Approximately 200,000 women undergo inpatient procedures for pelvic organ prolapse in the United States each year.1 Currently, there are no population-based data that describe the stage or degree of prolapse in women undergoing surgery. Thus, it is not clear whether figures that focus on the number of surgical procedures for pelvic organ prolapse accurately reflect its prevalence or represent merely the tip of the iceberg. In 2 large studies in which pelvic organ prolapse was defined as any descent of the uterus or the anterior or posterior vagina, 30.8%2 and 41%3 of participants had some degree of prolapse. These studies have added substantially to our knowledge but are limited by pelvic organ prolapse assessment performed without a validated staging system and by limited medical and/or obstetrical information about study participants. In 1996, the International Continence Society defined a system of pelvic organ prolapse quantification,4 which has demonstrated good intraexaminer and interexaminer reliability.5 The suggested International Continence Society staging system is summarized in the box on page 490.
The Pelvic Organ Prolapse Quantification system is a major advance in studying prolapse because it allows groups of researchers to report findings in a standardized fashion. However, the current staging system is based on the working group's clinical opinion, pending further input from the research community.
The aims of this cross-sectional study were to 1) describe pelvic organ support in a quantifiable, standardized fashion in a population of older women participating in one site of the Women's Health Initiative (WHI) Hormone Replacement Therapy randomized clinical trial and 2) determine factors (including hormone replacement therapy) that are associated with decreased pelvic organ support. Because pelvic organ prolapse has not yet been clearly defined, we explored different dichotomous measures to represent the presence of prolapse.
International Continence Society Stages of Pelvic Organ Prolapse Determined by Pelvic Organ Prolapse Quantification System Measurements
Stage 0 No prolapse; anterior and posterior points are all −3 and C (cervix) or D (posterior fornix) is between −TVL (total vaginal length) and −(TVL − 2) cm.
Stage I The criteria for stage 0 are not met, and the most distal prolapse is > 1 cm above the level of the hymen (< −1 cm).
Stage II The most distal prolapse is between 1 cm above and 1 cm below the hymeneal ring (at least one point is −1, 0, or +1).
Stage III The most distal prolapse is > 1 cm below the hymeneal ring but no further than 2 cm less than TVL.
Stage IV Represents complete vault eversion; the most distal prolapse protrudes to at least (TVL − 2) cm.
Women with an intact uterus who were enrolled in the WHI Hormone Replacement Therapy clinical trial at 1 Midwestern site were approached for enrollment in this ancillary study. At that time, most women had been participants in the WHI for 5 to 6 years. The ancillary study participants underwent a pelvic examination and completed an additional written questionnaire at enrollment and annually thereafter. This article presents rates of pelvic organ prolapse prevalence and risk factors from the baseline data only. This study was approved by the University of Iowa Institutional Review Board, and each subject completed an informed consent document.
At each evaluation, subjects completed the standard pelvic examination performed by the WHI research team and then immediately underwent a second examination by 1 of 2 experienced urogynecology research nurses. A Pelvic Organ Prolapse Quantification examination was performed with women in the dorsal lithotomy position.6 In this system, anterior, apical, and posterior vaginal points are measured in relation to their distance above or below the hymeneal ring. Negative values denote support above and positive values support below the hymeneal ring. A “0” value indicates that the area of vagina being measured rests at the level of the hymeneal ring. All measurements, with the exception of the total vaginal length, were taken when the subject was performing a maximal Valsalva maneuver. Measurements were taken with a marking stick marked at 1-cm intervals. The bottom half of a narrow speculum was used to support the anterior vagina when making the posterior measurements and vice versa. Apical points were measured with a whole speculum in place, which was slowly withdrawn until maximal descensus was reached. In a pilot study, the interobserver agreement (assessed using weighted kappa) between the principal investigator and research nurse was 0.63 for pelvic organ prolapse stage, 0.96 for genital hiatus, and 0.50 for perineal body measurements. A focused neurological examination, rectal examination, and assessment of the levator ani muscles were completed per the recommendation of the National Institutes of Health Female Pelvic Floor Disorders Terminology report.6 Anal sphincter tone was described as either subjectively normal or markedly decreased. Evaluation of the pelvic muscles included assessment of the presence or absence of palpable levator ani muscles on each side and a subjective assessment of squeeze pressure, which was rated on a 1–4 scale (1 = flicker, very weak; 4 = strong inward pull, very strong). The bulbocavernosus reflex was described as present or absent.
