Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study

We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. A total of 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and age stratified Cox proportional hazards models were fit to estimate relative risks (RRs) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95% CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95% CI=0.83-1.33) overall or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95% CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.     

Reproductive factors, hormone use and the risk of lung cancer among middle-aged never-smoking Japanese women: a large-scale population-based cohort study

Although a link between female hormonal factors and the risk of lung cancer has been suggested, few studies have examined this association in detail. We investigated the associations between reproductive factors, hormone use and the risk of lung cancer in a population-based prospective study. Self-administered questionnaires were distributed to 44,677 lifelong never-smoking women in 1990-1994 to assess menstrual and reproductive factors and hormone use. After 8-12 years of follow-up, 153 lung cancer cases were diagnosed. Relative risk (RR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazards model. Age at menopause, age at menarche, number of children, age at first live birth, breast feeding and use of hormones were not associated with a risk of lung cancer, either overall or among postmenopausal women or women with natural menopause. Compared to women with both late age at menarche (> or =16) and early age at menopause (< or =50), those with either early age at menarche or late age at menopause had a >2-fold, significant increase in the risk of lung cancer. Induced menopausal women with experience of hormone replacement therapy had a significantly elevated risk compared to naturally menopausal women without female hormone use, with an RR of 2.40 (95% CI 1.07-5.40). These findings suggest that both endogenous and extraneous estrogen may be involved in the etiology of lung cancer.     

Reproductive risk factors for incident bladder cancer: Iowa Women's Health Study

We studied the association between reproductive factors and bladder cancer incidence in a prospective cohort study of 37,459 Iowa women aged 55-69 years and initially free from cancer in 1986. Women reported reproductive history and were followed prospectively through 2003. After adjusting for age and smoking, there was an inverse association between age at menopause and incident bladder cancer (n = 192). Compared with menopause at age > or =48, the hazard ratio (HR) of bladder cancer was 1.32 (95% CI; 0.90-1.94) for menopause at 43-47, and 1.60 (95% CI; 1.06-2.39) for < or =42 (p-trend = 0.02). The associations were similar for ages at natural and surgical menopause. In addition, women with a history of bilateral oophorectomy had an increased risk of bladder cancer compared with those who did not undergo bilateral oophorectomy: HR = 1.58 (95% CI; 1.12, 2.22). Finally, there was an indication of a positive association between bladder cancer and shorter lifetime years of ovulation (p-trend = 0.09). There were no associations between incident bladder cancer and age at first birth, number of births, age at menarche, use of hormone replacement therapy or any other reproductive characteristics. This study provides evidence that increased risk of bladder cancer is associated with earlier age at menopause in postmenopausal women.     

Reproductive, menstrual, and other hormone-related factors and risk of renal cell cancer

A role of hormone-related factors in renal cell cancer (RCC) etiology has been hypothesized, but the epidemiological evidence is inconsistent. The present study aimed at evaluating the effect of reproductive, menstrual and other gender-specific variables on RCC risk among women. This study is part of a larger hospital-based, case-control study on RCC risk, conducted in northern, central and southern Italy. Cases were 273 women, below age 80, with histologically confirmed, incident RCC. Controls were 546 women hospitalized for acute, nonneoplastic conditions, frequency-matched to cases by age and center. Odds ratios (OR) and 95% confidence intervals (CI) were computed using multiple logistic regression models. RCC risk was inversely related to age at first birth (OR = 0.7, 95% CI 0.5-1.0, for >/= 25 years vs. <25 years). Hysterectomy was found to double RCC risk (OR = 2.3, 95% CI 1.3-4.2). A negative association of borderline-statistical significance emerged for age at menarche, whereas, no associations were found between RCC risk and parity, menopausal status, age at menopause and use of hormone replacement therapy or oral contraceptives. Our findings give support to a role of hysterectomy in increasing RCC risk without corroborating, however, a major role of female hormone-related factors.     

Menstrual and reproductive factors in relation to risk of endometrial cancer in Chinese women

Menstrual, reproductive and contraceptive factors have been associated with risk of endometrial cancer in populations where the incidence of this tumor is high. To investigate associations between these factors in a low-risk population with a low prevalence of hormone replacement therapy, we conducted a cohort study among 267,400 women employed in the textile industry in Shanghai, China. Menstrual, reproductive and other factors were ascertained at baseline in 1989–1991, and women were followed for incident endometrial cancer through 31 December 1998 (n = 206). Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Risk of endometrial cancer decreased with increasing age at menarche (p-trend = 0.004). Among menopausal women, risk increased with age at menopause and increasing years of menstruation. Compared to women with one live birth, risk was increased in relation to nulliparity (Hazard ratio = 3.95, 95% CI 1.43–10.86). Risk was decreased with increasing age at first live birth (p-trend = 0.03). There was a decreased risk associated with ever use of an intrauterine device (HR = 0.56, 95% CI 0.35–0.88) and use of oral contraceptives for ≥2 years (HR = 0.50, 95% CI 0.23–1.07). This prospective study confirms findings from previous case–control studies relating menstrual, reproductive, and contraceptive factors and endometrial carcinoma.     

