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PubMed1998

Oral contraceptives and the risk of subarachnoid hemorrhage: a meta-analysis.

OBJECTIVE: The objective of this study is to estimate the risk of subarachnoid hemorrhage produced by oral contraceptive use. METHODS: Studies published since 1960 were identified using MEDLINE, Cumulated Index Medicus, Dissertation Abstracts On-line, and bibliographies of pertinent articles. Two independent reviewers screened published cohort and case-control studies that evaluated the risk of subarachnoid hemorrhage associated with oral contraceptives. Eleven of 21 pertinent studies met predefined quality criteria for inclusion in the meta-analysis. Relative risk (RR) estimations evaluating subarachnoid hemorrhage risk in oral contraceptive users compared with nonusers were extracted from each study by two independent reviewers. Study heterogeneity was assessed by design type, outcome measure (mortality versus incidence), exposure measure (current versus ever use), prevailing estrogen dose used, and control for smoking and hypertension. RESULTS: The overall summary RR of subarachnoid hemorrhage due to oral contraceptive use was 1.42 (95% CI, 1.12 to 1.80; p = 0.004). When the two study results failing to control for smoking were excluded from the analysis, a slightly greater effect was seen, with an RR of 1.55 (95% CI, 1.26 to 1.91; p < 0.0001). In the six studies controlling for smoking and hypertension the RR was 1.49 (95% CI, 1.20 to 1.85; p = 0.0003). High-estrogen oral contraceptives appeared to impart a greater risk than low-dose preparations in studies controlling for smoking, but the difference was not significant (high-dose RR, 1.94; 95% CI, 1.06 to 3.56; low-dose RR, 1.51; 95% CI, 1.18 to 1.92). CONCLUSIONS: This meta-analysis of observational studies suggests that oral contraceptive use produces a small increase in the risk of subarachnoid hemorrhage.

Case-Control Studies↗
PubMed1989

Elevated plasma levels of oxytocin in women taking low-dose oral contraceptives. Identification of the plasma oxytocin with high performance liquid chromatography.

The aim of the present study was to investigate whether low-dose oral contraceptives affect oxytocin concentrations in plasma. Twenty women participated in an open cross-over study. Six consecutive blood samples were drawn twice, with a 4-week interval, in the luteal phase of the menstrual cycle when the women were/were not taking oral contraceptives. Plasma levels of oxytocin were analysed with a radio-immunoassay specific for oxytocin. A significant increase in oxytocin concentrations was observed following ingestion of oral contraceptives (p less than 0.02). Women with the highest oxytocin levels during a normal menstrual cycle increased their levels the most when on oral contraceptives. Analysis with high performance liquid chromatography demonstrated that immunoreactive oxytocin found in plasma, whether with or without oral contraceptives, co-eluted with synthetic oxytocin standard. An interesting possibility could be that the mental side effects and effects on glucose metabolism occurring after treatment with oral contraceptives might be related to elevated oxytocin levels, since metabolic and CNS effects of oxytocin are known.

Adult↗
PubMed1981

Contraception and lactation.

Lactation worldwide is estimated to prevent more births than all organized family planning programs, and thus has a definite contraceptive action. In addition, it contributes to better infant nutrition and well-being. In some societies women do not cohabit while lactating and therefore need no contraception. This situation is being eroded, and in any case does not apply generally. The risk of pregnancy increases with the length of lactation, and thus some form of added contraception needs to be adopted during lactation. Because of the nutritional value of lactation, the CMC deprecates the exploitative commercial advertising and promotion of bottlefeeding that exists in many parts of the world. It recommends that the IPPF and its member associations should actively promote breastfeeding. Since pregnancy can occur during lactation, additional contraception is desired. It should be remembered that IUDs, spermicides, mechanical methods, depot medroxyprogesterone acetate, progestagen-only oral contraceptives (OCs), and sterilization have no adverse effects on lactation. Evidence is accumulating that combined OCs have an adverse effect on the quantity and possibly the quality of breastmilk. Therefore, much greater caution should be exercised in distributing combined OCs than previously. Combined OCs should not be started until lactation is well established, and ideally not before 6 months or until the infant is weaned, whichever occurs 1st. If, however, no alternative contraception is available then OCs may be used earlier.

Breast Feeding↗
PubMed1984

Fertile inventions: new contraceptive techniques.

