Deborah Goodman | University of California, Irvine (original) (raw)

Papers by Deborah Goodman

Research Square (Research Square), Aug 23, 2019

Background This study investigated the relationship between smoking and hearing loss and deafness... more Background This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modi ed by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identi ed genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models.Results After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (OR=4.58 (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR=5.22 (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identi ed when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21).Conclusions To our knowledge this was the rst report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these ndings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.

NPJ breast cancer, Jun 17, 2021

Breast cancer risk reduction has been validated by large-scale clinical trials, but uptake remain... more Breast cancer risk reduction has been validated by large-scale clinical trials, but uptake remains low. A risk communication tool could provide personalized risk-reduction information for high-risk women. A low-literacy-friendly, visual, and personalized tool was designed as part of the Women Informed to Screen Depending On Measures of risk (WISDOM) study. The tool integrates genetic, polygenic, and lifestyle factors, and quantifies the risk-reduction from undertaking medication and lifestyle interventions. The development and design process utilized feedback from clinicians, decision-making scientists, software engineers, and patient advocates. We piloted the tool with 17 study participants, collecting quantitative and qualitative feedback. Overall, participants felt they better understood their personalized breast cancer risk, were motivated to reduce their risk, and considered lifestyle interventions. The tool will be used to evaluate whether risk-based screening leads to more informed decisions and higher uptake of risk-reduction interventions among those most likely to benefit.

We performed a 318-participant validation study of an individualized risk assessment tool in wome... more We performed a 318-participant validation study of an individualized risk assessment tool in women identified as having high- or highest-risk of breast cancer in the personalized arm of the Women Informed to Screen Depending on Measures of risk (WISDOM) trial. Per protocol, these women were educated about their risk and risk reducing options using the Breast Health Decisions (BHD) tool, which uses patient-friendly visuals and 8th grade reading level language to convey risk and prevention options. Prior to exposure to the educational tool, 4.7% of women were already taking endocrine risk reduction, 38.7% were reducing alcohol intake, and 62.6% were exercising. Three months after initial use of BHD, 8.4% of women who considered endocrine risk reduction, 33% of women who considered alcohol reduction, and 46% of women who considered exercise pursued the risk-reducing activities. Unlike lifestyle interventions which are under the control of the patient, additional barriers at the level o...

Diabetology & Metabolic Syndrome

Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and ... more Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our...

Cancer Research

Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing trad... more Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing traditional annual screening to personalized risk-based breast screening. The novelty of WISDOM personalized screening is the integration of previously validated genetic and clinical risk factors (age, family history, breast biopsy results, ethnicity, mammographic density) into a single risk assessment model that directs the starting age, timing, and frequency of screening. The goal of WISDOM is to determine if personalized screening, compared to annual screening, is as safe, less morbid, enables prevention, and is more accepted by women. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer, DCIS or previous double mastectomy can join the study online at wisdomstudy.org. Participants can either elect randomization or self-select a study arm. Then, they provide electronic consent and sign the Release for Medical Informati...

Journal of the American Geriatrics Society, 1999

OBJECTIVE: To determine if endogenous hormone levels predict cognitive function in older women.DE... more OBJECTIVE: To determine if endogenous hormone levels predict cognitive function in older women.DESIGN: A longitudinal, population‐based study.SETTING: Rancho Bernardo, CaliforniaPARTICIPANTS: A total of 393 community‐dwelling women aged 55 to 89 years who were not using replacement estrogen.METHODS: Between 1984 and 1987, sera were collected for measurement of total and bioavailable testosterone, total and bioavailable estradiol, and estrone Between 1988 and 1991, 12 standard neuropsychological tests were administered, including two items from the Blessed Information‐Memory‐Concentration Test, three measures of retrieval from the Buschke‐Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini‐Mental State Examination (MMSE) with individual analysis of the Serial 7's and the “World” Backwards components, and the Trail‐Making Test part B (Trails B). The association between the five hormones and the 12 cogniti...

