Oral contraceptives and breast cancer in northern Italy. Final report from a case-control study.

To assess the relation between oral contraceptive (OC) use and breast cancer, we analysed data from a case-control study conducted in Northern Italy between 1983 and 1991 on 2,309 cases below age 60 and 1,928 controls admitted to hospital for acute diseases unrelated to OC use and to any of the known or potential risk factors for breast cancer. OC use was reported by 16% of cases and 14% of controls. The multivariate relative risk (RR) for ever vs never use of combination OC was 1.2 (95% confidence interval (CI) 1.0-1.4). However, there was no trend in risk with duration. The RR was elevated for very short use, but declined to 0.8 (95% CI = 0.5-1.0) for five or more years'' use. No noteworthy relationship was found for other major measures of OC use, although RR estimates were above unity for women who had stopped use less than 5 years before (RR = 1.5, 95% CI = 1.1-2.0), started use less than 10 years before (RR = 1.3, 95% CI = 1.0-1.9), started when 25 or more years old (RR = 1.4, 95% CI = 1.1-1.7), or after first birth (RR = 1.2, 95% CI = 1.0-1.5). No interaction was observed between OC use and family history of breast cancer, parity and age at first birth. A separate analysis of 373 cases and 456 control below age 40 showed no association with ever use (RR = 0.9, 95% CI = 0.6-1.2).     

A pooled analysis of case-control studies of thyroid cancer¶ III. Oral contraceptives, menopausal replacement therapy and other female hormones

Objective: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe.Methods: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity.Results: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR=1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR=1.1 for >10 years since stopping). The association was stronger for papillary cancers (OR=1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR=0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment.Conclusions: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.     

Risk factors for hepatocellular carcinoma in northern Italy

The role of socio-demographic factors, lifestyle habits and selected dietary factors on the risk of hepatocellular carcinoma was evaluated in a hospital-based case-control study conducted in Northern Italy on 151 patients with hepatocellular carcinoma and 1,051 controls in hospital for acute, non-neoplastic or digestive conditions, unrelated to any of the known or potential risk factors for primary liver cancer. There were significant inverse relationships with levels of education and social class (relative risk, RR = 1.9 and 2.4 for lower vs. upper categories), and positive associations with clinical history of hepatitis (RR = 3.5, 95% confidence interval = 2.0-6.0) or liver cirrhosis (RR = 15.6, 95% CI = 8.3-29.4). The relative risk was not elevated in smokers and light or moderate alcohol drinkers, but the point estimate was above unity among heavy drinkers (RR = 1.5, 95% CI = 1.0-2.4). Among 14 food items considered, including important sources of vitamin A, protein and fats in the Italian diet, 5 were inversely and significantly related to liver cancer risk. This suggests that a diet deficient in several aspects may be related to hepatocellular carcinoma.     

Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study

Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.     

Large bowel cancer in women in relation to reproductive and hormonal factors: a case-control study

A community-based case-control study of the effect of reproductive factors on risk of large bowel cancer in Australia is described. The study involved 155 cases (99 colon cancer, 56 rectal cancer) and 311 controls who were interviewed with regard to pregnancies and their outcomes, lactation, menstrual history, and oral contraceptive (OC) use. Increasing parity was associated with a decreasing risk of colon cancer; para 0, relative risk (RR)=1; para 1-2, RR=0.9, 95% confidence interval (CI)=0.4-1.8; para greater than or equal to 3, RR=0.4, 95% CI=0.2-0.8; later age at first live birth (AFLB) was associated with increasing risk (AFLB less than or equal to 21 yr, RR=1; 22-25 yr, RR=2.3, 95% CI=1.0-5.5; greater than or equal to 26 yr, RR=2.7, 95% CI=1.2-6.2). These effects were independent of each other. Parity appeared to exert its predominant effect on risk of cancer of the right colon. OC use was more common among controls than cases (RR=0.5; 95% CI=0.3-1.2 for ever vs. never users) and showed a dose-response effect in multiple logistic analysis. The pattern of point-estimate RR for rectal cancer was largely congruent with those for colon cancer but was not significantly different from 1.0.     

Hormone replacement therapy and oral contraceptives and risk of oesophageal adenocarcinoma: A systematic review and meta‐analysis

There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results. We conducted a systematic literature search and meta‐analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel–Haenszel random‐effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR = 0.75; 95% CI: 0.58–0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR = 0.76; 95% CI: 0.57–1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted.     

Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women.

