S. Gene McNeeley

A randomized comparison of total or supracervical hysterectomy: surgical complications and clinical outcomes

Abstract Objective To compare surgical complications and clinical outcomes after total versus supracervical abdominal hysterectomy for control of abnormal uterine bleeding, symptomatic uterine leiomyomata, or both. Methods We conducted a randomized intervention trial in four US clinical centers among 135 patients who had abdominal hysterectomy for symptomatic uterine leiomyomata, abnormal uterine bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a total or supracervical hysterectomy performed using the surgeons customary technique. Using an intention-to-treat approach, we compared surgical complications and clinical outcomes for 2 years after randomization. Results Sixty-eight participants were assigned to supracervical hysterectomy (SCH) and 67 to total abdominal hysterectomy (TAH). Hysterectomy by either technique led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain, urinary incontinence, and voiding dysfunction. Patients randomly assigned to (SCH) tended to have more hospital readmissions than those randomized to TAH, but this difference was not statistically significant. There were no statistically significant differences in the rate of complications, degree of symptom improvement, or activity limitation. Participants weighing more than 100 kg at study entry were twice as likely to be readmitted to the hospital during the 2-year follow-up period (relative risk [RR] 2.18, 95% confidence interval [CI] 1.06, 4.48, P = .034). Conclusion We found no statistically significant differences between (SCH) and TAH in surgical complications and clinical outcomes during 2 years of follow-up.

Statin Use, Clinical Fracture, and Bone Density in Postmenopausal Women: Results from the Women's Health Initiative Observational Study

