Two US randomized trials found a lower incidence of type 2 diabetes among women treated by menopausal hormone therapy (MHT) with oral conjugated equine estrogen combined with medroxyprogesterone acetate. The purpose of this study was to evaluate the influence of various MHTs, according to their formulation and route of administration, on new-onset diabetes in a cohort of postmenopausal French women.
The association between MHT use and new-onset diabetes was investigated by Cox regression analysis in 63,624 postmenopausal women of the French E3N cohort. Cases of diabetes were identified through self-report or drug reimbursement record linkage, and further validated.
1220 new-onset diabetes cases were validated. We observed a lower risk of new-onset diabetes among women having ever used MHT (Hazard ratio: HR=0.82 [0.72 – 0.93]), compared to MHT never users. Adjustment for BMI during follow-up rather than baseline BMI did not substantially modify this association. An oral route of estrogen administration was associated with a greater decrease in diabetes risk than a cutaneous route (HR=0.68 [0.55–0.85] vs 0.87 [0.75–1.00], P for homogeneity=0.028). When further taking into account the type of progestagen used in combined MHT, we were not able to show significant differences between progestagens.
MHT appeared to be associated with a lower risk of new-onset diabetes. This relation was not mediated by changes in BMI. Further studies are needed to confirm the stronger effect of oral administration of estrogen compared to cutaneous administration.
Adult; Aged; Diabetes Mellitus; epidemiology; Estrogens, Conjugated (USP); therapeutic use; Female; Hormone Replacement Therapy; Humans; Medroxyprogesterone Acetate; therapeutic use; Middle Aged; Postmenopause; Proportional Hazards Models; Questionnaires; Randomized Controlled Trials as Topic; adult diabetes; postmenopause; menopausal hormone therapy; cohort study
Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype.
Women in the California Teachers Study cohort provided detailed data in 1995–1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68–1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54–1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype.
Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL.
Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22–84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61–1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.
body mass index; body size; cohort studies; exercise; hip; lymphoma, non-Hodgkin; waist-hip ratio
Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995–1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18–22 years, at ages 30–35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.
alcohol drinking; cohort studies; lymphoma, non-Hodgkin; multiple myeloma
The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers.
Materials and methods
Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case–control studies (1983–2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses.
Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled ORtrend = 0.88, 95% CI 0.81–0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04–1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65–1.16).
Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.
case–control studies; diffuse large B-cell lymphoma; follicular lymphoma; hormonal contraceptives; non-Hodgkin lymphoma; reproductive history
We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women.
Between 1995-1996 and December 31, 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time-scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies.
Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ≥12.1 vs. <2.7 mcM/day=0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ≥2.2 vs. <0.9 μM Trolox equiv/g/day=0.68, 95% CI: 0.42-1.10; ptrend=0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds.
Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease risk of selected subtypes.
lymphoma; diet; isothiocyanates; antioxidants; cohort studies
Few studies of reproductive hormone exposures and non-Hodgkin lymphoma (NHL) have examined NHL subtypes. Associations between reproductive hormonal factors and risk of all NHL and of two predominant subtypes, diffuse large-cell lymphoma (DLCL) (n = 233) and follicular lymphoma (n = 173), were investigated among women (n = 581) in a large, population-based, case-control study (1,591 cases, 2,515 controls). Controls (n = 836) identified by random digit dialing were frequency matched by age and county to incident NHL cases ascertained in the San Francisco Bay Area of California in 1988–1993. Adjusted unconditional logistic regression was used to obtain odds ratios. More than four pregnancies indicated a possible lower risk of all NHL (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.55, 1.2; p-trend = 0.06) and of DLCL (OR = 0.53, 95% CI: 0.31, 0.90; p-trend = 0.01). Exclusive use of menopausal hormone therapy for ≥5 years was associated with a reduced risk of all NHL (OR = 0.68, 95% CI: 0.48, 0.98) and of DLCL (OR = 0.50, 95% CI: 0.30, 0.85). Oral contraceptive use indicated a lower risk of all NHL (OR = 0.68, 95% CI: 0.49, 0.94), and perhaps DLCL (OR = 0.79, 95% CI: 0.51, 1.2), and of follicular lymphoma (OR = 0.75, 95% CI: 0.46, 1.2). Results suggest that endogenous and exogenous reproductive hormones confer different risks by NHL subtype and are associated with a reduced risk of DLCL in women.
case-control studies; contraception; estrogens; hormone replacement therapy; lymphoma, non-Hodgkin; menopause; pregnancy; reproduction
Menopausal hormone therapy (MHT) is a well established factor in endometrial carcinogenesis, and therefore, could have prognostic implications. We investigated the effects of ever use of MHT on tumour grade and depth of myometrial invasion, and 5-year relative survival in postmenopausal endometrial cancer patients.
