Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Bleeding patterns during the menopausal transition in the multi-ethnic Study of Women's Health Across the Nation (SWAN): a prospective cohort study.

OBJECTIVE: Previous studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population. DESIGN: Prospective community-based cohort study. SETTING USA: southeastern Michigan, northern California and Los Angeles, California. POPULATION: A total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women. METHODS: Women completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data. MAIN OUTCOME MEASURES: Menses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days. RESULTS: At least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding. CONCLUSIONS: These data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

Indoor carbon monoxide and PM2.5 concentrations by cooking fuels in Pakistan.

UNLABELLED: In developing countries biomass combustion is a frequently used source of domestic energy and may cause indoor air pollution. Carbon monoxide (CO)and particulate matter with an aerodynamic diameter of 2.5 lm or less (PM2.5)were measured in kitchens using wood or natural gas (NG) in a semi-rural community in Pakistan. Daytime CO and PM2.5 levels were measured for eight continuous hours in 51 wood and 44 NG users from December 2005 to April 2006. The laser photometer PM2.5 (Dustrak, TSI) was calibrated for field conditions and PM2.5 measurements were reduced by a factor of 2.77. CO was measured by an electrochemical monitor (Model T15v, Langan). The arithmetic mean for daytime CO concentration was 29.4 ppm in wood users; significantly higher than 7.5 ppm in NG users (P < 0.001). The arithmetic mean for daytime PM2.5 concentrations was 2.74 mg/m3 in wood users; significantly higher than 0.38 mg/m3 in NG users (P < 0.001). Higher peak levels of CO and PM2.5 were also observed in wood users. Time spent in the kitchen during fuel burning was significantly related to increasing CO and PM2.5 concentrations in wood users.These findings suggest that cooking with wood fuel may lead to hazardous concentrations of CO and PM2.5. PRACTICAL IMPLICATIONS: Biomass combustion is frequently used in developing countries for cooking. This study showed very high level of air pollution in kitchens using wood as the cooking fuel. Many people, especially women and children, are vulnerable to exposure to very high levels of air pollutants as they spend time in the kitchen during cooking hours.

Factors related to declining luteal function in women during the menopausal transition.

CONTEXT: Reproductive hormones are incompletely characterized during the menopause transition (MT). HYPOTHESIS: Increased anovulation and decreased progesterone accompany progress through the MT. DESIGN: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr. MAIN OUTCOME MEASURES: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables. RESULTS: Ovulatory-appearing cycles declined from 80.9% at baseline to 64.7% by the third assessment (H3). Cycles presumed anovulatory and not ending with bleeding by 50 d (anovulatory/nonbleeding) increased from 8.4 to 24% by H3 and were associated with progress to early perimenopause [odds ratio (OR) = 2.66; confidence interval (CI) = 1.17-6.04] or late perimenopause (OR = 56.21; CI = 18.79-168.12; P < 0.0001), African-American ethnicity (OR = 1.91; CI = 1.06-3.43), and less than high school education (OR = 3.51; CI = 1.62-7.62). Anovulatory cycles ending with bleeding remained at about 10% from baseline to H3; compared with ovulatory cycles, they were associated with obesity (OR = 4.68; CI = 1.33-16.52) and more than high school education (OR = 2.12; CI = 1.22-3.69; P = 0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pregnanediol glucuronide decreased 6.6% for each year on study. Insulin sensitivity measures did not relate strongly to menstrual cycle hormones. CONCLUSIONS: Anovulation without bleeding represents progression of the MT. A small but detectable decrease in luteal progesterone excretion occurs as women progress through the MT.

Premature menopause in a multi-ethnic population study of the menopause transition.