Journal of women's health & gender-based medicine

Clinical trials of isoflavone supplementation and bone density have been of relatively short dura... more Clinical trials of isoflavone supplementation and bone density have been of relatively short duration and yielded inconsistent results. Few studies examined the effects of usual dietary isoflavone intake on bone density, and none examined the effects on markers of bone turnover. This cross-sectional study examines the association of usual, unsupplemented dietary soy intake with bone density at the lumbar spine and hip and markers of bone turnover in postmenopausal women. Participants were 208 postmenopausal Southern California women aged 45-74 years. Information on behavioral and lifestyle factors was obtained, and dietary intake of isoflavones over the past year was assessed with a standardized questionnaire. Bone density was measured at the spine and hip with dual energy x-ray absorptiometry (DEXA). Urinary type I collagen cross-linked N-telopeptides (N-Tx) and pyridinium cross-links (PYR), both markers of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone form...

Open Journal of Epidemiology, 2019

Demographics, access to new treatment, altruistic motivations and continuity of care have been sh... more Demographics, access to new treatment, altruistic motivations and continuity of care have been shown to influence motivation to participate in clinical trials. Less is known however, about factors that motivate research participants to agree to take part in observational studies and provide a biologic specimen. This study evaluates and quantitates factors that motivate participation in observational studies and provide a biospecimen among cancer patients, their family members, and controls. An online survey was completed by 450 participants from a cancer genetics registry, including cancer patients, their relatives, and controls. Overall, the benefit to society and the research institution reputation were the most important motivators for participation. Cancer cases were significantly more likely to endorse personal meaningfulness as a factor for participation compared to those without cancer and women were 50% more likely than men to believe that a family benefit is an important determinant of research participation. Researcher and institutional trustworthiness as well as security of stored data were most important when deciding whether to provide a biological sample, with differences seen by gender and history of cancer. This study demonstrated which factors are most important to participants when considering participation in an observational study and donating a biospecimen. Motivational factors significantly differed by gender as well as history and stage of cancer. The application of these study results may improve participation rates in cohort studies.

Journal of Pelvic Medicine and Surgery, 2005

To histologically evaluate the posterior aspect of the pelvic floor; specifically the relationshi... more To histologically evaluate the posterior aspect of the pelvic floor; specifically the relationship between the perineum, posterior vagina, anterior rectum and all other intervening tissue. MATERIALS AND METHODS: The perineum, posterior vaginal wall, and upper part of the rectum were removed enbloc from four fresh cadavers without pelvic prolapse. Length of the specimens ranged from 6-7 cm with a perineal thickness of 2.1 to 3.5 cm. Seven to 26 serial sections were taken from each specimen starting distally at the perineal body moving proximally to the vaginal apex with at least one sagittal section per specimen. Sections extended laterally to include the levator muscles. All sections were stained with H&E, and selected sections from each case were also stained with Masson trichrome and an elastic stain. RESULTS: All 4 specimens showed dense connective tissue and no plane of cleavage for 3-3.5 cm proximally from the posterior forchette. Proximal to this, in all 4 specimens the space between the muscular wall of the vagina and the muscular wall of the rectum was composed of adipose tissue with discontinuous bands of fibrous tissue (or loose areolar tissue). This appears to be a natural line of cleavage. Histologically, no well defined evidence of fascia or a rectovaginal septum was identified. CONCLUSIONS: Histologically there is no evidence of a distinct fascial layer between the posterior vaginal wall and the anterior wall of the rectum. There is a dense layer of fused connective tissue that extends approximately 3-4 cm inside the posterior forchette. The "adventitial layer" of vagina, which has been termed fascia, is composed of adipose tissue and discontinuous bands of fibrous tissue that become thinner in the upper two thirds of the vagina. Clinically, it is the splitting of the adventitial layer from the overlying vagina that accounts for the "fascial layer" seen surgically. Defect specific rectocele repairs use the split adventitial layers to support the anterior wall of the rectum.

Journal of Women's Health & Gender-Based Medicine, 2001

Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. ... more Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. However, all previous studies examined women during pregnancy and early postpartum. None examined the long-term association of parity and lactation with cortisol levels. We examined the relation of reproductive history to cortisol levels in postmenopausal women. Subjects were 749 women, aged 50-89, who were not using estrogen in 1984-1987 when morning cortisol was measured. Parity was not significantly associated with cortisol. However, women who breast-fed for >12 months had significantly higher cortisol levels than women who breast-fed for shorter durations or not at all (p = 0.003). This association was stronger among women with three or more births. Duration of breast-feeding is a determinant of cortisol levels in postmenopausal women. Because both increased cortisol and increased duration of breast-feeding may play protective roles in certain autoimmune diseases, such as rheumatoid arthritis, we suggest that the beneficial effect of lactation on the course of these diseases may be mediated by cortisol.

