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Jacques E Rossouw,
Ross L Prentice,
Joann E Manson,
Aaron K Aragaki,
Judith Hsia,
Lisa W Martin,
Lewis Kuller,
Karen C Johnson,
Charles Eaton, Rebecca Jackson,
Maurizio Trevisan,
Matthew Allison,
Ron C Hoogeveen
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ABSTRACT: Menopausal hormone therapy (MHT) increases the risk of coronary heart disease (CHD) in older women with elevated low-density lipoprotein (LDLC) levels. The endogenous estrogen receptor antagonist 27-hydroxycholesterol (27OHC) is correlated with LDLC levels and may block the beneficial effects of estrogen on the cardiovascular system.
We conducted a nested case-control study in the Women's Health Initiative trials of 350 CHD cases and 813 matched controls to explore potential mediation by 27OHC of the dependence of the CHD risk elevation with MHT on LDLC. Baseline levels of 27OHC were not associated with CHD risk when LDLC was included in the multivariable models. The odds ratio for CHD associated with increased LDLC was 1.15 (95% confidence interval, 1.08-1.23) and was unchanged at 1.14 (95% confidence interval, 1.07-1.22) when 27OHC was added to the model. Baseline 27OHC did not interact with MHT on CHD risk (P=0.81). In contrast, LDLC levels modified the effect of MHT on CHD risk (P for interaction=0.02), and adding 27OHC did not affect this result. With the use of log scales, the effect of MHT on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at ≈3.36 mmol/L (130 mg/dL).
This study found that 27OHC does not independently increase the risk of CHD, does not modify the increased risk of CHD resulting from MHT, and does not mediate the interaction of LDLC with MHT. Measuring blood lipids may aid in counseling individual women about initiating MHT and cardiovascular risk mitigation.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
Circulation 08/2012; 126(13):1577-86. · 14.74 Impact Factor
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Marius Racovan,
Brian Walitt,
Christopher E Collins,
Mary Pettinger,
Christine G Parks,
James M Shikany,
Jean Wactawski-Wende,
Joann E Manson,
Larry Moreland,
Nicole Wright, Rebecca Jackson,
Barbara V Howard
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ABSTRACT: To determine whether calcium plus vitamin D supplementation (CaD) affects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women's Health Initiative CaD trial (n = 36,282) were randomized to 1,000 mg calcium carbonate plus 400 IU of vitamin D(3) daily or to placebo. Incident RA cases were identified via self-report and validated rheumatic medication use. Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups. The analysis included 32,435 women without the history of RA, of which 163 incident RA cases were identified over an average of 5.1 years. No significant differences in demographics, total personal vitamin D intake [P = 0.36], or solar irradiance [P = 0.68] were seen between the groups. In intention-to-treat analyses, no differences were observed in RA incidence [HR 1.04, 95% CI 0.76, 1.41]. No significant modifying effects were seen for stratum of age, solar irradiance, or total vitamin D intake, overall or when adjusted for adherence. Significant effect modifications were seen between CaD and total vitamin D intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure. CaD supplementation did not demonstrate a significant effect on RA incidence in postmenopausal women. Modifying effects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence. Further research is needed to fully explore the benefits and possible adverse effects of vitamin D supplementation on RA.
Rheumatology International 12/2011; · 1.88 Impact Factor
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Phoebe Lee,
Yi-Ping Fu,
Jonine D Figueroa,
Ludmila Prokunina-Olsson,
Jesus Gonzalez-Bosquet,
Peter Kraft,
Zhaoming Wang,
Kevin B Jacobs,
Meredith Yeager,
Marie-Josèphe Horner, [......],
Rowan Chlebowski,
Jolanta Lissowska,
Beata Peplonska,
Louise A Brinton,
Margaret Tucker,
Joseph F Fraumeni,
Robert N Hoover,
Gilles Thomas,
David J Hunter,
Stephen J Chanock
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ABSTRACT: In the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) genome-wide association study of breast cancer, a single nucleotide polymorphism (SNP) marker, rs999737, in the 14q24.1 interval, was associated with breast cancer risk. In order to fine map this region, we imputed a 3.93 MB region flanking rs999737 for Stages 1 and 2 of the CGEMS study (5,692 cases, 5,576 controls) using the combined reference panels of the HapMap 3 and the 1000 Genomes Project. Single-marker association testing and variable-sized sliding-window haplotype analysis were performed, and for both analyses the initial tagging SNP rs999737 retained the strongest association with breast cancer risk. Investigation of contiguous regions did not reveal evidence for an additional independent signal. Therefore, we conclude that rs999737 is an optimal tag SNP for common variants in the 14q24.1 region and thus narrow the candidate variants that should be investigated in follow-up laboratory evaluation.