Research into contraception is producing new techniques that involve everything from vaccinations to nasal sprays. Steroids are the basis of the conventional contraceptive pill and much current research is on alternative ways of introducing the same drugs into the woman's reproductive system. Norplant is 1 approach. It involves implanting 6 tiny silicone-rubber tubes just beneath the skin of a woman's underarm. The tubes contain a drug, widely used as an ingredient of the contraceptive pill, which is slowly released from the tubes over a period of 5 years. It is understandable that much contraceptive research is focused on the womb. The brain, however, seems a strange place to be concerned with when trying to prevent conception. But it is the brain that controls a woman's ovulation by sending signals to the reproductive system via the pituitary gland. And now it is possible to synthesize chemicals which, when given in the form of a nasal spray, will inhibit ovulation by mimicking the brain's signals to the pituitary gland. It may even be possible to develop drugs which act directly on parts of the brain itself--a prospect we should be aware of, whether we would approve of it or not. There has been such an explosion of knowledge of the neural transmission systems that this may not be so far-fetched as it sounds. Research in China tends to concentrate more on naturally occurring substances--like a new form of female sterilization which involves not anesthetics or surgery but a substance called "mucilage"--1 of the ingredients of birds-nest soup. If mucilage is passed through the cervix into the fallopian tubes it causes them to block up and so prevents the passage of the ovum. There is a Western "high-tech" alternative to this, called methylcyanoacrylate--you might be more familiar with it as "superglue" or "crazy glue." Used carelessly it can stick your fingers together, but this tendency to join human tissues can be more productively used to block up the fallopian tubes. The Chinese are also looking at another natural substance as the basis of the possible "male pill." This is gossypol which occurs in cottonseed. A major reason why most research has been focused on contraception for women is that men present problems of quite a different order of magnitude. While a woman only ovulates once every 28 days or so, male sperm are produced continuously, with 200-400 million of them in each ejaculation. But drugs based on gossypol, which seems to have the effect of reducing the sperm count, may be the answer. Under the auspices of the World Health Organization, research on gossypol and other plants with contraceptive potential is now going on over all the world. Some 350 have been put under the microscope so far and about 30 look worth pursuing.

Contraception↗
PubMed1992

Contraception for the postpartum woman.

The postpartum woman has the full array of contraception options available to her to prevent a subsequent pregnancy. Two factors may influence the choice of the method and the timing of the onset of use (when pregnancy risk increases): the infant feeding mode chosen and the reproductive involution process. The major controversial area regarding contraception postpartum is the use of oral contraceptives if the mother is breastfeeding (ie, if and how do steroids affect the lactation process or infant health). This article reviews the physiologic and hormonal changes that occur after birth, examines the data available in relation to the influence of steroidal contraceptives on lactation, and presents postpartum implications of the use of the spectrum of contraceptive choices. The nurse can provide an important role in counseling postpartum women regarding contraceptive alternatives and supporting families in attaining their childbearing goals.

Breast Feeding↗
PubMed1982

[Advantages and risks of hormonal contraception].

Among modern contraceptive methods hormonal contraceptive agents, due to their reliability, are preferred. Nevertheless, it has to be considered that these steroidal hormones and their metabolites do not only possess an ovulation inhibitory effect, but that they also influence other systems, such as carbohydrate and lipid metabolism, blood clotting, fluid balance, plasma proteins as well as the entire hormonal system. These multiple side effects have positive and negative influences. By reducing the doses of estrogens and progestagens occurrence of unpleasant adverse reactions has been decreased. Some years ago, the estrogen content of oral contraceptive preparations was considered to be noxious while a favourable effect was attributed to the progestagen content. The results of biochemical studies yielded a better understanding of the effect of steroidal hormones on lipid metabolism. Fertility problems occurring after discontinuation of oral contraceptive treatment are mainly observed in women who, prior to use of oral contraceptive agents have already been suffering from functional cycle disturbances. Ovulation inhibitory preparations may also be given to adolescent girls with immature cycles. As the juvenile endocrine system is adaptable, after cessation of the ovulation inhibitory effect, the cycle returns to pretreatment patterns. It may now even be possible to administer hormonal contraceptive agents to treat endocrine disturbances.

Adult↗
PubMed1990

Effects of newer oral contraceptives on the inhibition of coagulation and fibrinolysis in relation to dosage and type of steroid.

