Breast cancer and oral contraceptives: findings in Oxford-Family Planning Association contraceptive study.

Among the 17 032 women taking part in the Oxford-Family Planning Association contraceptive study, 72 were first diagnosed as having breast cancer between the date they were admitted to the study and 1 September 1980. The relative risk of developing the disease in women who had used oral contraceptives in comparison with those who had never used them was estimated to be 0.96 (95% confidence limits 0.59 to 1.63). Among women aged under 35 years, the corresponding relative risk (based on only 14 women with breast cancer) was estimated to be 0.61. No relation was apparent between the risk of developing breast cancer and duration of oral-contraceptive use or interval since first oral-contraceptive use in any age group. The data in this study are thus reassuring; but observations based on women with long-term use of oral contraceptives, especially those starting to use the preparations at an early age, are few.     

Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer.

OBJECTIVE--To determine whether use of the injectable contraceptive depot medroxyprogesterone acetate (Depo-Provera) affects the risk of breast cancer in women. DESIGN--A population based case-control study. SETTING--Nationwide community study. SUBJECTS--891 Women aged 25-54 with newly diagnosed breast cancer were compared with 1864 women selected at random from the electoral rolls. INTERVENTION--Women were interviewed by telephone about past use of contraceptives and about possible risk factors for breast cancer. MAIN OUTCOME MEASURE--Relative risk of breast cancer in women who had used medroxyprogesterone. RESULTS--Medroxyprogesterone had been used by 110 patients and 252 controls. Overall, the relative risk of breast cancer associated with any duration of use was 1.0 (95% confidence interval 0.80 to 1.3). In women aged 25-34 the relative risk was 2.0 (1.0 to 3.8). The relative risk was highest in women aged 25-34 who had used the drug for six years or longer, although there were few women in this category. Women who had used it for two years or longer before age 25 had an increased risk of breast cancer (relative risk 4.6; 1.4 to 15.1). CONCLUSION--Despite the lack of an overall association these findings suggest that medroxyprogesterone may increase the risk of breast cancer in young women.     

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.     

Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions

Objective: To investigate whether users of oral contraceptives who are carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. Design: Comparison of a prospective series of cases of cerebral sinus thrombosis with population data. Setting: Neurological teaching hospitals from different regions in the Netherlands (cases) and a representative sample of the non-institutionalised Dutch population (controls). Subjects: 40 women aged 18-54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years (controls). Main outcome measure: Current use of oral contraceptives at the time of the thrombosis (cases) or at the time of the questionnaire (controls). Prevalences of a hereditary prothrombotic condition in patients and in the population with odds ratios. Results: 34 of 40 (85%) women with cerebral sinus thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37). Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in the population; this corresponds to a threefold to fourfold increase in risk. In women who used oral contraceptives and also carried a prothrombotic defect, the odds ratio for cerebral sinus thrombosis was about 30 relative to women who had neither risk factor. Conclusion: The use of oral contraceptives and being a carrier of a hereditary prothrombotic condition increase the risk of and interact in a multiplicative way in the development of cerebral sinus thrombosis.

Key messages

• The use of oral contraceptives is associated with an increased risk of cerebral venous sinus thrombosis
• This risk of cerebral venous sinus thrombosis in women who use oral contraceptives is larger if there is an additional hereditary prothombotic factor (protein C, S, or antithrombin deficiency, factor V Leiden mutation)
• The association between oral contraceptives, thrombophilia, and deep vein thrombosis is also valid for cerebral sinus thrombosis
• Women do not need to stop using oral contraceptives as the absolute risk of cerebral sinus thrombosis is very small

     

Epidemiology of endometriosis in women attending family planning clinics.

OBJECTIVE--To describe the epidemiology of endometriosis in women attending family planning clinics with special reference to contraceptive methods. DESIGN--Non-randomised cohort study with follow up of subjects for up to 23 years. Disease was measured by first hospital admission rates since endometriosis can be diagnosed with accuracy only at laparotomy or laparoscopy. SETTING--17 family planning centres in England and Scotland. SUBJECTS--17,032 married white women aged 25-39 years at entry during 1968-74 who were taking oral contraceptives or using an intrauterine device or diaphragm. About 99% of the women approached agreed to participate and annual loss to follow up was about 0.3%. MAIN OUTCOME MEASURES--Diagnosis of endometriosis, age, parity, and history of contraceptive use. RESULTS--Endometriosis was significantly related to age, peaking at ages 40-44 (chi 2 for heterogeneity = 30.9, p < 0.001). Endometriosis was not linked to duration of taking oral contraceptives. Nevertheless, the risk of endometriosis was low in women currently taking oral contraceptives (relative risk 0.4; 95% confidence interval 0.2 to 0.7), but higher in women who had formerly taken them (1.8; 1.0 to 3.1 in women who had stopped 25-48 months previously) compared with women who had never taken the pill. A similar pattern was seen for use of intrauterine devices (relative risk 0.4 (0.2 to 0.7) in current users and 1.4 (0.4 to 3.2) in users 49-72 months previously compared with never users). No association was found between endometriosis and use of the diaphragm. CONCLUSIONS--Oral contraceptives seem to temporarily suppress endometriosis. Endometriosis may be diagnosed late in women using intrauterine devices as pain and bleeding occur with both.     