Demographic and background data were abstracted from the WHI database, and subjects provided additional information about obstetrical, medical, and surgical history in the additional written questionnaire.
Data were entered into SAS 8.0 (SAS Institute Inc, Cary, NC). Univariate analyses of categorical data were performed with χ2 test or the Fisher exact test. The normality of continuous data was tested. The assumption of normality was not met in most of the continuous variables and therefore these were analyzed with nonparametric Wilcoxon 2-sample tests. Variables that were associated with pelvic organ prolapse at P < .10 in the univariate analyses were entered into logistic regression models. Given the current ambiguity of pelvic organ prolapse staging, we compared the associations between pelvic organ prolapse and various risk factors using 2 different dichotomous definitions of prolapse. In the first definition, prolapse was defined as International Continence Society stage II or greater. In the second method, pelvic organ prolapse was considered present if the leading edge of prolapse was measured at or past the hymen (≥ 0 cm). Some variables had substantial missing data. Models were repeated without these variables to assess whether this changed the odds ratios (OR) for the primary risk factors significantly. Most continuous variables did not meet the assumption of linearity. Based on the distribution of data relative to pelvic organ prolapse, we categorized variables in the regression models as follows: body mass index (BMI) less than 27 kg/m2 versus 27 kg/m2 or greater; waist circumference less than 88 cm versus 88 cm or greater; high school education or less versus greater than high school education; age at first delivery younger than 20 years, 20–24 years, or 25 years or older; age at last delivery 29 years or younger, 30–34 years, or 35 years or older; birthweight of largest baby 3.69 kg or less (the median) versus more than 3.69 kg; age 68 or younger versus more than 68 years; and vaginal deliveries, 0 versus 1–2, 3–4, and 5 or more.
Of 337 women approached, 297 (88%) were enrolled in this ancillary study. After enrollment, 27 women agreed to complete questionnaires only but not pelvic examinations. Thus, 270 women are included in this study (80% of those approached). Their mean age was 68.3 years (standard deviation [SD] 5.6, range 57–84 years), mean number of vaginal deliveries was 3.5 (SD 2.1, range 0–12), and mean BMI was 30.4 kg/m2 (SD 6.2, range 16.3–48.3). Seven percent of the women had 1 or more cesarean deliveries. The women were almost exclusively of Caucasian race.
Applying the published International Continence Society staging system to the study group, only 6 (2.3%, 95% confidence interval [CI] 0.8–4.8%) women were classified as stage 0 pelvic organ prolapse, whereas 88 (33.0%, 95% CI 27.4–39.0%), 168 (62.9%, 95% CI 56.8–68.7%), and 5 (1.9%; 95% CI 0.6–4.3%) were stages I, II, and III, respectively. No woman had stage IV pelvic organ prolapse. The distribution of vaginal measurements obtained during the Pelvic Organ Prolapse Quantification examination is shown in Table 1. This table shows the percentage of women who demonstrated maximal descensus of the specific compartment at each level. The cumulative percentage demonstrates the proportion of women with maximal descensus at or above (that is, more negative Pelvic Organ Prolapse Quantification values) that level.
The mean and median values for the leading edge of prolapse (that is, the most distal point measured) were both −1.0 cm (1 cm above the hymeneal ring). The distribution of the leading edge of prolapse is shown in Figure 1. Most women fell into the rather broad International Continence Society stage II, which includes 3 possible points to which the leading edge can descend (–1 cm, 0 cm, and +1 cm). Therefore, for our multivariable analyses, we elected to define prolapse in the 2 ways described in Materials and Methods section. The proportion of women with prolapse using both definitions also is illustrated in Figure 1. Eight women had undergone previous surgery for either pelvic organ prolapse or urinary incontinence. In these 8, the leading edge of prolapse ranged from 0 to −2. Excluding them from analysis did not change the mean stage or leading edge of prolapse measurement, and they are thus included in all analyses.
