Vitamin A,Pregnancy, and Oral Contraceptives

It has been shown that women receiving oral contraceptives have increased levels of serum vitamin A. High vitamin A levels may constitute a teratogenic hazard and it has been suggested that women who conceive soon after discontinuing oral contraceptive therapy may be especially at risk to this hazard.We have confirmed a significant increase in vitamin A levels in women taking oral contraceptives. During early pregnancy there is no significant difference in vitamin A levels between women who have recently been taking oral contraceptives and those who have not. We have been unable to show that either taking oral contraceptives shortly before pregnancy or a high vitamin A level during the first trimester of pregnancy, comparable to that of a woman taking oral contraceptives, has any detrimental effect on the outcome of pregnancy. It seems unlikely that women who conceive soon after discontinuing oral contraception run any teratogenic risk from increased vitamin A levels.     

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.     

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.     

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.     

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.     

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.     

Altered haemorheology in oral-contraceptive users.

The haemorheological profile of the menstrual cycle was determined in 12 women who did not take oral contraceptives and compared with that in two groups of women (n = 8 and n = 30) who had been taking oral contraceptives for at last six months. Packed cell volume, platelet count, erythrocyte deformability, plasma fibrinogen concentration, and plasma and whole-blood viscosity varied cyclically throughout the menstrual cycle in the 12 non-users. This variation was abolished by the use of oral contraceptives, and the values of these indices were raised by an amount likely to predispose to thrombosis.     

Treatment of diminished sexual response associated with the use of oral contraceptives (author's transl)]

Loss of libido associated with the use of oral contraceptives has been studied in 113 women of reproductive age who had taken a combined pill for periods ranging from 1 to 3 years. The patients were divided in four groups. In the first group (I) of 24 women oral contraceptive treatment was discontinued and all women received in intra-uterine contraceptive device (IUCD). The second group (II) of 36 patients, the brand of oral contraceptive was changed. Women in group (III) had their oral contraceptive maintained receiving in addition a mixture of an androgen and an estrogen (methyltestosterone 4 mg and ethynilestradiol 0.002 mg) daily. To women of group (IV) the oral contraceptive was discontinued but the androgen-estrogen mixture was given. All women in this group received an IUCD. Evaluation of the psyco-sexual parameters included changes in libido, time to reach an orgasm, duration and intensity or orgasms. Frequency of intercourse and response to autostimulation was also investigated. Libido was restored in 94.2% of patients in group II, in 97.3% of group III and in 92.8% of group IV. In group I only 55.6% of patients had libido fully restored. In view of the prompt restoration of libido in all groups except in patients discontinuing oral contraceptive therapy, it is suggested that loss of libido in oral contraceptive users has an important physological component which can be overcome probably by psychotherapy. Short term treatment with a mixture of methyltestosterone and ethynilestradiol seems to be highly effective in restoring libido in all patients.     

Duloxetine: a summary of published clinical experience

Effective oral therapy for genuine stress urinary incontinence (SUI) in women has, to date, been an unattainable goal. Although oral pharmacologic agents have been used for this condition, none has ultimately been successful, because of side effects, lack of efficacy, or problematic compliance with drug ingestion. The availability of an effective oral agent for SUI would increase the range of therapeutic options for symptom management and possibly make treatment accessible to more women who otherwise feel that surgical therapy is not an option because of social, personal, or medical reasons. Duloxetine is a selective serotonin (5-HT) and norepinephrine reuptake inhibitor that has been shown to increase rhabdosphincter activity. Rhabdosphincter contractility changes are thought to occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2) receptors in the sacral spinal cord, resulting in increased efferent pudendal nerve activity, producing increased pelvic floor tonus. Two large-scale studies have been completed employing subjective and objective outcomes to assess the therapeutic index of duloxetine as a therapy for SUI.     

Liver Hamartomas in Patients on Oral Contraceptives

Three cases are reported of tumour-like lesions of the liver in women who had been on oral contraceptives for long periods. These malformations have a prominent vascular component and may present with haemoperitoneum and shock. The possibility of an association between liver hamartomas and oral contraceptive therapy has to be considered.     

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.     

