Marilyn F. Vine

Cigarette smoking and semen quality.

OBJECTIVE To determine whether cotinine levels provide stronger evidence for an association between smoking and semen quality than the number of cigarettes smoked per day or years smoked controlling for potential confounders and effect modifiers. DESIGN Cross-sectional study. SETTING Male volunteers at the Reproductive Endocrinology-Fertility Laboratory. PARTICIPANTS Eighty-eight men (ages 18 to 35 years) provided a semen, urine, and blood specimen and completed a self-administered questionnaire concerning smoking and demographic information as well as caffeine and alcohol consumption. Urine, blood, and semen cotinine levels were analyzed via RIA. MAIN OUTCOME MEASURE Standard clinical semen analysis. RESULTS Number of cigarettes smoked per day, years smoked, and log-transformed cotinine levels were associated negatively with semen quality (density, total count, and motility). The association was evident among men age > or = 22 years. For example, the correlation coefficient for the overall association between logged urine cotinine and logged sperm density was -0.23; those stratified by age were 0. 13 (age < 22 years) and - 0. 39 (age > or = 22 years). Potential confounders included in regression models did not diminish the associations. CONCLUSIONS Smoking is associated with lowered semen quality.

Use of fluorescence in situ hybridization (FISH] to assess effects of smoking, caffeine, and alcohol on aneuploidy load in sperm of healthy men

Aneuploidy is a common cause of poor reproductive outcomes in humans and is associated with severe medical problems in liveborn offspring, yet little is known about its underlying cause. A substantial amount of aneuploidy is known to be contributed by the father through cytogenetically abnormal sperm. The purpose of this cross‐sectional, observational study was to investigate the potential contribution of common lifestyle exposures (smoking, caffeine, and alcohol) to the aneuploidy load in sperm from 45 healthy male volunteers 19–35 years of age. Sperm FISH (fluorescence in situ hybridization) was used to determine aneuploidy and diploidy frequencies for chromosomes X, Y and 18 across varying exposure levels of smoking, caffeine, and alcohol. Caffeine was significantly associated with increased frequencies of sperm aneuploidy XX18 and XY18, diploidy XY18‐18 and the duplication phenotype YY18‐18 controlling for alcohol, smoking and donor age. Alcohol was significantly associated with increased frequencies of sperm aneuploidy XX18, diploidy XY18‐18 and the duplication phenotype XX18‐18 controlling for caffeine, smoking and donor age. There was a suggestive, but unstable, association between smoking and XX18. Even within our truncated age range, we were able to confirm an increased risk for XX18 aneuploidy with increasing donor age. Sperm FISH proved to be a useful biomarker to detect and compare numerical cytogenetic abnormalities in human sperm cells across differing levels of exposure to smoking, caffeine, and alcohol. Environ. Mol. Mutagen. 30:175–183, 1997.

Ovulation and ovarian cancer: a comparison of two methods for calculating lifetime ovulatory cycles (United States)

Objective: To compare two methods for calculating lifetime ovulatory cycles (LOC) to determine if more detailed menstrual cycle information results in stronger associations with ovarian cancer. Methods: Using data from 232 cases and 242 controls in a population-based study of ovarian cancer, we compared a standard method for calculating LOC with a second method that had more detailed information on menstrual characteristics. Odds ratios for ovarian cancer by number of LOC were estimated using unconditional logistic regression. Results: The average number of LOC was 29 fewer for the second method that had more detailed menstrual cycle information, as compared to the standard method (p < 0.0001). The difference was due primarily to the second method considering episodes of missed/irregular periods. Associations between LOC and ovarian cancer were weaker for the second method than the standard method. Further analyses suggested that a reduced number of ovulatory cycles due to menstrual irregularity was associated with increased ovarian cancer risk, in contrast to the protective effects observed for fewer ovulatory cycles due to pregnancy or oral contraceptive use. Conclusion: Obtaining additional details on menstrual factors that affect LOC, particularly missed or irregular cycles, provides important information on ovarian cancer risk. Our data suggest that episodes of anovulation due to menstrual disturbances should be evaluated separately from anovulation due to pregnancy or oral contraceptive use.

Age at diagnosis and multiple primary cancers of the breast and ovary

SummaryThis nested case-control study assessed the relationship between a womans age at the time of her initial primary breast or ovarian cancer diagnosis and the risk of a second primary cancer at the other of these two sites. Multiple primary breast and ovarian cancer cases whose initial breast or ovarian diagnosis occurred in 1970–1989 and a random sample of single primary breast or ovarian cancer controls diagnosed in the same years were identified through tumor registries at Duke University Medical Center and the University of North Carolina. Women diagnosed with an initial primary breast cancer at age ≤ 50 years were 4.3 times (95% CI: 1.8–10.6) more likely to have developed a subsequent ovarian cancer compared to those diagnosed after age 50. A relationship between an early age at diagnosis (≤ 50) of ovarian cancer and subsequent diagnosis of breast cancer was not found (odds ratio (OR) = 0.6; 95% CI: 0.2–2.0). Adjustment for stage at diagnosis, treatment, year of diagnosis and length of follow-up using Cox Proportional Hazards modeling techniques supported these relationships, yielding a hazard ratio (HR) for the development of a second primary cancer at the alternate site of 4.6 (95% CI: 1.8–11.5) for women with an initial breast cancer diagnosis and 0.6 (95% CI: 0.2–2.2) for women with an initial ovarian cancer diagnosis. Multiple primary breast and ovarian cancer patients diagnosed with an initial breast cancer at or prior to age 50 may represent a distinct subgroup of women with a germline mutation that confers susceptibility to both breast and ovarian cancers.

Gender differences in response to the Multitest CMI skin test in the general population

BACKGROUND Previous studies of gender differences in response to the Multitest CMI skin test have produced conflicting results. OBJECTIVE To determine whether gender is associated with response to the Multitest CMI skin test. METHODS Two-hundred ninety-seven adults, aged 18 to 64 years, recruited originally for a study of the immune effects associated with living near a hazardous waste site containing primarily organochlorine pesticides, underwent a skin test using the Multitest CMI skin test. Six of seven antigens were tested: tetanus toxoid, diphtheria toxoid, Candida, Tricophyton, Streptococcus, and Proteus. The tuberculin antigen was excluded. Lymphocyte function was also evaluated in vitro using standardized methods of mitogen stimulation with phytohemaglutinin (PHA), concanavalin A (CON-A), and pokeweed mitogen. RESULTS The frequency of positive responses to the skin tests was significantly (P < .001) higher among males (80.4%) than among females (55.7%). Males were more likely than females to respond to all six antigens tested (P < .05). The mean diameter of positive skin test measurements for males statistically significantly (P < .05) exceeded female responses for tetanus and diphtheria. Although not statistically significant, male response size exceeded that of females for all other antigens except Trycophyton. Controlling for age, race, smoking, income, and plasma DDE levels did not change these results. Skin test positivity was not associated with mitogen stimulation assay results overall or within gender groups. CONCLUSION Significant gender differences in response to the Multitest CMI skin test could limit its use as a marker of anergy in general population studies.