The mean genital hiatus measurement was 3.3 cm (SD 1.3, median 3, range 1–7) and mean perineal body measurement was 3.6 cm (SD 0.84, median 3, range 2–6). The mean vaginal length measurement was 9.2 cm (SD 1.1, median 9, range 6–12,). In 35 (13.6%) women, the levator ani muscles were asymmetric on examination. The overall median muscle function score was 2 (range 1–4). Fifty-two (19%) women initially strained when instructed to contract the levator ani muscles (ie, “Kegel”). In 184 women (68.1%), a bulbocavernosus reflex could be elicited, and the anal tone with squeeze was felt to be normal by the examiner in 256 patients (95%). There was no association between pelvic organ prolapse, using either of the definitions above, and levator ani muscle asymmetry (P > .4 for both definitions), presence of bulbocavernosus reflex (P > .1 for both definitions), anal tone (P > .4 for both definitions), or perineal body measurement (P > .1 for both definitions). There was no statistically significant association between pelvic organ prolapse and median muscle function score: 2.2 in those with pelvic organ prolapse (defined as ≥ stage II) versus 2.5 with no pelvic organ prolapse (P = .06). The genital hiatus was larger in women with prolapse (3.6 versus 2.7 cm using the ≥ stage II definition, P < .01; 4.3 versus 2.9 cm using the leading edge cut point definition, P < .01).
The univariate associations between pelvic organ prolapse (using both definitions) and potential risk factors are summarized in Table 2. There was no association between pelvic organ prolapse and previous employment history, current exercise (mild, moderate, or strenuous), or self-report of past strenuous exercise at ages 18, 35, and 50 years (data not shown). However, only 12 women reported a past occupation that involved heavy labor. There was no association between the presence of pelvic organ prolapse and the WHI Hormone Replacement Therapy clinical trial randomization assignment (estrogen plus progesterone versus placebo), with prolapse occurring in almost exactly the same percentage of women in each group. We asked women whether female first- and second-degree relatives had surgery for either pelvic organ prolapse or urinary incontinence. We recognize the high likelihood of ascertainment bias for this type of question and, therefore, rather than considering this as an a priori risk factor, we chose to simply describe what women believed about their female relatives. Thirty-eight women (14.1%) and 28 women (10.4%) reported that a female relative had surgery for prolapse and urinary incontinence, respectively.
After adjusting for BMI, waist circumference, ages at first and last deliveries, and birth weight of largest baby, only lower education level and greater vaginal deliveries predicted prolapse defined as stage II or greater, with OR 2.16 (95% CI 1.10–4.24) and OR 1.61 (95% CI 1.03–2.50), respectively. The OR for these factors did not change when we sequentially analyzed models excluding ages at first and last deliveries (because of missing data) and waist circumference (because of colinearity between BMI and waist circumference). To further explore the contribution of vaginal deliveries, we also constructed separate models entering vaginal parity as an ordinal variable in 1 set of models (response range, 0–12) and as a categorical variable in the other set of models (0, 1–2, 3–4, ≥ 5). When analyzed as an ordinal variable, vaginal delivery was still significantly related to pelvic organ prolapse defined by the staging system, but the OR decreased to 1.21 (95% CI 1.07–4.94) in the main model and was similar in the other 2. When we analyzed vaginal parity as a categorical variable, women with 0 deliveries had a marked reduction in risk for pelvic organ prolapse compared with parous women (OR 0.04, 95% CI 0.004–0.37 for 0 versus 1–2 deliveries; OR 0.05, 95% CI 0.005–0.48 for 0 versus 3–4 deliveries; and OR 0.06 95% CI 0.007–0.57 for 0 versus ≥ 5 deliveries). However, increasing levels of parity were not associated with further increases in prolapse risk. For example, the OR for women with 3–4 deliveries versus 1–2 deliveries was 0.73 (95% CI 0.33–1.65), and for women with ≥ 5 deliveries versus 1–2, the OR was 1.16 (95% 0.39–3.44).