Hormonal and reproductive factors and risk of glioma: a prospective cohort study

The etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. Given the lower incidence rate of glioma in women than in men, it has been hypothesized that reproductive and hormonal factors may be involved in the etiology of glioma. We conducted a secondary analysis of data from the National Breast Screening Study, which included 89,835 Canadian women, aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between hormonal and reproductive factors and risk of glioma. During a mean of 16.4 years of follow-up, we observed 120 incident glioma cases. Compared with women with a relatively early age at menarche (< or =12 years), women who were 13-14 years of age at menarche had a 64% increased risk of glioma (95% CI = 1.01-2.65), and women who were older than 14 years of age at menarche had a 66% increased risk of glioma (95% CI = 0.86-3.20, p(trend) = 0.06). Age at first live birth, parity, menopausal status, use of oral contraceptive and use of hormone replacement therapy were not associated with altered glioma risk in our study population. Additional prospective studies are needed to confirm our findings.     

Postmenopausal hormone therapy and breast cancer risk: the Multiethnic Cohort

Epidemiological studies indicate that menopausal estrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. Further data are needed on whether this association varies by specific prognostic factors and ethnicity. We conducted a cohort study among 55,371 African-American, Native Hawaiian, Japanese-American, Latina and White postmenopausal women aged 45-75 years old in the Multiethnic Cohort Study (MEC). A total of 1,615 incident invasive breast cancer cases were identified over an average of 7.3 years. Adjusted relative risks (RRs) were computed for the various forms of hormone therapy (HT). Assuming current users continued HT use to the end of follow-up, current EPT use was associated with a 29% increased risk of breast cancer per 5 years of use (95% confidence interval (CI) = 23-35%), and current estrogen therapy (ET) use with a 10% increase in risk per 5 years of use (95% CI = 5-16%). These figures increased to only a very small extent when we adjusted for the estimated 3% of such women who stop HT use per year of follow-up. EPT and ET use were associated with greater risk among leaner women, but the increase in risk with EPT use was still very evident in women with BMI > or =30 kg/m(2). Current EPT use was associated with increased risk for ER+/PR+, ER+/PR- and ER-/PR- tumors. There was little difference in risk by stage of disease or histologic subtype. The increase with EPT use was clearly seen in all 5 ethnic groups; and the increase with ET in 4 of the 5 groups.     

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.     

Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States)

Evidence for an effect of reproductive factors on colorectal carcinogenesis is inconsistent and little is known about their role in development of precursor adenomatous polyps. We evaluated the relation between reproductive factors and distal colorectal adenomas (n = 982) during14 years of follow up of 26,983 participants in the Nurses' Health Study(United States). The women were free of diagnosed cancer or polyps in 1980,underwent endoscopy 1980-94, and had reported on their parity, oral contraceptive (OC) use, and ages at menarche, first term-pregnancy, and menopause. We calculated relative risks (RR) and 95 percent confidence intervals (CI) using multiple logistic regression. Women with higher parity had an increased risk of adenomas of the distal colorectum (P trend = 0.004;6+ cf 0 parity: RR = 1.3, CI = 0.9-1.8) or distal colon (P trend = 0.002, RR= 1.7, CI = 1.2-2.6). This association was significantly stronger among women with a family history of colorectal cancer ( P interaction = 0.03); comparing6+ term-pregnancies with nulliparity, among those with a family history, the RR for distal colon adenoma was 3.2 (CI = 1.4-7.2), while among those without a family history, the RR was 1.3 (CI = 0.8-2.2). We observed no association for distal colorectal adenoma and age at menarche, age at first term-pregnancy, ever use of OCs, or menopausal status. Further work is needed to clarify the relation of parity with colon adenoma risk. This revised version was published online in July 2006 with corrections to the Cover Date.     

The role of age at menarche and at menopause on breast cancer risk: combined evidence from four case-control studies.

