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PubMed1990

Oral contraceptives and rheumatoid arthritis: new data from the Royal College of General Practitioners' oral contraception study.

From data available at April 1987 it was found that the standardised risk ratio for rheumatoid arthritis between current users of oral contraceptives and never users was 0.82 (95% confidence interval 0.59 to 1.15); the ratio between former users and never users was 0.94 (95% confidence interval 0.72 to 1.22). Important secular trends have occurred within our study population. The incidence of rheumatoid arthritis among former and never users has declined over the past two decades. Current users have not experienced this temporal trend, and the ratio between current and never users has, therefore, approached unity. These secular changes may explain why some studies have found that oral contraceptives have a protective effect, while others have been unable to show such an effect.

Adult↗
PubMed1996

Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women.

OBJECTIVE: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism. DESIGN: Matched case-control study. SETTING: 10 centres in Germany and United Kingdom. SUBJECTS: Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables. RESULTS: Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year. CONCLUSIONS: Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Adolescent↗
PubMed1992

Oral contraceptive use and breast cancer risk: a meta-analysis of variations with age at diagnosis, parity and total duration of oral contraceptive use.

OBJECTIVE: To review published reports of risk of breast cancer with oral contraceptive use. DESIGN: Meta-analysis of study results, using regression techniques to explore the inter-study heterogeneity. SETTING: Twenty-seven epidemiological studies of breast cancer risk and oral contraceptive use published 1980-1989. MAIN OUTCOME MEASURES: Relative risk of breast cancer with oral contraceptive use; variations by age at diagnosis, parity, and total duration of use, and with study design characteristics. RESULTS: The overall relative risk estimate was 1.16 (95% CI 1.07-1.25) for the less than 45 years group, 1.21 (95% CI 0.99-1.47) for the nulliparous subgroup, and 1.27 (95% CI 1.12-1.44) for durations of use of more than 8 years. Source of subjects, their marital status, the type of study, data collection methods, matching for geographical area, the number of adjustment factors used in the study analysis, the country of study and the calendar period in which the study ended were all important explanatory factors for inter-study variation, but a substantial proportion of inter-study variation remained unexplained. CONCLUSIONS: These meta-analyses suggest that risk of breast cancer may be raised by around 20% in younger, nulliparous and long use duration subgroups of oral contraceptive users. Risk estimates appear to be influenced by several study design factors, which should be considered carefully in designing and reviewing future studies.

Age Factors↗
PubMedDate not supplied

Recent oral contraceptive use patterns in four European countries: evidence for selective prescribing of oral contraceptives containing third-generation progestogens.

A survey among oral contraceptive (OC) prescribers in the United Kingdom, Germany, Sweden and the Netherlands was performed to investigate OC prescription patterns before and after recent publicity in the media about studies reporting a higher risk of venous thromboembolism with OCs containing third-generation progestogens as compared to OCs containing second-generation progestogens. Before this publicity, most physicians prescribed third-generation OCs as their first-choice formulations for normal healthy women as well as for young girls (< 20 years) and older fertile women (30-35 years). In women presenting with cardiovascular risk factors, third-generation progestogens (desogestrel, gestodene) were considered safer and were five times more often prescribed than second-generation preparations (71% versus 14%). Most prescribers considered ethinylestradiol to be the most important component in relation to the risk of venous thromboembolism (71%), myocardial infarction (66%) and stroke (67%). In addition, for women presenting with cardiovascular risk factors, OC preparations containing 20 or 30 micrograms ethinylestradiol were considered safer than preparations containing 35 or 50 micrograms ethinylestradiol. Although the vast majority of prescribers (78%) stated that their attitudes towards safety of third-generation OCs had not changed since the recent publicity and the regulatory actions in some countries, 56% had changed their prescribing practice, largely due to patient concern about the safety of third-generation OCs. The results from this survey strongly suggest that, prior to the recent publicity, most prescribers considered third-generation OCs to be safer than second-generation preparations. Because of this perceived better safety profile, physicians have selectively been prescribing third-generation OCs to women at increased risk of cardiovascular disease. This pattern of selective OC prescribing may have seriously biased the results of the recently published studies on OCs and venous thromboembolism in favor of second-generation OCs.