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 1995

In pre and postmenopausal women low levels of sex hormone binding globulin (SHBG) have been shown... more In pre and postmenopausal women low levels of sex hormone binding globulin (SHBG) have been shown to be associated with a large waist-hip ratio (WHR), a measure of visceral adiposity. Previous studies of WHR and testosterone, however, have been inconclusive. We examined the prospective association between endogenous total and bioavailable testosterone and SHBG levels at baseline with WHR measured 12-15 years later in a community-based cohort of older women. Rancho Bernardo, California. 334 postmenopausal women. Endogenous total and bioavailable testosterone and SHBG levels and WHR. Only age-adjusted SHBG levels and the testosterone/SHBG ratio were associated with BMI. Age-adjusted SHBG levels and total testosterone decreased with increasing WHR. Neither measured nor estimated (testosterone/SHBG ratio) bioavailable testosterone was associated with WHR before or after adjustment for age, BMI, and cigarette smoking. These prospective data confirm the reported cross-sectional associatio...

Journal of Women's Health & Gender-Based Medicine, 2001

Although a common symptom of von Willebrand disease is menorrhagia or metrorrhagia, the prevalenc... more Although a common symptom of von Willebrand disease is menorrhagia or metrorrhagia, the prevalence of this inherited bleeding disorder in women with heavy bleeding is not known. This pilot study compared the prevalence rate of von Willebrand disease in women with dysfunctional uterine bleeding with the prevalence rate in the general population. On average, these women bled for 11.5 days per month and experienced heavy bleeding for >16 years. Over 60% had been treated previously for heavy bleeding. One woman was diagnosed with type 1 von Willebrand disease (5% prevalence rate). Larger studies are needed to confirm this increased rate of von Willebrand disease in women with abnormal uterine bleeding.

Obstetrics & Gynecology, 2005

Objective.-To compare sexual functioning and health-related qualityof-life outcomes of total abdo... more Objective.-To compare sexual functioning and health-related qualityof-life outcomes of total abdominal hysterectomy (TAH) and supracervical hysterectomy (SCH) among women with symptomatic uterine leiomyomata or abnormal uterine bleeding refractory to hormonal management. Methods.-We randomly assigned 135 women scheduled to undergo abdominal hysterectomy in 4 U.S. clinical centers to either a total or supracervical procedure. The primary outcome was sexual functioning at 2 years, as assessed by the Medical Outcomes Study Sexual Problems Scale. Secondary outcomes included specific aspects of sexual functioning and health-related quality-of-life at 6 months and 2 years. Results.-Sexual problems improved dramatically in both randomized groups during the first 6 months and plateaued by 1 year. Health-related quality-of-life scores also improved in both groups. At 2 years, both groups reported few problems with sexual functioning (mean score on the Sexual Problems Scale for SCH group 82, TAH group 80, on a 0-to-100 scale with 100 indicating an absence of problems; difference ϭ ϩ2, 95% confidence interval Ϫ8 to +11), and there were no significant differences between groups. Conclusion.-Supracervical and total abdominal hysterectomy result in similar sexual functioning and health-related quality of life during 2 years of follow-up. This information can help guide physicians as they discuss surgical options with their patients.

Menopause, 2003

Previous studies suggest an association between isoflavone supplementation and improved body comp... more Previous studies suggest an association between isoflavone supplementation and improved body composition. The purpose of this study was to investigate the cross-sectional association between isoflavone consumption from a typical Western diet and measures of total body fat, body fat distribution and lean body mass. This study examined 208 healthy, postmenopausal women, aged 45 to 74 years. At screening, demographic and behavioral characteristics and medical history were obtained. One month later, dietary intake for the past year was assessed with a standardized questionnaire. Anthropometric measurements were obtained, and bioelectric impedance was used to measure total body fat (lb) and lean body mass (lb). Isoflavone consumption did not vary by age, smoking, exercise, or daily alcohol intake. A significant inverse relation was shown between genistein consumption and weight, body mass index, waist circumference, and total body fat mass by bioelectric impedance analysis (P < 0.05). These findings remained significant after adjustment for potential confounders. No association was seen, however, between genistein, daidzein, or total isoflavone intake and body fat distribution or lean body mass. This study suggests that usual dietary isoflavone intake is associated with reduced total body fat and may consequently have a role in the prevention of chronic disease.

