Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women.

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (ß), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (ß=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (ß=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (ß=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (ß=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml--indicators of low ovarian reserve--were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

Are prenatal, obstetric, and infant complications associated with postpartum psychosis among women with pre-conception psychiatric hospitalisations?

OBJECTIVE: To examine the associations of maternal and infant complications with postpartum hospitalisation for psychosis in women with a pre-conception history of psychiatric hospitalisation. DESIGN: Population-based study. SETTING: Swedish medical birth register. POPULATION: Primiparous women who gave birth between 1 January 1987 and 31 December 2001, and who had a pre-conception history of psychiatric hospitalisation but who were not hospitalised during pregnancy (n = 1842). METHODS: International Classification of Diseases (ICD) codes were used to identify prenatal, obstetric, postpartum maternal complications, and newborn health conditions. We used multivariable logistic regression to describe the associations between maternal and infant health conditions and the odds for postpartum hospitalisation for psychosis. MAIN OUTCOME MEASURE: Psychiatric hospitalisation within 90 days of delivery. RESULTS: Compared with women who did not have a postpartum psychiatric hospitalisation, hospitalised women were at 2.3 times higher odds (95% CI 1.0-4.9) of having non-psychiatric puerperium complications (e.g. infection, lactation problems or venous complications). No other maternal complications were associated with postpartum psychiatric hospitalisation. Although their infants were at no higher odds for health complications, the offspring of women who had a postpartum psychiatric hospitalisation were at 4.1 times higher odds (95% CI 1.3-12.6) of death within the first 365 days of life than those of women who were not hospitalised. CONCLUSIONS: We found no prenatal indicators of postpartum risk for psychiatric hospitalisation among high-risk women, but they had higher odds of postpartum pregnancy-related medical problems and, rarely, offspring death.

The influence of depression, body mass index, and smoking on serum inhibin B levels in late reproductive-aged women.

CONTEXT: Women experiencing depression have difficult psychosocial functioning, and recent data suggest an earlier onset of menopause. Understanding the biological mechanism for the impairment of reproductive function associated with depression is important. OBJECTIVE: The objective of the study was to determine whether a lifetime history of depression is associated with reduced ovarian reserve as reflected in serum levels of the granulosa cell product, inhibin B. DESIGN: Residual serum samples from a subset of patients in the Harvard Study of Cycles and Moods were collected. SETTING: Patients were recruited from seven Boston-area communities. PATIENTS: Women with or without a history of major depression, based on structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were enrolled. A subset of patients who had provided an early follicular phase blood specimen at study enrollment and two or more other samples over the first 18-month period of follow-up were included. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURE: Serum inhibin B levels were measured. RESULTS: Serum FSH levels were higher in women with a history of depression, whereas inhibin B levels did not differ between groups. Body mass index and age were significantly and inversely related to serum inhibin B levels. Smoking history was noted, for the first time, to have a significant negative association with inhibin B levels. CONCLUSIONS: Smoking has a direct negative effect on ovarian reserve, as suggested by decreased serum inhibin B levels. In contrast, effects of depression on the reproductive axis may occur at the level of the pituitary and/or hypothalamus rather than at the gonadal level, as suggested by increased serum FSH levels.

Live births, cesarean sections and the development of menstrual abnormalities.

OBJECTIVES: To examine the relationship between number of livebirths and cesarean sections on the development of menstrual abnormalities. METHODS: The effect of number of livebirths and cesarean sections on menstrual abnormalities in the late reproductive period was evaluated using data from the Harvard Study of Moods and Cycles. RESULTS: There were 298 women with no livebirths and 606 women with livebirths of which 184 had a history of cesarean section. Among all women, increasing number of livebirths was associated with an increasing trend in reported heavy menses, prolonged flow >6 days, and a decreasing trend in reported dysmenorrhea. This effect was amplified among women with a history of cesarean section. CONCLUSIONS: Increasing number of livebirths is associated with heavy and prolonged menstrual flow during the late reproductive period. This association is particularly stronger in women with a history of cesarean section.

Childhood abuse and risk of smoking onset.

STUDY OBJECTIVE: To determine the association between childhood abuse and becoming a smoker. DESIGN: Retrospective cohort study. SETTING: Boston, Massachusetts. PARTICIPANTS: 722 women aged 36-45 years who completed the baseline questionnaire for the Harvard study of moods and cycles and the survey of interpersonal relationships. MAIN RESULTS: Women who experienced either physical or sexual abuse as a child were 40% more likely to begin smoking compared with women with no history of abuse (95% CI 1.0 to 2.0). Virtually all of this association was confined to sexual abuse (OR = 2.2, 95% CI 1.1 to 4.3) as compared with physical abuse (OR = 0.7, 95% CI 0.7 to 1.6). However, the joint effect of experiencing both physical and sexual abuse as a child led to a 3.5-fold increase in the likelihood of becoming a smoker (95% CI 1.3 to 9.4) compared with women who did not experience any childhood abuse after adjustment for religion, social class, and poverty. CONCLUSIONS: Women who experience childhood abuse, even in the absence of depression, are at increased risk of becoming cigarette smokers.

