577 +/- 0.040) and conductivity (mean = 0.410 +/- 0.050). There was no evidence of differences in prominence of rhythm across groups for [Na+] and conductivity. [K+] showed less evidence of rhythms and much greater variability between groups (mean correlation coefficient = 0.198 +/- 0.055). Rhythms in [glucose] (mean correlation coefficient = 0.409 +/- 0.051) were evident in all groups except men B (0.016), menopausal women (0.151) and post-menopausal women (0.310). Model analysis of the data showed no discernible rhythmic trend with age for either conductivity, [Na+] or [K+], where any differences were explainable by the group characteristics. The rhythm in [glucose] showed a significant weakening with age over all groups (F-ratio = 7.46**), and was different between men A and men B (F-ratio = 6.95**). It was concluded that circadian rhythms were present in whole unstimulated saliva for conductivity and [Na+] and that these rhythms were independent of reproductive state, whereas circadian rhythms in [K+] were dependent on reproductive state. Circadian rhythms for [glucose] were dependent on age. The loss of a rhythm in [glucose] with age indicates that glucose, Na+ and K+ are not linked in their entry into saliva. The influence of entry and reabsorption on the final concentrations of glucose, Na+ and K+ in saliva is discussed.     

Epidemiology of endometriosis in women attending family planning clinics.

OBJECTIVE--To describe the epidemiology of endometriosis in women attending family planning clinics with special reference to contraceptive methods. DESIGN--Non-randomised cohort study with follow up of subjects for up to 23 years. Disease was measured by first hospital admission rates since endometriosis can be diagnosed with accuracy only at laparotomy or laparoscopy. SETTING--17 family planning centres in England and Scotland. SUBJECTS--17,032 married white women aged 25-39 years at entry during 1968-74 who were taking oral contraceptives or using an intrauterine device or diaphragm. About 99% of the women approached agreed to participate and annual loss to follow up was about 0.3%. MAIN OUTCOME MEASURES--Diagnosis of endometriosis, age, parity, and history of contraceptive use. RESULTS--Endometriosis was significantly related to age, peaking at ages 40-44 (chi 2 for heterogeneity = 30.9, p < 0.001). Endometriosis was not linked to duration of taking oral contraceptives. Nevertheless, the risk of endometriosis was low in women currently taking oral contraceptives (relative risk 0.4; 95% confidence interval 0.2 to 0.7), but higher in women who had formerly taken them (1.8; 1.0 to 3.1 in women who had stopped 25-48 months previously) compared with women who had never taken the pill. A similar pattern was seen for use of intrauterine devices (relative risk 0.4 (0.2 to 0.7) in current users and 1.4 (0.4 to 3.2) in users 49-72 months previously compared with never users). No association was found between endometriosis and use of the diaphragm. CONCLUSIONS--Oral contraceptives seem to temporarily suppress endometriosis. Endometriosis may be diagnosed late in women using intrauterine devices as pain and bleeding occur with both.     

Depressive Symptoms and Oral Contraceptives

Of 261 women who completed a self-rating scale for measuring depression, 168 were taking oral contraceptives and 93 were using physical methods of contraception. Of the group of women taking oral contraceptives 6·6% were more severely depressed than any of the control group. There was a significant variation in the depth of depression related to the day of the menstrual cycle in the control group. This association was not found in the oral contraceptive group, where premenstrual depression was limited to the one or two days preceding menstruation.Women taking a contraceptive containing lynoestrenol 2·5 mg. and mestranol 0·075 mg. showed a significantly increased incidence of pessimism, feelings of dissatisfaction, crying, and tension, compared with women taking other oral contraceptives and the control group.     

Chromatographic separation of multiple renin substrates in women: effect of pregnancy and oral contraceptives

Chromatographic separation of multiple renin substrates was carried out to study the effect of pregnancy and oral contraceptives (OCs) in women. Blood plasma proteins were separated on a Sephadex G-200 column and the amount of renin substrate in each fraction was determined. The molecular weight of the renin substrate peaks was estimated by comparison with the elution position of proteins of known molecular weight. Normal nonpregnant women revealed the presence of 2 renin substrates: a major 1 with a molecular weight of 65000 and 1 amounting to 3-5% of the quantity of the major peak with a molecular weight of 450000-500000. In women taking OCs the same 2 peaks were seen but the quantity of each was increased markedly. In pregnant women at term, a 3rd renin substrate of intermediate size was seen (molecular weight 350000 daltons). The quantities of the intermediate and low molecular weight renin substrates were found to be greatly increased in pregnancy.     

The effect of high-intensity breastfeeding on postpartum glucose tolerance in women with recent gestational diabetes

Background

Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes.

Methods

In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum.