Oral contraceptives influence plasma proteins, causing changes in plasma procoagulants and fibrinolytic effectors. Estrogen is thought to be responsible for these changes, whereas progestogens, in particular those with an androgenic effect, may influence the magnitude of the changes. This concept is consistent with epidemiologic studies, suggesting a correlation between estrogen dose and cardiovascular episodes in oral contraceptive users. A delayed resolution of fibrin might contribute to an increased risk caused by decreased coagulation inhibition or fibrinolytic efficacy. Estrogen (30 micrograms or more) has a dose-dependent effect on clotting factors, including antithrombin III and proteins C and S. The effect of high- and low-dose oral contraceptives containing various progestogens on the fibrinolytic system is less clear. We have found that low-dose oral contraceptives containing levonorgestrel or lynestrenol enhance fibrinolysis, as revealed by an increase in plasminogen (30% to 40%), a decrease in histidine-rich glycoprotein (15% to 26%), an increase in tissue plasminogen activator activity (greater than 150%), and a decrease in tissue plasminogen activator inhibition (30% to 40%), concomitant with a slight decrease in tissue plasminogen activator antigen level (15% to 20%). New oral contraceptives contain less androgenic progestogens. Preliminary results of an ongoing study of women receiving either 20 micrograms of ethinyl estradiol with 150 micrograms of desogestrel or 30 micrograms of ethinyl estradiol plus 75 micrograms of gestodene revealed no change or changes similar to the older low-dose preparations after 6 months of treatment. Of particular importance was the finding that coagulation activation, expressed by the levels of thrombin-antithrombin III-complexes, fibrin formation, and the efficacy of fibrinolysis, expressed by the levels of fibrin degradation products, was identical in the two groups.

Blood Coagulation↗
PubMed1988

The association between vaginal bleeding patterns and reasons for discontinuation of contraceptive use.

This paper describes the relationship between menstrual bleeding patterns recorded and reasons for discontinuing method use given by women using one of four types of hormonal contraception: combined oral pills, progestogen-only oral pills, a vaginal ring or depot-medroxyprogesterone acetate (DMPA). The women were recruited to five clinical trials, each of which lasted at least 48 weeks. The subject's reason for discontinuation was recorded if she stopped contraceptive use before the scheduled time. Overall, the reason expressed for discontinuing method use was a close reflection of the subject's experience. Among women using either type of oral contraceptive or a vaginal ring, subjects who discontinued for a non-menstrual reason or were lost to follow-up had bleeding patterns which did not differ markedly from those of women who continued method use. Only in the DMPA group was there any evidence that women who complained of non-menstrual side effects or were lost to follow-up might have ceased method use because they were unwilling or unable to tolerate their bleeding patterns. Subjects who discontinued because of amenorrhea had few bleeding/spotting days and at least one prolonged bleeding-free interval; women who complained of longer bleeding had long episodes and short intervals. Women who reported heavier bleeding had patterns which were similar to, but less extreme, than those of subjects who reported longer bleeding. The complaint of irregular bleeding, however, did not concur with the bleeding patterns recorded, regardless of contraceptive method. The predominant menstrual disturbance in this group of women was frequency of bleeding. They had no special difficulty in predicting either the time of onset or the length of their bleeding episodes. There were marked differences between individuals in terms of their acceptance of bleeding disturbances. Nevertheless, the results of this study confirm the importance of counselling. Women using DMPA tolerated far greater menstrual disruption than subjects using any other method. Subjects using an oral contraceptive were unlikely to have been warned of potential bleeding problems; when they encountered any, they tended to cease method use. In contrast, subjects using DMPA would have been advised to expect irregular patterns and possibly amenorrhea; prepared for such disturbances, their perseverance was remarkable.

Administration, Intravaginal↗
PubMed1994

Menstrual impact of contraception.

Persistent bleeding is a common reason for the discontinuation of contraception. Standard terminology for describing bleeding patterns by reference period is presented. Observed bleeding patterns with oral contraceptives, depot medroxyprogesterone acetate, the levonorgestrel subdermal implant, and intrauterine devices are described. Bleeding days are least with oral contraceptives that are highest in progestin and estrogen potency and dose, but the ratio of the two steroids is also important. Published studies suggest that oral contraceptives containing new nonandrogenic progestins have bleeding patterns as acceptable as older low estrogen formulations. Approaches to the evaluation and treatment of intermenstrual bleeding with contraceptive methods are reviewed. Patient education on expected bleeding patterns is essential to compliance and continuation.