Postpartum mood disorders: a review of clinical and epidemiological factors.

The postpartum period is a time of risk for mood disturbance in women. Postpartum blues occurs commonly, but is self-limited. Postpartum depression occurs in 13% of postpartum women. However, it is estimated that nearly one-half of all cases go undetected. Postpartum psychosis is rare, affecting 1-2 per 1000 women. Postpartum mood disorders can have far-reaching consequences and have been shown to affect the social and psychological development of children. It is critical that healthcare providers understand these disorders and their risk factors to increase detection and to educate women about the risks and treatments of postpartum mood disorders. This review is intended to provide healthcare providers with a better understanding of the descriptive epidemiology, risk factors, and treatments of postpartum mood disorders. The utility of specific screening instruments is also discussed.

Lifetime socioeconomic position in relation to onset of perimenopause.

STUDY OBJECTIVE: To assess the association between lifetime socioeconomic position and onset of perimenopause. DESIGN: Prospective cohort study. SETTING: Boston, Massachusetts. PARTICIPANTS: 603 premenopausal women aged 36-45 years at baseline who completed a cross sectional survey on childhood and adult socioeconomic position. MAIN OUTCOME MEASURES: Time to perimenopause, defined as time in months from baseline interview to a woman's report of (1) an absolute change of at least seven days in menstrual cycle length from baseline or subjective report of menstrual irregularity; (2) a change in menstrual flow amount or duration; or (3) cessation of periods for at least three months, whichever came first. MAIN RESULTS: Incidence of perimenopause was 1.75 times higher (95%CI 1.10 to 2.79) and median age at onset was 1.2 years younger (44.7 v 45.9 years) for women reporting childhood and adult economic distress compared with women reporting no lifetime economic distress. After adjustment for age, race/ethnicity, age at menarche, parity, oral contraceptive use, family history of early menopause, depression, smoking, and body mass index, the association weakened (incidence rate ratio (IRR)=1.59; 95%CI 0.97 to 2.61). Inverse associations were observed for most, but not all, measures of educational level. Measures of current household income were not associated with risk of perimenopause. CONCLUSIONS: This study suggests that adverse socioeconomic conditions across the lifespan, when measured in terms of economic hardship and low educational attainment, may be associated with an increased rate of entry into perimenopause.

Demographic, family, and occupational characteristics associated with major depression: the Harvard study of moods and cycles.

OBJECTIVE: This study assesses the extent to which women with and without major depression differ by demographic, familial, and occupational characteristics. METHOD: From a community-based sample, the authors identified 332 women with and 644 women without current or past major depression based on Structured Clinical Interviews for DSM-IV. Demographic and background interviews were conducted in-person. RESULTS: Depressed women were more likely to have gained >or =35 lbs between age 18 and study enrollment (OR=1.6, 95% CI 1.1-2.5), experienced divorce (OR=2.0, 95% CI 1.4-2.8), or changed occupations (OR=1.5, 95% CI 1.1-2.1) compared with non-depressed women. Compared with women with no brothers, those with > or =1 brothers were less likely to have a history of depression (OR=0.8, 95% CI 0.6-1.1), whereas compared with women with no sisters, those with > or =1 sisters were more likely to have current or past depression (OR=1.4, 95% CI 1.0-1.9). These findings were not influenced by family sibship size. CONCLUSION: These results illustrate demographic differences between women with and without major depression and that sibship gender rather than size may also influence risk.

Determinants of early follicular phase gonadotrophin and estradiol concentrations in women of late reproductive age.

BACKGROUND: FSH and estradiol measured during the menstrual (basal) phase of cycles predict the success of infertility treatment; but the role of these hormones as markers for ovarian reserve in normal populations needs further study. METHODS AND RESULTS: From a cohort study of depressed and non-depressed women, a subset of 406 non-depressed women between the ages of 36 and 45 years with spontaneous periods were selected and their concentrations and determinants of basal hormones measured at study entry, 6 and 12 months later were described. FSH and LH increased significantly over the 12 months of observation (P

Characteristics of women with premenstrual dysphoric disorder (PMDD) who did or did not report history of depression: a preliminary report from the Harvard Study of Moods and Cycles.