Context Some observational studies have shown fewer fractures in patients receiving statins, but other studies have shown no effect. The studies have been small and had limited ability to adjust for potential confounders. Contribution In this subanalysis of the Womens Health Initiative, postmenopausal women had similar rates of hip, lower arm or wrist, and other fractures whether or not they used statins. The authors adjusted for many potential confounders, and the estimates of fracture rates were very precise. Implications Statins do not seem to prevent fractures in postmenopausal women. The Editors The long-term efficacy and safety of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been established in large multicenter trials of cholesterol-lowering for preventing coronary events in both sexes (1-4). Recent laboratory studies have shown that statins stimulate bone formation in cultured osteoblasts, neonatal murine calvaria, and the cortical bone of mice (5). Statins administered orally increased the trabecular bone volume of female rats by 90%. These findings raise the possibility that statin treatment might prevent both coronary and fracture events, two major causes of morbidity in older women, later in life. Early epidemiologic studies examining the association of statin use with risk for hip fracture produced encouraging results (6-9). These studies were limited, however, by either small numbers of fractures (6) or lack of data on important potential confounders (7-9). More recent studies had mixed results (10-12), with some showing no association (11, 12). Few studies have examined associations with both fracture rates and bone density in the same study group. Therefore, we examined the association of statin use with levels of bone density and rates of hip, lower arm or wrist, and other clinical fractures in the Womens Health Initiative (WHI) Observational Study cohort of postmenopausal women. Methods Study Group The study group for this paper is the WHI Observational Study, a prospective cohort study that enrolled 93 716 women ages 50 to 79 years from 1994 to 1998 at 40 clinical centers throughout the United States. Study methods have been described in detail elsewhere (13). Briefly, women were eligible if they were postmenopausal, were unlikely to relocate or die within 3 years, were not enrolled in the WHI Clinical Trial, and were not participating in any other clinical trial. At baseline, women completed screening and enrollment questionnaires by interview and self-report, physical examination, and blood specimen collection. Human subjects review committees at each participating institution reviewed and approved the study. Follow-up and Outcome Ascertainment Women are sent questionnaires annually to report any hospitalization and a wide variety of outcomes, including clinical fractures of any type. Follow-up time ranged from 2 to 6 years per participant as of February 2001 (median duration, 3.9 years). At that time, 2.8% of participants (n = 2632) had withdrawn or were lost to follow-up [2.7% of statin users and 2.8% of nonusers]. Hip fractures are confirmed by central review of radiology reports. Other fractures are counted on the basis of self-report. Nonetheless, in the WHI Clinical Trial, in which all fractures are adjudicated, 81% of self-reported nonhip clinical fractures are confirmed by physician review of medical records, suggesting that the self-report of such fractures is reasonably accurate. For this report, we classified fractures into three mutually exclusive categories: 1) hip fractures, 2) lower arm or wrist fractures, and 3) other clinical fractures. Clinically recognized vertebral fractures were classified as other clinical fractures. Bone mineral density at the total hip, posterioranterior spine, and total body was measured at baseline in three clinical centers among 6442 women (97% of participants enrolled in Pittsburgh, Pennsylvania; Birmingham, Alabama; and Phoenix and Tucson, Arizona) with dual-energy x-ray absorptiometry using a Hologic QDR densitometer (Hologic, Inc., Waltham, Massachusetts). Standard protocols for positioning and analysis were used by technicians who were trained and certified by the University of California, San Francisco, Bone Density Coordinating Center, San Francisco, California. The ongoing quality assurance program includes monitoring spine and hip phantom scans; reviewing a random sample of all scans and flagging scans with specific problems; hardware or software change control, including in vitro and in vivo cross-calibration; and scanning calibration phantoms across instruments and clinical sites. Statin Exposure and Potential Confounders Participants were asked to bring all current prescription medications to their first screening interview. Clinic interviewers entered each medication name directly from the containers into the WHI database, which assigned drug codes using Medispan software (First DataBank, Inc., San Bruno, California). Women reported duration of use for each current medication. Information on dose was not recorded. Current medication use was ascertained by using identical methods at the year 3 clinic visit. Current statin medication use was defined as use of any HMG-CoA reductase inhibitor. Duration of use was examined in three categories (<1 year, 1 to 3 years, or >3 years). Statin medications were further categorized into three groups according to their demonstrated potency for lipid-lowering on the basis of a dose-efficacy trial (14): low potency (fluvastatin and lovastatin), medium potency (pravastatin), and high potency (atorvastatin, simvastatin). Other lipid-lowering medications were fibrate, colestipol, probucol, cholestyramine, niacin, or nicotinic acid. All covariates were ascertained at baseline. Current use of thiazide diuretics, alendronate, corticosteroid, and sedative or hypnotic medications was recorded by using the same procedures described. Current and previous use of hormone replacement therapy was ascertained by interview using a detailed questionnaire that measured type, route of administration, number of pills per day or week, and duration for each hormonal preparation ever taken. For the purposes of this report, hormone replacement therapy was defined as current use of any estrogen with or without progestin. Dietary supplements, including calcium preparations, taken at least twice weekly for the past 2 weeks were also entered into the database. Dietary intake of calcium was measured by using a semi-quantitative food-frequency questionnaire (15). Total calcium intake was defined as the sum of calcium from diet and supplements. Baseline questionnaires ascertained information on race or ethnicity, history of fracture or coronary heart disease (history of myocardial infarction or angina), current and past smoking, coffee consumption (cups per day), and time spent walking outside the home for more than 10 minutes without stopping (minutes per week). Alcohol consumption was estimated from the food-frequency questionnaire. Physical function was measured by using the 10-item Medical Outcomes Study scale (16). Weight was measured to the nearest 0.1 kg on a balance-beam scale with the participant dressed in indoor clothing without shoes. Height was measured to the nearest 0.1 cm by using a wall-mounted stadiometer. Body mass index was calculated as weight in kg/height in m2. Statistical Analysis The characteristics of women taking a statin medication at baseline were compared with those of women not taking statin medication by using chi-square tests to determine the statistical significance of the differences. Age-adjusted incidence rates of hip, lower arm or wrist, and other clinical fractures per 1000 person-years were calculated according to duration of statin use by the direct method, using the age distribution of the full cohort as the standard population. Women contributed follow-up time until the occurrence of fracture, death, or the end of follow-up, whichever came first. The a priori analysis plan specified selected stratified analyses to determine whether associations between statin use and fracture were apparent in key subgroups of women. For these analyses, women were stratified according to age group (50 to 64 years versus 65 years), current hormone replacement therapy use, body mass index (<25 kg/m2 versus 25 kg/m2, the standard threshold for overweight) (17), history of fracture, and history of coronary disease. Hazard ratios adjusted for age and corresponding 95% CIs were calculated by using Cox proportional-hazards survival models for each fracture category using PHREG in SAS software, version 8.2 (SAS Institute, Inc., Cary, North Carolina). To control for potential confounding factors, hazard ratios and corresponding 95% CIs for categories of duration and potency of statin use were calculated by using multivariate Cox proportional-hazards survival models, using the forced entry approach for variable selection. The multivariate models adjusted for age; race or ethnicity; body mass index; previous fracture; previous coronary disease; current and past hormone replacement therapy use; thiazide, alendronate, corticosteroid, or psychoactive drug use; calcium intake; walking; current and past smoking; coffee intake; and physical function. The multivariate models included individual clinical center as a stratification (or blocking) variable to allow the underlying hazard to be estimated separately for each clinical center. Interaction by clinical center was evaluated by comparing log likelihood statistics (chi-squares) for a model with interaction terms for each clinical center and a reduced model without these terms. Tests for the proportional hazards assumption were conducted by examining plots of the baseline hazard by statin duration categories and by testing interaction terms of statin use by time. Multivariate models were based on 81 896 individuals after exclusion