The Journal of Clinical Endocrinology & Metabolism, 1996

The Journal of Clinical Endocrinology & Metabolism, 1999

The objective of this study was to determine whether endogenous sex hormone levels predict cognit... more The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59–89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the “World” Backwards components, and the Trail-Making Test Part B. In age- and edu...

Journal of Bone and Mineral Research, 1998

Insulin-like growth factor-I (IGF-I) clearly plays a role in bone metabolism and maintenance, as ... more Insulin-like growth factor-I (IGF-I) clearly plays a role in bone metabolism and maintenance, as evidenced by in vitro and animal studies. In clinical studies, the age-related decrease in IGF-I parallels the age-related decrease in bone mineral density (BMD), but several age-adjusted cross-sectional studies show no consistent association of IGF-I and BMD. We report here a cross-sectional study of serum IGF-I and BMD levels in 483 men and 455 postmenopausal women not using estrogen; subjects were 55 years of age and older, community-dwelling, ambulatory, and unselected for bone density. IGF-I was measured by a highly specific radioimmunoassay. BMD was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry. Men had higher IGF-I and BMD levels than women. In age-adjusted and age-stratified models, IGF-I was associated with BMD only in women (test for interaction, p < 0.0001). Gender differences persisted in gender-specific multiple regression analyses adjusted for age, body mass index, thiazide diuretic use, current smoking, alcohol intake, physical activity, and weight change; IGF-I was significantly associated with BMD at the spine (p = 0.0001) and hip (p = 0.02) in women, but not in men (p's > 0.6). Circulating estradiol levels were not associated with IGF-I levels in either gender, testosterone was inversely associated with IGF-I and only in men. This striking gender difference has not been described previously. Its etiology is unknown. The answer could lead to improved understanding of gender differences in osteoporosis and in response to treatment with IGF-I or growth hormone.

Journal of Bone and Mineral Research, 2002

Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineraliza... more Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineralization, yet its role in osteoporosis has received little evaluation. We studied the associations of retinol intake with bone mineral density (BMD) and bone maintenance in an ambulatory community-dwelling cohort of 570 women and 388 men, aged 55-92 years at baseline. Regression analyses, adjusted for standard osteoporosis covariates, showed an inverse U-shaped association of retinol, assessed by food-frequency questionnaires in 1988-1992, with baseline BMD, BMD measured 4 years later, and BMD change. Supplemental retinol use, reported by 50% of women and 39% of men, was an effect modifier in women; the associations of log retinol with BMD and BMD change were negative for supplement users and positive for nonusers at the hip, femoral neck, and spine. At the femoral neck, for every unit increase in log retinol intake, supplement users had 0.02 g/cm2 (p = 0.02) lower BMD and 0.23% (p = 0.05) greater annual bone loss, and nonusers had 0.02 g/cm2 (p = 0.04) greater BMD and 0.22% (p = 0.19) greater bone retention. However, among supplement users, retinol from dietary and supplement sources had similar associations with BMD, suggesting total intake is more important than source. In both sexes, increasing retinol became negatively associated with skeletal health at intakes not far beyond the recommended daily allowance (RDA), intakes reached predominately by supplement users. This study suggests there is a delicate balance between ensuring that the elderly consume sufficient vitamin A and simultaneously cautioning against excessive retinol supplementation.

Circulation, 1995

Background High levels of dehydroepiandrosterone sulfate (DHEAS) appear to be associated with a r... more Background High levels of dehydroepiandrosterone sulfate (DHEAS) appear to be associated with a reduced risk of fatal cardiovascular disease (CVD) in men. We examined the association between baseline DHEAS levels and the 19-year CVD and ischemic heart disease (IHD) mortality rates in 942 postmenopausal women free of known heart disease at baseline. Methods and Results The 199 CVD deaths and 102 IHD deaths were not related to baseline DHEAS levels. DHEAS was not related to body mass index, fasting plasma glucose, or family history of coronary heart disease, but significantly higher DHEAS levels were found in women who had elevated total or HDL cholesterol or blood pressure, were current smokers, or were nonusers of estrogen replacement therapy. After we adjusted for age, cholesterol, blood pressure, smoking, estrogen replacement therapy, obesity, fasting plasma glucose, and family history of heart disease, the relative risk of fatal CVD and IHD was 1.11 (95% confidence interval, 0.81...