Materials and Methods
We used a nationwide, population-based case-case design, of 683 Swedish women aged 50–74 years diagnosed with endometrial cancer during 1994 to 1995, followed up to 5 years after diagnosis. We applied polytomous multiple logistic regression to investigate the associations between use of MHT and tumour grade, and myometrial invasion and Poisson regression for modelling 5-year excess mortality.
Compared to never use, ever use of any MHT entailed lower risks of having moderately and poorly differentiated tumours. The lowest odds ratios for poorly differentiated tumours were seen for ever users of cyclically combined oestrogen-progestin [OR = 0.23 (95% CI = 0.07–0.73)]. Ever users of any form of MHT; particularly, medium potency MHT users, had significantly lower risks for tumours with deep myometrial invasion. Adjusted estimated relative excess hazard ratios revealed significantly improved survival for ever users of any form of MHT [RER = 0.40 (95% CI = 0.16–0.97)]; in particular ever users of any form of oestrogens [RER = 0.38 (95% CI = 0.15–0.99)].
Endometrial cancer patients who were ever users of MHT had more favourable tumour characteristics and better survival compared to never users of MHT. These findings support the notion that MHT induces endometrial cancer with less aggressive characteristics.
Endometrial cancer; menopause hormone therapy; postmenopausal; tumour grade; myometrial invasion; relative survival; mortality
To examine the differences in menopausal hormone therapy (MHT) use and user profiles among women in Germany before and after the communication of the Women's Health Initiative (WHI) trial and other study results concerning the risks and benefits of MHT.
Current MHT use was ascertained in two periodic German national health surveys conducted in 1997–1999 and 2003–2004. MHT prevalence and user profiles were assessed within each survey. The association of the survey period (2003–2004 vs. 1997–1999) with current MHT use was analyzed in weighted multivariable logistic regression (MLR) models, pooling data from both surveys.
The overall prevalence of current MHT use decreased by 40.2% from 16.9% of the sample in 1997–1999 to 10.1% in 2003–2004. The difference in prevalence between surveys varied with age decade with the smallest decreases among women 60–69 years of age (20.3% vs. 18.5%), compared to women of younger and older age groups (40–49: 10.7% vs. 3.9%; 50–59: 36.3% vs. 21.3%; 70–79: 5.7% vs. 3.2%). Variables independently associated with higher current MHT use in both health surveys included age category (curvilinear relationship with highest use among women 50–59 years) and residence in West vs. East Germany. A higher social status, lower body mass index, and more health-conscious behaviour were significantly associated with higher current MHT use in the 1997–1999 survey, but these associations were not found in the later survey. MLR analyses confirmed a significant decline in MHT use between the 1997–1999 and 2003–2004 surveys, however, the effect was modified by social status and was not significant among lowest social-status women.
Current MHT use considerably declined among women in Germany between the pre- and post-WHI era. A convergence of current MHT use among women of higher social status with pre-existing patterns of use among lower social-status women suggests that MHT in Germany is now less likely to be used for health promotion.
Reasons for higher incidence of lymphoid neoplasms among men than women are unknown. Because female sex hormones have immunomodulatory effects, reproductive factors and exogenous hormone use may affect risk for lymphoid malignancies. Previous epidemiologic studies on this topic have yielded conflicting results. Within the National Institutes of Health-AARP Diet and Health Study cohort, we prospectively analyzed detailed, questionnaire-derived information on menstrual and reproductive factors and use of oral contraceptives and menopausal hormone therapy among 134,074 US women. Using multivariable proportional hazards regression models, we estimated relative risks (RRs) for 85 plasma cell neoplasms and 417 non-Hodgkin lymphomas (NHLs) identified during follow-up from 1996-2002. We observed no statistically significant associations between plasma cell neoplasms, NHL, or the three most common NHL subtypes and age at menarche, parity, age at first birth, oral contraceptive use, or menopausal status at baseline. For menopausal hormone therapy use, overall associations between NHL and unopposed estrogen and estrogen plus progestin were null, with the potential exception of an inverse association (RR=0.49, 95% CI, 0.25-0.96) between use of unopposed estrogen and diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype, among women with a hysterectomy. These data do not support an important role for reproductive factors or exogenous hormones in modulating lymphomagenesis.