Chromosomal abnormalities in the Kaiser-Permanente Birth Defects Study, with special reference to contraceptive use around the time of conception

Chromosomal abnormalities were studied in 33,551 abortions and births to women whose contraceptive histories had been recorded at their first antenatal visit in 1975-1977. Chromosome examinations were performed exclusively on clinical grounds. There were 45 de novo abnormalities detected (1.34/1,000); three of them were detected at amniocentesis. Trisomy 21 was observed in 27 cases (0.80/1,000), trisomy 18 in nine (0.27), other trisomies in three (0.09), and translocations or deletions in five (0.15). One case of triploidy and six cases of inherited abnormalities were detected. There were no significant racial variations. No increase in risk for chromosomal abnormalities was found among women who had used oral contraceptives prior to becoming pregnant or among women who experienced oral contraceptive breakthrough pregnancies. Two cases of trisomy 18 were observed among the 814 deliveries following oral contraceptive breakthrough conceptions (2.46/1,000), two cases of trisomy 21 occurred in 338 births following failures of rhythm contraception (5.92/1,000), and no cases of trisomy 21 or 18 among the 1,569 women using spermicides at the time of conception.     

Effects of Progestogen Oral Contraception with Norethisterone on Blood Clotting and Platelets

The effects on clotting tests and platelet function of six months'' continuous administration of the 19-norsteroid, progestogen-only contraceptive, norethisterone, have been studied in four groups of women. In a group of women who have not previously taken oral contraceptive no acceleration of clotting or platelet factors was found, but in contrast a tendency to reduced coagulability was observed. Women who had previously been taking combined oestrogen-progestogen preparations showed reduced clotting and platelet parameters when norethisterone was substituted. No changes in clotting or platelets were found in women who changed from 17-acetoxysteroid progestogen chloramadinone acetate or in a group of women started postpartum.     

Oral contraceptive use in older women and fatal myocardial infarction.

A previous study of women who had died from myocardial infarction and of a control group of women matched with them for age suggested a fivefold increase in the risk of death from myocardial infarction among users of oral contraceptive aged 40-44 years compared with women not using such preparations. Only a small proportion of women in the infarction and control groups had used oral contraceptives, however, so the margin of error was wide. We therefore investigated a further 54 women in this age group who died from myocardial infarction and compared their oral contraceptive histories with those of age-matched, living controls. Combination of the findings from the present investigation with the previous results have enabled a revised estimate of a threefold increase in risk to be made. Although this risk estimate is similar to that previously shown for a younger age group, the total mortality attributable to complications associated with the use of oral contraceptives remained considerably greater among women over the age of 40.     

Survivors of sexual abuse: clinical,lifestyle and reproductive consequences

BACKGROUND: In recent years, an increase in the prevalence of sexual abuse of women has been reported in Canada and elsewhere. However, there are few empirical data on the extent of the problem in Canadian aboriginal populations. The authors investigated the presence of a reported history of sexual abuse and other health determinants in a sample of women attending a community health centre with a substantial aboriginal population. This allowed determination of whether reported sexual abuse and its associated demographic and health-related effects were different for aboriginal and non-aboriginal women. METHODS: A sample of 1696 women was selected from women attending a community health centre in a predominantly low-income inner-city area of Winnipeg for a cross-sectional survey designed to study the association between sexual behavior and cervical infections. The survey was conducted between November 1992 and March 1995 and involved a clinical examination, laboratory tests and an interviewer-administered questionnaire. A substudy was conducted among 1003 women who were asked 2 questions about sexual abuse. RESULTS: The overall response rate for the main study was 87%. Of the 1003 women who were asked the questions about sexual abuse, 843 (84.0%) responded. Among the respondents, 368 (43.6%) were aboriginal. Overall, 308 (36.5%) of the respondents reported having been sexually abused, 74.0% of the incidents having occurred during childhood. The prevalence was higher among aboriginal women than among non-aboriginal women (44.8% v. 30.1%, p < 0.001). Women who had been sexually abused were younger when they first had sexual intercourse, they had multiple partners, and they had a history of sexually transmitted diseases. In addition, non-aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have had abnormal Papanicolaou smears. The proportion of smokers was higher among the abused women than among the non-abused women in both ethnic groups. INTERPRETATION: A history of sexual abuse was associated with other clinical, lifestyle and reproductive factors. This suggests that sexual abuse may be associated with subsequent health behaviors, beyond specific physical and psychosocial disorders. Aboriginal and non-aboriginal women who have suffered sexual abuse showed substantial differences in their subsequent health and health-related behaviours.     