BACKGROUND: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established. METHODS: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin <15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% CI, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated > or =10 years after last use (RR, 1.5; 95% CI, 1.0-2.1). CONCLUSIONS: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research.     

Oral contraceptives and colorectal cancer risk: a meta-analysis

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69-0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72-0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74-0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30-0.71). A better understanding of this potential relation may help informed choice of contraception.     

Oral contraceptive use and risk of melanoma in premenopausal women.

Melanoma has been increasing in white populations. Incidence rates rise steeply in women until about age 50, suggesting oestrogen as a possible risk factor. Oestrogens can increase melanocyte count and melanin content and cause hyperpigmentation of the skin. We examined prospectively the association between oral contraceptive (OC) use and diagnoses of superficial spreading and nodular melanoma among 183,693 premenopausal white women in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. One hundred and forty six cases were confirmed in NHS during follow-up from 1976 to 1994, and 106 cases were confirmed in NHS II from 1989 to 1995. Skin reaction to sun exposure, sunburn history, mole counts, hair colour, family history of melanoma, parity, height and body mass index were also assessed and included in logistic regression models. A significant twofold increase in risk of melanoma (relative risk (RR) = 2.0, 95% confidence interval (CI) 1.2-3.4) was observed among current OC users compared to never users. Risk was further increased among current users with 10 or more years of use (RR = 3.4, 95% CI 1.7-7.0). Risk did not appear elevated among past OC users, even among those with longer durations of use, and risk did not decline linearly with time since last use. In conclusion, risk of premenopausal melanoma may be increased among women who are current OC users, particularly among those with longer durations of use. Further research is needed to determine whether low-dose oestrogen pills in particular are associated with an increase in risk and to describe possible interactions between OC use and sun exposure or other risk factors for melanoma.     

Oral contraceptive use and mammographic patterns.

High-risk mammographic patterns represent an increased risk of contracting breast cancer and may be used as a surrogate endpoint for the disease. We examined the relationship between oral contraceptive (OC) use and mammographic patterns among 3218 Norwegian women, aged 40-56 years. Information on ever OC use, duration, and age of first OC use and other epidemiological data were obtained through questionnaires. The mammograms were categorized into five groups. Patterns I-III were combined into a low-risk group and patterns IV and V into a high-risk group. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression and adjusted for age, menopausal status, parity, age at first birth, and body mass index. Women who reported ever having used OCs were 20% more likely (OR 1.27, 95% CI 1.0-1.6) to have high-risk mammographic patterns compared with those reporting never having used OCs. There was no dose response between different measures of OC use and high-risk patterns. Among nulliparous women, ever OC users were four times more likely (OR 4.65, 95% CI 2.1-10.3) to have high-risk patterns compared with never users. Our findings suggest that, especially among nulliparous women, ever OC use may exert its effect on breast cancer risk through changes in breast tissue, which can be observed on a mammogram.     

Is use of hormone replacement therapy associated with increased detection of human papillomavirus and potential risk of HPV-related genital cancers?

Oral contraceptives (OC) are a risk factor for female genital cancers and in vivo studies have shown that progestins stimulate human papillomavirus (HPV) gene expression. A similar role for hormone replacement therapy (HRT) has received little evaluation. Cervical/vaginal specimens were obtained to detect HPV from postmenopausal women (n = 429) seeking annual gynaecologic care. HPV was detected in 14% of women and 4.4% had high-risk, oncogenic types. HPV prevalence was similar across current, past and never HRT users. After adjustment for HPV-related risk factors, current and past user status showed no increased viral detection compared with never users. HRT duration also did not elevate risk among current users. However, longer duration (adj. OR 1.5/year, 95% CI 1.0-2.3) and longer latency (adj. OR 1.2/year, 95% CI 0.9-1.7) among past users of oestrogen/progestin regimens were associated with greater risk. Overall use of HRTs was not associated with HPV detection or disease. However, past users of combination HRTs had significantly greater risk of HPV detection with longer HRT duration and latency, similar to OC-HPV findings. The recommendation that postmenopausal women continue HRTs long term may lead to an increased development of HPV-related diseases, of particular concern among those who discontinue HRTs and subsequent gynaecologic care for early cancer detection.     