Research Square (Research Square), Aug 23, 2019

Background This study investigated the relationship between smoking and hearing loss and deafness... more Background This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modi ed by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identi ed genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models.Results After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (OR=4.58 (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR=5.22 (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identi ed when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21).Conclusions To our knowledge this was the rst report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these ndings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.

NPJ breast cancer, Jun 17, 2021

Breast cancer risk reduction has been validated by large-scale clinical trials, but uptake remain... more Breast cancer risk reduction has been validated by large-scale clinical trials, but uptake remains low. A risk communication tool could provide personalized risk-reduction information for high-risk women. A low-literacy-friendly, visual, and personalized tool was designed as part of the Women Informed to Screen Depending On Measures of risk (WISDOM) study. The tool integrates genetic, polygenic, and lifestyle factors, and quantifies the risk-reduction from undertaking medication and lifestyle interventions. The development and design process utilized feedback from clinicians, decision-making scientists, software engineers, and patient advocates. We piloted the tool with 17 study participants, collecting quantitative and qualitative feedback. Overall, participants felt they better understood their personalized breast cancer risk, were motivated to reduce their risk, and considered lifestyle interventions. The tool will be used to evaluate whether risk-based screening leads to more informed decisions and higher uptake of risk-reduction interventions among those most likely to benefit.

We performed a 318-participant validation study of an individualized risk assessment tool in wome... more We performed a 318-participant validation study of an individualized risk assessment tool in women identified as having high- or highest-risk of breast cancer in the personalized arm of the Women Informed to Screen Depending on Measures of risk (WISDOM) trial. Per protocol, these women were educated about their risk and risk reducing options using the Breast Health Decisions (BHD) tool, which uses patient-friendly visuals and 8th grade reading level language to convey risk and prevention options. Prior to exposure to the educational tool, 4.7% of women were already taking endocrine risk reduction, 38.7% were reducing alcohol intake, and 62.6% were exercising. Three months after initial use of BHD, 8.4% of women who considered endocrine risk reduction, 33% of women who considered alcohol reduction, and 46% of women who considered exercise pursued the risk-reducing activities. Unlike lifestyle interventions which are under the control of the patient, additional barriers at the level o...

Diabetology & Metabolic Syndrome

Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and ... more Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our...

Cancer Research

Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing trad... more Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing traditional annual screening to personalized risk-based breast screening. The novelty of WISDOM personalized screening is the integration of previously validated genetic and clinical risk factors (age, family history, breast biopsy results, ethnicity, mammographic density) into a single risk assessment model that directs the starting age, timing, and frequency of screening. The goal of WISDOM is to determine if personalized screening, compared to annual screening, is as safe, less morbid, enables prevention, and is more accepted by women. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer, DCIS or previous double mastectomy can join the study online at wisdomstudy.org. Participants can either elect randomization or self-select a study arm. Then, they provide electronic consent and sign the Release for Medical Informati...

Journal of the American Geriatrics Society, 1999

OBJECTIVE: To determine if endogenous hormone levels predict cognitive function in older women.DE... more OBJECTIVE: To determine if endogenous hormone levels predict cognitive function in older women.DESIGN: A longitudinal, population‐based study.SETTING: Rancho Bernardo, CaliforniaPARTICIPANTS: A total of 393 community‐dwelling women aged 55 to 89 years who were not using replacement estrogen.METHODS: Between 1984 and 1987, sera were collected for measurement of total and bioavailable testosterone, total and bioavailable estradiol, and estrone Between 1988 and 1991, 12 standard neuropsychological tests were administered, including two items from the Blessed Information‐Memory‐Concentration Test, three measures of retrieval from the Buschke‐Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini‐Mental State Examination (MMSE) with individual analysis of the Serial 7's and the “World” Backwards components, and the Trail‐Making Test part B (Trails B). The association between the five hormones and the 12 cogniti...

Journal of women's health & gender-based medicine

Clinical trials of isoflavone supplementation and bone density have been of relatively short dura... more Clinical trials of isoflavone supplementation and bone density have been of relatively short duration and yielded inconsistent results. Few studies examined the effects of usual dietary isoflavone intake on bone density, and none examined the effects on markers of bone turnover. This cross-sectional study examines the association of usual, unsupplemented dietary soy intake with bone density at the lumbar spine and hip and markers of bone turnover in postmenopausal women. Participants were 208 postmenopausal Southern California women aged 45-74 years. Information on behavioral and lifestyle factors was obtained, and dietary intake of isoflavones over the past year was assessed with a standardized questionnaire. Bone density was measured at the spine and hip with dual energy x-ray absorptiometry (DEXA). Urinary type I collagen cross-linked N-telopeptides (N-Tx) and pyridinium cross-links (PYR), both markers of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone form...

