Effects of Oral Contraceptives on Human Plasma Vitamin-A Levels

Vitamin-A levels have been determined in healthy non-pregnant women and in women taking synthetic steroids to suppress ovulation. A significant increase has been found in those receiving oral contraceptives. Further work is necessary to determine whether this may affect the fetus in patients who become pregnant shortly after discontinuing oral contraception.     

Return of fertility after use of the injectable contraceptive Depo Provera: up-dated data analysis

796 Thai women who stopped using the long-acting injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo Povera), 437 women who stopped using oral contraceptives and 125 women who had an IUD removed to have a planned pregnancy, were followed up to ascertain the delay to conception after the end of contraception and to determine the proportion of women who did not conceive in the 4 years after discontinuation. The median delay to conception was 5.5 months plus the estimated duration of the effect of the last injection of DMPA, 3 months for oral contraceptives and 4.5 months after discontinuing the IUD. The proportion of women who did not conceive within 9 months after discontinuation of DMPA is similar to that of ex-IUD users, and by 3 years to that of the ex-pill sample. There is no evidence to suggest that prolonged use of DMPA increases the delay to conception. The return of fertility among never pregnant ex-users resembled that of ever pregnant ex-users. There were comparable proportons of live births among ex-DMPA users and ex-pill users and both of these showed higher proportions of live-births than ex-IUD users. There was no evidence to suggest that previous use of DMPA had any significant adverse effect on the outcome of pregnancy of the subsequent births. This study did not show any association between infertility and the previous use of DMPA or other contraceptives.     

Oral contraceptives: effect of folate and vitamin B12 metabolism.

Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant.     

Breast cancer and oral contraceptives: findings in Royal College of General Practitioners' study.

The incidence of breast cancer was studied among women taking part in the continuing cohort study organised by the Royal College of General Practitioners. An overall relative risk of 1.19 (not significant) was found in those who had used oral contraceptives. The risk ratio in women under 35 years old was 2.81, but this too was not significant. There was evidence that the estimated increased risk for younger women could be a chance occurrence. No convincing evidence of any adverse effects of oral contraceptives on breast cancer has been shown, but because of the long latent period of this tumour there is a need for longer observation.     

Oral contraceptives,pregnancy, and endogenous oestrogen in gall stone disease--a case-control study.

A case-control study of gall stone disease in women in relation to use of contraceptives, reproductive history, and concentrations of endogenous hormones was undertaken. The study population comprised 200 hospital patients with newly diagnosed gall stone disease, 182 individually matched controls selected from the community, and 234 controls who were patients in hospital. Use of oral contraceptives was associated with an increased risk of developing gall stones among young subjects but a decreased risk among older subjects. The risk of developing gall stone disease increased in association with increasing parity, particularly among younger women. The risk fell with increasing age at first pregnancy, independent of parity. Mean urinary excretion over 24 hours of oestrone, but not of pregnanediol, was significantly (p less than 0.05) greater for postmenopausal patients than controls. The age dependence of the relative risk associated with exposure to oral contraceptives and pregnancy suggests that there are subpopulations of women susceptible to early formation of gall stones after exposure to either oral contraceptives or pregnancy.     

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.     

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.     

Oral contraceptives and fatal subarachnoid haemorrhage.

A case-control study was conducted of the deaths from subarachnoid haemorrhage (SAH) in women aged 15-44 in England and Wales in 1976. There was a small excess of oral contraceptive use by the women who died from SAH compared with their generally healthy practice-matched controls; this was not, however, statistically significant. Out of 134 women who died from SAH, 34 had a history of hypertension compared with only six of their controls. Renal disease and pre-eclamptic toxaemia were more commonly associated with hypertension in the dead women than in controls. No change in the annual mortality from SAH has been observed in the past 20 years such as might have been expected if the risks were high. Although current or past use of oral contraceptives may have increased the blood pressure and risk of SAH in a few women, the most important factor in determining this risk was hypertension. SAH should thus probably not be regarded as serious cause for concern in healthy non-hypertensive women using oral contraceptives.     