Human Genetics 09/2011; 131(3):479-90. · 5.07 Impact Factor
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[show abstract]
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ABSTRACT: To study whether use of β-blockers increases survival in patients with malignant melanoma because experimental data suggest that catecholamine hormones may be involved in stimulating the aggressiveness of malignant melanoma.
A total of 4,179 patients diagnosed with malignant melanoma in Denmark with a median follow-up of 4.9 years and identified in the Danish Cancer Registry participated. Data on β-blocker use, comorbidity, and survival were obtained from medical and administrative databases. Cox proportional hazards models were used to estimate HRs for all-cause mortality with 95% CIs with adjustment for prognostic factors.
A total of 372 (8.9%) patients with malignant melanoma were treated with β-blockers within 90 days of melanoma diagnosis. The median β-blocker duration for exposure within 90 days of melanoma diagnosis, more than 90 days, and no prior exposure was 7.6, 1.4, and 0 years, respectively. The patients receiving β-blockers were older, had more comorbidities, and more cardiovascular and psychotropic drug user than the patients receiving no β-blockers prior to melanoma diagnosis. After adjustment for age and comorbidity index, the HR for melanoma death was 0.87 (95% CI: 0.64-1.20) and for all-cause mortality was 0.81 (95% CI: 0.67-0.97).
Increased survival time of patients with melanoma receiving β-blockers suggests that this class of drugs may hold promise in treatment strategy for these patients.
The observations described here suggest that catecholamines may retard melanoma progression and that β-blockers may have unrecognized potential as a therapeutic intervention for melanoma.
Cancer Epidemiology Biomarkers & Prevention 09/2011; 20(10):2273-9. · 4.12 Impact Factor
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Vanessa L Jacoby,
Deborah Grady,
Jean Wactawski-Wende,
JoAnn E Manson,
Matthew A Allison,
Miriam Kuppermann,
Gloria E Sarto,
John Robbins,
Lawrence Phillips,
Lisa W Martin,
Mary Jo O'Sullivan, Rebecca Jackson,
Rebecca J Rodabough,
Marcia L Stefanick
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ABSTRACT: Elective bilateral salpingo-oophorectomy (BSO) is routinely performed with hysterectomy for benign conditions despite conflicting data on long-term outcomes.
This is a prospective cohort of 25 448 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study who had a history of hysterectomy and BSO (n = 14 254 [56.0%]) or hysterectomy with ovarian conservation (n = 11 194 [44.0%]) and no family history of ovarian cancer. Multivariable Cox proportional hazards regression models were used to examine the effect of BSO on incident cardiovascular disease, hip fracture, cancer, and death.
Current or past use of estrogen and/or progestin was common irrespective of BSO status (78.6% of cohort). In multivariable analyses, BSO was not associated with an increased risk of fatal and nonfatal coronary heart disease (hazard ratio, 1.00 [95% confidence interval, 0.85-1.18]), coronary artery bypass graft/percutaneous transluminal coronary angioplasty (0.95 [0.82-1.10]), stroke (1.04 [0.87-1.24]), total cardiovascular disease (0.99 [0.91-1.09]), hip fracture (0.83 [0.63-1.10]), or death (0.98 [0.87-1.10]). Bilateral salpingo-oophorectomy decreased incident ovarian cancer (0.02% in the BSO group; 0.33% in the ovarian conservation group; number needed to treat, 323) during a mean (SD) follow-up of 7.6 (1.6) years, but there were no significant associations for breast, colorectal, or lung cancer.
In this large prospective cohort study, BSO decreased the risk of ovarian cancer compared with hysterectomy and ovarian conservation, but incident ovarian cancer was rare in both groups. Our findings suggest that BSO may not have an adverse effect on cardiovascular health, hip fracture, cancer, or total mortality compared with hysterectomy and ovarian conservation.