Open Journal of Epidemiology, 2019

Demographics, access to new treatment, altruistic motivations and continuity of care have been sh... more Demographics, access to new treatment, altruistic motivations and continuity of care have been shown to influence motivation to participate in clinical trials. Less is known however, about factors that motivate research participants to agree to take part in observational studies and provide a biologic specimen. This study evaluates and quantitates factors that motivate participation in observational studies and provide a biospecimen among cancer patients, their family members, and controls. An online survey was completed by 450 participants from a cancer genetics registry, including cancer patients, their relatives, and controls. Overall, the benefit to society and the research institution reputation were the most important motivators for participation. Cancer cases were significantly more likely to endorse personal meaningfulness as a factor for participation compared to those without cancer and women were 50% more likely than men to believe that a family benefit is an important determinant of research participation. Researcher and institutional trustworthiness as well as security of stored data were most important when deciding whether to provide a biological sample, with differences seen by gender and history of cancer. This study demonstrated which factors are most important to participants when considering participation in an observational study and donating a biospecimen. Motivational factors significantly differed by gender as well as history and stage of cancer. The application of these study results may improve participation rates in cohort studies.

Journal of Pelvic Medicine and Surgery, 2005

To histologically evaluate the posterior aspect of the pelvic floor; specifically the relationshi... more To histologically evaluate the posterior aspect of the pelvic floor; specifically the relationship between the perineum, posterior vagina, anterior rectum and all other intervening tissue. MATERIALS AND METHODS: The perineum, posterior vaginal wall, and upper part of the rectum were removed enbloc from four fresh cadavers without pelvic prolapse. Length of the specimens ranged from 6-7 cm with a perineal thickness of 2.1 to 3.5 cm. Seven to 26 serial sections were taken from each specimen starting distally at the perineal body moving proximally to the vaginal apex with at least one sagittal section per specimen. Sections extended laterally to include the levator muscles. All sections were stained with H&E, and selected sections from each case were also stained with Masson trichrome and an elastic stain. RESULTS: All 4 specimens showed dense connective tissue and no plane of cleavage for 3-3.5 cm proximally from the posterior forchette. Proximal to this, in all 4 specimens the space between the muscular wall of the vagina and the muscular wall of the rectum was composed of adipose tissue with discontinuous bands of fibrous tissue (or loose areolar tissue). This appears to be a natural line of cleavage. Histologically, no well defined evidence of fascia or a rectovaginal septum was identified. CONCLUSIONS: Histologically there is no evidence of a distinct fascial layer between the posterior vaginal wall and the anterior wall of the rectum. There is a dense layer of fused connective tissue that extends approximately 3-4 cm inside the posterior forchette. The "adventitial layer" of vagina, which has been termed fascia, is composed of adipose tissue and discontinuous bands of fibrous tissue that become thinner in the upper two thirds of the vagina. Clinically, it is the splitting of the adventitial layer from the overlying vagina that accounts for the "fascial layer" seen surgically. Defect specific rectocele repairs use the split adventitial layers to support the anterior wall of the rectum.

Journal of Women's Health & Gender-Based Medicine, 2001

Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. ... more Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. However, all previous studies examined women during pregnancy and early postpartum. None examined the long-term association of parity and lactation with cortisol levels. We examined the relation of reproductive history to cortisol levels in postmenopausal women. Subjects were 749 women, aged 50-89, who were not using estrogen in 1984-1987 when morning cortisol was measured. Parity was not significantly associated with cortisol. However, women who breast-fed for >12 months had significantly higher cortisol levels than women who breast-fed for shorter durations or not at all (p = 0.003). This association was stronger among women with three or more births. Duration of breast-feeding is a determinant of cortisol levels in postmenopausal women. Because both increased cortisol and increased duration of breast-feeding may play protective roles in certain autoimmune diseases, such as rheumatoid arthritis, we suggest that the beneficial effect of lactation on the course of these diseases may be mediated by cortisol.