Contraceptive Agents↗
PubMed1999

Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.

This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene (EE/GSD) or 150 micrograms of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.

Adolescent↗
PubMed1989

Oral contraceptives: significance of their effects in man and relationship to findings in animal models.

Combination oral contraceptives have been available since 1960. They contain both an estrogen and a progestogen and have been studied extensively in both lower animals and humans and have been the subject of special regulatory requirements for toxicological and clinical studies. The initial oral contraceptives, by today's standards, contained very high levels of both hormones. There has been a continuous decrease in the dose of both the estrogen and the progestogen during the past quarter century, with continued maintenance of high degree of effectiveness. This decrease of dosage has been stimulated by findings from prospective clinical trials and retrospective case control trials. As additional information has been gained with oral contraceptives, new benefits beyond their effectiveness as contraceptives have been realized. Today's oral contraceptives provide a high degree of effectiveness, low incidence of nuisance side effects, and low incidence of major adverse effects.

Animals↗
PubMed1990

Knowledge and use of postcoital contraception: a survey among health professionals in Tower Hamlets.

The knowledge and estimated retrospective use of postcoital contraception was ascertained from health professionals in Tower Hamlets in the summer of 1988 using a postal questionnaire. Eighty five per cent of general practitioners responded and 91% of these had received requests for postcoital contraception within the previous six months. Only one third of general practitioners had information about postcoital contraception available in their surgeries. Family planning doctors and nurses had the most accurate knowledge of the method but many health professionals appeared to lack sufficient knowledge to ensure appropriate prescribing and to publicize this method to their women patients. It is concluded that if the high rate of abortion in the borough is to be reduced, health professionals as well as women need to be further educated as part of a postcoital contraception publicity campaign. Use of the term 'emergency contraception' rather than the non-medical term 'the morning after pill' may be more effective and reduce the present confusion among both groups.

Adult↗
PubMedDate not supplied

Contraceptive use and fertility in Honduras, 1981-84.

This paper presents data on contraceptive use and fertility in Honduras obtained from a household survey conducted in 1984, and compares these data with similar information obtained from surveys carried out in 1981 and 1983. About half of the increase that has taken place in contraceptive use in Honduras is accounted for by sterilization. In 1981, 27 percent of women in union aged 15-49 years were practicing contraception; in 1984, the percentage of those 15-44 was 35 percent. The increase in urban areas was smaller (from 47 percent to 51 percent) than in rural areas (from 16 percent to 24 percent). Also, fertility remained almost unchanged in urban areas while declining in rural areas. Information from questions on place of purchase, price, and brand of contraceptive (for orals) was used to determine source of supply. The use of multiple questions to determine source results in a higher percentage of contraceptive use attributed to the Honduran Family Planning Association as compared with answers to a single question. The duration of breastfeeding in Honduras has increased, with the greatest changes occurring among women in urban areas and women with the highest levels of education. Efforts have been made to promote breastfeeding in urban areas and these results suggest that the efforts have been successful.

Adolescent↗
PubMed1995

Unintended pregnancies and use, misuse and discontinuation of oral contraceptives.

Unintended pregnancies are a recognized occurrence among women using oral contraceptives (OCs) as a consequence of both user and method failure. However, OCs also influence the occurrence of unintended pregnancies through an additional, poorly recognized, route: cessation of OC use by women who do not wish to become pregnant but stop using OCs because of side effects or other reasons. Many such women fail to immediately substitute a new contraceptive and/or adopt a less reliable contraceptive. This is a particularly important consideration for the approximately 3.7 million women who begin taking OCs in the United States each year since this group commonly experiences side effects and has a high discontinuation rate. Using a decision tree to follow a cohort of OC users over one year, we estimate that over 1 million unintended pregnancies are related to OC use, misuse or discontinuation. The greatest proportion of these, 61%, occur in women who discontinue OCs; of these, 66.6% occur in women who fail to immediately substitute other contraceptives and 33.3% because of the adoption of less reliable contraceptive methods. Of continuing OC users, the majority, exhibiting good compliance, contribute 24% of pregnancies because of their large numbers. Continuing OC users who are poor compliers, though many fewer, are responsible for 15% due to their high pregnancy rate. Unintended pregnancies in women who discontinue OCs account for approximately 20% of the 3.5 million annual unintended pregnancies in the United States, incurring costs of nearly +2.6 billion.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraception Behavior↗
PubMed1995

[Pharmacology of oral contraceptives].