Archives of internal medicine 04/2011; 171(8):760-8. · 11.46 Impact Factor
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ABSTRACT: The Women's Health Initiative (WHI) Study of Cognitive Aging studies have investigated the effects of specific treatment regimens containing a combination of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) or CEE only on longitudinal changes in domain-specific cognitive function in older postmenopausal women. In the previous reports, CEE + MPA had a deleterious impact on verbal memory but appeared to have a positive effect on figural memory over time in older postmenopausal women. The present study tests the possibility that CEE alone (unopposed by MPA) could protect against age-related declines in both verbal and figural memory.
This randomized, double-blind, placebo-controlled clinical trial investigated the effects of CEE alone on changes in domain-specific cognitive function and affect in older postmenopausal women. The study was conducted between 1999 and 2004 at 14 WHI clinical centers. The study subjects were 886 postmenopausal women (mean age, 74 years) with prior hysterectomy who were free of probable dementia and were enrolled in the WHI and WHI Memory Study CEE-Alone trial for a mean of 3 years and followed for an additional 2.7 years. Participants were randomized to receive one daily tablet containing CEE, 0.625 mg or a matching placebo. The primary outcome measures were mean differences in annual rates of change of specific cognitive functions and affect, adjusted for time since randomization using analyses of covariance.
The data showed that CEE alone had no significant effects on cognitive functions and affect. Compared with the placebo, women in the CEE only group had significantly lower scores on a measure of spatial rotational ability (P < 0.01) after an average of 3 years of treatment, but over the additional 2.7 years of treatment there was a greater rate of improvement in spatial rotational performance indicating some recovery of their initially poorer performance.
These findings show that CEE does not improve cognitive domains, including figural memory or affect in postmenopausal women with prior hysterectomy. Accordingly, it does not slow the decline of age-related changes in memory in this population. Spatial rotational ability was lower after 3 years of CE treatment but appears to recover with continued treatment.
Obstetrical and Gynecological Survey 03/2010; 65(4):242-243. · 2.51 Impact Factor
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ABSTRACT: To identify static and time-varying sociodemographic, clinical, health-related quality-of-life and attitudinal predictors of use and satisfaction with hysterectomy for noncancerous conditions.
The Study of Pelvic Problems, Hysterectomy, and Intervention Alternatives (SOPHIA) was conducted from 1998 to 2008. English-, Spanish-, or Chinese-speaking premenopausal women (n=1,420) with intact uteri who had sought care for pelvic pressure, bleeding, or pain from an academic medical center, county hospital, closed-panel health maintenance organization, or one of several community-based practices in the San Francisco Bay area were interviewed annually for up to 8 years. Primary outcomes were use of and satisfaction with hysterectomy.
A total of 207 women (14.6%) underwent hysterectomy. In addition to well-established clinical predictors (entering menopause, symptomatic leiomyomas, prior treatment with gonadotropin-releasing hormone agonist, and less symptom resolution), greater symptom impact on sex (P=.001), higher 12-Item Short Form Health Survey mental component summary scores (P=.010), and higher scores on an attitude measure describing "benefits of not having a uterus" and lower "hysterectomy concerns" scores (P<.001 for each) were predictive of hysterectomy use. Most participants who underwent hysterectomy were very (63.9%) or somewhat (21.4%) satisfied in the year after the procedure, and we observed significant variations in posthysterectomy satisfaction across the clinical sites (omnibus P=.036). Other determinants of postsurgical satisfaction included higher pelvic problem impact (P=.035) and "benefits of not having a uterus" scores (P=.008) before surgery and greater posthysterectomy symptom resolution (P=.001).
Numerous factors beyond clinical symptoms predict hysterectomy use and satisfaction. Providers should discuss health-related quality of life, sexual function, and attitudes with patients to help identify those who are most likely to benefit from this procedure.
Obstetrics and Gynecology 03/2010; 115(3):543-51. · 4.73 Impact Factor
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ABSTRACT: Different menopausal hormone therapies may have varied effects on specific cognitive functions. We previously reported that conjugated equine estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women.
The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy.
This was a randomized, double blind, placebo-controlled clinical trial.
The study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers.