The following variables were entered into the logistic regression model for the outcome of prolapse defined as the most dependent edge of prolapse at 0 cm or lower: age, education, vaginal deliveries, weight of largest baby, and history of cigarette smoking. Women 68 years and older had a lower risk of prolapse than did those younger than 68 years (OR 0.50, 95% CI 0.27–0.92). Those with a lower education level and larger babies had an increased risk of prolapse (OR 2.38, 95% 1.31–4.32 and OR 1.97, 95% 1.07–3.64, respectively). Vaginal deliveries were not significant in this model (OR 1.28, 95% CI 0.87–1.88). As above, we also constructed models entering vaginal deliveries as both an ordinal and a categorical variable and found no association with pelvic organ prolapse.
To determine whether apical prolapse may be associated with different risk factors than prolapse defined by the most dependent vaginal compartment (as above), we created a separate definition in which apical prolapse was defined as prolapse of the posterior fornix at least 2 cm below the total vaginal length measurement. Fifty-four women (20%) had apical prolapse. The only risk factor associated with apical prolapse was past history of an occupation involving heavy labor (reported by only 12 women). Of women with apical prolapse, 11.1% reported past heavy labor compared with 2.8% of those without apical prolapse (P = .02).
In this population of older women, we found that vaginal wall descensus was common but that more clinically important prolapse was rare. In the absence of data at the time of a recent National Institutes of Health Terminology Workshop, pelvic organ prolapse was defined by the panel as the presence of stage I or greater prolapse (see the box on page 490).7 By this definition, 97.7% of women in our study had prolapse, suggesting that this proposed definition of prolapse is not clinically relevant. Using other possible definitions of prolapse, we found that 65.5% of our study group had prolapse when it was defined as International Continence Society stage II or greater, and 25.6% were considered to have prolapse when defined as the leading edge of vaginal descensus at or below the hymeneal ring. Stage II of the current International Continence Society staging system includes women with the leading edge of prolapse ranging from 1 cm above to 1 cm below the hymeneal ring. Given that so many women fall into this broad category, consideration should be given to revising the staging system such that early prolapse can be better studied.
We included only women with an intact uterus because it is likely that hysterectomy changes the natural history of pelvic organ prolapse. Seven to 14% of all hysterectomies are performed for pelvic organ prolapse,7–9and the cumulative risk of surgically treated prolapse after hysterectomy increases in a linear fashion with a 5% risk after 15 years10; therefore, the study of the natural history of pelvic organ prolapse should begin in women with a uterus. The purpose of our study is to build a foundation for understanding the prevalence of pelvic organ prolapse in women without surgical disruption of pelvic structures. However, given the high rate of hysterectomies in the United States, it will be important for future work to further delineate the role hysterectomy may play in the incidence of pelvic organ prolapse.
We also chose our population because women enrolled in WHI are of the age group most likely to undergo surgical treatment of pelvic organ prolapse.1 Prevalence rates previously described in younger populations may underestimate prolapse in older women. Of interest, in this group of older women, age was not a risk factor for prolapse when defined by pelvic organ prolapse stage II or greater. Counterintuitively, age was protective against prolapse in the multivariable analysis when pelvic organ prolapse was defined by the more stringent leading edge cut point. We were not able to standardize the Valsalva maneuver effort among these women, and it is possible that the oldest women were not able to strain as hard as the younger women, creating a spurious finding of lower degrees of prolapse. Furthermore, all women in this study were older, and the lack of a younger control group precludes conclusions about age itself as a risk factor. Education level was an independent risk factor for pelvic organ prolapse, using either definition of prolapse, after adjusting for other factors. This suggests that lower education level is associated with some unmeasured risk factor, such as socioeconomic status, nutritional status, or a lifetime of work.
Of interest, in our multivariable models, vaginal delivery was only weakly associated with pelvic organ prolapse defined by the staging system and not associated at all with pelvic organ prolapse defined by the leading edge cut point definition. As evidenced by a small study of women examined after their first delivery,11 vaginal delivery results in relatively mild pelvic support defects. It appears that these changes persist into older age in most women. Given that some nulliparous women develop pelvic organ prolapse, it is clear that childbirth is not necessary in the pathway to developing pelvic organ prolapse. Our data suggest that childbirth also is not always sufficient as an etiologic agent and that other factors play a role. It is important to note that risk factors for pelvic organ prolapse likely differ between older and younger women, and our data do not indicate that childbirth is not a risk for pelvic organ prolapse in younger women.