We examined the characteristics of 33 women with a diagnosis of premenstrual dysphoric disorder (PMDD) who did (n = 19) or did not (n = 14) report a history of major depression. Five hundred thirteen older premenopausal women (ages 36-44) from a community-based sample completed a prospective evaluation of PMDD with daily records. The diagnosis of PMDD was confirmed in 33 women (6.3%), and 14 subjects met criteria for PMDD with no history of depression. Demographic characteristics, cigarette smoking, and menstrual and reproductive history of subjects with PMDD who did or did not report a history of depression were compared. Women with PMDD and no history of depression were more educated and more frequently had a marital disruption (p < 0.05). No significant differences were observed with respect to reproduction-related characteristics or past cigarette smoking. These preliminary data suggest the existence of characteristics particularly related to women who meet criteria for PMDD and have no history of depression. Given the significant psychosocial impairment commonly associated with PMDD symptoms and the existing data that support its classification and adequate treatment as a distinct clinical entity, further studies are needed to better identify predictors of this syndrome unrelated to a lifetime history of depression.

Prevalence of body dysmorphic disorder in a community sample of women.

OBJECTIVE: In a large population-based study, the authors examined the prevalence and correlates of body dysmorphic disorder, a debilitating and chronic condition characterized by an imagined defect in appearance. METHOD: Rates and diagnostic correlates of body dysmorphic disorder were examined by using data from the Harvard Study of Moods and Cycles. This study used in-person structured clinical interviews to characterize the diagnostic status of a population-based, cross-sectional sample of 318 depressed and 658 nondepressed women between the ages of 36 and 44 who were selected from seven Boston metropolitan area communities. RESULTS: The presence of body dysmorphic disorder was significantly associated with the presence of major depression and anxiety disorders. The authors estimated the overall point prevalence of body dysmorphic disorder as 0.7% in women in this age range in the community. CONCLUSIONS: The authors found that the presence of body dysmorphic disorder was linked to the presence of major depression and anxiety disorders, which is similar to findings in clinical studies. Their estimate of the point prevalence of body dysmorphic disorder is consistent with data from a community-based sample of Italian women and suggests a prevalence similar to that of other serious psychiatric disorders in women (e.g., schizophrenia and drug abuse and dependence). These prevalence data encourage the further development of treatment options for this debilitating condition.

Ovarian function in late reproductive years in relation to lifetime experiences of abuse.

The objective of this study was to investigate the relation between violence victimization and levels of ovarian hormones during women's late reproductive years, as measured by serum levels of follicle-stimulating hormone and estradiol, which respectively rise and fall with onset of menopause. In March 1999, 732 women 36-45 years of age from the Harvard Study of Moods and Cycles cohort completed a survey of lifetime experiences of physical and sexual harm. Follicle-stimulating hormone and estradiol levels were measured during the menstrual period after entry into the cohort. Associations for violence and follicle-stimulating hormone and estradiol levels were estimated using crude and adjusted risk differences. Overall, women who experienced abuse during childhood or adolescence relative to never-abused women had a slight positive association of violence with high follicle-stimulating hormone. However, a positive association with high follicle-stimulating hormone was not observed among women whose first abuse occurred during adulthood. Age stratification indicated modification of the association between violence and low estradiol. Women 36-40 years of age had no evidence of a positive association between violence before adulthood and low estradiol, whereas first violence in adulthood was associated with an 11% increase in the estimate of risk difference [95% confidence limits (CL) = -0.14, 0.36]. Among women 41-45 years, there was a 17-23% increase in the estimate of risk difference for low estradiol, regardless of life stage at first experience of abuse (before adulthood, 95% CL = 0.06, 0.28; during adulthood, 95% CL = 0.01, 0.46). This investigation supports the credibility of a hypothesis that physical and sexual abuse may lead to neuroendocrine disruption, thereby affecting ovarian function and potentially leading to altered age at perimenopausal transition.

Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women.

An inverse association between ovarian cancer risk, carotenoids and antioxidant vitamins has been suggested by several epidemiologic studies and 1 experimental trial of a vitamin A analogue. From a population-based study of 549 cases of ovarian cancer and 516 controls, we estimated the consumption of the antioxidant vitamins A, C, D and E and various carotenoids, including alpha- and beta-carotene and lycopene, using a validated dietary questionnaire. Multivariate logistic regression was used to calculate the exposure odds ratios adjusted for established ovarian cancer risk factors. Intakes of carotene, especially alpha-carotene, from food and supplements were significantly and inversely associated with risk for ovarian cancer, predominantly in postmenopausal women. Intake of lycopene was significantly and inversely associated with risk for ovarian cancer, predominantly in premenopausal women. Food items most strongly related to decreased risk for ovarian cancer were raw carrots and tomato sauce. Consumption of fruits, vegetables and food items high in carotene and lycopene may reduce the risk of ovarian cancer.

Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

OBJECTIVE: To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. INTERVENTION(S): A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. MAIN OUTCOME MEASURE(S): FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. RESULT(S): Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. CONCLUSION(S): Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

Prevalence and predictors of chronic lower genital tract discomfort.

OBJECTIVE: We sought to determine the prevalence of chronic lower genital tract discomfort in the general population and to identify demographic and reproductive characteristics associated with this disorder. STUDY DESIGN: We surveyed a random sample of 480 women (age range, 20 to 59 years; 60 women for each 5-year age category) from 1 Boston area suburban community. Participants were asked to complete a 1-page self-administered optically scannable questionnaire that pertained to current and previous genital tract discomfort. RESULTS: After 2 mailings and 1 telephone follow-up, as well as the elimination of 42 ineligible women, 303 (70%) questionnaires were returned. Fifty-six women (18.5%) reported a history of lower genital tract discomfort that persisted for >3 months. Approximately 12% reported a history of chronic knife-like or excessive pain on contact to the genital area, whereas 6.6% experienced persistent lower genital tract itching or burning. Women who reported their age at menarche to be

Adult onset of major depressive disorder in relation to early life violent victimisation: a case-control study.

BACKGROUND: Major depressive disorder is a significant cause of morbidity among women in the USA. Women are twice as likely as men to be diagnosed with major depressive disorder, yet no known risk factors can account for this sex difference. We aimed to assess violent victimisation as a risk factor for depression in women. METHODS: We undertook a case-control study to assess the association between violent victimisation early in life and major depressive disorder in women. We randomly selected a population-based sample of women, aged 36-45 years, from the greater Boston area. In 1999, 236 cases and 496 controls (n=732) completed a self-administered questionnaire designed to ascertain a lifetime history of exposure to violent victimisation. Our main outcome measure was major depressive disorder, assessed by structured clinical interview for Diagnostic Statistical Manual IV (DSM-IV) criteria. FINDINGS: 363 (50%) of 732 respondents reported experience or fear of abuse as a child or adolescent. 68 were excluded because they reported violence as an adult only. Compared with women who reported no abuse, risk of depression was increased in women who reported any abuse as a child or adolescent (relative risk 2.5, 95% CI 1.9-3.0), physical abuse only (2.4, 1.8-3.0), sexual abuse only (1.8, 1.2-2.8), and both physical and sexual abuse (3.3, 2.5-4.1). Severity of abuse had a linear dose-response relation with depression. INTERPRETATION: Our results suggest a positive association between violent victimisation early in life and major depressive disorder in women.

Postpartum sexual functioning and its relationship to perineal trauma: a retrospective cohort study of primiparous women.

OBJECTIVE: Our goal was to evaluate the relationship between obstetric perineal trauma and postpartum sexual functioning. STUDY DESIGN: Our study was carried out with a retrospective cohort design in 3 groups of primiparous women after vaginal birth: Group 1 (n = 211) had an intact perineum or first-degree perineal tear; group 2 (n = 336) had second-degree perineal trauma; group 3 (n = 68) had third- or fourth-degree perineal trauma. These sample sizes reflect a 70% response rate. Outcomes were time to resuming sexual intercourse, dyspareunia, sexual satisfaction, sexual sensation, and likelihood of achieving orgasm. RESULTS: At 6 months post partum about one quarter of all primiparous women reported lessened sexual sensation, worsened sexual satisfaction, and less ability to achieve orgasm, as compared with these parameters before they gave birth. At 3 and 6 months post partum 41% and 22%, respectively, reported dyspareunia. Relative to women with an intact perineum, women with second-degree perineal trauma were 80% more likely (95% confidence interval, 1.2--2.8) and those with third- or fourth-degree perineal trauma were 270% more likely (95% confidence interval, 1.7--7.7) to report dyspareunia at 3 months post partum. At 6 months post partum, the use of vacuum extraction or forceps was significantly associated with dyspareunia (odds ratio, 2.5; 95% confidence interval, 1.3--4.8), and women who breast-fed were > or = 4 times as likely to report dyspareunia as those who did not breast-feed (odds ratio, 4.4; 95% confidence interval, 2.7--7.0). Episiotomy conferred the same profile of sexual outcomes as did spontaneous perineal lacerations. CONCLUSIONS: Women whose infants were delivered over an intact perineum reported the best outcomes overall, whereas perineal trauma and the use of obstetric instrumentation were factors related to the frequency or severity of postpartum dyspareunia, indicating that it is important to minimize the extent of perineal damage incurred during childbirth.

