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PubMed1994

Breast cancer among young U.S. women in relation to oral contraceptive use.

BACKGROUND: While most studies have found no association between oral contraceptive use and breast cancer, several studies of younger women have reported an association with long-term oral contraceptive use. PURPOSE. We studied the relationship of patterns of oral contraceptive use to breast cancer risk among younger women. These women have had oral contraceptives available their entire reproductive lives and are now entering the breast cancer-prone years. METHODS: A population-based, case-control study of breast cancer was conducted in three counties in western Washington State among women born in 1945 or later, ages 21-45. Case patients were 747 women with breast cancer diagnosed in 1983-1990 and identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry. Control subjects were 961 women identified by random-digit telephone dialing. Subjects were interviewed in person, using pictures of brands of oral contraceptives and calendars of life events as recall aids. RESULTS: There was no increased incidence of breast cancer associated with ever having used oral contraceptives. Because only 8% of this cohort had never used oral contraceptives, short-term users (< 1 year) were combined with never users as the reference group for further analyses. A small increased risk of breast cancer was associated with long duration of oral contraceptive use (odds ratio for > or = 10 years = 1.3; 95% confidence interval [CI] = 0.9-1.9; P for trend = .03), particularly among women aged 35 years or younger (odds ratio for > or = 10 years = 1.7; 95% CI = 0.9-3.1). Breast cancer was also modestly related to oral contraceptive use early in reproductive life (odds ratio for use within 5 years of menarche = 1.3; 95% CI = 1.0-1.8; P for trend = .04) and to use of high-progestin-potency oral contraceptives for at least 1 year (odds ratio = 1.5; 95% CI = 1.1-2.1). These associations were adjusted for age, age at menarche, term pregnancy, induced abortion, and family history of breast cancer. The associations were not further confounded by case-control differences in education, religion, breast feeding of offspring, or infertility; in oral contraceptive contraindications, indications, or complications; or in measures of breast cancer detection such as mammography or breast biopsy. CONCLUSIONS: Long-term oral contraceptive use among young women or use beginning near menarche may be associated with a small excess breast cancer risk, possibly due to susceptibility to genetic damage in breast epithelial cells at ages of high breast cell proliferative activity. IMPLICATIONS: Future studies should investigate whether the patterns of risk we reported are present as this cohort ages.

Adult↗

PubMed1993

Combined oral contraception with desogestrel/ethinyl estradiol: tolerability profile.

Since their introduction nearly 30 years ago, oral contraceptives have been widely researched regarding their contraceptive and noncontraceptive effects. With proper usage, oral contraceptives provide highly effective contraception. In addition, oral contraceptives confer significant noncontraceptive health benefits, including prevention of ovarian and endometrial cancer and reduction in the incidence of pelvic inflammatory disease, endometriosis, benign breast disease, and dysmenorrhea, among others. Today's low-dose oral contraceptives have an improved safety profile when contrasted with their early higher dose counterparts. Yet oral contraceptive use continues to be associated with a variety of minor side effects, which range from menstrual changes such as breakthrough bleeding, spotting, or amenorrhea, to androgenic effects, including weight gain and acne. These androgenic effects are important factors in patient discontinuation of oral contraceptives. Progestins with increased selectivity have the potential to cause fewer androgenic side effects while retaining appropriate progestin suppression of the endometrium and hypophyseal-pituitary-ovarian axis. A combination oral contraceptive (30 micrograms of ethinyl estradiol with 150 micrograms of desogestrel) has been evaluated extensively by European investigators. This literature suggests that a low-dose oral contraceptive formulated with the selective progestin desogestrel offers a favorable profile of reduced androgenic side effects while retaining the cycle control associated with low-dose oral contraceptives currently marketed in the United States.

Acne Vulgaris↗

PubMed1997

Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.