BACKGROUND: Premature menopause, also termed premature ovarian failure (POF), is characterized by cessation of menstruation before the age of 40 years. Little information is available on the general prevalence of POF or on the prevalence by ethnic group. There is also a lack of information on the association of POF with health indicators. METHODS: A cross-sectional survey of women aged 40-55 years was conducted at seven sites in the USA to determine eligibility for a community-based, multi-ethnic longitudinal study of the peri-menopause (The Study of Women Across the Nation, SWAN). Interview data were used to (i). determine the prevalence of self-reported POF overall and by ethnic group, and (ii). assess the association of POF with selected self-reported variables related to health. Cases of POF included only women with no discernible cause for POF. RESULTS: POF was reported by 1.1% (126/11 652) of women. By ethnicity, 1.0% (95% CI, 0.7-1.4) of Caucasian, 1.4% (95% CI, 1.0-2.1) of African American, 1.4% (95% CI, 0.8-2.5) of Hispanic, 0.5% (95% CI, 0.1-1.9) of Chinese and 0.1% (95% CI, 0.02-1.1) of Japanese women experienced POF. The differences in frequency across ethnic groups were statistically significant (P = 0.01). Only Caucasian, African American and Hispanic women were included in further analyses since too few Asian women had POF. In a multivariate model, POF was independently associated with osteoporosis, female hormone use (excluding oral contraceptives), higher body mass index (BMI) and current smoking after adjustment for education level, ability to pay for basics, site and age at interview. In Caucasian women, use of female hormones, osteoporosis, severe disability and smoking were significantly associated with POF. In contrast, POF in African American women was associated with higher BMI and female hormone use, but not osteoporosis. CONCLUSIONS: The prevalence of POF appears to vary by ethnicity. Health factors associated with POF also vary by ethnicity but because of the cross-sectional study design, it is not possible to determine cause and effect relationships. Health risks of POF would benefit from further study.

Assessing menstrual cycles with urinary hormone assays.

The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of middle-aged women enrolled at seven US sites. A subset of 848 women completed a substudy in which their urinary gonadotropins and sex steroid metabolites were assessed during one complete menstrual cycle or up to 50 consecutive days. Urine was analyzed for LH, FSH, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg). To prepare for serial analysis of this large, longitudinal database in a population of reproductively aging women, we examined the performance of algorithms designed to identify features of the normal menstrual cycle in midreproductive life. Algorithms were based on existing methods and were compared with a "gold standard" of ratings of trained observers on a subset of 396 cycles from the first collection of Daily Hormone Substudy samples. In evaluating luteal status, overall agreement between and within raters was high. Only 17 of the 396 cycles evaluated were considered indeterminate. Of the 328 cycles rated as containing evidence of luteal activity (ELA), 320 were considered ELA by use of a Pdg threshold detection algorithm. Of 51 cycles that were rated as no evidence of luteal activity, only 2 were identified by this algorithm as ELA. Evaluation of the day of the luteal transition with methods that detected a change in the ratio of E1c to Pdg provided 85-92% agreement for day of the luteal transition within 3 days of the raters. Adding further conditions to the algorithm increased agreement only slightly, by 1-8%. We conclude that reliable, robust, and relatively simple objective methods of evaluation of the probability and timing of ovulation can be used with urinary hormonal assays in early perimenopausal women.

Factors associated with age at natural menopause in a multiethnic sample of midlife women.

An unprecedented number of women will experience menopause in the next decade. Although the timing of menopause affects long-term disease risk, little is known about factors that affect this timing. In the present 1995--1997 cross-sectional study, the Study of Women's Health Across the Nation, the relation of demographic and lifestyle factors to age at natural menopause was examined in seven US centers and five racial/ethnic groups. All characteristics were self-reported by women aged 40--55 years (n = 14,620). Cox proportional hazards models were used to estimate the probability of menopause by age. Overall, median age at natural menopause was 51.4 years, after adjustment for smoking, education, marital status, history of heart disease, parity, race/ethnicity, employment, and prior use of oral contraceptives. Current smoking, lower educational attainment, being separated/widowed/divorced, nonemployment, and history of heart disease were all independently associated with earlier natural menopause, while parity, prior use of oral contraceptives, and Japanese race/ethnicity were associated with later age at natural menopause. This sample is one of the largest and most diverse ever studied, and comprehensive statistical methods were used to assess factors associated with age at natural menopause. Thus, this study provides important insights into this determinant of long-term disease risk in women.

Risk factors for primary biliary cirrhosis in a cohort of patients from the united states.

Although the etiology of primary biliary cirrhosis (PBC) remains unknown, environmental factors may act to trigger the disease in genetically susceptible hosts. To assess specific risk factors, we conducted a survey using standardized NHANES questions to 241 PBC patients in the United States, 261 of their siblings, and 141 friends without PBC. The overall response rate was 199 of 241 (83%) among PBC cases, 171 of 261 (67%) among siblings, and 141 of 225 (62. 7%) among friend controls. The female-to-male ratio among cases in this sample was approximately 10:1; the mean age was 53 years, and 97% were Caucasian. Other autoimmune diseases reported most frequently by PBC cases included Sjogren's syndrome (17.4%) and Raynaud's syndrome (12.5%). Approximately 6% of cases reported at least one family member with PBC. Adjusted odds ratios (OR) were elevated for cases compared with friends for other autoimmune diseases (OR = 4.92, 95% confidence interval [CI] = 2.38, 10.18), smoking (OR = 2.04, 95% CI = 1.10, 3.78), tonsillectomy (OR = 1.86, 95% CI = 1.02, 3.39), and vaginal or urinary tract infection (UTI) in females only (OR = 2.12, 95% CI = 1.10, 4.07). Similarly elevated ORs were observed for these risk factors when cases were compared with their siblings. The higher rate of UTI among cases is particularly interesting in light of previous data, and raises the possibility of an infectious etiology for PBC and of molecular mimicry as an etiologic mechanism. The significance of smoking in the multivariate models supports the findings of previous studies and raises the issue of the influence of smoking on a Th1 response.

Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age.

A community-based survey was conducted during 1995-1997 of factors related to menopausal and other symptoms in a multi-racial/ethnic sample of 16,065 women aged 40-55 years. Each of seven sites comprising the Study of Women's Health across the Nation (SWAN) surveyed one of four minority populations and a Caucasian population. The largest adjusted prevalence odds ratios for all symptoms, particularly hot flashes or night sweats (odds ratios = 2.06-4.32), were for women who were peri- or postmenopausal. Most symptoms were reported least frequently by Japanese and Chinese (odds ratios = 0.47-0.67 compared with Caucasian) women. African-American women reported vasomotor symptoms and vaginal dryness more (odds ratios = 1.17-1.63) but urine leakage and difficulty sleeping less (odds ratios = 0.64-0.72) than Caucasians. Hispanic women reported urine leakage, vaginal dryness, heart pounding, and forgetfulness more (odds ratios = 1.22-1.85). Hot flashes or night sweats, urine leakage, and stiffness or soreness were associated with a high body mass index (odds ratios = 1.15-2.18 for women with a body mass index > or =27 vs. 19-26.9 kg/m2). Most symptoms were reported most frequently among women who had difficulty paying for basics (odds ratios = 1.15-2.05), who smoked (odds ratios = 1.21-1.78), and who rated themselves less physically active than other women their age (odds ratios = 1.24-2.33). These results suggest that lifestyle, menstrual status, race/ethnicity, and socioeconomic status affect symptoms in this age group.

The use of complementary/alternative medicine for the treatment of asthma in the United States.

Despite our advances in the diagnosis and treatment of asthma, the incidence of mortality is increasing in developed countries. As patients and health care providers seek new options for the treatment and prevention of asthma, various complementary and alternative medical therapies are being used. With funding from the Office of Alternative Medicine, National Institutes of Health, our goal was to identify the type and prevalence of complementary and alternative treatments for asthma in use in the United States in order to establish a research agenda for the study of the most promising therapies. A survey was developed by an expert panel. After undergoing a preliminary round of testing and improvement, the survey was then sent along with a postage-paid return envelope as inserts in the May 1996 issue of Alternative Therapies in Health and Medicine, a peer-reviewed periodical of complementary and alternative medical research and scholarly activity; 10,000 surveys were distributed. We asked that only those who treated asthma respond. The surveys were designed to identify characteristics of the respondent, their particular practice type, use of complementary and alternative medicine, or conventional medicine in general, patient characteristics and numbers, and their use of 20 specific potential therapies to treat asthma. A total of 564 surveys were returned. The 5.64% response rate was low but was reflective of the demographics of the readership of this journal of complementary and alternative medicine. The survey population was 46% male and 43% female; 11% did not specify gender. They ranged in age from under 31 years old to over 70. The largest group (37%) of respondents held degrees as medical doctors, 27% held doctorates in complementary and alternative medicine related disciplines, 11% had registered nursing degrees, 4% were acupuncturists and 18% did not specify their training. Practice characteristics between MD and non-MD asthma care providers did not differ. The majority had general practices (75%) seeing all ages of patients. MDs were less likely to employ complementary and alternative medicine techniques for asthma compared to non-MDs. Both groups identified dietary and nutritional approaches as their most prevalent and useful asthma treatment option. Use of botanicals, meditation and homeopathy were frequently cited; statistically significant differences appeared in the rankings of treatment usefulness and prevalence between MD and non-MDs. Non-MD asthma care providers were more likely to ask patients about their use of complementary and alternative treatments for asthma than MDs (92% vs. 70%), while both groups showed statistically significant increases in their levels of patient inquiries compared to 2 years previously (up 9% and 8% for MDs and non-MDs respectively). The predominance of diet and nutrition supplementation used by MDs and non-MDs suggests that further attention and research efforts should be directed toward this area of complementary and alternative practice. Other complementary and alternative medicine practices such as botanicals, meditation and homeopathy appear to warrant research efforts. Differences between MDs and non-MDs in their use of such therapies may reflect different philosophies as well as training.

Epidemiology of and risk factors for pancreatic cancer.

In the United States, incidence of and mortality from pancreatic cancer increased for several decades earlier in this century but have tended to level off in recent years. Rates increase with age and are higher in blacks than in whites and higher in men than in women. Cigarette smoking increases the risk of pancreatic cancer, while alcohol consumption largely shows no relationship, coffee consumption shows little, if any, association, and a number of occupational exposures seem to be associated but the results are not fully consistent. Finally, human studies have suggested positive associations with meat consumption and carbohydrate intake and a protective effect of dietary fiber and consumption of fruits and vegetables. Thus, much progress has been made in the last two decades in identifying risk factors, but much epidemiologic work is needed to identify and reduce putative exposures.

Risk factors for systemic illnesses following agricultural exposures to restricted organophosphates in California, 1984-1988.

Organophosphate (OP)-related systemic illnesses reported to the Worker Health and Safety (WH&S) Branch, and restricted OP-related agricultural use data reported to the Information Services Branch at the California Department of Food and Agriculture (CDFA) (now CAL-EPA) during 1984-1988 were used to assess factors associated with OP-related systemic illnesses. Counts of OP-related systemic illnesses (numerator), relative to OP-related use data (denominator), such as pounds applied, number of applications, and acres treated (pounds applied/acres treated), were analyzed by crop treated, season of application, method of application, geographic region, and by specific OP applied. A Relative Illness/Use Ratio (RIUR) was calculated by Poisson regression. The highest risk of systemic illness was associated with OP applications to fleshy fruit (mainly fruit trees) compared to all other crops combined (RIUR = 2.9, 95%CI = 2.2-3.9) using pounds applied in the denominator, followed by vegetables and melons (RIUR = 1.9, 95%CI = 1.4-2.4). Air applications resulted in higher RIURs for systemic illness than did ground applications (RIUR = 2.1, 95%CI = 1.7-2.5). Specific OPs that showed significantly elevated RIURs for systemic illness when compared to other OPs were Mevinphos (RIUR = 5.8, 95%CI = 5.0-6.8), Demeton (RIUR = 4.3, 95%CI = 2.6-7.1), Oxydemeton-Methyl (RIUR = 3.8, 95%CI = 3.0-4.9), Methamidophos (RIUR = 1.6, 95%CI = 1.2-2.0) and Azinphos-Methyl (RIUR = 1.3, 95% CI = 1.1-1.6).

Case-control studies and their application to endocrinology.

The steps for undertaking the case-control approach to studying potential causal factors (i.e., host or environmental factors) related to diseases or conditions of interest are outlined, together with warnings of the potential pitfalls and biases to be avoided. Guidelines are provided for appropriate selection of cases and controls and for ascertaining and valid exposure or host information. In addition, the elements needed to determine the sample size needed for a case-control study, the approach to the analysis of case-control data, and criteria for assessing whether associations observed in epidemiologic studies are actually causal also are provided. Finally, the strengths and limitations of the case-control approach, compared with the cohort approach, are described. Published studies are cited to provide endocrinologic examples of the methodologies and issues raised by the case-control study approach.

Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm.

The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.

Association of spontaneous abortion and other reproductive effects with work in the semiconductor industry.

This study tested the hypothesis that fabrication room (fab) work in the silicon-based semiconductor industry is associated with an increased risk of spontaneous abortion (SAB). The study was conducted nationwide at 14 companies representing a spectrum of large to small manufacturers. A small increase in risk of SAB was observed among fab workers compared with nonfabrication room (nonfab) workers in two cohorts, historical (adjusted RR = 1.43, 95% confidence interval [CI] 0.95-2.09) and prospective (adjusted RR = 1.25, 95% CI = 0.63-1.76). Analysis of specific fab exposures in the historical cohort showed a consistent, dose-response association of SAB with photoresist and developer solvents, whose major component was ethylene-based glycol ethers. The consistency of our findings and the toxicological data for these agents suggest that this is a causal association. Independent associations of SAB with self-reported stress and with etching fluorides were observed and require further research. No significant decrease in fertility was observed among men or women working in fabs, but reduced fecundability was suggested for some women fab workers.

Laboratory methods for evaluating early pregnancy loss in an industry-based population.

Laboratory methods were adapted or developed to analyze approximately 70,000 daily urine samples collected during more than 2,500 menstrual cycles from 448 women working in the semiconductor industry. An immunoenzymometric assay (IEMA) for human chorionic gonadotropin (hCG) was employed for screening cycles in order to optimize laboratory resources and to reduce the number of samples requiring analysis by less efficient methods. The presence of hCG in urine was confirmed by the definitive immunoradiometric assay (IRMA). The screening assay eliminated 78% of cycles from further analysis because there was no evidence of conception. Thirty-eight of 448 cycles identified as having significant levels of hCG with the IEMA were confirmed as hCG positive with the IRMA. HCG-positive cycles were further evaluated by examination of daily diary data and by laboratory assays for ovarian and pituitary hormones. As a result of these evaluations, 17 of the 38 cycles identified by the IRMA as positive for hCG were found to be nonconceptive cycles. These results demonstrate the effectiveness of screening assays for hCG, as well as the importance of using multiple urinary biomarkers for the detection of early fetal loss with daily urine samples.

Epidemiologic methods for prospective assessment of menstrual cycle and reproductive characteristics in female semiconductor workers.

Methods were developed to assess potential adverse effects of semiconductor fabrication work in a prospective study of reproductive health. All women aged 18-44 years who worked in seven silicon-wafer fabrication sites in five companies and a frequency-matched sample of women in nonfabrication jobs were included. Among 3,480 selected for screening, 2,639 (75%) completed a self-administered questionnaire to identify women at risk of pregnancy. Among the 739 (28%) eligible women, 481 (65%) completed baseline interviews and 402 (83.6%) completed at least one menstrual cycle of follow-up by providing daily diaries and daily urine samples. Menstrual cycle characteristics were assessed from questionnaires and diaries. Urine samples were assayed for reproductive hormones to identify conceptions. The usual cycle length recalled at baseline was 28 days. The mean cycle length (MCL) recorded in diaries was 29 days, with greater dispersion than at baseline. The median of the MCL from diary data was 28 days for women reporting regular cycles at baseline but 34 days for women reporting irregular cycles at baseline, and the median standard deviation in cycle length per woman was 2.5 days and 7.5 days, respectively. The prospective method, while expensive and labor intensive, showed good compliance. Nevertheless, recall also provided reasonably accurate estimates and distinguished women with regular and irregular cycles.

Prospectively assessed menstrual cycle characteristics in female wafer-fabrication and nonfabrication semiconductor employees.

Women aged 18-44 years in silicon-wafer fabrication-room (fab) jobs and frequency-matched women in nonfab jobs were screened for a prospective study of reproductive health (n = 2,639). Among the 739 (28%) eligible women, 481 (65%) completed a baseline interview; 402 completed at least one menstrual cycle of follow-up with daily diaries and urinary assays to exclude conceptive cycles. Adjusted mean cycle lengths (MCL) did not differ between fab and nonfab women (p = 0.97). Women working in thin film and ion implantation (TFII) had the highest adjusted MCL (34.8 +/- 1.7 days) compared with nonfab workers (32.5 +/- 1.4 days, p = 0.07). Among women working exclusively in one group, TFII women had significantly higher MCL (36.1 +/- 2.04 days) than nonfab women (32.0 +/- 1.38 days, p = 0.017). TFII women were also more likely to have all cycles > 35 days (adjusted relative risk [RR] = 2.45; 95% CI = 0.85-6.06). Variability was assessed by logarithmic transformation of the mean standard deviation (MLSD) in cycle length per woman and adjusted for age and ethnicity (4.5 days for fab vs. 4.0 days for nonfab, p = 0.16). Women working exclusively in TFII or photolithography (PHOTO) had significantly higher adjusted MLSD in cycle length (6.68 +/- 1.28 and 5.72 +/- 1.24 days, respectively) than women in nonfab (4.1 +/- 1.16 days, p = 0.013 and 0.019, respectively). Fab and nonfab women did not differ significantly in mean days of bleeding or risk of having cycles > 35 or < 24 days. However, elevated risks of having cycles < 24 days were seen in supervisor engineers (adjusted RR = 2.46, 95% CI = 1.19-3.63) and PHOTO women (adjusted RR = 1.83, 95% CI = 0.94-2.88).

Prospective assessment of fecundability of female semiconductor workers.

To investigate a possible effect of reduced fecundability (probability of conception per menstrual cycle) among women who fabricate silicon wafers, 152 fabrication-room (fab) and 251 nonfab workers were followed for an average of five menstrual cycles. Daily urine samples were analyzed to confirm clinical spontaneous abortions (SABs) and early fetal losses (EFLs). Adjusted fecundability odds ratios (FRs) for fab workers ranged from 0.59 to 0.72 (p = 0.09-0.28 vs. nonfab). For clinical pregnancies only, the adjusted FR ranged from 0.43-0.50 (p = 0.04-0.09 vs. nonfab). This lower fecundability was most pronounced among dopants and thin-film workers [adjusted FR = 0.61, 95% confidence interval (CI) = 0.27-1.40 for all pregnancies; adjusted FR = 0.22, 95% CI = 0.05-0.96 for clinical pregnancies] and in workers exposed to ethylene-based glycol ethers (adjusted FR = 0.37, 95% CI = 0.11-1.19).

Prospective monitoring of early fetal loss and clinical spontaneous abortion among female semiconductor workers.

Women who work in silicon wafer fabrication rooms (fabs) have been reported to have an increased risk of spontaneous abortion (SAB). Although previous studies have included only clinically recognized SABs, more than two-thirds of SABs may be clinically unrecognized. To determine whether fab work is associated with SAB, we recruited 152 fab and 251 nonfab workers, who collected urine samples for a 6-month period. Samples were analyzed by immunoradiometric assay for the presence of human chorionic gonadotropin to detect early fetal losses. Approximately 63% of fab and 46% of nonfab pregnancies ended in SAB [adjusted relative risk (RR) = 1.25; 95% confidence interval (CI) = 0.63-1.76]. Similar RR were seen for women who worked in dopant and thin-film processes (adjusted RR = 1.30; 95% CI = 0.51-1.96) or in masking (adjusted RR = 1.30; 95% CI = 0.59-1.84). The four pregnancies among women who worked with ethylene-based glycol ethers ended in SAB.