An epidemiological study of oral contraceptives and breast cancer

During 1968-77, 707 women aged 16-50 years with newly diagnosed breast cancer and 707 matched controls were interviewed at eight teaching hospitals in London and Oxford about their use of oral contraceptives. Eighty-six of the patients with breast cancer were matched with controls with gall-bladder disease; these subjects were omitted from the main analyses, which thus related to 621 case-control pairs.The results were reassuring. A few statistically significant differences in oral contraceptive use were found between the breast cancer and control groups, but the data were subdivided in many ways, so that some “significant” differences would have been expected to occur by chance. The only subgroup in which the evidence for a positive association between pill use and breast cancer was at all convincing comprised women aged 46-50 years, but trends in those aged 41-45 were by and large in the opposite direction and results of combined analysis gave no cause for concern.Information on clinical stage was available for 487 patients with breast cancer treated before the end of 1975. Those who had never used oral contraceptives had appreciably more advanced tumours at presentation than those who had been using the pill during the year before detection of the lump, while past users of the pill occupied an intermediate position. This difference in staging was reflected in the pattern of survival. Oral contraceptives may have had a beneficial effect on tumour growth and spread, though diagnostic bias could not be definitely excluded.     

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.     

Invasive cervical cancer and combined oral contraceptives. WHO collaborative study of neoplasia and steroid contraceptives.

A multicentre, hospital based case-control study is being conducted under the auspices of the World Health Organisation to determine whether steroid contraceptives alter the risk of gynaecological, breast, and hepatic neoplasms. Preliminary results, largely from developing countries, on the relation between combined oral contraceptives and invasive cervical carcinoma showed a relative risk of 1.19 (95% confidence interval 0.99-1.44) in women who had ever used oral contraceptives. The risk increased with duration of use, giving a relative risk of 1.53 after five years. This finding supports a causal interpretation, but it could also be due to incomplete control for confounding sexual variables and other sources of bias.     

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

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

Risk factors for benign breast disease: a 30-year cohort study.

Data on the menstrual history, family history and degree of obesity of 1374 Vancouver nursing students were collected in 1945 and from 1947 to 1956. In 1979, 768 of these women were located; 726 (94%) responded and participated in a follow-up study, providing information on their subsequent medical history and on breast-related problems. No major differences were found between the early histories of these participants and those who were not located or did not respond. Among the respondents 215 gave a history of symptoms compatible with benign breast disease; in 107 this diagnosis was confirmed by biopsy. By age 50 the cumulative risk for benign breast disease was 17% for biopsied and 31% for symptomatic disease. Biopsied benign breast disease was associated with premenstrual breast discomfort, irregular menses, a history of abortions, a family history of both benign and malignant breast disease, lack of use of oral contraceptives, a low index of obesity and small breasts, obesity and breast size being independent. Factors associated with symptomatic benign breast disease were usually associated with a greater likelihood of biopsy for symptomatic disease; hence, the relative risks for biopsied disease were generally greater than those for symptomatic disease. Although the risk factors for benign breast disease differ from those for breast cancer, the findings are consistent with the hypothesis of excessive circulating estrogen.     

Ovarian neoplasms,functional ovarian cysts,and oral contraceptives.

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

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.     

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

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

Oral 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.     

Incidence and Risk Factors of Striae Distensae Following Breast Augmentation Surgery: A Cohort Study

Background

The significant increase in the popularity of breast augmentation surgeries has led to an increase in the number and types of complications; among these is the postoperative occurrence of Striae Distensae (SD). The objective of this study was to investigate the incidence of SD and describing its occurrence in association with age, breast implant volume, history of SD, history of pregnancies and breastfeeding, body mass index (BMI), changes in postoperative weight, smoking habits, and use of oral contraceptives.

Methods

A cohort study was conducted and the patient data from a specific social group that underwent augmentation mammaplasty with silicone breast implants in a private clinic was analyzed.

Results

563 patients entered the cohort, while 538 completed the study. The SD incidence was 7.06%. The risk was almost the double at 22–28 years of age and triple in women of 21 years of age or less. The women who did not use oral contraceptives were 2.59 times more likely of developing SD. A higher incidence of SD was observed among those with normal or low BMI values, smokers, and in those who had implants larger than 300 ml.

Conclusions

Young age, larger implant volumes, smoking, and normal or low BMI values were the risk factors responsible for the development of SD; while using oral contraceptives was found to be a protective factor.     