Oral contraceptives include two types of steroids; ethinyl-estradiol as the main estrogenic component which dose vary from 20 to 50 micrograms per tablet (mostly 30 to 35 micrograms) and progestins essentially derivatives of 19 nortestosterone. Derivatives of 19 norprogesterone such as nomegestrol acetate or ST 1435 are not used as oral contraceptives but are being evaluated through parenteral administration, e.g. implants or transdermal systems. The assessment of the pharmacological properties of these progestins indicate a high antigonadotropic and a high antiestrogenic properties for levonorgestrel and for the newer gestagens as well. Therefore very low doses are being used in the current oral contraceptives. However, there is a lower margin of security with the low dose contraceptives than with previous standard combinations and especially when concomitant medications are ingested such as enzyme-inducing agents. Selection of contraceptive methods should be discussed when specific co-medications are necessary.

Contraceptives, Oral, Synthetic↗
PubMed1985

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.

Abnormalities, Drug-Induced↗
PubMed1989

The effect of triphasic oral contraceptives on plasma lipids and lipoproteins.

To determine the effect of triphasic oral contraceptives on plasma lipid transport, 150 nonsmoking women with normolipidemia, ages 18 to 35 years, were randomly assigned to receive one of three contraceptive formulations: (1) ethinyl estradiol, 30, 40, and 30 micrograms/day, each for 6, 5, and 10 days per menstrual cycle, and levonorgestrel, 50, 75, and 125 micrograms/day, each for 6, 5, and 10 days; (2) ethinyl estradiol, 35 micrograms/day for 21 days, and phased norethindrone, 500, 750, and 1000 micrograms/day each for 7 consecutive days; and (3) ethinyl estradiol, 35 micrograms/day for 21 consecutive days, and norethindrone, 500, 1000, and 500 micrograms/day for 7, 9, and 5 days, respectively. A control group consisting of 49 women taking a nonhormonal form of contraception was also included. After 6 months of oral contraceptive treatment, significant increases in plasma triglyceride (28% to 52%) and plasma apolipoprotein B levels (20% to 23%) were observed in each treatment group. The changes in total plasma cholesterol (3% to 10%) and low-density lipoprotein cholesterol values (0% to 11%) were less striking. Changes in total high-density lipoprotein cholesterol levels were statistically insignificant (-2% to -4%); however, high-density lipoprotein2 cholesterol levels decreased by 29% to 33% and high-density lipoprotein3 cholesterol levels increased by 20% to 23%. Concomitantly, plasma apoliporprotein A-1 values increased by 5% to 12%. No consistent significant differences among analyses were observed between and of the groups receiving different oral contraceptives for 6 months.

Adolescent↗
PubMed1990

Clinical aspects of the relationship between oral contraceptives and abnormalities of the hemostatic system: relation to the development of cardiovascular disease.

Epidemiologic evidence has established that oral contraceptives increase the risk of both arterial and venous thromboembolic disease. This is dose related in the case of the estrogen component for both arterial and venous events and in the case of progestogens for arterial events. It is probable that the increased rate of thromboembolic events caused by estrogen is related to hypercoagulability. Plasma levels of several clotting factors have been shown to be elevated in oral contraceptive users, and this increase is graduated according to the dose of estrogen. In pregnancy, factor VIIc is increased after cold activation of plasma at 4 degrees C overnight. Likewise, in users of oral contraceptives, both factors VIIc and XIIc are increased, which suggests a direct effect of factor XIIc on the extrinsic system. In men, the risk of ischemic heart disease is strongly and independently related to factor VIIc and fibrinogen levels; thus it is possible that in women taking oral contraceptives, the mechanism of risk is similarly mediated. There is a good case for factor VIIc as the index of flux in the coagulation system and hence of a hypercoagulable state, and indeed it may directly contribute to the generation of thrombin. This article examines the available evidence on clotting factor activity in the risk of cardiovascular disease in oral contraceptive users.

Blood Coagulation Factors↗