Lymphocyte transformation in newborns, women and those who had used oral contraceptives.

Lymphocyte transformation, utilizing the mitotic index parameter has been assessed in newborns' cord blood, adults and women who had been on oral contraceptives and their babies. The results show that the newborns' cord blood response is significantly higher to PHA when compared with the respective adults' response. No significant difference was observed between the women taking oral contraceptives and their respective controls.     

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.     

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.     

Abortion experience among obstetric patients at Korle-Bu Hospital, Accra, Ghana

Hospital admissions for complications of abortion have been increasing in Africa, indicating a rise in the incidence of abortion. In all pregnant women ever admitted to Korle-Bu hospital in Accra, Ghana, the chance that the outcome of their last pregnancy was an induced abortion decreased as the number of previous pregnancies increased. Women with higher levels of education were more likely to have their 1st pregnancy terminated in an induced abortion. Younger women were more likely than older women at each level of education to have an induced abortion terminate a 1st pregnancy. The use of contraceptives during the last pregnancy interval increased with the level of education of the woman and the number of previous pregnancies. Contraceptive use was also highest among women whose last pregnancy outcome was an induced abortion. The mean pregnancy interval decreased with increasing number of previous pregnancies for both women who used and who did not use contraceptives during their last pregnancy interval. But the mean pregnancy interval was higher among women who used contraceptives. It appears that the abortion experience in this region of Africa is most common in lower parity young women with high levels of education who desire to delay a 1st birth or to space births. This is in contrast in Latin America and other developing countries in which abortion is used mainly by older, married, urban women to limit family size. Contraceptive use in this region of Africa is low, indicating the need for more family planning programs and increasing use of existing programs.     

Ovarian neoplasms,functional ovarian cysts,and oral contraceptives.

The incidence of ovarian neoplasms and functional ovarian cysts diagnosed at laparotomy or laparoscopy among the 17,000 women taking part in the Oxford Family Planning Association contraceptive study was investigated. Epithelial cancer of the ovary was only 25% as common among those who had ever taken oral contraceptives as those who had never done so (95% confidence interval 8% to 67%). There was little evidence of any important association between use of oral contraceptives and benign teratoma or cystadenoma. Functional cysts of the ovary occurred much less commonly in women who had recently (in the six months preceding diagnosis) taken combined oral contraceptives (but not in those who had taken progestogen only oral contraceptives) than in those who had never taken oral contraceptives or had taken them in the past. This protective effect was more pronounced for corpus luteum cysts (78% reduction; 95% confidence interval 47% to 93%) than for follicular cysts (49% reduction; 95% confidence interval 20% to 70%). It is estimated that about 28 (95% confidence interval 16 to 35) operations for functional ovarian cysts are avoided among every 100,000 women who take oral contraceptives each year.     

Recurrence of Venous Thromtoembolic Disease and Use of Oral Contraceptives

In 1969 this department reported on 42 women who had developed “idiopathic” venous thromboembolism while using oral contraceptives and 42 women who had developed the disease in the absence of such exposure. We have traced the subsequent history of these women to obtain information about recurrence of the disease.During the follow-up period the risk of recurrence of thromboembolism during pregnancy or the puerperium appeared to be much the same irrespective of whether or not oral contraceptives had been in use at the time of the index attack. Recurrences unassociated with childbearing however, occurred about four times more often among women who had not been using oral contraceptives at the time of the index attack than among women who had been doing so. None of these findings was influenced by the use of oral contraceptives during the follow-up period, since exposure to the preparations was negligible after the index attack.     

Contraceptives,counselling, and pregnancy in women with sickle cell disease.