Results

Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n?=?70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n?=?18) (46% vs. 78%, p?=?0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41?±?1.02 vs. 2.28?±?1.05, p?=?0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding.

Conclusions

In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

     

Carbohydrate tolerance,serum albumin and protein values of normal and “waster” marmosets (Callithrix jacchus)

The major objective of this study was to establish standard glucose and lactose tolerance curves for the common marmoset (Callithrix jacchus). These data were utilized to establish criteria for detection of abnormal glucose tolerance and characterization of some aspects of the “marmoset wasting syndrome” which has been observed in this species. Glucose and lactose tolerance tests were performed on healthy animals and typical “marmoset wasters.” Eighteen normal animals were 18 to 36 months old and weighed 194–280 g. Six “wasters” were in the age range of 24 to 84 months and weighed 163–253 g. Seven experiments were carried out for each glucose tolerance test. In each trial it was observed that the serum glucose concentration (SGC) of the healthy animal after 90 min was two times higher than the pre-administration concentrations. The SGC returned to the pre-administration concentration within 150–300 min in animals administered glucose at dosages of 2 g/kg and 1 g/kg of body weight. However, at the dosage level of 5 g/kg body weight, the SGC of the animals tripled after 30 min and required 300 min to return to the pre-administration level. The 2 g/kg dosage level was chosen as typical. When similar experiments were conducted with animals identified as “chronic wasters,” all of the animals except one were observed to be inefficient in the absorption of glucose. When lactose was administered at a level of 4 g/kg, similar results were obtained. Normal and “waster” marmosets were also subjected to serum total protein, albumin and electrophoresis determinations in an effort to establish additional criteria that may be utilized in the identification of the “marmoset wasting” syndrome. Serum albumin was significantly higher in the “waster” marmosets 30 min following an oral administration of glucose than was observed in normal animals. Total protein values were not significantly lower in the “wasters” when subjected to the same tolerance test. The albumin level in normal animals was not affected by similar glucose tolerance tests. The electrophoretic patterns of serum protein for normal animals exhibited more bands than was observed in patterns of serum protein for “waster” marmosets. From these data, it seems logical that these diagnostic tests may be useful in developing a profile for the early detection of the “wasting” syndrome in marmosets.     

Malignant hypertension in women of childbearing age and its relation to the contraceptive pill.

Eleven of 34 women aged 15-44 with malignant phase hypertension were taking oral contraceptives at presentation. All had had normal blood pressure before starting to take the pill. In four the interval between the start of oral contraception and the diagnosis of malignant hypertension was less than four months, and in eight no other cause for the hypertension was found. Underlying renal disease and renal failure were less common among pill users than among non-users with malignant hypertension who were of similar age. No pill user became normotensive after withdrawal of the pill, but blood pressure was well controlled (diastolic less than 90 mm Hg) in three patients taking only one drug. By contrast, all 23 non-users needed two or more antihypertensive drugs to control blood pressure. Ten year survival was 90% among pill users and 50% among non-users. These results suggest that oral contraceptives may be a common cause of malignant hypertension in women of child-bearing age. If the pill is stopped and underlying renal disease excluded the long term prognosis for such patients is excellent.     

The role of oral glucose intolerance test in reducing pregnancy complications

The influence of glucose monitoring during pregnancy on newborn body weight, and complications during pregnancy and labor was assessed. We performed a retrospective analysis of macrosomal children, fetal growth, caesarean sections, malformations, still-births and the number of oral glucose tolerance test (OGTT) carried out in a five-year period. The proportion of women participating in OGTT tests increased from 20% to 40% (p<0.05) between 2000 and 2004. Gestation diabetes mellitus (GDM) proportions among pregnant women seen at the Department of Obstetrics and Gynecology at Slavonski Brod General Hospital, Croatia increased from 1% to 6.7% (p < 0. 05) during the observed period. Proportion of births identified as macrosomal decreased from 13.3% to 12.2% (p<0.05). Additionally, infant mortality and still-births along with other fetal and maternal complications declined during the same period. These results suggest that regular measurements of glucose tolerance during pregnancy may prevent preterm birth, decrease the proportion of macrosomal newborns, lower mortality and decrease fetal and maternal complication incidence during pregnancy and delivery.     

Blood Pressure in Women Taking Oral Contraceptives

A controlled prospective survey of women taking oestrogen-progestogen oral contraceptives showed increases in mean systolic and diastolic blood pressure of 14·2 mm Hg and 8·5 mm Hg respectively after four years. The largest increases in individual cases were 36 mm Hg systolic and 20 mm Hg diastolic. Blood pressure returned to pretreatment levels within three months after oral contraceptives had been stopped. These changes in blood pressure were unrelated to the progestogenic potencies of the preparations being taken.