The relationship between menopausal hormone therapy (MHT) and cardiovascular risk remains controversial, with a number of studies advocating the use of MHT in reducing risk of cardiovascular diseases, while others have shown it to increase risk. The aim of this study was to determine the association between menopausal hormone therapy and high blood pressure.
Methods and Findings
A total of 43,405 postmenopausal women were included in the study. Baseline data for these women were sourced from the 45 and Up Study, Australia, a large scale study of healthy ageing. These women reported being postmenopausal, having an intact uterus, and had not been diagnosed with high blood pressure prior to menopause. Odds ratios for the association between MHT use and having high blood pressure were estimated using logistic regression, stratified by age (<56 years, 56–61 years, 62–70 years and over 71 years) and adjusted for demographic and lifestyle factors. MHT use was associated with higher odds of having high blood pressure: past menopausal hormone therapy use: <56 years (adjusted odds ratio 1.59, 99% confidence interval 1.15 to 2.20); 56–61 years (1.58, 1.31 to 1.90); 62–70 years (1.26, 1.10 to 1.44). Increased duration of hormone use was associated with higher odds of having high blood pressure, with the effect of hormone therapy use diminishing with increasing age.
Menopausal hormone therapy use is associated with significantly higher odds of having high blood pressure, and the odds increase with increased duration of use. High blood pressure should be conveyed as a health risk for people considering MHT use.
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.
To assess postmenopausal breast cancer risk in relation to particular patterns of oral contraceptive (OC) use according to hormone replacement therapy (HRT) exposure.
Time-dependent Cox regression models were used to analyse information on postmenopausal women from a large-scale French cohort. Among a total of 68,670 women born between 1925 and 1950, 1405 primary invasive postmenopausal breast cancer cases were identified from 1992 to 2000.
A non-significant decrease in risk of around 10% was associated with ever OC use as compared to never OC use in postmenopausal women. No significant interaction was found between OC and HRT use on postmenopausal breast cancer risk. Breast cancer risk decreased significantly with increasing time since first OC use (test for trend: p = 0.01); this was consistent after adjustment for duration of use or for time since last use.
No increase in breast cancer risk was associated with previous OC exposure among postmenopausal women, probably because the induction window had closed. Some women may develop breast cancer soon after exposure to OCs, leading to a deficit of cases of older women. Further investigation is therefore required to identify young women at high risk.
Adult; Breast Neoplasms; epidemiology; Cohort Studies; Contraceptives, Oral, Hormonal; therapeutic use; Female; Follow-Up Studies; France; epidemiology; Hormone Replacement Therapy; Humans; Middle Aged; Postmenopause; Proportional Hazards Models; Questionnaires; Risk Assessment; Time Factors; breast cancer; postmenopausal women; oral contraceptives; patterns of use; hormone replacement therapy
Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to a reduction in fibrinolytic activity.
Menopausal hormonal therapy (MHT); Plasminogen activator inhibitor type 1 (PAI-1); Leptin receptor; Ghrelin; Menopause
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.
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.
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.
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.
reproductive history; oral contraceptive use; ovarian cancer; cohort 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.
reproductive factors; non-reproductive factors; histology; ovarian cancer; prospective study
The Surveillance Epidemiology and End Results data demonstrate that the risk of non-Hodgkin lymphoma is lower for women, but that the incidence increases after fifty years of age, at which menopause is regularly reached, suggesting that female hormones may be protective for NHL. This study examines the influence of sex on lymphoma risk in a relevant large animal model. Records for dogs in the Veterinary Medical Database were analyzed from 1964 to 2002. Risk ratios were calculated to evaluate associations between sex, neutering status, and lymphoma occurrence. A total of 14,573 cases and 1,157,342 controls were identified. Intact females had a significantly lower risk of developing lymphoma, Odds Ratio 0.69 (0.63–0.74) with a P < .001. We conclude that there is a sex effect on NHL risk in dogs similar to humans. We hypothesize that the hormone levels of intact females lower the risk of NHL. The possibility of a protective role of endogenous estrogens in the etiology of NHL should be investigated.