Menstrual and reproductive factors in relation to ovarian cancer risk.

We assessed menstrual and reproductive factors in relation to ovarian cancer risk in a large, population-based, case-control study. 563 cases in Massachusetts and New Hampshire were ascertained from hospitals and statewide tumour registries; control women (n = 523) were selected through random digit dialing and matched to case women by age and telephone sampling unit. We used multivariate logistic regression to evaluate factors in relation to risk of ovarian cancer and the major tumour histologic subtypes. Ovarian cancer risk was reduced among parous women, relative to nulliparous women (OR = 0.4; 95% CI = 0.3-0.6). Among parous women, higher parity (P = 0.0006), increased age at first (P = 0.03) or last (P = 0.05) birth, and time since last birth (P = 0.04) were associated with reduced risk. Early pregnancy losses, abortions, and stillbirths were unrelated to risk, but preterm, term, and twin births were protective. Risk was lower among women who had breast-fed, relative to those who had not (OR = 0.7; 95% CI = 0.5-1.0), but the average duration of breast-feeding per child was unrelated to risk (P for trend = 0.21). Age at menarche and age at menopause were unrelated to risk overall, although increasing menarcheal age was protective among premenopausal women (P = 0.02). Menstrual cycle characteristics and symptoms were generally unrelated to risk, although cycle-related insomnia was associated with decreased risk (OR = 0.5; 95% CI = 0.3-0.8). We found no association between the type of sanitary product used during menstruation and ovarian cancer risk. In analyses by histologic subtype, reproductive and menstrual factors had most effect on risk of endometrioid/clear cell tumours, and least influential with regard to risk of mucinous tumours. Overall, our findings offer some support to current hypotheses of ovarian pathogenesis, and show aetiologic differences among the tumour subtypes.

Complications of hysteroscopic surgery: predicting patients at risk.

OBJECTIVE: To determine the frequency of operative complications and whether they can be predicted by specific patient characteristics or type of hysteroscopic procedure. METHODS: We collected demographic and medical history information on 925 women who had hysteroscopies from 1995 through 1996. We compared differences in rates of operative complications of specific hysteroscopic procedures. Operative complications were defined as uterine perforation, excessive glycine absorption (1 L or more), hyponatremia, hemorrhage (500 mL or more), bowel or bladder injury, inability to dilate the cervix, and procedure-related hospital admissions. RESULTS: Operative complications occurred in 25 (2.7%) of 925 hysteroscopies. Excessive fluid absorption was the most frequent complication. Hysteroscopic myomectomy and resection of uterine septum were associated with greater odds of complications (odds ratio [OR] 7.4, 95% confidence interval [CI] 3.3, 16.6 and OR 4.0, 95% CI 0.9, 19.6, respectively). Hysteroscopic polypectomy and endometrial ablation were associated with lower odds of complications (OR 0.1, 95% CI 0.0, 0.7 and OR 0.4, 95% CI 0.1, 3.3, respectively). Hysteroscopies done by reproductive endocrinologists and preoperative GnRH agonist therapy were associated with 4-7 times higher odds for operative complications. CONCLUSION: Complications during hysteroscopic surgery are rare. Among hysteroscopic procedures, myomectomies and resections of uterine septa have significantly higher rates of complications, especially excessive fluid absorption. Meticulous fluid management might limit the number of serious complications of these higher-risk procedures.

Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer.

Coffee, alcohol and tobacco use have been examined in many epidemiologic studies of ovarian cancer but findings have generally been inconclusive. To explain prior inconsistent findings, we sought to determine whether associations with these exposures might vary by histologic subtype of ovarian cancer or menopausal status at diagnosis. We conducted a population-based case-control study in eastern Massachusetts and New Hampshire involving 549 women with newly-diagnosed epithelial ovarian cancer and 516 control women selected either by random digit dialing or through lists of residents. Coffee and alcohol consumption was assessed through a semi-quantitative food-frequency questionnaire, and information on tobacco smoking was collected through personal interview. Consumption of coffee and caffeine was associated with increased risk for ovarian cancer but only among premenopausal women. There was no increase in risk for ovarian cancer overall associated with tobacco or alcohol use in either pre- or post-menopausal women. Association of borderline significance for tobacco and invasive serous cancers and alcohol and mucinous cancers were observed but reduced after adjustment for coffee consumption. We conclude that coffee and caffeine consumption may increase risk for ovarian cancer among premenopausal women and are findings that have some epidemiologic and biologic support.