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 1995

In pre and postmenopausal women low levels of sex hormone binding globulin (SHBG) have been shown... more In pre and postmenopausal women low levels of sex hormone binding globulin (SHBG) have been shown to be associated with a large waist-hip ratio (WHR), a measure of visceral adiposity. Previous studies of WHR and testosterone, however, have been inconclusive. We examined the prospective association between endogenous total and bioavailable testosterone and SHBG levels at baseline with WHR measured 12-15 years later in a community-based cohort of older women. Rancho Bernardo, California. 334 postmenopausal women. Endogenous total and bioavailable testosterone and SHBG levels and WHR. Only age-adjusted SHBG levels and the testosterone/SHBG ratio were associated with BMI. Age-adjusted SHBG levels and total testosterone decreased with increasing WHR. Neither measured nor estimated (testosterone/SHBG ratio) bioavailable testosterone was associated with WHR before or after adjustment for age, BMI, and cigarette smoking. These prospective data confirm the reported cross-sectional associatio...

Journal of Women's Health & Gender-Based Medicine, 2001

Although a common symptom of von Willebrand disease is menorrhagia or metrorrhagia, the prevalenc... more Although a common symptom of von Willebrand disease is menorrhagia or metrorrhagia, the prevalence of this inherited bleeding disorder in women with heavy bleeding is not known. This pilot study compared the prevalence rate of von Willebrand disease in women with dysfunctional uterine bleeding with the prevalence rate in the general population. On average, these women bled for 11.5 days per month and experienced heavy bleeding for >16 years. Over 60% had been treated previously for heavy bleeding. One woman was diagnosed with type 1 von Willebrand disease (5% prevalence rate). Larger studies are needed to confirm this increased rate of von Willebrand disease in women with abnormal uterine bleeding.

Obstetrics & Gynecology, 2005

Objective.-To compare sexual functioning and health-related qualityof-life outcomes of total abdo... more Objective.-To compare sexual functioning and health-related qualityof-life outcomes of total abdominal hysterectomy (TAH) and supracervical hysterectomy (SCH) among women with symptomatic uterine leiomyomata or abnormal uterine bleeding refractory to hormonal management. Methods.-We randomly assigned 135 women scheduled to undergo abdominal hysterectomy in 4 U.S. clinical centers to either a total or supracervical procedure. The primary outcome was sexual functioning at 2 years, as assessed by the Medical Outcomes Study Sexual Problems Scale. Secondary outcomes included specific aspects of sexual functioning and health-related quality-of-life at 6 months and 2 years. Results.-Sexual problems improved dramatically in both randomized groups during the first 6 months and plateaued by 1 year. Health-related quality-of-life scores also improved in both groups. At 2 years, both groups reported few problems with sexual functioning (mean score on the Sexual Problems Scale for SCH group 82, TAH group 80, on a 0-to-100 scale with 100 indicating an absence of problems; difference ϭ ϩ2, 95% confidence interval Ϫ8 to +11), and there were no significant differences between groups. Conclusion.-Supracervical and total abdominal hysterectomy result in similar sexual functioning and health-related quality of life during 2 years of follow-up. This information can help guide physicians as they discuss surgical options with their patients.

Menopause, 2003

Previous studies suggest an association between isoflavone supplementation and improved body comp... more Previous studies suggest an association between isoflavone supplementation and improved body composition. The purpose of this study was to investigate the cross-sectional association between isoflavone consumption from a typical Western diet and measures of total body fat, body fat distribution and lean body mass. This study examined 208 healthy, postmenopausal women, aged 45 to 74 years. At screening, demographic and behavioral characteristics and medical history were obtained. One month later, dietary intake for the past year was assessed with a standardized questionnaire. Anthropometric measurements were obtained, and bioelectric impedance was used to measure total body fat (lb) and lean body mass (lb). Isoflavone consumption did not vary by age, smoking, exercise, or daily alcohol intake. A significant inverse relation was shown between genistein consumption and weight, body mass index, waist circumference, and total body fat mass by bioelectric impedance analysis (P < 0.05). These findings remained significant after adjustment for potential confounders. No association was seen, however, between genistein, daidzein, or total isoflavone intake and body fat distribution or lean body mass. This study suggests that usual dietary isoflavone intake is associated with reduced total body fat and may consequently have a role in the prevention of chronic disease.