Use of postmenopausal hormone replacement therapy (HRT) has been hypothesised to be associated with a reduced risk of non-Hodgkin's lymphoma (NHL), but the epidemiologic evidence is conflicting. To examine the risk of NHL in HRT users aged 40 and older, we conducted a cohort study in the County of North Jutland, Denmark (population 0.5 million) using data from population-based health registries for the period 1989–2002. We computed age-standardised NHL incidence rates and used Cox regression analysis to compute the relative risk (RR) and corresponding 95% confidence intervals (CI) of NHL among HRT users compared with non-users, adjusting for age and calendar period. The number of prescriptions redeemed (1, 2–4, 5–9, 10–19, or 20 or more prescriptions) was used as a proxy for duration of HRT. We identified 40 NHL cases among HRT users during 179 838 person-years of follow-up and 310 NHL cases among non-users during 1 247 302 person-years of follow-up. The age-standardised incidence rates of NHL were 25.7 per 100 000 among HRT users and 24.2 per 100 000 among non-users, yielding an adjusted RR of 0.99 (95% CI: 0.71–1.39). Our data did not support an association between HRT use and risk of NHL.
postmenopausal hormone replacement therapy; non-Hodgkin's lymphoma; population-based study; risk; cohort study
Epidemiological studies have suggested that female hormones might play a role in asthma and that menopausal hormone therapy (MHT or HRT) might increase the risk of asthma in postmenopausal women. The only prospective study addressing this issue reports an increase in the risk of developing asthma which was similar for estrogen alone and estrogen/progestagen treatment.
The association between the use of different types of MHT and the risk of asthma onset in postmenopausal women was investigated prospectively from 1990 to 2002 by biennial questionnaire as part of the French E3N cohort study. Asthma onset was considered to be the time of medical diagnosis of asthma cases occurring during the follow up of women who were asthma free at baseline. Cox proportional hazards models were used, adjusting for potential confounding factors.
Among 57,664 women free of asthma at menopause 569 incident cases of asthma were identified during 495,448 years of follow-up. MHT was related to an increased risk of asthma onset (HR= 1.20, 95% CI 0.98–1.46) among recent users. The increase in risk of asthma onset was only significant among women reporting the use of estrogen alone (HR= 1.54, 95% CI 1.13–2.09).particularly in never smokers (HR= 1.80 95% CI 1.15–2.80) and women reporting allergic disease prior to asthma onset (HR= 1.86 95% CI 1.18–2.93). A small increase in the risk of asthma onset associated with the use of estrogen/progestagen was also observed in these subgroups.
Postmenopausal use of estrogen alone was associated with an increased rate of newly diagnosed asthma in menopausal women.
Asthma; Epidemiology; Menopausal hormone therapy (MHT); Hormone replacement therapy (HRT); Asthma; chemically induced; epidemiology; Body Mass Index; Drug Combinations; Estrogen Replacement Therapy; adverse effects; utilization; Estrogens; adverse effects; Female; France; epidemiology; Humans; Middle Aged; Postmenopause; Progesterone; adverse effects; Prospective Studies; Risk Factors
Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative.
non-Hodgkin's lymphoma; family history; haematopoietic malignancy; lymphoma; leukaemia
Epidemiologic studies conducted to date have shown evidence of a causal relation between smoking and non-Hodgkin lymphoma (NHL) risk. However, previous studies did not account for passive smoking exposure in the never-smoking reference group. The California Teachers Study collected information about lifetime smoking and household passive smoking exposure in 1995 and about lifetime exposure to passive smoking in 3 settings (household, workplace, and social settings) in 1997–1998. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2007. Compared with never smokers, ever smokers had a 1.11-fold (95% confidence interval (CI): 0.94, 1.30) higher NHL risk that increased to a 1.22-fold (95% CI: 0.95, 1.57) higher risk when women with household passive smoking were excluded from the reference category. Statistically significant dose responses were observed for lifetime cumulative smoking exposure (intensity and pack-years; both P ’s for trend = 0.02) when women with household passive smoking were excluded from the reference category. Among never smokers, NHL risk increased with increasing lifetime exposure to passive smoking (relative risk = 1.51 (95% CI: 1.03, 2.22) for >40 years vs. ≤5 years of passive smoking; P for trend = 0.03), particularly for follicular lymphoma (relative risk = 2.89 (95% CI: 1.23, 6.80); P for trend = 0.01). The present study provides evidence that smoking and passive smoking may influence NHL etiology, particularly for follicular lymphoma.
