Faculty Bibliography

OBJECTIVE: Bone fractures are an important cause of morbidity and mortality among the elderly in the US. The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures. METHODS: We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study. RESULTS: After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI: 0.32-0.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist. CONCLUSIONS: The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity

BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight

While irregular menstruations have been associated with lower cumulative exposure to the ovarian steroids, shorter regular cycles have been postulated to increase the cumulative exposure. Epidemiological correlates with menstrual patterns were analyzed among 4900 premenopausal women aged 45 or younger from the New York University Women's Health Study. The length of regular menstrual cycles increased with increasing age at menarche, body mass index and parity, but decreased with age, nonwhite racial background and current smoking. The likelihood of irregular cycles increased with increasing age, body mass index and number of cigarettes smoked per day. With adjustment for age, body mass index and number of cigarettes smoked per day, the risk of irregular cycles was marginally positively associated with total fat intake

Lower serum folate and higher serum homocysteine levels are known risk factors for various conditions. Thus, epidemiologic correlates with these measurements were studied for 256 multivitamin users and 230 non-users who were middle-aged women. Both serum folate and homocysteine levels increased with advancing age in both multivitamin users (P < 0.01 and P < 0.01) and non-users (P = 0.08 and P < 0.01). Among non-users, higher intake of vegetables, fruits, cold cereals and total protein were associated positively with serum folate and inversely with homocysteine levels. There were 25-74% increases in serum folate and 10-15% decreases in serum homocysteine between 1st and 4th quartiles of intake of these food/nutrients. In addition, 26% lower serum folate and 18% higher serum homocysteine were observed for those smoking 20 or more cigarettes per day compared with non-smokers. Among multivitamin users, body weight was correlated inversely with serum folate (P < 0.01) and positively with serum homocysteine levels (P = 0.04), while no correlates were found among lifestyle factors. Regular use of multivitamins increased serum folate about fourfold and decreased homocysteine twofold. These results suggest that multivitamin use can offset the effects of an unhealthy lifestyle on these serum markers, and that levels of serum folate and homocysteine can also be favorably influenced by healthier diet and abstinence from smoking

Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials

Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet

In contrast to the objective of most clinical trials, which is to demonstrate superiority of an experimental treatment over a standard or placebo, the aim of an equivalence trial is to show that two treatments are equivalent in outcome or only marginally different. This would be of interest when an experimental treatment offers advantages such as reduced toxicity, ease of administration, or cost relative to the standard. Demonstrating equivalence may also be a goal when evaluating the safety of certain drugs because similarity in the risks of an adverse event in subjects exposed and unexposed to the drug is an indication of its safety. The classical formulation of the null hypothesis of treatment equality that is used in superiority trials is not applicable to equivalence trials because absolute equivalence between treatment groups cannot be proven. The strategy in equivalence trials is to define a maximum difference between treatment groups that is clinically acceptable and then assess whether there is sufficient evidence from the trial to conclude that the true treatment difference is within this acceptable range. In this paper, we discuss issues surrounding the planning, conduct, and analysis of equivalence trials in the context of SLE, with examples from the SELENA study

Late or early menopause has been implicated in risk of several chronic diseases in women. To study factors influencing the onset of natural menopause, the authors analyzed the follow-up data of 4694 premenopausal women who enrolled in the New York University Women Study at ages 34-61. In an average of 5.4 years of observation, there were 2035 incidences of menopause, with the median age of 51.3 years. Current smokers experienced menopause 0.75 years earlier than never-smokers. Those who smoked more than 10 cigarettes per day had a 40% increase in risk of earlier menopause. In contrast, women who had three or more children experienced menopause 0.86 years later than nulliparous women, and Jewish women, 0.66 years later than Catholic women. There was also a modest increase in the age at menopause with increasing body mass index. This prospective study provides solid epidemiologic evidence that several factors other than cigarette smoking have impact on the onset of natural menopause