The effect of hormone treatment on pelvic floor support in postmenopausal women is not clearly understood. We found no association between pelvic organ prolapse and conjugated estrogens plus medroxyprogesterone treatment when we compared groups of women randomly assigned to hormone therapy and to placebo. This finding is strengthened by the subjects’ assignment to treatment, eliminating treatment bias (and other biases encountered in observational studies) as an explanation of the results. Additionally, the women in this study had been taking hormone therapy (or placebo) for an average of 6 years (range 4–8 years) before our examinations were performed. We do not have prospective data on hormone use before entering the WHI trial and thus cannot study the effect of earlier hormone use on pelvic organ prolapse. Our sample size was limited to those women participating in the WHI at 1 site. However, a post-hoc power calculation for the association of hormone therapy compared with placebo on pelvic organ prolapse indicates that we had 80% power to detect a difference of 15% or more in the rate of pelvic organ prolapse between the groups (α = .05). This detectable difference would correspond to detectable relative risks of 0.8 or 1.2 (by pelvic organ prolapse stage definition) and 0.6 or 1.5 (by leading edge of prolapse definition) in hormone users for pelvic organ prolapse, depending on the direction of the effect.
Of interest, there is emerging evidence that selective estrogen receptor modulators may impact pelvic floor dysfunction in varying ways. In randomized trials, women receiving raloxifene were less likely to undergo surgery for prolapse during the 3-year study period than those receiving placebo (0.7% versus 1.5%),12 but women receiving levormeloxifene (an investigational drug) had marked increases in urinary incontinence (17% incidence in the study group compared with 4% in the placebo group) and pelvic organ prolapse (7% in the study group versus 2% in the placebo group).13
Increased body mass is associated with urinary incontinence in nearly every epidemiological study that has addressed this association. Researchers have hypothesized that weight, as well as other factors, such as obstructive lung disease or heavy work, promote incontinence by chronically maintaining a high intra-abdominal pressure. However, on multivariable analysis, we found no association between BMI, waist circumference, or smoking and pelvic organ prolapse. Although we found no association between past heavy labor and overall prolapse, we did find that women reporting past heavy labor were more likely to have uterine prolapse than those without this history. However, the number of women reporting past heavy labor was small, and this finding serves only to highlight the possibility that apical prolapse may differ in etiology from anterior or posterior vaginal wall prolapse. It is possible that heavy labor may cause structural weakness in the suspensory support mechanism but not in the levator muscle support mechanism.
Overall, our findings suggest that different factors promote pelvic organ prolapse than urinary incontinence. Few risk factors were identified in our study. A more complete picture of factors associated with pelvic organ prolapse would include not only demographic factors, such as those studied here, but also molecular and genetic ones.
Strengths of our study include using a validated outcome tool to describe vaginal support, including women who were not specifically presenting for gynecologic care and describing prolapse in a detailed manner. Because of the randomized nature of the trial in which our participants were enrolled, we were also able to study the effect of hormone therapy on pelvic organ prolapse. Although the response rate was high, it is possible that the 20% of women that declined an examination differed from those that participated, which may have underestimated or overestimated the prevalence of prolapse.
The older age of our population is both a strength and a limitation. For example, women in this age group are most likely to have surgeries for prolapse and, therefore, by inference, prolapse on examination. However, by including only women in a narrow age range, certain associations cannot be easily studied. For example, we had hypothesized that women that delivered children at an advanced maternal age would be more likely to have prolapse because older women have less muscle mass than younger women. Our population of older women had children at younger ages than today's new mothers, and therefore, too few women were represented in older age groups to definitively study this potential association. Another major limitation of our study is the absence of racial and ethnic diversity. In a prior analysis of all women enrolled in the WHI hormone replacement arm nationwide,4 in which a nonvalidated prolapse examination was performed, African-American women demonstrated the lowest and Hispanic women the highest risk for prolapse compared with Caucasians. Thus, our results are not generalizable to the entire population of U.S. women. Finally, given the cross-sectional nature of this study, we can describe only associations between pelvic organ prolapse and various risk factors but cannot assign causality.