cohort studies; lymphoma, non-Hodgkin; smoking; tobacco smoke pollution
Polymorphisms in chemokine genes have been associated with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) but are understudied in non-HIV-related NHL. Associations of NHL and NHL subtypes with polymorphisms and haplotypes in CCR5, CCR2, CCL5, CXCL12 and CX3CR1 were explored in a pooled analysis of three case-control studies (San Francisco Bay Area, California; United Kingdom; total: cases N=1610, controls N=1992). Adjusted unconditional logistic regression was used to estimate relative risks among HIV-negative non-Hispanic Caucasians. The CCR5M Δ32 deletion reduced the risk of NHL (odds ratio=0.56, 95% confidence interval=0.38-0.83) in men but not women with similar effects observed for diffuse large-cell and follicular lymphoma (FL). NHL risk also was reduced in men with the CCR2/CCR5 haplotype characterized by the CCR5 Δ32 deletion. The CCL5 −403A allele conferred reduced risks of FL and chronic lymphocytic leukemia/small lymphocytic lymphoma. Results should be interpreted conservatively. Continued investigation is warranted to confirm these findings.
Lymphoma non-Hodgkin; Chemokines; Polymorphism, genetic; Case-Control
STUDY OBJECTIVE--The aim was to investigate the relationship between oral contraceptives, non-contraceptive oestrogens, and the risk of gallstone disease requiring surgery. DESIGN--This was a hospital based case-control study carried out between 1987 and 1990. Main outcome measures were frequency of consumption of oral contraceptives and non-contraceptive oestrogens, and the corresponding multivariate relative risk estimates and 95% confidence intervals (CI) in relation to various measures of use of the preparations. SETTING--A network including major teaching and general hospitals in the greater Milan area, northern Italy. SUBJECTS--Subjects were 235 women with gallstones requiring surgery and 538 controls admitted for acute diseases, other than digestive or hormonal diseases or those potentially influencing the use of female hormone preparations. MAIN RESULTS--For oral contraceptives, the relative risk for ever use was 0.8 with 95% CI 0.4 to 1.5. With reference to duration of use, the multivariate relative risk was 1.0 for less than two and 0.5 for two or more years of use. The relative risk was 1.7 (95% CI 0.6 to 4.7) in women who had last used the pill less than five years before diagnosis, but declined to 0.4 (95% CI 0.2 to 1.0) in those who had stopped more than five years before. With reference to oestrogen replacement treatment, the relative risk for ever use was 1.9 (95% CI 1.0 to 3.1). The relative risk, however, was not related to duration of use, since it was 1.8 for less than two and 1.5 for two or more years of use. Relative risk was higher for women who had last used non-contraceptive oestrogens 10 or more years before diagnosis (2.4) than for shorter periods since last use (1.3). CONCLUSIONS--On a clinical and public health scale, oral contraceptives and non-contraceptive oestrogens are unlikely to have an important influence in the aetiology of gallbladder disease.
There is extensive epidemiological evidence that menopausal hormone therapy (MHT) increases breast cancer risk, particularly combinations of estrogen and progestagen (EP). We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen), and time interval between onset of menopause and start of MHT were examined.
We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls). Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated.
We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49) for progesterone-derived and 3.35 (1.07-10.4) for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment.
This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.
Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers but the relation of body mass index (BMI) to ovarian cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, data addressing whether the relation of BMI to ovarian cancer differs by MHT use are very sparse. We prospectively investigated the association between BMI and ovarian cancer among 94,525 U.S. women, followed from 1996–1997 to December 31, 2003. During 7 years of follow-up, we documented 303 epithelial ovarian cancer cases. As compared with normal weight women (BMI 18.5–24.9 kg/m2), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI ≥30 kg/m2) in the cohort as a whole was 1.25 (95%-CI=0.93–1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.80 (95%-CI=1.16–2.80). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR=0.96; 95%-CI=0.64–1.43; P-interaction=0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese versus normal weight women=1.36; 95%-CI=0.99–1.85), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR=0.73; 95%-CI=0.34–1.60; P-interaction=0.02). We suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism.