Influence of exposure assessment methods on risk estimates in an epidemiologic study of total trihalomethane exposure and spontaneous abortion.

Trihalomethanes are common contaminants of chlorinated drinking water. Studies of their health effects have been hampered by exposure misclassification, due in part to limitations inherent in using utility sampling records. We used two exposure assessment methods, one based on utility-wide sampling averages, and one based on measurements from the utility sampling site closest to the subject's residence, to reestimate total trihalomethane (TTHM) exposure for 4212 participants in a preexisting study of risk factors for spontaneous abortion (SAB). For both approaches we performed unweighted, weighted, and subset analyses. The weighted and subset analyses were intended to reduce exposure misclassification, and were based on within-utility variance in TTHM measurements for the utility-wide average approach, and the distance between the subject's residence and sampling site for the closest-site approach. In general, the utility-wide average methods produced odds ratios equivalent to or slightly higher than the closest-site methods. Odds ratios obtained using the utility-wide average, but not the closest-site, approach also became progressively stronger in the weighted and subset analyses. A dose-response was seen between SAB and an exposure metric incorporating both TTHM concentration (utility-wide average approach) and personal ingestion, with SAB rates ranging from 8.3% to 13.7% (unweighted), 7.9% to 16.6% (variance weighted), and 6.6% to 23.1% (low-variance subset). Utility-wide average TTHM exposure assessment methods together with variance-based weights and subsets are relatively simple exposure assessment techniques, which may increase the epidemiologic usefulness of utility sampling records.

The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996.

In 1992 Carlsen et al. reported a significant global decline in sperm density between 1938 and 1990 [Evidence for Decreasing Quality of Semen during Last 50 Years. Br Med J 305:609-613 (1992)]. We subsequently published a reanalysis of the studies included by Carlsen et al. [Swan et al. Have Sperm Densities Declined? A Reanalysis of Global Trend Data. Environ Health Perspect 105:1228-1232 (1997)]. In that analysis we found significant declines in sperm density in the United States and Europe/Australia after controlling for abstinence time, age, percent of men with proven fertility, and specimen collection method. The declines in sperm density in the United States (approximately 1.5%/year) and Europe/Australia (approximately 3%/year) were somewhat greater than the average decline reported by Carlsen et al. (approximately 1%/year). However, we found no decline in sperm density in non-Western countries, for which data were very limited. In the current study, we used similar methods to analyze an expanded set of studies. We added 47 English language studies published in 1934-1996 to those we had analyzed previously. The average decline in sperm count was virtually unchanged from that reported previously by Carlsen et al. (slope = -0.94 vs. -0.93). The slopes in the three geographic groupings were also similar to those we reported earlier. In North America, the slope was somewhat less than the slope we had found for the United States (slope = -0.80; 95% confidence interval (CI), -1.37--0.24). Similarly, the decline in Europe (slope = -2.35; CI, -3.66--1.05) was somewhat less than reported previously. As before, studies from other countries showed no trend (slope = -0.21; CI, -2.30-1.88). These results are consistent with those of Carlsen et al. and our previous results, suggesting that the reported trends are not dependent on the particular studies included by Carlsen et al. and that the observed trends previously reported for 1938-1990 are also seen in data from 1934-1996.

Prenatal active or passive tobacco smoke exposure and the risk of preterm delivery or low birth weight.

We examined the association of exposure to environmental tobacco smoke with birth weight and gestational age in a large, prospective study. We also compared these endpoints between infants of active maternal smokers and those of non-smoking, non-ETS exposed women. Pregnant women were interviewed by telephone during the first trimester, and pregnancy outcome was determined for 99%. Among the 4,454 singleton live births that could be linked to their birth certificate, we confirmed increased risks of low birth weight and small for gestational age with heavier maternal smoking (> 10 cigarettes/day), as well as noting an increased risk for "very preterm" birth (< 35 weeks). These associations were generally stronger among infants of older (> or = 30 years) than those of younger mothers, as well as among non-whites. High environmental tobacco smoke exposure (> or = 7 hours/day in non-smokers) was moderately associated with low birth weight (adjusted odds ratio (AOR) 1.8, 95% confidence limits (95% CL) = 0.82, 4.1), preterm birth (AOR 1.6, 95% CL = 0.87, 2.9), and most strongly with very preterm birth (AOR 2.4, 95% CL = 1.0, 5.3). These associations were generally greater among non-whites than whites. The data support earlier studies suggesting that prenatal environmental tobacco smoke exposure, in addition to maternal smoking, affects infant health.

Utilization of cholecystectomy-a prospective outcome analysis in 1325 patients.

The advent of laparoscopic techniques has resulted in an increased incidence of cholecystectomy, creating a need to reevaluate utilization. The new outcomes research movement emphasizes patient-derived data as well as traditional clinical outcomes. One of the purposes of this prospective study was to seek possible correlations between a variety of variables, both patient- and physician-derived, to the patient's degree of overall satisfaction with the outcome. From July 1992 to May 1997, five different data collection forms were prospectively implemented-three physician-derived (preoperative, intraoperative, and postoperative) and two patient-derived sets of data. In the postoperative patient instrument, patients were asked to rate their degree of satisfaction with the outcome of their surgery on a scale of 1 to 5, with 5 being "extremely satisfied" and 1 being "not at all satisfied." We then sought differences between those patients rating their satisfaction as 5 vs. those rating their satisfaction as 1 to 3. Age, sex, and the presence of comorbid conditions did not correlate with eventual satisfaction. The following were correlated with a statistically significant better degree of satisfaction: the preoperative presence of known gallstones or a preoperative physician-derived history of typical biliary pain. No preoperative patient-derived data were associated with satisfaction; however, the postoperative presence of abdominal pain predicted dissatisfaction. Not surprisingly, continued problems with abdominal pain strongly correlated with dissatisfaction, but this finding supports the accuracy of our assessment instrument. Furthermore, the more typical and clear-cut the clinical presentation, the greater the patient satisfaction with the outcome of cholecystectomy. Satisfaction and pain relief are strongly associated. In patients with pain preoperatively, measurement of either pain relief or satisfaction may be adequate to assess correct utilization of this operative procedure.

Caffeine consumption and menstrual function.

The relation between caffeine intake and menstrual function was examined in 403 healthy premenopausal women who belonged to Kaiser Permanente Medical Care Program in 1990-1991. A telephone interview collected information about caffeinated beverage intake as well as other lifestyle, demographic, occupational, and environmental factors. Subjects collected daily urine samples and completed a daily diary for an average of five menstrual cycles. Metabolites of estrogen and progesterone were measured in the urine, each cycle was characterized as anovulatory or ovulatory, and a probable day of ovulation was selected when appropriate. Logistic regression and repeated measures analyses were performed on menstrual parameters. Women whose caffeine consumption was heavy (>300 mg of caffeine per day) had less than a third of the risk for long menses (> or =8 days) compared with women who did not consume caffeine (adjusted odds ratio = 0.30, 95% confidence interval 0.14-0.66). Those whose caffeine consumption was heavy also had a doubled risk for short cycle length (< or =24 days) (adjusted odds ratio = 2.00, 95% confidence interval 0.98-4.06); this association was also evident in those whose caffeine consumption was heavy who did not smoke (adjusted odds ratio = 2.11, 95% confidence interval 1.03-4.33). Caffeine intake was not strongly related to an increased risk for anovulation, short luteal phase (< or =10 days), long follicular phase (> or =24 days), long cycle (> or =36 days), or measures of within-woman cycle variability.

Exposure to environmental and mainstream tobacco smoke and risk of spontaneous abortion.

The authors examined the risk of spontaneous abortion from environmental tobacco smoke (ETS) exposure in a prospective study of over 5,000 women conducted in California during 1990-1991. Among nonsmokers, there was little association by hours of ETS exposure at home or work (adjusted odds ratio (OR) for any exposure = 1.01, 95% confidence interval (CI) 0.80-1.27), or by paternal smoking. However, the risks associated with ETS exposure were increased among nonsmokers who had moderate alcohol or heavy caffeine consumption. A moderate association with maternal smoking was observed (adjusted OR for > or = 5 cigarettes per day = 1.3, 95% CI 0.91-1.9).

Psychological stress in the workplace and menstrual function.

The relation between psychological stress at work and menstrual function was examined for 276 healthy, working, premenopausal women who participated in the California Women's Reproductive Health Study in 1990-1991. Subjects collected daily urine samples and completed a daily diary for an average of five menstrual cycles. Metabolites of estrogen and progesterone were measured in the urine, and computer algorithms were developed to characterize each cycle as ovulatory or anovulatory and to select a probable day of ovulation. A telephone interview collected information about psychological stress at work as well as other occupational, demographic, lifestyle, and environmental factors. Logistic regression was used to model stressful work and risk of anovulation (> or = 36 days without ovulating) and measures of within-woman cycle variability. Repeated measures analyses were performed on other menstrual cycle parameters. Stressful work (high demand in combination with low control) was not strongly related to an increased risk for anovulation or cycle variability or to any of the following cycle endpoints: short luteal phase (< or = 10 days), long follicular phase (> or = 24 days), long menses (> or = 8 days), or long cycle (> or = 36 days). However, women in stressful jobs had a more than doubled risk for short cycle length (< or = 24 days) compared with women not working in stressful jobs (adjusted odds ratio = 2.24, 95% confidence interval 1.09-4.59).

Cigarette smoking and effects on menstrual function.

OBJECTIVE: To examine the relationship between smoking and menstrual function, using biologic measures rather than self-report of menstrual cycle characteristics. METHODS: In a prospective study, 408 women collected urine daily for one to seven menstrual segments (cycles), maintained daily diaries, and completed detailed interviews. Smoking data from the diaries were averaged over each segment and verified by cotinine assay. Urine samples were analyzed for metabolites of steroid hormones to define the day of ovulation and various menstrual characteristics, including: 1) segment, follicular, luteal phase, and menses length, 2) variability, and 3) anovulation. RESULTS: Heavy smoking (at least 20 cigarettes per day) was associated with nearly four times the risk of short segment (less than 25 days) as was nonsmoking (adjusted odds ratio 3.8, 95% confidence limits 1.1, 12.7). Mean segment length was on average 2.6 days shorter with heavy versus no smoking (95% confidence limits 0.14, 5.0), due almost entirely to shortening of the follicular phase. Women who smoked an average of ten or more cigarettes per day had significantly more variable segment and menses lengths than nonsmokers. Based on small numbers, the data suggested that with greater smoking, there was a possible increased risk of anovulation and short luteal phase. Segments of exsmokers with ten or more pack-years of exposure were more likely to be short and have shorter luteal phases than those of never smokers. CONCLUSION: The effects found in this study of smoking on the menstrual cycle might explain in part associations of smoking with other reproductive endpoints, such as subfecundity and early menopause.

Effect of surgery on health-related quality of life in patients with inflammatory bowel disease: a prospective study.

BACKGROUND: Health-related quality of life (HRQL) has increasingly become a factor in management decisions in patients with chronic diseases. OBJECTIVE: To measure the effect of surgical resection on quality of life in patients with inflammatory bowel disease (IBD). DESIGN: A consecutive series of patients undergoing surgery for IBD between June 1994 and December 1997 were prospectively investigated as a cohort outcomes study. PATIENTS: Data were obtained in 63 patients. The primary diagnoses were Crohn's disease (n = 36) and ulcerative colitis (n = 27). INTERVENTION: Patients with Crohn's disease underwent resection with or without stricturoplasty for intractable disease; all but 3 patients with ulcerative colitis underwent ileoanal anastomoses with ileoanal reservoir. MAIN OUTCOME MEASURE: Health status was measured using the Health Status Questionnaire preoperatively and every 3 months postoperatively. RESULTS: Preoperative measures of HRQL of the patients were low, with values well below the general population in all 8 scales of the Health Status Questionnaire. Postoperatively, HRQL measures improved significantly (P < .05) in both patients with Crohn's disease and those with ulcerative colitis, with scores equal to the general population in most scales. For example, average raw scores for general health in previously studied patient groups were 59 in patients with asthma, 55 in those with diabetes mellitus, 74 in the general population, and 54 and 73 preoperatively and postoperatively, respectively, in the present study. CONCLUSIONS: The results of this study confirm that HRQL scores are low in many patients with IBD referred for operation and HRQL scores improve postoperatively to levels comparable to those of the general population. We believe these data justify early surgical intervention in many patients with symptomatic IBD.

Use of urine biomarkers to evaluate menstrual function in healthy premenopausal women.

A total of 403 healthy, premenopausal women, residing near Santa Clara, California, were recruited from a large health care plan in California for a study of menstrual function. After a telephone interview, participants collected daily urine samples and recorded bleeding and other information in diaries. Data were collected during 1990-1991. Urine samples were analyzed for creatinine and for estradiol and progesterone metabolites by enzyme-linked immunoassay. Computer algorithms were developed to derive menstrual segment length, ovulatory status, day of ovulation, and other parameters from the urine and diary data. (We use "segment" rather than "cycle" to avoid implying that normal cycling occurred.) The average length of participation was 141 (standard deviation, 45) days. The mean segment length was 28.8 (standard deviation, 4.4) days; follicular phase length, 16.0 (standard deviation, 4.4) days; and luteal phase length, 12.9 (standard deviation, 1.7) days; 19 (4.7%) women experienced anovulatory episodes. In exploratory multivariate analyses, important associations included the following: age of > or = 35 years with decreased segment and follicular phase lengths; heavier weight (upper quartile) with anovulation and increased follicular phase and decreased luteal phase lengths; Hispanic ethnicity with anovulation and increased segment length; and past difficulty in achieving pregnancy with anovulation and increased length and variability of segments and follicular phases. Urine biomarkers can be used successfully to evaluate menstrual function in epidemiologic studies.

Rate of caffeine metabolism and risk of spontaneous abortion.

In a case-control study of 73 women with and 141 women without spontaneous abortion, the authors determined the activity of the three principal caffeine-metabolizing enzymes--cytochrome P-4501A2 (CYP1A2), xanthine oxidase, and N-acetyltransferase 2--by measuring levels of caffeine metabolites in urine. After examining the effect of enzyme activity and different levels of caffeine intake, they concluded that there was no evidence that an interaction between enzyme activity and caffeine intake during pregnancy resulted in risk of spontaneous abortion. In a subsample comparing 24 cases with recurrent (two or more) spontaneous abortions and 21 controls with two or more livebirths and no previous spontaneous abortions, the unadjusted odds ratio for low CYP1A2 enzyme activity (below the median) was 0.92 (95% confidence interval (CI) 0.28-3.04) compared with higher CYP1A2 activity. The odds ratio for risk of recurrent spontaneous abortion and low xanthine oxidase activity (below the median) versus higher activity was 0.37 (95% CI 0.10-1.29). Phenotypically slow acetylators (N-acetyltransferase 2 index <0.37) had an odds ratio of 1.58 (95% CI 0.48-5.13) for recurrent loss compared with rapid acetylators. Thus, some association of the latter two caffeine-metabolizing enzymes with recurrent spontaneous abortion is suggested but may also be due to chance.

A prospective study of spontaneous abortion: relation to amount and source of drinking water consumed in early pregnancy.

In 1992, we published four retrospective studies, conducted primarily within a single California county, which found higher spontaneous abortion rates among women who drank more tapwater than bottled water in early pregnancy. The current prospective study extends that investigation to other water systems. Pregnant women from three regions in California were interviewed during their first trimester. Multivariate analyses modeled the amount and type of water consumed at 8 weeks' gestation in each region in relation to spontaneous abortion rate. In Region I, which was within the previous study area, the adjusted odds ratio (OR) comparing high (> or = 6 glasses per day) consumption of cold tapwater with none was 2.17 [95% confidence interval (CI) = 1.22-3.87]. Furthermore, when women with high cold tapwater and no bottled water consumption were compared with those with high bottled water and no cold tapwater consumption, the adjusted odds ratio was 4.58 (95% CI = 1.97-10.64). Conversely, women with high bottled water consumption and no tapwater had a reduced rate of spontaneous abortion compared with those drinking tapwater and no bottled water (adjusted OR = 0.22; 95% CI = 0.09-0.51). Neither tap nor bottled water consumption altered the risk of spontaneous abortion in Regions II and III. Although controlling for age, prior spontaneous abortion, race, gestational age at interview, and weight somewhat strengthened the association in Region I, the distribution of these confounders did not vary appreciably across regions. This study confirms the association between cold tapwater and spontaneous abortion first seen in this county in 1980. If causal, the agent(s) is not ubiquitous but is likely to have been present in Region I for some time.

Moderate maternal alcohol consumption and risk of spontaneous abortion.

Maternal alcoholism is known to have adverse effects on reproduction and fetal development, but the effects of moderate consumption remain controversial. In a previous case-control study, we found a doubled risk of spontaneous abortion with an average consumption of seven or more drinks per week during the first trimester. To confirm this finding while avoiding potential biases from the case-control design, we examined moderate alcohol consumption in a prospective cohort study of over 5,000 pregnant women. An interview in the first trimester asked about alcohol consumption during the week before interview ("during the first trimester") and before pregnancy. We found an increased risk of spontaneous abortion in women who drank more than three drinks per week during the first trimester, with an adjusted odds ratio (OR) of 2.3 [95% confidence interval (CI) = 1.1-4.5]. The increased risk associated with this moderate alcohol consumption may be higher in first than in second trimester abortions, and it is even higher in the first 10 weeks (OR = 3.8; 95% CI = 1.7-8.7), based on small numbers. Consumption of alcohol before pregnancy was not strongly associated with spontaneous abortion.

Caffeinated beverages, decaffeinated coffee, and spontaneous abortion.

We examined the relations between spontaneous abortion and the consumption of caffeine, individual caffeine-containing beverages (coffee, tea, and soda), and decaffeinated coffee in a prospective study of 5,144 pregnant women. We collected information about potential risk factors for spontaneous abortion, including consumption of caffeinated beverages and decaffeinated coffee before and during pregnancy, by interview in the first trimester. Neither total estimated caffeine nor individual caffeinated beverage consumption during the first trimester was associated with an appreciable increase in risk for spontaneous abortion. The adjusted odds ratio for consumption of greater than 300 mg per day of caffeine was 1.3 [95% confidence interval (CI) = 0.8-2.1] after adjustment for maternal age, pregnancy history, cigarette and alcohol consumption, employment, race, gestational age at interview, and marital and socioeconomic status. The adjusted odds ratio for spontaneous abortion related to consumption of three or more cups of decaffeinated coffee during the first trimester was 2.4 (95% CI = 1.3-4.7) in the same model. Although we could not demonstrate this with available data, we suspect that this association was due to bias resulting from the relations among fetal viability, symptoms of pregnancy such as nausea, and consumption patterns during pregnancy.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. III. Guidelines for field studies of male reproductive disorders.

Exposures to environmental toxicants can have detrimental effects on several aspects of human male reproduction: fertility, sexual function, hormone status, and pregnancy/birth outcomes. However, no simple prescreening methods are available for reliably identifying potential hazards; questionnaires alone are relatively imprecise and inefficient in the absence of field data. Multidisciplinary field studies are required that include detailed exposure information, health and reproductive histories, physical examinations, semen analyses, and possibly, hormone analyses. Semen analysis is a critical component of field studies for evaluating two aspects of male reproduction: 1) changes in sperm or seminal content, which may be indicative of adverse effects on the male reproductive system with possible implications for fertility potential; and 2) defects in sperm DNA or chromosomes, which may be associated with subsequent changes in viability during embryonic development and health risks to the offspring. Semen analyses may be tiered: 1) initially, each semen study may include conventional semen assays (concentration, motility, and morphology) as well as specific biomarkers indicated by the health effect of concern in the study cohort: and 2) archived samples (i.e., frozen, videotaped, or smeared) may be utilized in later second-tier analyses to further characterize specific findings. Before initiating any field study, it is cost effective to critically evaluate the suitability of the cohort by confirming exposure and determining that there are adequate numbers of male participants in each exposure category. Such evaluations must be based on the statistical sensitivities of the specific tissue biomarkers and health endpoints for detecting changes. This article summarizes the components of the ideal field study and identifies research needs for improving field studies of male effects and for understanding the mechanisms of male reproductive toxicity. Several promising semen methods currently under development are also discussed.

Effects of psychological stress on human semen quality.

We investigated the relationship between psychological stress and sperm concentration, motility, and morphometry in a prospective study of 157 volunteers who were enrolled in a prepaid health plan. We measured psychological job stress and life-event stress by telephone interview. Sperm-kinematic and nuclear-morphometric variables were measured using computer-assisted image analyses. Sperm concentration, percent motility, and semen volume were determined by objective visual methods. We performed multiple linear regression for each semen variable to examine its relationship to stress, controlling for potential confounders. Stress at work and total number of life events were not related to differences in semen quality. However, the recent death of a close family member was associated with a reduction in straight-line velocity (P = 0.002) and percent of progressively motile sperm (P = 0.02); it was also marginally associated with an increase in the fraction of sperm with larger and more tapered nuclei. These findings suggest that the fecundity of men experiencing the stress of a family member's death might be temporarily diminished.

A prospective study of work-related physical exertion and spontaneous abortion.

We examined the relation of physical exertion to spontaneous abortion in a prospective study of 5,144 pregnant women. In a first trimester interview, we obtained data on employment and physical activity at work and at home, as well as other potential risk factors for spontaneous abortion. We measured exertion as follows: time spent working, standing and bending at work, hours between breaks, and hours spent doing housework or yardwork; shift worked; number of times lifted weights and more than 15 pounds at work or at home; number of children under age 5 years cared for at home. None of the exertion measures was appreciably associated with an increased risk of spontaneous abortion overall. In addition, physical activity at work and at home combined was not related to increased risk. For women with a history of two or more spontaneous abortions, standing at work more than 7 hours per day was associated with an adjusted odds ratio (OR) of 4.3 [95% confidence limits (CL) = 1.6, 11.7], whereas standing at work for 7 hours or less was associated with an adjusted OR of 1.7 (95% CL = 1.1, 2.6). Women without such a history who stood more than 7 hours at work had an adjusted OR near unity.

Have sperm densities declined? A reanalysis of global trend data.

In 1992 a worldwide decline in sperm density was reported; this was quickly followed by numerous critiques and editorials. Because of the public health importance of this finding, a detailed reanalysis of data from 61 studies was warranted to resolve these issues. Multiple linear regression models (controlling for abstinence time, age, percent proven fertility, specimen collection method, study goal and location) were used to examine regional differences and the interaction between region (United States, Europe, and non-Western countries) and year. Nonlinear models and residual confounding were also examined in these data. Using a linear model (adjusted R2 = 0. 80), means and slopes differed significantly across regions (p = 0. 02). Mean sperm densities were highest in Europe and lowest in non-Western countries. A decline in sperm density was seen in the United States (studies from 1938-1988; slope = -1.50; 95% confidence interval (CI), -1.90--1.10) and Europe (1971-1990; slope = -3.13; CI, -4.96- -1.30), but not in non-Western countries (1978-1989; slope = 1.56; CI, -1.00-4.12). Results from nonlinear models (quadratic and spline) were similar. Thus, further analysis of these studies supports a significant decline in sperm density in the United States and Europe. Confounding and selection bias are unlikely to account for these results. However, some intraregional differences were as large as mean decline in sperm density between 1938 and 1990, and recent reports from Europe and the United States further support large interarea differences in sperm density. Identifying the cause(s) of these regional and temporal differences, whether environmental or other, is clearly warranted.

Bone mass and subtle abnormalities in ovulatory function in healthy women.

Women with occasional anovulatory or short luteal phase menstrual cycles have been reported to lose bone mineral density (BMD) at a greatly accelerated rate compared to women without such abnormalities. To investigate this association, we performed a longitudinal study of BMD in a group of healthy premenopausal women enrolled in a comprehensive study of ovulatory function. Subjects had collected daily urine samples that were analyzed for estrone and progesterone metabolites by enzyme-linked immunoassay. The 53 participants collected urine for an average of 4.1 cycles. Computer algorithms identified 7 (13.2%) women with luteal phase abnormalities (> 1 anovulatory cycle or cycle with luteal phase length < or = 10 days) and 17 (32.1%) women with other menstrual abnormalities. Areal BMD (grams per cm2) was measured at the lumbar spine, hip, and whole body using dual energy x-ray absorptiometry; BMD was measured 2-3 times over an average observation period of 17.5 months. At baseline, women with luteal abnormalities had mean BMD similar to those of the 29 women with no abnormal cycles: lumbar spine, 1.06 vs. 1.09 g/cm2; total hip, 0.95 vs. 0.94 g/cm2; whole body, 1.15 vs. 1.11 g/cm2 (P > 0.10; adjusted for age and weight at baseline, parity, physical activity level, and calcium intake). When compared at follow-up to women with no abnormal cycles, women with luteal abnormalities tended to gain BMD at the spine and hip (P > 0.10). On whole body measurement, women with luteal abnormalities tended to lose BMD compared to women with no abnormal cycles (-1.1%/yr vs. 0%/yr; P = 0.08); however, the magnitude of loss was not unusual for women in this age range and was within the coefficient of variation for replicate measurements. Neither mean luteal phase length, percent time in luteal phase, nor average daily excretion of progesterone metabolites was associated with baseline BMD or percent annual change in BMD at any measurement site. Thus, we did not confirm a relationship between luteal abnormalities and accelerated bone loss in this population of healthy premenopausal women.

Psychologic stress in the workplace and spontaneous abortion.

The relation of work-related psychologic stress to spontaneous abortion was examined in a prospective study of 3,953 pregnant, employed members of a prepaid health plan in California, recruited between 1990 and 1991. Information on occupation, psychologic stress-related factors at work, social support at work, physical exertion at work, life events, pregnancy worries, and potential confounders was obtained by a telephone interview. Psychologic job stress and social support at work were assessed using an abbreviated version of the instrument developed by Karasek and colleagues (Los Angeles: University of Southern California, 1986). Results from the multivariate model indicated that, overall, stressful work was not associated with an increased risk of spontaneous abortion. However, interactions were observed between stressful work and maternal age over 32 years (p = 0.04), cigarette smoking (p = 0.02), and primigravidity (p = 0.06). Relative to the odds ratio for stressful work in young, nonsmoking, multigravid women without a history of two or more spontaneous abortions, the odds ratios for spontaneous abortion given stressful work were higher by 2.45 (95% confidence interval (CI) 1.03-5.81) for older women, 2.96 (95% CI 1.16-7.52) for smokers, and 2.27 (95% CI 0.97-5.27) for primigravid women.