Participants were 886 postmenopausal women with prior hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr.
Intervention was 0.625 mg of CEE daily or placebo.
Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.
Compared with placebo, unopposed CEE was associated with lower spatial rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr of continued treatment. CEE did not significantly influence change in other cognitive functions and affect.
CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy. CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment. Overall, CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women.
The Journal of clinical endocrinology and metabolism 11/2009; 94(11):4152-61. · 6.50 Impact Factor
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Laufey Amundadottir,
Peter Kraft,
Rachael Z Stolzenberg-Solomon,
Charles S Fuchs,
Gloria M Petersen,
Alan A Arslan,
H Bas Bueno-de-Mesquita,
Myron Gross,
Kathy Helzlsouer,
Eric J Jacobs, [......],
Stephen K Van Den Eeden,
Jarmo Virtamo,
Jean Wactawski-Wende,
Brian M Wolpin,
Herbert Yu,
Kai Yu,
Anne Zeleniuch-Jacquotte,
Stephen J Chanock,
Patricia Hartge,
Robert N Hoover
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ABSTRACT: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
Nature Genetics 09/2009; 41(9):986-90. · 35.53 Impact Factor
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ABSTRACT: To identify possible factors associated with undergoing bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy among women with benign conditions.
This was a cross-sectional analysis using the 2005 Nationwide Inpatient Sample. Women aged 18 years or older who underwent hysterectomy with BSO or hysterectomy only for a benign condition were included. We examined a broad range of factors associated with undergoing BSO in multivariable analyses.
Fifty-two percent of 461,321 hysterectomies included BSO, with a mean age of 49 years compared with 43 years in the hysterectomy-only group (P<.001). The odds of BSO were two times higher in the Midwest and South and 1.67 times higher in the West as compared with the Northeast (P<.001). Women who were uninsured or had Medicaid were more likely to undergo BSO compared with those with private insurance (odds ratio 1.86, 95% confidence interval 1.14-3.04 for "no charge/charity," odds ratio 1.21, 95% confidence interval 1.08-1.35 for Medicaid) Although BSO was more common among white women than African-American, Latina, and Asian women (P<.001), lower income was associated with BSO among African-American and white women only, not among Asian and Latina women (P=.007 for test for interaction). BSO was eight times as likely with a laparoscopic hysterectomy and 12 times as likely with an abdominal hysterectomy compared with a vaginal approach (P<.001). Women who had endometriosis, pelvic infection, or an ovarian cyst were more likely to undergo BSO (P<.001) compared with women who did not have these diagnoses.
There is significant nationwide variation in the practice of BSO. Age, route of hysterectomy, and diagnosis at surgery affect BSO rates. Nonclinical factors such as race or ethnicity, insurance status, income, and geographic location are also associated with BSO practice.
II.
Obstetrics and Gynecology 06/2009; 113(6):1259-67. · 4.73 Impact Factor
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Hiroyuki Katayama,
Sophie Paczesny,
Ross Prentice,
Aaron Aragaki,
Vitor M Faca,
Sharon J Pitteri,
Qing Zhang,
Hong Wang,
Melissa Silva,
Jacob Kennedy,
Jacques Rossouw, Rebecca Jackson,
Judith Hsia,
Rowan Chlebowski,
Joann Manson,
Samir Hanash
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ABSTRACT: ABSTRACT : BACKGROUND : The availability of serum collections from the Women's Health Initiative (WHI) conjugated equine estrogens (CEE) randomized controlled trial provides an opportunity to test the potential of in-depth quantitative proteomics to uncover changes in the serum proteome related to CEE and to assess their relevance to trial findings, including elevations in the risk of stroke and venous thromboembolism and a reduction in fractures. METHODS : Five independent large scale quantitative proteomics analyses were performed, each comparing a set of pooled serum samples collected from 10 subjects, 1 year following initiation of CEE at 0.625 mg/d, relative to their baseline pool. A subset of proteins that exhibited increased levels with CEE by quantitative proteomics was selected for validation studies. RESULTS : Of 611 proteins quantified based on differential stable isotope labeling, the levels of 116 (19%) were changed after 1 year of CEE (nominal P < 0.05), while 64 of these had estimated false discovery rates <0.05. Most of the changed proteins were not previously known to be affected by CEE and had relevance to processes that included coagulation, metabolism, osteogenesis, inflammation, and blood pressure maintenance. To validate quantitative proteomic data, 14 proteins were selected for ELISA. Findings for ten - IGF1, IGFBP4, IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ - were confirmed in the initial set of 50 subjects and further validated in an independent set of 50 additional subjects who received CEE. CONCLUSIONS : CEE affected a substantial fraction of the serum proteome, including proteins with relevance to findings from the WHI CEE trial related to cardiovascular disease and fracture. CLINICAL TRIALS REGISTRATION : ClinicalTrials.gov identifier: NCT00000611.