Our findings are similar to most other studies that have used the Pelvic Organ Prolapse Quantification system to evaluate pelvic support in younger women. With the exception of Bland et al,14 most investigators reported stage 0 prolapse in less than half of examined women.11,15 The proportion with prolapse increased as patient age increased and also increased during and after pregnancy. In a study of 497 women presenting for routine care with a mean age of 44 years, Swift16 summarized prolapse stages as follows: stage 0, 6.4%; stage I, 43.3%; stage II, 47.7%; and stage III, 2.6%.
In conclusion, pelvic organ prolapse is common, and some degree of prolapse is normal, especially in older women. A staging system should reflect delineation between normal and abnormal. Our findings, when examined in concert with those of several other recent studies, suggest that a more appropriate definition of the condition of prolapse may be prolapse at or below the hymeneal ring. Future work will address the correlation of symptoms and anatomic findings, which will aid in the effort to define clinically significant prolapse.
1. Boyles SH, Weber AM, Meyn L. Procedures for pelvic organ prolapse in the United States, 1979–1997. Am J Obstet Gynecol 2003;188:108–15.
2. Samuelsson EC, Arne Victor FT, Tibblin G, Svardsudd KF. Signs of genital prolapse in a Swedish population of women 20–59 years of age and possible related factors. Am J Obstet Gynecol 1999;180:299–305.
3. Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity. Am J Obstet Gynecol 2002;186:1160–6.
4. Bump RC, Mattiasson A, Bo K, Brubaker LP, DeLancey JO, Klarskov P, et al. The standardization of terminology of female pelvic organ prolapse and pelvic organ dysfunction. Am J Obstet Gynecol 1996;175:10–7.
5. Hall AF, Theofrastous JP, Cundiff GW, Harris RL, Hamilton LF, Swift SE, et al. Interobserver and intraobserver reliability of the proposed International Continence Society, Society of Gynecologic Surgeons, and American Urogynecologic Society pelvic organ prolapse classification system. Am J Obstet Gynecol 1996;175:1467–9.
6. Weber AM, Abrams P, Brubaker L, Cundiff G, Davis G, Dmochowski RR, et al. The Standardization of terminology for researchers in female pelvic floor disorders. Int Urogynecol J Pelvic Floor Dysfunct 2001;12:178–86.
7. Allard P, Rochette L. The descriptive epidemiology of hysterectomy, Province of Quebec, 1981–1988. Ann Epidemiol 1991;1:541–9.
8. Weaver F, Hynes D, Goldberg JM, Khuri S, Daley J, Henderson W. Hysterectomy in Veterans Affairs Medical Centers. Obstet Gynecol 2001;97:880–4.
9. Farquhar CM, Steinar CA. Hysterectomy rates in the United States 1990–1997. Obstet Gynecol 2002;99:229–34.
10. Mant J, Painter R, Vessey M. Epidemiology of genital prolapse: observations from the Oxford Family Planning Association study. Br J Obstet Gynaecol 1997;104:579–85.
11. O'Boyle AL, Woodman PJ, O'Boyle JD, Davis GD, Swift SE. Pelvic organ support in nulliparous pregnant and nonpregnant women: a case control study [published erratum appears in Am J Obstet Gynecol. 2003;188:301]. Am J Obstet Gynecol 2002;187:99–102.
12. Goldstein SR, Neven P, Zhou L, Taylor YL, Ciaccia AV, Plouffe L. Raloxifene effect on frequency of surgery for pelvic floor relaxation. Obstet Gynecol 2001;98:91–6.
13. Goldstein SR, Nanavati N. Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Am J Obstet Gynecol 2002;187:521–7.
14. Bland DR, Earle BB, Vitolins MZ, Burke G. Use of the pelvic organ prolapse staging system of the International Continence Society, American Urogynecologic Society, and Society of Gynecologic Surgeons in perimenopausal women. Am J Obstet Gynecol 1999;181:1324–8.
15. Sze EH, Sherard GB, Dolezal JM. Pregnancy, labor, delivery, and pelvic organ prolapse. Obstet Gynecol 2002;100:981–6.
16. Swift SE. The distribution of pelvic organ support in a population of female subjects seen for routine gynecologic health care. Am J Obstet Gynecol 2000;183:277–85.