BACKGROUND: The association between oral contraceptive (OC) use and acute myocardial infarction (AMI) was established in studies from northern Europe and the USA, which took place during the 1960s and 1970s. Few data are available to quantify the risk worldwide of AMI associated with use of OCs introduced since those early studies. This hospital-based case-control study examined the association between a first AMI and current OC use in women from Africa, Asia, Europe, and Latin America (21 centres). METHODS: Cases were women aged 20-44 years who had definite or possible AMI (classified by history, electrocardiographic, and cardiac-enzyme criteria), who were admitted to hospital, and who survived for at least 24 h. Up to three hospital controls matched by 5-year age-band were recruited for each of the 368 cases (941 controls). All participants were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, lifetime contraceptive use, and blood-pressure screening before the most recent episode of OC use. Odds ratios compared the risk of AMI in current OC users and in non-users (past users and never-users combined). FINDINGS: The overall odds ratio for AMI was 5.01 (95% CI 2.54-9.90) in Europe and 4.78 (2.52-9.07) in the non-European (developing) countries; however, these risk estimates reflect the frequent coexistence of other risk factors among OC users who have AMI. Very few AMIs were identified among women who had no cardiovascular risk factors and who reported that their blood pressure had been checked before OC use; odds ratios associated with OC use in such women were not increased in either Europe or the developing countries. Among OC users who smoked ten or more cigarettes per day, the odds ratios in Europe and in the developing countries were over 20. Similarly, among OC users with a history of hypertension (during pregnancy or at any other time), odds ratios were at least ten in both groups of countries. No consistent association between odds ratios for AMI and age of OC users or oestrogen dose was apparent in either group of countries. No significant increase in odds ratios was apparent with increasing duration of OC use among current users, and odds ratios were not significantly increased in women who had stopped using OCs, even after long exposure. The study had insufficient power to examine whether progestagen dose or type had any effect on AMI risk. INTERPRETATION: Current use of combined OCs is associated with an increased risk of AMI among women with known cardiovascular risk factors and among those who have not been effectively screened, particularly for blood pressure. AMI is extremely rare in younger (< 35 years) non-smoking women who use OCs, and the estimated excess risk of AMI in such women in the European centres is about 3 per 10(6) woman-years. The risk is likely to be even lower if blood pressure is screened before, and presumably during, OC use. Only among older women who smoke is the degree of excess risk associated with OCs substantial (about 400 per 10(6) woman-years).

Adult↗

PubMed1999

Oral contraceptives and ovarian cancer.

The protection conveyed by oral contraceptives against ovarian cancer risk is one of the best established and most important features of epithelial ovarian cancer on a public health scale. Ovarian cancer incidence and mortality rates have been declining in most developed countries for women born after 1920, and the decline was greater in countries where oral contraceptive use has been more widespread. Thus, data from descriptive epidemiology are consistent with a favourable effect of oral contraceptives on ovarian cancer risks. The overall estimated protection from cohort and case-control studies is approximately 40% in ever oral contraceptive users, and increases with duration of use to more than 50% for users of 5 years or longer. The favourable effect of oral contraceptives against ovarian cancer risk persists for at least 10-15 years after use has ceased, and it is not confined to any particular type of oral contraceptive formulation. However, available data do not provide definite evidence for more recent low-dose formulations and for longer periods of latency or recency of use. The protection is also observed on borderline malignancy ovarian neoplasms, and probably on benign epithelial cysts as well. There is suggestive evidence of some protection for sex-cord-stromal cancers, but not for germ cell neoplasms. In terms of biological mechanisms, oral contraceptives are thought to act on ovarian cancer risk by affecting the lifetime number of ovulations. The protection attributable to oral contraceptives on ovarian cancer risk is one of the major issues on any individual risk/benefit assessment and public health evaluation of this type of contraceptive use.

Adolescent↗

PubMed1989

Epithelial ovarian cancer and combined oral contraceptives. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship between use of combined oral contraceptives and risk of epithelial ovarian cancer was investigated in a hospital-based case-control study conducted from 1979-1986 in seven countries. Three hundred and sixty-eight women with histologically confirmed epithelial ovarian cancer were compared to 2397 hospital controls matched for age, study centre, hospital and year of interview. The relative risk (RR) in women who ever used combined oral contraceptives, controlling for the confounding effect of number of pregnancies, was 0.75 (95% confidence interval (Cl) 0.56, 1.01). The relative risk decreased with increasing duration of oral contraceptive use and with increasing time since cessation of use. Except for mucinous tumours, oral contraceptive use was associated with lower risk of all histological subtypes of epithelial ovarian cancer. While the reduced risk associated with oral contraceptive use was present in parous women (RR = 0.85), it was most pronounced in nulliparous women (RR = 0.16). The magnitude of the negative association between oral contraceptives and ovarian cancer in five developing countries (RR = 0.77) was similar to that reported in developed countries.