Chlamydia trachomatis infection in pregnancy and effect of treatment on outcome.

The effect of Chlamydia trachomatis on pregnancy outcome and the effect of treatment of positive cervical cultures was studied by culturing 11,544 women for chlamydia at their first prenatal visit. Chlamydia culture was positive in 2433 (21.08%) and prevalence was related to age and race. Of the positive cultures, 1110 were classified as untreated. The untreated group demonstrated a significant increase in the incidence of premature rupture of the membranes and low birth weight and a decrease in survival when compared with either those with positive cultures who received treatment (N = 1323) or those with negative cultures (N = 9111). Screening of populations at high risk of chlamydia is recommended and treatment of chlamydia-positive patients may improve pregnancy outcome.

Sexual functioning after total compared with supracervical hysterectomy: a randomized trial.

OBJECTIVE: To compare sexual functioning and health-related quality-of-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 = +2, 95% confidence interval –8 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. LEVEL OF EVIDENCE: I

Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health Initiative Randomized Clinical Trial

Background: In separate Womens Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial. Participants and Methods: 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined, but information on their use was collected. Results: After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95% confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34% compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19). Conclusions: In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2609–18)

Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative.

OBJECTIVE Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer. METHODS We studied 86937 postmenopausal women enrolled in the Womens Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade. RESULTS During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade. CONCLUSIONS Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival.

Effectiveness of treatment strategies of some women with pelvic inflammatory disease: a randomized trial.

Objective: Among all women with pelvic inflammatory disease (PID), prevention of adverse reproductive consequences appears to be similarly achieved by outpatient treatment and inpatient treatment. We assessed whether outpatient is as effective as inpatient treatment in relevant age, race, and clinical subgroups of women with PID. Methods: Women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease (n = 831) were randomized into a multicenter trial of inpatient treatment, initially employing intravenous cefoxitin and doxycycline compared with outpatient treatment consisting of a single intramuscular injection of cefoxitin and oral doxycycline. Comparisons between treatment groups during a mean of 84 months of follow-up were made for pregnancies, live births, time to pregnancy, infertility, PID recurrence, chronic pelvic pain, and ectopic pregnancy. Results: Outpatient treatment assignment did not adversely impact the proportion of women having one or more pregnancies, live births, or ectopic pregnancies during follow-up; time to pregnancy; infertility; PID recurrence; or chronic pelvic pain among women of various races; with or without previous PID; with or without baseline Neisseria gonorrhoeae and/or Chlamydia trachomatis infection; and with or without high temperature/white blood cell count/pelvic tenderness score. This was true even in teenagers and women without a previous live birth. Ectopic pregnancies were more common in the outpatient than the inpatient treatment group, but because these were so rare, the difference did not reach statistical significance (5 versus 1, odds ratio 4.91, 95% confidence interval 0.57–42.25). Conclusion: Among all women and subgroups of women with mild-to-moderate PID, there were no differences in reproductive outcomes after randomization to inpatient or outpatient treatment. Level of Evidence: I

Chlamydia antibodies, chlamydia heat shock protein, and adverse sequelae after pelvic inflammatory disease: the PID Evaluation and Clinical Health (PEACH) Study.