Platelet aggregation during oral contraception

Platelet aggregation has been found to be significantly accelerated with the coagulation-induced Chandler''s tube technique in women taking combined oestrogen-progestin oral contraceptives, though this was less than in the third trimester of pregnancy. Women taking the pure progestogen, chlormadinone acetate, have not shown this change up to the sixth month of study. In contrast the accelerated platelet aggregation resulting from conventional oral contraception became normal one month after changing to the progestogen. There was no change in the platelet aggregation response to adenosine diphosphate (A.D.P.) during oral contraception.     

Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations.

The fluctuations of serum lipid and lipoprotein concentrations within one cycle were studied both in women using and not using oral contraceptives. High-density lipoprotein cholesterol decreased significantly from 1.47 mmol/l (57 mg/100 ml) to 1.30 mmol/l (50 mg/100 ml) during one contraceptive cycle in eight women and rose again to the initial value during the pill-free days. The mean concentration of total cholesterol also fell significantly as a result of the decrease of high-density lipoprotein cholesterol and of a not significant decrease of low-density lipoprotein cholesterol. The mean serum triglyceride concentration did not change significantly. The fluctuations in the concentration of serum lipids and lipoproteins in 10 women not using oral contraceptives were smaller than in the women using oral contraceptives and no significant changes in the concentrations were found during one cycle. Thus, high-density lipoprotein cholesterol concentration decreases during each contraceptive cycle. The time of blood sampling during the cycle is, therefore, of vital importance in interpreting the effect of oral contraceptives on high-density lipoprotein cholesterol. In women not using oral contraceptives blood can be sampled on random days during the cycle.     

Isometric strength and endurance during the menstrual cycle.

Seven healthy young women, 3 whom had been taking oral contraceptives, were examined during the course of 2 menstrual cycles to assess their isometric strength, their endurance during a series of 5 fatiguing isometric contractions at a tension of 40% MVC, and their blood pressures and heart rates during those fatiguing contractions. Two sets of experiments were performed, one in which the subject's forearm temperature was allowed to vary as a function of T A, and one with the muscle temperature stabilized by immersion of the forearm in water at 37 degrees C. During exposure to ambient temperatures, isometric strength and both the heart rate and blood pressure responses at rest and at the end of a fatiguing, sustained isometric exercise, were not significantly different during any phase of the menstrual cycle in any subject. In contrast, the isometric endurance in the women not taking oral contraceptives varied sinusoidally in all 5 contractions with a peak endurance midway through the ovulatory phase and the lowest endurance mid-way through the luteal phase of the menstrual cycle. The isometric endurance of the women taking oral contraceptives did not vary during their menstrual cycle. After stabilization of the temperature of the muscles of the forearm in water at 37 degrees C, the isometric endurance of the normal subjects showed a hyperbolic response with the maximal endurance at the beginning and end of their cycles, and the shortest endurance at mid-cycle. Here again, however, the isometric endurance of the women taking oral contraceptives did not vary after immersion of their forearms in the 37 degree C water.     

Vaginal and oral cytology of the menopause. A comparative study

A comparative cytologic study was made of the hormonal content of the vaginal and oral mucosa of menopausal women. Twenty-three women between one and ten years (early menopause) and 33 patients more than ten years (late menopause) after cessation of menstruation had oral and vaginal smears taken. Comparable smears from 21 young women, and oral smears from 18 males served as controls. The smears were evaluated by the maturation value method, and averages were established for each group. The vaginal smears had low maturation values of 40 and 22 in the early and late menopausal groups, respectively. In these women, the buccal smears' maturation values were high, above 70. Similar high maturation values were found in buccal smears of the young women and men. It was concluded that the high maturation values found in the oral smears of the menopausal women are not the result of hormonal effect but that of local mechanisms or irritative factors.