Adult↗

PubMed1980

Use-effectiveness of standard-dose and low-dose oral contraceptives in Dacca.

Five hundred women accepting oral contraceptives at an urban clinic were alternately prescribed standard-dose (50 microgram of estrogen) or low-dose (30 microgram of estrogen) combined pills. Life-table continuation rates at 12 months were approximately 40% for both groups, with no significant differences between or within the two groups after controlling for sociodemographic variables and nutritional status. Approximately three fifths of those who discontinued using both formulations cited medical reasons, especially dizziness. The low-dose oral contraceptive appeared to be as acceptable to these urban Bangladeshi women as the higher-dose pill.

Adult↗

PubMed2002

A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use.

Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma.

Adolescent↗

PubMed1996

The role of thromboxane A2 in increased whole blood platelet aggregation in oral contraceptive users.

Epidemiological studies have shown that oral contraceptives increase the risk of thromboembolic disease in susceptible women however the mechanisms involved are unclear. We investigated whole blood platelet aggregation in 44 women randomly allocated to 6 cycles of treatment with either gestodene (75ug) or desogestrel (150ug) combined with 30ug ethinyloestradiol (EE). The in vitro effects of aspirin and a thromboxane synthetase inhibitor, dazmegrel (UK38485) were also investigated. Oral contraceptive treatment caused a significant increase in collagen, arachidonic acid (AA) and ADP induced whole blood platelet aggregation. PAF induced aggregation was unchanged. There were no significant differences in the levels of platelet aggregation between the desogestrel/30ugEE and gestodene/30ugEE groups. In vitro incubation of platelets with aspirin and dazmegrel prevented the oral contraceptive induced increase in platelet aggregation. Dazmegrel caused an on treatment decrease in PAF induced aggregation in the desogestrel/30ugEE but not the gestodene/30ugEE group. The results of this study indicate that the use of oral contraceptives is associated with an increase in platelet aggregation that is mediated by changes in thromboxane/prostacyclin ratio(TXA2/PGI2). Although no significant differences were found between the two different progestogen combinations, the effects of dazmegrel on PAF induced aggregation suggest a possible difference in the progestogen modifying effects of desogestrel and gestodene which is unmasked when thromboxane synthetase is inhibited.

Adolescent↗

PubMed2001

Oral contraceptives, hormone replacement therapy and thrombosis.

Oral contraceptives and hormone replacement therapy are used by hundreds of millions of women worldwide. Since the early 1960s it is known that female hormones increase the risk of venous thrombosis, myocardial infarction and stroke. This risk is still present with current low-dose oral contraceptives and, even though in absolute terms the risk is small, oral contraceptives form the major cause of thrombotic disease in young women. The risk is higher during the first year of use (up to I per 1000 per year), with the use of desogestrel- or gestodene-containing oral contraceptives ("third generation progestogens") and among women with a prothrombotic predispositon. Hormone replacement therapy increases the risk of venous thrombosis, while results of randomised trials so far do not substantiate the expectation of a beneficial effect on the risk of arterial cardiovascular disease. First results are emerging that specific subgroups of women, with prothrombotic or other abnormalities, may be at risk, especially during the first years of use of hormone substitution.

Clinical Trials as Topic↗

PubMed2005

Combined oral contraceptives in women with systemic lupus erythematosus.

BACKGROUND: Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. METHODS: A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. RESULTS: The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). CONCLUSIONS: Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.

Adolescent↗

PubMed1976

Veno-occlusive disease of the liver associated with oral contraceptives: case report and review of literature.

This report concerns a young woman who, after taking a contraceptive preparation orally for three years, developed the Budd-Chiari syndrome as the result of a widespread chronic obliterative process involving the intrahepatic efferent venous system. Her prolonged course, which failed to respond to an end-to-side portacaval shunt procedure, mimicked chronic hepatitis evolving to cirrhosis. Additional noteworthy features were the presence of two small benign hepatic adenomas, observed both at biopsy and at necropsy, a lesion recently recognized as a complication of anovulatory drugs, and widespread hepatic calcifications found at autopsy.