Background: Among women with pelvic inflammatory disease (PID), we assessed the associations among antibodies to Chlamydia trachomatis elementary bodies (EB), antibodies to chlamydia heat shock protein (Chsp60), rates of pregnancy, and PID recurrence. Methods: Four hundred forty-three women with clinical signs and symptoms of mild to moderate PID enrolled in the PID Evaluation and Clinical Health Study were followed for a mean of 84 months for outcomes of time-to-pregnancy and time-to-PID recurrence. Antibodies to EB and Chsp60 were assessed in relation to these long-term sequelae of PID. Results: Rates of pregnancy were significantly lower (adj. hazard ratio 0.47, 95% confidence interval 0.28–0.79) and PID recurrence higher (adj. hazard ratio 2.48, 95% confidence interval 1.00–6.27) after adjusting for confounding factors among women whose antibody titers to chlamydia EB measured in the final year of follow-up were in the highest tertile. Conclusion: Among women with mild to moderate PID, antibodies to C. trachomatis were independently associated with reduced rates of pregnancy and elevated rates of recurrent PID.

Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women

The purpose of this study was to assess the relationship between daily coffee consumption and nonmelanoma skin cancer. This study was a cross-sectional analysis of women enrolled in the Womens Health Initiative Observational Study (n=93 676). As nearly all cases of self-reported nonmelanoma skin cancer occurred among Caucasian women (97.8%), we focused our analyses on this group. Compared with nondrinkers, women drinking only caffeinated coffee on a daily basis had a 10.8% lower prevalence of nonmelanoma skin cancer. Consumption of six or more cups of caffeinated coffee per day was associated with a 36% reduction in nonmelanoma skin cancer. After adjusting for various demographic and life style variables, daily consumption of six or more cups was associated with a 30% reduced prevalence of nonmelanoma skin cancer. In contrast to caffeinated coffee, daily consumption of decaffeinated coffee was not associated with a significant change in self-reported nonmelanoma skin cancer for Caucasian women. Daily caffeinated coffee consumption was associated with a dose-related decreased prevalence of nonmelanoma skin cancer in Caucasian women.

Correlates of Sexual Satisfaction Among Sexually Active Postmenopausal Women in the Women’s Health Initiative-Observational Study

BACKGROUNDSatisfaction with sexual activity is important for health-related quality of life, but little is known about the sexual health of postmenopausal women.OBJECTIVEDescribe factors associated with sexual satisfaction among sexually active postmenopausal women.DESIGNCross-sectional analysis.PARTICIPANTSAll members of the Women’s Health Initiative-Observational Study (WHI-OS), ages 50–79, excluding women who did not respond to the sexual satisfaction question or reported no partnered sexual activity in the past year (N = 46,525).MEASUREMENTSPrimary outcome: dichotomous response to the question, “How satisfied are you with your sexual activity (satisfied versus unsatisfied)?” Covariates included sociodemographic factors, measures of physical and mental health, and gynecological variables, medications, and health behaviors related to female sexual health.RESULTSOf the cohort, 52% reported sexual activity with a partner in the past year, and 96% of these answered the sexual satisfaction question. Nonmodifiable factors associated with sexual dissatisfaction included age, identification with certain racial or ethnic groups, marital status, parity, and smoking history. Potentially modifiable factors included lower mental health status and use of SSRIs. The final model yielded a c-statistic of 0.613, reflecting only a modest ability to discriminate between the sexually satisfied and dissatisfied.CONCLUSIONSAmong postmenopausal women, the variables selected for examination yielded modest ability to discriminate between sexually satisfied and dissatisfied participants. Further study is necessary to better describe the cofactors associated with sexual satisfaction in postmenopausal women.