Reproductive factors and breast cancer risk in Palestine: A case control study

BackgroundEarly age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer (breast ca). This study aims to investigate the reproductive determinants of breast cancer among women in the West Bank of Palestine.A structured questionnaire was used to collect data in a case-control study (237 registered cases and 237 controls). A multivariate analysis model was used to adjust for the association between women’s reproductive factors and breast ca risk. This study was approved by Al Quds University Ethical Research Committee and the Ministry of Health research unit.ResultsIn the multivariate analysis, menarche after 13 years of age, use of oral contraceptives for more than two months, and hormonal contraceptives use significantly doubled the risk for breast ca (Adjusted Odds Ratio (AOR) = 2.03, 95 % CI: 1.21–4.37, p < 0.011 and AOR = 2.2, 95 % CI: 1.24–4.01, p = 0.008, respectively). Women who used hormone replacement therapy (HRT) were significantly associated with higher odds (5 folds) of having breast ca versus those who did not use them (AOR 5.02, 95 % CI: 1.93–13.06, p = 0.001). Similarly, nulliparous women showed 6 times the odds of breast ca compared with women with one or more children (p = 0.005). Also, parental consanguinity marriage (AOR 2.59, 95 % CI: 1.53–4.36, p = 0.001) and positive family history (AOR 3.88, 95 % CI: 2.19–6.87, p = 0.001) of the condition can be strong determinants for breast ca in this study.ConclusionThis study provides clear evidence that the use of reproductive hormones, whether as a birth control tool or for therapeutic purposes, must be rationalized worldwide and in Palestine in particular.     

Side effects and discontinuation of oral contraceptive use in southern Brazil

Oral contraceptives have many advantages, but sometimes also have side effects which can cause users to switch appropriately or inappropriately to less effective methods or abandon contraception. In Brazil, 2/3 of married women of childbearing age were using contraception in 1981, and 1/2 of these were using orals. Contraceptive behavior following reported side effects in users of oral contraceptives in Southern Brazil is examined in this study, in relation to diverse factors. Among 2904 currently-married women, aged 15-44, almost 75% reported that they had used the pill at some time, and of these, 45.6% were still doing so. Data on perceived side effects were gathered for all women. There was no independent medical evaluation of the effects, so the data did not necessarily represent actual prevalence of pill related problems. Women who reported problems with the pill were less likely to be current users (25%) than women who did not (65%). However, overall contraceptive prevalence was about the same in both groups (66.2% and 67.0% respectively), indicating that women who stop using oral contraceptives usually switch to another method. However, they are more likely to be using traditional methods than women in the general population, especially if they want more children. Termination of pill use varies little according to the type of problem reported. Women with problems who sought medical attention were more likely to stop using the pill, and 82.4% of women advised to stop by their physician did so, but the major factor affecting discontinuation was the reported experience of a problem. The most frequently reported problems were headaches (38.1%), nausea (34.1%), nervousness (27.9%), and vertigo (18.3%). Physician intervention should help to avoid women's abandoning oral contraceptives unnecessarily.     

Investigation of Relation between Use of Oral Contraceptives and Thromboembolic Disease. A Further Report

The results of a previous study of the use of oral contraceptives by married women discharged from hospital with a diagnosis of thromboembolic disease in the years 1964–6 were reported by us last year. The present paper adds results relating to patients discharged during 1967 and a few data, that could not be sought previously, for patients discharged with cerebral or coronary thrombosis from three of the hospitals in the earlier period.Of 84 patients with deep-vein thrombosis or pulmonary embolism 42 (50%) had used oral contraceptives during the month preceding the onset of their illness, while only 23 of the 168 controls (14%) had done so. No differences in risk were found either for the types of preparation or for the duration of use. After allowance for age and height, the patients with venous thromboembolism were about 10 lb. (4,535 g.) heavier than the control patients, irrespective of whether they were using oral contraceptives or not. No appreciable difference was found between the smoking habits of patients with and without venous thromboembolism treated during 1967, nor between women who were using oral contraceptives and those who were not. The trend in hospital admissions for venous thromboembolism with time corresponded to the trend in the use of oral contraceptives, and there was no evidence to suggest that the number of admissions was affected by publicity about the risk of using the preparations. Of 19 patients with cerebral thrombosis 11 (58%) had been using oral contraceptives, compared with an expected figure of 3.5 from the experience of the control subjects. All the published data (clinical, angiographic, and post-mortem) show that the thrombosis affects the cerebral arteries rather than the cerebral veins. Of 17 patients with coronary thrombosis 2 (12%) had been using oral contraceptives, compared with an expected figure of 2.1. The patients with coronary thrombosis smoked more than the control patients and were, on average, 8.3 lb. (3,765 g.) heavier than control women of the same age and height.The new evidence strengthens the belief that oral contraceptives are a cause of venous thromboembolism and cerebral thrombosis but does not indicate that they are a cause of coronary thrombosis.