A case-control study of oral contraceptive use and breast cancer

Among 989 cases of breast cancer and 9,890 controls selected from a cohort of married, female registered nurses aged 30-55 years, the relative risk (RR) of breast cancer for women who had ever used oral contraceptives (OC) compared with those who had never used them was 1.0, with 95% confidence limits 0.9-1.2. Among OC users, there was no consistent pattern of excess risk with increasing duration; in fact, the few women who had used OC longest (greater than 10 yr) had a slightly lower risk than never-users. Moreover, there was no association between OC use and breast cancer among women with a positive history of breast cancer in the mother or sister or with OC use before their first pregnancy. The only subgroup of women among whom any adverse effect was apparent was current OC users aged 50-55 years (two onsets expected vs. seven observed). This finding is consistent with earlier reports of an increased risk of breast cancer among older OC users; however, it is also likely to reflect, at least to some extent, the play of chance, since at ages 45-49 and in each younger age group fewer cases than expected were observed among current OC users.     

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO)

Background:

The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated.

Methods:

We performed a pooled analysis of six case–control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types.

Results:

A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68–0.97) and HRT ever users (OR=0.77; 95% CI: 0.66–0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61–0.94, and OR=0.66; 95% CI: 0.49–0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37–0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66–0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19–0.71) in HRT users. No interaction with smoking status or BMI was observed.

Conclusion:

Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.     

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).     

Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and Health Study

Data suggest that risk factors for ovarian carcinoma vary by histologic type, but findings are inconsistent. We prospectively evaluated risk factors by histological subtypes of incident ovarian cancer (n = 849) in a cohort of 169,391 women in the NIH-AARP Diet and Health Study. We constructed Cox models of individual exposures by comparing case subtypes to the entire non-case group and assessed p-heterogeneity in case-case comparisons using serous as the reference category. Substantial risk differences between histologic subtypes were observed for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity and body mass index (p-heterogeneity = 0.01, 0.03, 0.05, 0.03, respectively). MHT users were at increased risk for all histologic subtypes except for mucinous carcinomas, where risk was reduced (relative risk (RR) = 0.37; 95% confidence interval (CI): 0.18, 0.80). OC users were only at significantly decreased risk for serous cancers (RR = 0.69; 95% CI: 0.55, 0.85). Although parity was inversely associated with risk of all subtypes, the RRs ranged from 0.28 (clear cell) to 0.83 (serous). Obesity was a significant risk factor only for endometrioid cancers (RR = 1.64; 95% CI: 1.00, 2.70). Our findings support a link between etiological factors and histological heterogeneity in ovarian carcinoma.     

Oral contraceptives, hormone replacement therapy and the risk of colorectal cancer.

The relationship between oral contraceptives (OCs), menopausal hormone replacement therapy (HRT) and the risk of colorectal cancer was investigated in a case-control study conducted in northern Italy between 1985 and 1992 on 709 women with incident colorectal cancer and 992 controls admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract, non-hormone-related disorders. A reduced risk of colorectal cancer was observed in women who had ever used OCs [multivariate odds ratio (OR) = 0.58; 95% confidence interval (CI): 0.36-0.92]. The OR was 0.52 (95% CI 0.27-1.02) for use over 2 years. For women ever using HRT, the multivariate OR was 0.40 (95% CI 0.25-0.66). The risk was inversely related to duration of use, with ORs of 0.46 for 2 years or less and 0.25 for more than 2 years of use. No consistent pattern of trends was observed with time since first or last use. This study provides further evidence that OC and HRT do not increase, and possibly decrease, the risk of colorectal cancer. These results, if confirmed, would have important implications for the ultimate risk-benefit assessment of female hormone preparations.     

Prospective study of talc use and ovarian cancer

BACKGROUND: Perineal talc use has been associated with an increased risk of ovarian cancer in a number of case-control studies; however, this association remains controversial because of limited supporting biologic evidence and the potential for recall bias or selection bias in case-control studies. In this study, we conducted a prospective analysis of perineal talc use and the risk of ovarian cancer. METHODS: The Nurses' Health Study is a prospective study of 121 700 female registered nurses in the United States who were aged 30-55 years at enrollment in 1976. Talc use was ascertained in 1982 by use of a self-administered questionnaire: after exclusions, 78 630 women formed the cohort for analysis. Three hundred seven epithelial ovarian cancers subsequently diagnosed in this cohort through June 1, 1996, were confirmed by medical record review and met inclusion criteria. Proportional hazards models by use of pooled logistic regression were used to derive relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: In 1982, 40.4% (n = 31 789) of the cohort reported ever using talc, and 14.5% (n = 11 411) reported ever using talc daily. We observed no overall association with ever talc use and epithelial ovarian cancer (multivariate RR = 1.09; 95% CI = 0.86-1.37) and no increase in risk of ovarian cancer with increasing frequency of use. There was a modest elevation in risk for ever talc use and invasive serous ovarian cancer (multivariate RR = 1.40; 95% CI = 1.02-1.91). The risk of epithelial ovarian cancer for talc users was not greater among women who had never had a tubal ligation (multivariate RR = 0.97; 95% CI = 0.71-1.32). CONCLUSION: Our results provide little support for any substantial association between perineal talc use and ovarian cancer risk overall; however, perineal talc use may modestly increase the risk of invasive serous ovarian cancer.     

Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin.

We investigated the association of oral contraceptive (OC) use and reproductive factors with colorectal cancer risk in a large population-based case-control study. Cases were women ages 20 to 74 years, living in Wisconsin, with a new diagnosis of colon (n = 1,122) or rectal (n = 366) cancer. Control participants were randomly selected from population lists of similarly aged female Wisconsin residents (n = 4,297). Risk factor information was collected through structured telephone interviews. Compared with never users, OC users had an odds ratio (OR) of 0.89 [95% confidence interval (95% CI), 0.75-1.06] for colorectal cancer. OC use associations did not differ significantly between colon and rectal cancer sites; however, when compared with never users, recent OC users (<14 years) seemed at reduced risk of rectal cancer (OR, 0.53; 95% CI, 0.28-1.00). Women with age at first birth older than the median (23 years) had 0.83 times the risk of colon cancer compared with women with age at first birth below the median (95% CI, 0.70-0.98). We observed an inverse trend between increasing parity and rectal cancer risk (P = 0.05). Compared with nulliparous women, women with five or more births had 0.66 times the risk of rectal cancer (95% CI, 0.43-1.02). Compared with postmenopausal women, premenopausal women were at reduced risk (OR, 0.67; 95% CI, 0.47-0.97) of colorectal cancer. No significant associations were observed between colorectal cancer risk and age at menarche or age at menopause. These findings suggest differential roles of reproductive factors in colon and rectal cancer etiology.     

Oral contraceptives and the risk of endometrial cancer

The relationship between the use of combbination oral contraceptives (OCs) and the risk of endometrial cancer was assessed in a case-control study conducted in the Swiss Canton of Vaud between 1 January 1988 and 31 July 1990. Subjects included 122 women aged 75 or less with histologically confirmed endometrial cancer, and 309 control women in hospital for acute conditions unrelated to OC use. Overall, 14 percent of cases and 27 percent of controls had ever used OCs, corresponding to a multivariate relative risk (RR) of 0.5 (95 percent confidence interval [CI]: 0.3. 0.8). The risk of endometrial cancer was found to be related inversely to duration of OC use: RR=1.0 for less than two years of OC use; 0.5 for two to five years; and 0.3 (95 percent CI: 0.1, 0.7) for more than five years. The protection appeared greater within 20 years since last use, and the RR rose to 0.8 after 20 or more years since last use; numbers are too small, however, for reliable inference from these subanalyses. No significant interaction or modifying effect was observed with other major factors related to endometrial cancer, including parity, body mass index, estrogen replacement therapy, and cigarette smoking. While this study provides further evidence for the protective effect of OCs against risk of endometrial cancer, the relationship requires continued evaluation to assess the long-term implications and public health impact of OC use.This work was supported in part by the Swiss National Science Foundation Grant No. 3.866-0.88.     

Oral contraceptive use and the risk of ovarian cancer: An Italian case-control study

The association between oral contraceptive (OC) use and the risk of ovarian cancer was analysed in a case-control study, conducted between 1985 and 1989 on 505 epithelial ovarian cancer cases under 60 years of age, and 1375 controls in hospitals for a spectrum of acute conditions, not gynaecological, hormonal or neoplastic, apparently unrelated to OC use. 41 (8.1%) women with epithelial ovarian cancer and 192 (14.0%) controls reported OC use. The multivariate relative risk (RR) for ever use was 0.7 (95% confidence interval (CI) = 0.5–1.0). The risk decreased with duration of use: compared with never users the multivariate RRs were 0.9 and 0.5 respectively for less than 2 years and 2 years or more users (X²₁ trend = 6.17, P = 0.01). The risk of ovarian cancer decreased with recency and latency of use: the estimated RR were 0.5 and 0.9 in women reporting last OC use less than 10 or 10 years or more from the diagnosis of the disease, and 0.6 and 0.8 in those reporting first OC use less than 10 or 15 or more years before. The protective effect of OC was consistent in separate strata of selected covariates, including parity and other major known or suspected risk factors for ovarian cancer. There was some indication that the protection declines with advancing age, but the risk estimates were similar in premenopause and postmenopause.