Sickle cell disease is listed in the manufacturers'' data sheets in the United Kingdom as a contraindication to the use of most combined contraceptive pills; the result is confused advice on family planning to a group of women who are at substantial risk from both planned and unplanned pregnancy. A study in north London on the use of contraceptives by women with sickle cell disease indicates that the use of combined oral contraceptives is common. Although medical staff usually advised against pregnancy, such advice was almost always ignored. Over half of the women surveyed had some knowledge about antenatal diagnosis. Family planning advice should be an integral part of the care of women with sickle cell disease. In the absence of specific data to the contrary all methods of contraception may be considered, although with appropriate caution.     

Oral contraceptive use and venous thromboembolism: absence of an effect of smoking.

We conducted a case-control study to test the hypothesis that women smokers who use oral contraceptives have an increased risk of developing venous thrombosis. Patients and controls were drawn from two sets of hospital patients already included in the Boston Collaborative Drug Surveillance Programme. Sixty patients with uncomplicated thromboembolism were matched with 180 controls with other diagnoses; all were premenopausal women taking oral contraceptives. Patients with conditions that might predispose to thromboembolism or be related to smoking were excluded. We found no association between smoking habits and thromboembolism. Similarly, we found no association between thromboembolism, smoking, and duration of oral contraceptive use. Thus we conclude that differences in fibrinolytic activity between smokers and non-smokers are not major factors in the aetiology of uncomplicated thromboembolism in women using oral contraceptives.     

Reproductive and external hormonal factors and the risk of renal cell cancer in the Netherlands Cohort Study

BackgroundSeveral reproductive and hormonal factors, like age at menarche, parity, age at menopause, use of oral contraceptives and postmenopausal treatment, have been associated with the risk of renal cell cancer (RCC) in women, but results have not always been consistent. We therefore investigated the association between these factors and the risk of RCC in postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer.MethodsInformation on reproductive history, exogenous hormone use and gynecological surgery was obtained through a self-administered questionnaire at baseline in 1986. After 20.3 years of follow-up, 204 cases and 2280 subcohort members were available for case-cohort analysis. Multivariable hazard ratios (HR) were calculated using Cox Proportional Hazard analysis.ResultsWomen who reported a hysterectomy had an increased RCC risk compared to women who did not (HR, 1.42, 95%CI, 1.01–2.00). Women with a natural age at menopause between 45 and 49 years compared to 50–54 years had an increased RCC risk (HR, 1.61; 95%CI, 1.10–2.35). RCC risk was slightly and not statistically significant increased among parous women with three or more children and age at first birth before 25 years compared to nulliparous women (HR, 1.36; 95% confidence interval (CI), 0.84–2.20). No associations were observed with RCC risk for age at menarche, use of oral contraceptives and use of hormonal replacement therapy.ConclusionHysterectomy and age at natural menopause were associated with an increased RCC risk. Other hormonal and reproductive factors and RCC risk were not increased. Further studies are required to establish the mechanism(s) that explain the observed association.     

Proceedings: Correlation of various clinical parameters with glucose tolerance test in women using oral contraceptives

A study was carried out to determine whether oral contraceptives affect carbohydrate metabolism as assessed by glucose tolerance curves. Glucose tolerance tests were carried out in seventy-six women. The women were divided into two groups. The first group constituted the control and the second group comprised women taking combination oral contraceptives. The glucose tolerance curves were correlated with: (1) the duration of thereapy; (2) the family history of diabetes; (3) the obstetric history; (4) age: (5) weight gain; (6) parity; and (7) changes in blood pressure. The combination type of oral contraceptives were observed to affect adversely the glucose tolerance test. A significant correlation was recorded between the familial diabetic history, intake of combination contraceptives and abnormal glucose tolerance tests. A history of birth of a large baby was found to be an important indicator of abnormal values of glucose tolerance in women taking a combination type of oral contraceptive. Such women showed an abnormal curve pattern at a much earlier age in life compared with controls. It was also observed that a high percentage of women who had gained excessive weight on combination contraceptives had an altered glucose tolerance test. Parity and blood pressure were two parameters which did not reveal any correlation with abnormal glucose tolerance curves.     

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.