Genome Medicine 04/2009; 1(4):47.
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ABSTRACT: The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished.
We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD).
Postmenopausal women (n = 48,835) aged 50-79 y (18.6% of minority race-ethnicity) were randomly assigned to receive the Dietary Modification intervention (40%, n = 19,541) (daily goal: < or =20% of energy as fat, > or =5 servings of vegetables and fruit, and > or =6 servings of grains) or to a comparison group that received no dietary changes (60%; n = 29,294).
After a mean 8.1 y of follow-up, 215 women in the intervention group and 285 women in the comparison group (annualized rate: 0.14% and 0.12%, respectively) experienced a hip fracture (hazard ratio: 1.12; 95% CI: 0.94, 1.34; P = 0.21). The intervention group (n = 5423; annualized rate: 3.44%) had a lower rate of reporting > or =2 falls than did the comparison group (n = 8695; annualized rate: 3.67%) (HR: 0.92; 95% CI: 0.89, 0.96; P < 0.01). There was a significant interaction according to hormone therapy use; those in the comparison group receiving hormone therapy had the lowest incidence of hip fracture. In a subset of 3951 women, hip BMD at years 3, 6, and 9 was 0.4-0.5% lower in the intervention group than in the comparison group (P = 0.003).
A low-fat and increased fruit, vegetable, and grain diet intervention modestly reduced the risk of multiple falls and slightly lowered hip BMD but did not change the risk of osteoporotic fractures. This trial was registered at clinicaltrials.gov as NCT00000611.
American Journal of Clinical Nutrition 04/2009; 89(6):1864-76. · 6.67 Impact Factor
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Gilles Thomas,
Kevin B Jacobs,
Peter Kraft,
Meredith Yeager,
Sholom Wacholder,
David G Cox,
Susan E Hankinson,
Amy Hutchinson,
Zhaoming Wang,
Kai Yu, [......],
Lars J Vatten,
Kristian Hveem,
Merethe Kumle,
Richard B Hayes,
Margaret Tucker,
Daniela S Gerhard,
Joseph F Fraumeni,
Robert N Hoover,
Stephen J Chanock,
David J Hunter
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ABSTRACT: We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433; P = 6.74 x 10(-10) adjusted genotype test, 2 degrees of freedom) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen-receptor-positive tumors. A second SNP on chromosome 14q24.1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1.
Nature Genetics 04/2009; 41(5):579-84. · 35.53 Impact Factor
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Gilles Thomas,
Kevin B Jacobs,
Peter Kraft,
Meredith Yeager,
Sholom Wacholder,
David G Cox,
Susan E Hankinson,
Amy Hutchinson,
Zhaoming Wang,
Kai Yu, [......],
Lars J Vatten,
Kristian Hveem,
Merethe Kumle,
Richard B Hayes,
Margaret Tucker,
Daniela S Gerhard,
Joseph F Fraumeni,
Robert N Hoover,
Stephen J Chanock,
David J Hunter
[show abstract]
[hide abstract]
ABSTRACT: We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433;
Nature Genetics 03/2009; 41(5):579-584. · 35.53 Impact Factor
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Meryl S Leboff,
Rupali Narweker,
Andrea LaCroix,
Lieling Wu, Rebecca Jackson,
Jennifer Lee,
Douglas C Bauer,
Jane Cauley,
Charles Kooperberg,
Cora Lewis,
Asha M Thomas,
Steven Cummings
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ABSTRACT: Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy.
The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk.
We conducted a case-control study in the Women's Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed.
The risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61-4.87).
This study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function.