Adult↗
PubMed1999

Oral contraceptives: an update.

Oral contraceptives are used by large numbers of reproductive-aged women across the world. Recent data examining cardiovascular risk indicates a persistent risk for venous thromboembolism among all oral contraceptive users. This risk is enhanced by the presence of hemostatic disorders such as factor V Leiden. Whether the progestins gestodene and desogestrel also affect the risk of venous thromboembolism is controversial. Ischemic stroke is rare among users unless they smoke or have hypertension. Similarly, there appears to be no increased risk of hemorrhagic stroke among oral contraceptive users who do not have these risk factors present. Myocardial infarction is rare among oral contraceptive users. However, cigarette smoking coupled with age acts synergistically to substantially increase the risk of this disorder among oral contraceptive users. There is a small increase in risk of breast cancer among oral contraceptive users, although the risk disappears about 10 years after the last use of these preparations. Successful use of oral contraceptives appears to be significantly affected by side effects, understanding of the package insert and time of pill taking. Since serious sequelae are uncommon, improved compliance may be the most important challenge towards improving the use of oral contraceptives for the future.

Journal Article↗
PubMed2003

Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa).

BACKGROUND: Cervical cancer is caused by specific types of the human papilloma virus (HPV), but not all infected women develop cancer. It has been hypothesized that hormonal contraceptives may potentiate the oncogenicity of HPV infection. METHODS: In a case-control study of colored and black women in the Western Cape Province, South Africa, 524 incident cases of clinically evident invasive cervical cancer (stages 1b-1V) were compared with 1541 controls, and with a subgroup of 254 HPV-positive controls. FINDINGS: For injectable progestogen contraceptives (95% of which were depot medroxyprogesterone acetate) the overall relative risk, adjusted for confounding, was 1.0 (95% confidence interval 0.8-1.3); for combined estrogen/progestogen oral contraceptives the corresponding estimate was 0.8 (0.7-1.1). When the data were divided into categories of duration of use extending to > or = 15 years, or according to age, ethnic group, or recency of use, there was no consistent evidence of an increased risk. The findings were unchanged when the cases were compared with the HPV-positive controls. INTERPRETATION: The present findings suggest that neither injectable progestogen-only nor combined estrogen/ progestogen oral contraceptives increase the risk of clinically evident invasive cancer of the cervix.

Adult↗
PubMed2000

Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives.

The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC.

Adolescent↗
PubMed1980

Oral contraceptive steroids and atherosclerosis: lipogenesis in human arterial smooth muscle cells and dermal fibroblasts in presence of lipoprotein-deficient serum from oral contraceptive users.

The incorporation of [14C]-acetate into lipids by cultured human arterial smooth muscle cells and dermal fibroblasts was studied in the presence of lipoprotein-deficient serum from oral contraceptive users (OC) and control women. Exposure to OC serum: 1) significantly increased the synthesis of cholesterol above controls in both fibroblasts (+25-56%) and smooth muscle cells (+28-42%) without a significant change in the synthesis of lecithin; and 2) resulted in increased cholesterol/lecithin ratios in newly synthesized lipids which were higher than controls in both fibroblasts (+50%) and smooth muscle cells (+30%). In vitro addition of the steroid ingredients of the "pill" to the growth medium containing control serum did not result in a stimulation of lipogenesis by the cells. [3H] - mevalonate incorporation into cholesterol was no different with OC and control serum, indicating that the stimulation noted in cholesterol synthesis by OC serum was due to an increased HMG-CoA reductase activity. These findings suggest that increased sterol synthesis in arterial smooth muscle cells of oral contraceptive users may be one pathogenetic factor which adversely influences their risk of atherosclerosis.

Adult↗
PubMed1998

Oral contraceptive use before and after the latest pill scare in The Netherlands. Changes in oral contraceptive use and how users change.