The role of age at menarche and at menopause on breast cancer risk was reassessed in a combined analysis of four Italian case-control studies including a total of 6,075 cases and 5,492 controls. The risk of breast cancer was lower in women whose menarche occurred at age 15 or over, but there was no evidence for the risk to increase with decreasing age at menarche below age 15. Compared with women with earlier menarche, the relative risk (RR) was 0.9 (95% confidence interval, CI 0.7-1.0) for those with menarche at age 15, 0.8 (95% CI 0.6-0.9) for menarche at 16, and 0.7 (95% CI 0.5-0.8) for menarche at age 17 or over. There was no significant interaction between age at menarche and study centre or age at diagnosis, parity and age at first birth. In relation to age at menopause, compared with women whose menopause occurred at age 40 or less, the relative risk was 1.1 (95% CI 0.8-1.3) between 40 and 44, 1.2 (95% CI 0.9-1.4) between 45 and 49, 1.4 (95% CI 1.2-1.8) between 50 and 53, and 1.4 (95% CI 1.1-1.8) above 53. The risk estimates were comparable in various studies, and the trend in risk with age at menopause was statistically significant. The risk estimates tended to be somewhat higher at peri-menopausal age (45 to 54 years), but no consistent pattern was evident across subsequent strata of age, and the interaction with age was not significant. Likewise, no consistent interaction was observed with parity, age at first birth or body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Menopausal hormone therapy and risk of epithelial ovarian cancer.

Substantial increase in the use of menopausal hormone therapy (HT) throughout the 1990s, followed by widespread discontinuation after the 2002 publication of the Women's Health Initiative findings, has resulted in large numbers of former HT users among U.S. women. However, few studies have examined whether ovarian cancer risk varies according to recency and duration of specific HT regimens. We assessed risk of epithelial ovarian cancer among users of unopposed estrogen (ET) and combined estrogen/progestogen (EPT). In a population-based study in Washington state, 812 women with ovarian cancer diagnosed in 2002 to 2005 and 1,313 controls were interviewed in person about the use of HT and other characteristics. Women who used a single form of therapy (ET or EPT) were compared with women who never used HT using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). Risk was increased among current or recent (within the last 3 years) users of ET with > or = 5 years of use (ORs, 95% CIs: 1.6, 1.1-2.5 and 1.8, 0.8-3.7, respectively). Little increase in risk was noted among long-term ET users who discontinued use in the more distant past (OR, 1.2; 95% CI, 0.6-2.6). No increase in risk was noted among women who used only EPT, regardless of duration. Compared with women who never used HT, current users of EPT had an OR of 1.1 (95% CI, 0.8-1.5), and risk declined with increasing time since stopping; the OR was 0.7 (95% CI, 0.4-1.0) among women who had discontinued EPT within the last 3 years and 0.5 (95% CI, 0.3-0.7) among women who stopped at an earlier point. Long-term ET may be associated with an increased ovarian cancer risk that wanes after use ceases. We did not observe an increased risk with EPT, and with increasing time after stopping, a reduction in risk became increasingly evident. The progestogen component of HT may confer a risk reduction that is masked by an opposing effect of estrogen until, among former users, estrogenic influences have diminished. These findings, if replicated, may have implications both for public health and development of chemoprevention strategies.     

The effect of estrogen vs. combined estrogen-progestogen therapy on the risk of colorectal cancer

Studies suggest that estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) may have different associations with colorectal cancer (CRC) risk, but data are conflicting. Prior meta-analyses did not distinguish between ET and EPT. We conducted a meta-analysis to summarize the relative risks (RR) of CRC due to ET versus EPT among peri- or postmenopausal women. From a total of 2,661 articles, four randomized controlled trials, eight cohort and eight case-control studies were included. Variables assessed included study characteristics, duration and recency of menopausal hormone therapy (HT) use, method of assessment of HT use, outcome definition and its ascertainment method. RRs were synthesized by random-effects models. We found that EPT ever use was associated with a decreased risk of CRC (RR 0.74, 95% CI 0.68-0.81), and so was ET ever use (RR 0.79, 95% CI 0.69-0.91). While current use of ET was associated with a significantly reduced risk of CRC (RR 0.70, 95% CI 0.57-0.85), former use was not (RR 0.86, 95%CI 0.67-1.11). Recency did not significantly modify the association between EPT and CRC risk. EPT former use was associated with a lower RR of CRC compared to ET former use (p = 0.008) but no such difference was observed between EPT and ET current use (p = 0.12). Overall, we found consistent evidence supporting the association between EPT and CRC risk reduction, regardless of recency. While literature for the association between ET and CRC risk is heterogeneous, our analyses suggest only current use of ET is associated with a decreased CRC risk.     

Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.     

Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis

Estrogens may influence gastric cancer risk, but published studies are inconclusive. We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors and with use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR = 0.74, 95% CI: 0.63-0.86) and HRT (RR = 0.77; 95% CI: 0.64-0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR = 1.82; 95% CI: 1.39-2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms.     

Pooled analysis of 3 European case-control studies of ovarian cancer: II. Age at menarche and at menopause

The role of age at menarche and at menopause on epithelial ovarian cancer risk was re-assessed in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom and Greece, which produced a total of 1,140 cases and 2,724 controls. In the overall dataset, there was no evidence of an association with age at menarche: compared with women whose menarche occurred at age 15 or over, the relative risk (RR) estimates were 1.0 [95% confidence interval (CI) 0.8 to 1.2] for those with menarche at ages 12 to 14, and 1.0 (95% CI 0.8-1.2) for those with menarche below age 12. There was no consistent interaction between age at menarche and study centre or age at diagnosis. In relation to age at menopause, compared with women whose menopause occurred at age 44 or earlier, the RR was 1.4 between 45 and 49, 1.6 between 50 and 52 and 1.9 above 52. The strength of the association was apparently (but not significantly) greater in the British than in the Greek or Italian dataset. The effect of age at menopause tended to be long-lasting and, if anything, to increase across subsequent age-groups. The large dataset, and the replication of results in different studies, provide more definite and precise information than previously available on the absence of appreciable effect of age at menarche on subsequent ovarian cancer risk in developed countries. For age at menopause, there was a direct and consistent trend in risk, but the association was relatively weak, with RRs below 2 even between extreme categories.     

A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women

BACKGROUND: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. METHODS: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. RESULTS: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multivariable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. CONCLUSIONS: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.     

Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH‐AARP Diet and Health Study

The incidence of bladder cancer among women is at least one‐third to one‐fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH‐AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 1995–1996 among 201,492 females who were followed until December 31, 2006. During follow‐up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 1996–1997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.62–0.93) and women who reported late age at menarche (≥15 years) (HR=0.57; 95% CI 0.39–0.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.34–0.83) compared with women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.58–1.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.     

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations.     

Epidemiology of reproductive and hormonal factors in thyroid cancer: evidence from a case-control study in the Middle East.

Thyroid cancer is the second most common neoplasm among women in Kuwait and several other countries in the Middle East. Most of these countries also have relatively high birth and total fertility rates. To examine potential relationships between reproductive and hormonal factors and thyroid cancer, we conducted a population-based case-control interview study among 238 women diagnosed with thyroid cancer and a similar number of individually matched controls in Kuwait. Among the demographic variables, women with 12+ years of education had a significantly reduced risk of thyroid cancer (OR = 0.4; 95% CI: 0.2-0.8; p-trend <0.05). The average age at diagnosis (+/-SD) of thyroid cancer was 34.7 +/- 11 years. Events such as age at menarche, pregnancy, menopausal status and age at menopause were not associated with thyroid cancer. There was an association with age at last pregnancy and parity. Women who had their last pregnancy at ages > or = 30 years were at a significantly increased risk (OR = 2.1; 95% CI: 1.2-3.8); there was also a significant trend in risk with increasing age at last pregnancy. There was a modest increase in risk among women who had borne > or = 5 children (OR = 1.5; 95% CI: 0.9-2.5). A joint analysis of these factors showed that childbearing during the latter half of reproductive life had a substantial effect on the incidence of thyroid cancer; for any given level of parity, there was about a 2-fold increased risk if the age at last pregnancy was > or = 30 years. A substantial recent-birth effect, in relation to subsequent diagnosis of thyroid cancer, was observed during the second and third year after a birth (OR = 2.0; 95% CI: 1.0-4.1). In contrast, spontaneous abortion seemed to have a protective effect. There was a significant decrease in risk among women who had a miscarriage as outcome of first pregnancy (OR = 0.1; 95% CI: 0.03-0.4) and those who had experienced > or = 3 miscarriages (OR = 0.3; 95% CI: 0.1-0.8; p-trend <0.05). Overall, any female hormone use was not associated with thyroid cancer risk. New association is suggested for a history of post-partum thyroiditis (OR = 10.2; 95% CI: 2.3-44.8). These data support the hypothesis that reproductive factors and patterns may influence, or contribute to, the risk of thyroid cancer among women.     

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.

Methods:

We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.

Results:

Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.

Conclusion:

This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.