The Journal of clinical endocrinology and metabolism 02/2009; 94(4):1207-13. · 6.50 Impact Factor
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ABSTRACT: To provide insight into the experience of low-income immigrant Latino couples seeking infertility treatment.
Qualitative interview study.
Infertility clinic at a university-affiliated urban public teaching hospital.
Infertile low-income immigrant Latino couples (105 women and 40 men).
In-depth, tape-recorded interviews.
After transcription and translation, the interviews were coded and analyzed for thematic content.
Four major challenges to providing infertility services to this population were identified: [1] communication: language and cultural barriers resulted in patients having difficulty both in understanding diagnoses and treatments and in communicating their questions, concerns, and experiences to physicians; [2] continuity: because medical students and residents rotated frequently, patients usually saw a different physician at each visit; [3] bureaucracy: patients reported having difficulty with appointment scheduling, follow-up visits, and timed laboratory procedures; and [4] accessibility: patients faced issues of limited availability and affordability of treatment.
At a large, urban, university-affiliated infertility clinic, challenges related to communication, comprehension, continuity, bureaucracy, accessibility, availability, and affordability impeded the delivery of optimal infertility care to many low-income immigrant Latino patients. A greater availability of translators and both patient and physician cultural orientations to address these health care barriers is recommended.
Fertility and sterility 09/2008; 92(1):116-23. · 3.97 Impact Factor
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Matthew A Allison,
Joann E Manson,
Robert D Langer,
J Jeffrey Carr,
Jacques E Rossouw,
Mary B Pettinger,
Lawrence Phillips,
Barbara B Cochrane,
Charles B Eaton,
Philip Greenland,
Susan Hendrix,
Judith Hsia,
Julie R Hunt, Rebecca D Jackson,
Karen C Johnson,
Lewis H Kuller,
Jennifer Robinson
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ABSTRACT: Surgical menopause has been associated with an increased risk of coronary heart disease events. In this study, we aimed to determine the associations between coronary artery calcium (CAC) and hysterectomy, oophorectomy, and hormone therapy use with a focus on the duration of menopause for which there was no hormone therapy use.
In a substudy of the Women's Health Initiative placebo-controlled trial of conjugated equine estrogens (0.625 mg/d), we measured CAC by computed tomography 1.3 years after the trial was stopped. Participants included 1,064 women with previous hysterectomy, aged 50 to 59 years at baseline. The mean trial period was 7.4 years. Imaging was performed at a mean of 1.3 years after the trial was stopped.
Mean age was 55.1 years at randomization and 64.8 years at CAC measurement. In the overall cohort, there were no significant associations between bilateral oophorectomy, years since hysterectomy, years since hysterectomy without taking hormone therapy (HT), years since bilateral oophorectomy, and years of HT use before Women's Health Initiative enrollment and the presence of CAC. However, there was a significant interaction between bilateral oophorectomy and prerandomization HT use for the presence of any CAC (P = 0.05). When multivariable analyses were restricted to women who reported no previous HT use, those with bilateral oophorectomy had an odds ratio of 2.0 (95% CI: 1.2-3.4) for any CAC compared with women with no history of oophorectomy, whereas among women with unilateral or partial oophorectomy, the odds of any CAC was 1.7 (95% CI: 1.0-2.8). Among women with bilateral oophorectomy, HT use within 5 years of oophorectomy was associated with a lower prevalence of CAC.
Among women with previous hysterectomy, subclinical coronary artery disease was more prevalent among those with oophorectomy and no prerandomization HT use, independent of traditional cardiovascular disease risk factors. The results suggest that factors related to oophorectomy and the absence of estrogen treatment in oophorectomized women may be related to coronary heart disease.
Menopause 06/2008; 15(4 Pt 1):639-47. · 3.76 Impact Factor
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ABSTRACT: Intimate partner violence (IPV) during pregnancy poses a significant health risk to the mother and developing fetus. Practice guidelines recommend that prenatal providers screen for and counsel their patients about IPV, yet many physicians express reluctance or discomfort regarding such discussions. The Health in Pregnancy (HIP) computer program was designed to improve prenatal providers' counseling about behavioral risks.