Adenoma↗

PubMed1995

Combined oral contraceptives and risk of cervical carcinoma in situ. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

BACKGROUND: Although the possible influence of oral contraceptives on risk of cervical carcinoma in situ has been the subject of multiple prior investigations, the results have been inconsistent. METHODS: Data from a multinational, collaborative case-control study were analysed to investigate further this possible relationship. To assess potential screening bias, some statistical analyses were restricted to subgroups of cases with and without symptoms at the time of their diagnosis. RESULTS: Relative risk estimates in relation to various features of oral contraceptive use tended to be highest for asymptomatic disease, lowest for disease presenting with vaginal bleeding, and intermediate for disease presenting with other symptoms, suggesting the presence of a screening bias. In women with vaginal bleeding, who are least likely to have been detected by routine screening, no elevated risk of cervical carcinoma in situ was observed in relation to ever having used combined oral contraceptives, but there was an increased risk in users of over 60 months' duration. An increasing trend in risk with duration of use was most pronounced in these women who first used oral contraceptives in the past 5-10 years; and in women who used oral contraceptives for more than 60 months, risk declined with time since last use. CONCLUSION: These findings could reflect a reversible effect of long-term use of oral contraceptives at an intermediate stage in the carcinogenic process, or a non-causal relationship due to unidentified sources of bias or confounding.

Adult↗

PubMed1978

Mammary nodules in beagle dogs administered investigational oral contraceptive steroids.

Of 172 beagle dogs administered oral contraceptive steroids for 5-7 years, 114 developed 1,156 nodules in the mammary gland region. Most of these nodules arose 2.5-3.5 years after initiation of treatment. Approximately 16% of the nodules were transient and disappeared spontaneously from the mammary gland during the study. A total of 925 nodules were present in 99 dogs at the time of death or necropsy. These nodules were classified as benign mammary dysplasias (7.0%), lobular or intraductal hyperplasias (31.4%), simple adenomas (20.8%), complex adenomas (25.4%), benign mixed tumors (5.3%), malignant tumors (3.6%), or nonmammary lesions (6.5%). Histologically, the mammary nodules were representative primarily of the hyperplasias and tumors that occur spontaneously in the mammary glands of the dog. The only major exception was the presence of 82 simple adenomas that had basaloid features. Most of the contraceptive-related mammary nodules developed in dogs receiving the combination of progestion and mestranol at 10 or 25 times the proposed human dosage. Control dogs and dogs receiving mestrenol alone had few mammary nodules. Combinations of anagestone acetate and mestranol and chloroethynyl norgestrel (WY-4355) and mestranol produced large numbers of nodules at 10 and 25 times the proposed human dosage, whereas ethynerone plus mestranol produced large numbers of nodules only at 25 times the proposed human dosage. Ethynerone, when given alone at 25 times the proposed human dosage, was associated with fewer mammary nodules. Malignant neoplasms were seen in dogs given 10 and 25 times the proposed human dosage of anagestone acetate plus mestranol and 25 times the proposed human dosage of WY-4355 plus mestranol and ethynerone plus mestranol. This study strongly associates certain combinations of progestin and mestranol with mammary neoplasia in dogs.

Adenoma↗

PubMed1996

Increased levels of activated factor VII and decreased plasma protein S activity and circulating thrombomodulin during use of oral contraceptives.

In the present study the effect of oral contraceptive (OC) treatment on selected factors involved in the activation, i.e. circulating activated factor VII (cFVIIa), and in the inhibition of blood coagulation, i.e. plasma protein S activity and circulating thrombomodulin (cTM), were for the first time measured in OC users in a prospective study. Beside other coagulation variables, these parameters were measured during treatment with three low estrogen formulations containing different gestagen components (norgestimate, gestodene). During OC treatment increases in the activation markers prothrombin fragment F1 + 2 and D-Dimer were found, suggesting an increased activation of blood coagulation and fibrinolysis. Along with elevated plasma levels of FVII antigen, cFVIIa was also found increased in all three treatment groups, while inhibitory components of blood coagulation, plasma protein S activity and cTM, significantly and similarly decreased during treatment in all three treatment groups. We conclude that low dose estrogen pills induce similar changes in the plasma levels of main regulatory components of blood coagulation, despite differences in their gestagen components. Increased levels of activators and decreased activities of inhibitors may contribute to arterial and venous thrombotic complications seen in predisposed OC users.