The Journal of Clinical Endocrinology & Metabolism, 1996

The Journal of Clinical Endocrinology & Metabolism, 1999

The objective of this study was to determine whether endogenous sex hormone levels predict cognit... more The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59–89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the “World” Backwards components, and the Trail-Making Test Part B. In age- and edu...

Journal of Bone and Mineral Research, 1998

Insulin-like growth factor-I (IGF-I) clearly plays a role in bone metabolism and maintenance, as ... more Insulin-like growth factor-I (IGF-I) clearly plays a role in bone metabolism and maintenance, as evidenced by in vitro and animal studies. In clinical studies, the age-related decrease in IGF-I parallels the age-related decrease in bone mineral density (BMD), but several age-adjusted cross-sectional studies show no consistent association of IGF-I and BMD. We report here a cross-sectional study of serum IGF-I and BMD levels in 483 men and 455 postmenopausal women not using estrogen; subjects were 55 years of age and older, community-dwelling, ambulatory, and unselected for bone density. IGF-I was measured by a highly specific radioimmunoassay. BMD was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry. Men had higher IGF-I and BMD levels than women. In age-adjusted and age-stratified models, IGF-I was associated with BMD only in women (test for interaction, p < 0.0001). Gender differences persisted in gender-specific multiple regression analyses adjusted for age, body mass index, thiazide diuretic use, current smoking, alcohol intake, physical activity, and weight change; IGF-I was significantly associated with BMD at the spine (p = 0.0001) and hip (p = 0.02) in women, but not in men (p's > 0.6). Circulating estradiol levels were not associated with IGF-I levels in either gender, testosterone was inversely associated with IGF-I and only in men. This striking gender difference has not been described previously. Its etiology is unknown. The answer could lead to improved understanding of gender differences in osteoporosis and in response to treatment with IGF-I or growth hormone.

Journal of Bone and Mineral Research, 2002

Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineraliza... more Retinol is involved in bone remodeling, and excessive intake has been linked to bone demineralization, yet its role in osteoporosis has received little evaluation. We studied the associations of retinol intake with bone mineral density (BMD) and bone maintenance in an ambulatory community-dwelling cohort of 570 women and 388 men, aged 55-92 years at baseline. Regression analyses, adjusted for standard osteoporosis covariates, showed an inverse U-shaped association of retinol, assessed by food-frequency questionnaires in 1988-1992, with baseline BMD, BMD measured 4 years later, and BMD change. Supplemental retinol use, reported by 50% of women and 39% of men, was an effect modifier in women; the associations of log retinol with BMD and BMD change were negative for supplement users and positive for nonusers at the hip, femoral neck, and spine. At the femoral neck, for every unit increase in log retinol intake, supplement users had 0.02 g/cm2 (p = 0.02) lower BMD and 0.23% (p = 0.05) greater annual bone loss, and nonusers had 0.02 g/cm2 (p = 0.04) greater BMD and 0.22% (p = 0.19) greater bone retention. However, among supplement users, retinol from dietary and supplement sources had similar associations with BMD, suggesting total intake is more important than source. In both sexes, increasing retinol became negatively associated with skeletal health at intakes not far beyond the recommended daily allowance (RDA), intakes reached predominately by supplement users. This study suggests there is a delicate balance between ensuring that the elderly consume sufficient vitamin A and simultaneously cautioning against excessive retinol supplementation.

Circulation, 1995

Background High levels of dehydroepiandrosterone sulfate (DHEAS) appear to be associated with a r... more Background High levels of dehydroepiandrosterone sulfate (DHEAS) appear to be associated with a reduced risk of fatal cardiovascular disease (CVD) in men. We examined the association between baseline DHEAS levels and the 19-year CVD and ischemic heart disease (IHD) mortality rates in 942 postmenopausal women free of known heart disease at baseline. Methods and Results The 199 CVD deaths and 102 IHD deaths were not related to baseline DHEAS levels. DHEAS was not related to body mass index, fasting plasma glucose, or family history of coronary heart disease, but significantly higher DHEAS levels were found in women who had elevated total or HDL cholesterol or blood pressure, were current smokers, or were nonusers of estrogen replacement therapy. After we adjusted for age, cholesterol, blood pressure, smoking, estrogen replacement therapy, obesity, fasting plasma glucose, and family history of heart disease, the relative risk of fatal CVD and IHD was 1.11 (95% confidence interval, 0.81...