English-speaking women 18 years or older, less than 26-weeks pregnant, and receiving prenatal care at one of the five participating clinics in the San Francisco area, were randomized in parallel groups in a controlled trial (June 2006-present; data analyzed June 2007). Participants reporting one or more risks were randomized to intervention or control in stratified blocks. Providers received summary "cueing sheets" alerting them to their patient's risk(s) and suggesting counseling statements.
Thirteen percent (37/286) of the sample reported current IPV. Provider cueing resulted in 85% of the IPV-intervention group reporting discussions with their provider, compared to 23.5% of the control group (p<0.001).
IPV discussions were influenced strongly by cueing providers. Provider cueing is an effective and appropriate adjunct to routine risk counseling in prenatal care.
American Journal of Preventive Medicine 02/2008; 34(2):134-7. · 4.04 Impact Factor
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ABSTRACT: To identify risk factors for fractures in multi-ethnic women, we studied 159,579 women enrolled in the Women's Health Initiative. In general, risk factors for fractures were similar across ethnic groups. However, irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture. Targeting these high-risk women for screening and intervention could reduce fractures.
Fracture rates tend to be lower in minority women, but consequences may be greater. In addition, the number of fractures is expected to increase in minority women because of current demographic trends. There are limited prospective data on risk factors for fractures in minority women.
We studied 159,579 women 50-79 yr of age enrolled in the Women's Health Initiative. Information on risk factors was obtained by questionnaire or examination. Nonspine fractures that occurred after study entry were identified over an average follow-up of 8 +/- 2.6 (SD) yr.
Annualized rates (%) of fracture in whites, blacks, Hispanics, Asians, and American Indians were 2.0, 0.9, 1.3, 1.2, and 2.0, respectively. Significant predictors [HR (95% CI)] of fractures by ethnic group were as follows: blacks: at least a high school education, 1.22 (1.0, 1.5); (+) fracture history, 1.7 (1.4, 2.2); and more than two falls, 1.7 (1.9, 2.0); Hispanics: height (>162 cm), 1.6 (1.1, 2.2); (+) fracture history, 1.9 (1.4, 2.5); more than two falls, 1.8 (1.4, 2.3); arthritis, 1.3 (1.1, 1.6); corticosteroid use, 3.9 (1.9, 8.0); and parental history of fracture, 1.3 (1.0, 1.6); Asians: age (per 5 yr), 1.2 (1.0, 1.3); (+) fracture history, 1.5 (1.1, 2.0); current hormone therapy (HT), 0.7 (0.5, 0.8); parity (at least five), 1.8 (1.1, 3.0); more than two falls, 1.4 (1.1, 1.9); American Indian: (+) fracture history, 2. 9 (1.5, 5.7); current HT, 0.5 (0.3, 0.9). Women with eight or more risk factors had more than a 2-fold higher rate of fracture compared with women with four or fewer risk factors. Two ethnicity x risk factor interactions were identified: age and fall history.
Irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture. Targeting these high-risk women for screening and intervention could reduce fractures.
Journal of Bone and Mineral Research 12/2007; 22(11):1816-26. · 6.37 Impact Factor
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Bette Caan,
Marian Neuhouser,
Aaron Aragaki,
Cora Beth Lewis, Rebecca Jackson,
Meryl S LeBoff,
Karen L Margolis,
Lynda Powell,
Gabriel Uwaifo,
Evelyn Whitlock,
Judy Wylie-Rosett,
Andrea LaCroix
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ABSTRACT: Obesity in the United States has increased significantly during the past several decades. The role of calcium in the maintenance of a healthy body weight remains controversial.
A randomized, double-blinded, placebo-controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79 years, who were already enrolled in the dietary modification and/or hormone therapy arms of the Women's Health Initiative clinical trial. Women were randomized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily. Change in body weight was ascertained annually for an average of 7 years.
Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P = .001). After 3 years of follow-up, women with daily calcium intakes less than 1200 mg at baseline who were randomized to supplements were 11% less likely to experience small weight gains (1-3 kg) and 11% less likely to gain more moderate amounts of weight (>3 kg) (P for interaction for baseline calcium intake = .008).
Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain, which was observed primarily in women who reported inadequate calcium intakes.
clinicaltrials.gov Identifier: NCT00000611.
Archives of Internal Medicine 05/2007; 167(9):893-902. · 11.46 Impact Factor