APPENDIX: SHORT LIST OF WHI INVESTIGATORS
Barbara Alving, Jacques Rossouw, and Linda Pottern (National Heart, Lung, and Blood Institute, Bethesda, Maryland)
Clinical Coordinating Center
Ross Prentice, Garnet Anderson, Andrea LaCroix, Ruth E. Patterson, and Anne McTiernan (Fred Hutchinson Cancer Research Center, Seattle, Washington); Sally Shumaker and Pentti Rautaharju (Wake Forest University School of Medicine, Winston-Salem, North Carolina); Evan Stein (Medical Research Labs, Highland Heights, Kentucky); Steven Cummings (University of California at San Francisco, San Francisco, California); John Himes (University of Minnesota, Minneapolis, Minnesota); and Bruce Psaty (University of Washington, Seattle, Washington)
Sylvia Wassertheil-Smoller (Albert Einstein College of Medicine, Bronx, New York); Jennifer Hays (Baylor College of Medicine, Houston, Texas); JoAnn Manson (Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts); Annlouise R. Assaf (Brown University, Providence, Rhode Island); Lawrence Phillips (Emory University, Atlanta, Georgia); Shirley Beresford (Fred Hutchinson Cancer Research Center, Seattle, Washington); Judith Hsia (George Washington University Medical Center, Washington, DC); Rowan Chlebowski (Harbor-UCLA Research and Education Institute, Torrance, California); Cheryl Ritenbaugh (Kaiser Permanente Center for Health Research, Portland, Oregon); Bette Caan (Kaiser Permanente Division of Research, Oakland, California); Jane Morley Kotchen (Medical College of Wisconsin, Milwaukee, Wisconsin); Barbara V. Howard (MedStar Research Institute/Howard University, Washington, DC); Linda Van Horn (Northwestern University, Chicago/Evanston, Illinois); Henry Black (Rush-Presbyterian St. Luke's Medical Center, Chicago, Illinois); Marcia L. Stefanick (Stanford Center for Research in Disease Prevention, Stanford University, Stanford, California); Dorothy Lane (State University of New York at Stony Brook, Stony Brook, New York); Rebecca Jackson (The Ohio State University, Columbus, Ohio); Cora Beth Lewis (University of Alabama at Birmingham, Birmingham, Alabama); Tamsen Bassford (University of Arizona, Tucson/Phoenix, Arizona); Jean Wactawski-Wende (University at Buffalo, Buffalo, New York); John Robbins (University of California at Davis, Sacramento, California); Allan Hubbell (University of California at Irvine, Orange, California); Howard Judd (University of California at Los Angeles, Los Angeles, California); Robert D. Langer (University of California at San Diego, LaJolla/Chula Vista, California); Margery Gass (University of Cincinnati, Cincinnati, Ohio); Marian Limacher (University of Florida, Gainesville/Jacksonville, Florida); David Curb (University of Hawaii, Honolulu, Hawaii); Robert Wallace (University of Iowa, Iowa City/Davenport, IA); Judith Ockene (University of Massachusetts/Fallon Clinic, Worcester, Massachusetts); Norman Lasser (University of Medicine and Dentistry of New Jersey, Newark, New Jersey); Mary Jo O'Sullivan (University of Miami, Miami, Florida); Karen Margolis (University of Minnesota, Minneapolis, Minnesota); Robert Brunner (University of Nevada, Reno, Nevada); Gerardo Heiss (University of North Carolina, Chapel Hill, North Carolina); Lewis Kuller (University of Pittsburgh, Pittsburgh, Pennsylvania); Karen C. Johnson (University of Tennessee, Memphis, Tennessee); Robert Brzyski (University of Texas Health Science Center, San Antonio, Texas); Gloria Sarto (University of Wisconsin, Madison, Wisconsin); Denise Bonds (Wake Forest University School of Medicine, Winston-Salem, North Carolina); and Susan Hendrix (Wayne State University School of Medicine/Hutzel Hospital, Detroit, Michigan)
Former WHI Investigators
Catherine Allen (deceased, University of Wisconsin, Madison, Wisconsin); Gregory Burke (Wake Forest University School of Medicine, Winston-Salem, North Carolina); Sandy Dougherty (deceased, University of Nevada, Reno, Nevada); and Richard Carleton (deceased, Brown University, Providence, Rhode Island).