Adult↗

PubMed1997

A multicenter, uncontrolled clinical investigation of the contraceptive efficacy, cycle control, and safety of a new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel over six treatment cycles.

The aim of the trial was to demonstrate the contraceptive efficacy of a new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel and to observe cycle control and safety. Data from 805 treated women resulted in 4400 treatment cycles. One pregnancy occurred while on the trial medication as a result of method failure, resulting in a Pearl index of 0.29. Cycle control was good, and cycle length as well as duration and intensity of withdrawal bleeding were not significantly changed during the trial. Intermenstrual bleeding usually occurred as spotting and decreased considerably during the treatment phase. Spotting alone was reported in 12.4% of cycles, breakthrough bleeding alone in 4.5% of cycles, and breakthrough bleeding and spotting together in 1.4% of treatment cycles. The rate of absence of withdrawal bleeding declined throughout the trial to 2.4% in cycle 6. There were no serious adverse events related to treatment, and most adverse events were those commonly observed in clinical trials with oral contraceptives. Headache, breast tension, and nausea were reported by 17.3%, 11.0%, and 7.7% of the women, respectively. There were no clinically relevant changes in laboratory parameters, blood pressure, or weight. In this trial, the new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel was shown to be effective, safe, and well tolerated. Cycle control was found to be good and there was a low incidence of adverse events.

Adolescent↗

PubMed1997

Use of low-dose oral contraceptives and stroke in young women.

BACKGROUND: Low-dose oral contraceptives are widely used, but there are limited data on the cerebrovascular risks associated with these medications. OBJECTIVE: To determine whether use of low-dose oral contraceptives influences the risk for stroke. DESIGN: Population-based case-control study. SETTING: Women 18-44 years of age who resided in western Washington State between 1991 and 1995. PARTICIPANTS: Patients with ischemic stroke (n = 60), hemorrhagic stroke (n = 102), and other types of stroke (n = 11) and controls identified through random-digit dialing (n = 485). MEASUREMENTS: Details about oral contraceptive use and other risk factors for stroke were obtained through in-person interviews. RESULTS: The estimated incidences of hemorrhagic stroke and ischemic stroke were 6.4 and 4.3 per 100,000 women-years, respectively. Compared with women who had never used oral contraceptives (after adjustment for risk factors for stroke), current users of low-dose oral contraceptives had estimated odds ratios of 0.93 (95% CI, 0.37 to 2.31) for hemorrhagic stroke and 0.89 (CI, 0.27 to 2.94) for ischemic stroke. Compared with past users of oral contraceptives, current users had odds ratios of 1.41 (CI, 0.67 to 2.96) for hemorrhagic stroke and 1.37 (CI, 0.49 to 3.81) for ischemic stroke. For past users compared with never users, the odds ratios were 0.59 (CI, 0.30 to 1.18) for hemorrhagic stroke and 0.57 (CI, 0.25 to 1.32) for ischemic stroke. The odds ratio for hemorrhagic stroke in current users of low-dose oral contraceptives containing norgestrel or levonorgestrel was elevated (3.23 [CI, 1.24 to 8.41]). Among patients with hemorrhagic stroke, the odds ratio for aneurysmal bleeding associated with current use of low-dose oral contraceptives containing norgestrel or levonorgestrel was 4.46 (CI, 1.58 to 12.53). CONCLUSION: The overall risk for stroke and type of stroke was not increased among current users of low-dose oral contraceptives in the study population. Larger studies are needed to clarify both the relation of risk for stroke to past use of oral contraceptives and the possible association between current use of norgestrel-containing oral contraceptives and hemorrhagic stroke.

Adolescent↗

PubMed2003

Venous and arterial thrombosis during oral contraceptive use: risks and risk factors.

Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two- to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 microg to 20-30 microg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis.

Arterial Occlusive Diseases↗

PubMed1974

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.

Abnormalities, Drug-Induced↗