In October 1995, a "pill scare" developed in Europe. In the Netherlands, the recommendations given were 1) to not alarm women without risk for deep vein thrombosis (DVT), and 2) to be reserved in prescribing third generation oral contraceptives (OC) for young women who were beginning OC use. To determine whether there is a change in the prescription of third generation OC after the latest pill scare, prescription data from 1/10/94 to 1/10/96, covering a population of +/- 120,000 persons, were studied with respect to OC use before and after the pill scare. Trend analyses revealed a significant decline in third generation compared with total OC prescribing only in the youngest age category (p = 0.0034). Further, switch behavior was studied. Switches from third to second generation OC were more prevalent after the pill scare than before (odds ratio = 2.63; 95% confidence interval 1.84-3.75) and switches from second to third generation OC were significantly less prevalent after the pill scare. This indicates that Dutch prescribers have reacted to the pill scare in the way that the government recommended.

Adolescent↗
PubMed1994

Oral contraceptives and risk of breast cancer in women aged 20-54 years. Netherlands Oral Contraceptives and Breast Cancer Study Group.

Although the use of oral contraceptives (OCs) is not generally associated with increased risk of breast cancer, higher risks have been reported for some subgroups of users. We have carried out a population-based case-control study in the Netherlands to assess the effect of timing and duration of OC use on the risk of breast cancer developing at various ages. 918 women with breast cancer (20-54 years at diagnosis) were pair-matched by age with controls randomly selected from municipal registries. Information on OC use obtained from women and their prescribers was combined according to standard decision rules. Overall, long-term use of OCs (> or = 12 years) had an associated relative risk (RR) of 1.3 (95% CI 0.9-1.9; test for trend in risk with months of use p = 0.03). This positive trend was found in both the youngest (< 36 years; p = 0.08) and the oldest (46-54 years, p = 0.004) age groups, but not in women aged 36-45 years. The RR of developing breast cancer before age 36 was 2.1 (1.0-4.5) for 4 or more years of OC use compared with shorter use. In women younger than 36, risk increased for longer OC use before age 20 (1.44 per year, p = 0.04). Recent use (previous 3 years) was associated with increased risk in women of 46-54 (RR 1.9 [0.9-4.1], p = 0.02). We conclude that 4 or more years of OC use, especially if partly before age 20, is associated with an increased risk of breast cancer developing at an early age. There is limited evidence that the excess risk disappears as the cohort of young OC users ages, but this issue needs confirmation.

Adult↗
PubMed2001

Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill.

The oral contraceptive pill is one of the most extensively studied medications ever prescribed. The health benefits are numerous and outweigh the risks of their use. Definitive evidence exists for protection against ovarian and endometrial cancers, benign breast disease, pelvic inflammatory disease requiring hospitalization, ectopic pregnancy, and iron-deficiency anemia. It has also been suggested that oral contraceptives may provide a benefit on bone mineral density, uterine fibroids, toxic shock syndrome, and colorectal cancer. Minimal supportive evidence exists for oral contraceptives protecting against the development of functional ovarian cysts and rheumatoid arthritis. Treatment of medical disorders with oral contraceptives is an "off-label" practice. Dysmenorrhea, irregular or excessive bleeding, acne, hirsutism, and endometriosis-associated pain are common targets for oral contraceptive therapy. Most patients are unaware of these health benefits and therapeutic uses of oral contraceptives, and they tend to overestimate their risk. Counseling and education are necessary to help women make well-informed health-care decisions and improve compliance.

Bone Density↗
PubMed2001

Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.

This multicenter study compared the contraceptive efficacy, cycle control, and safety of a new triphasic norgestimate (180/215/250 microg)/ethinyl estradiol 25 microg regimen (Ortho Tri-Cyclen Lo) (n = 1,723) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg (Loestrin Fe 1/20) (n = 1,171). Healthy women were treated for up to 13 cycles. Demographics were similar between regimens. Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20. The overall and method failure probabilities of pregnancy through 13 cycles were 1.9% and 1.5%, respectively, with Ortho Tri-Cyclen Lo and 2.6% and 2.4%, respectively, with Loestrin Fe 1/20. Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group. At representative Cycles 1, 3, 6, 9, and 13, breakthrough bleeding and spotting rates were 16.3, 11.5, 10.3, 7.9, and 7.7%, respectively, in the Ortho Tri-Cyclen Lo group and 34.9, 22.9, 22.2, 15.9, and 13.1%, respectively, in the Loestrin Fe 1/20 group. Compliance and safety data were similar for the two regimens.

Administration, Oral↗