Skip Navigation


American Journal of Epidemiology Advance Access originally published online on November 3, 2007
American Journal of Epidemiology 2008 167(2):211-218; doi:10.1093/aje/kwm278
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
167/2/211    most recent
kwm278v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tworoger, S. S.
Right arrow Articles by Hankinson, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tworoger, S. S.
Right arrow Articles by Hankinson, S. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Plasma Androgen Concentrations and Risk of Incident Ovarian Cancer

Shelley S. Tworoger1,2, I-Min Lee2,3, Julie E. Buring2,3 and Susan E. Hankinson1,2

1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
2 Department of Epidemiology, Harvard School of Public Health, Boston, MA
3 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Correspondence to Dr. Shelley S. Tworoger, Channing Laboratory, 181 Longwood Avenue, 3rd Floor, Boston, MA 02115 (e-mail: nhsst{at}channing.harvard.edu).

Received for publication May 29, 2007. Accepted for publication August 27, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Androgens have been implicated in increasing ovarian cancer risk; however, results from prospective studies have been inconclusive. The authors examined whether plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were associated with risk of epithelial ovarian cancer in a nested-case control study, using data from three prospective cohort studies: the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Women's Health Study (WHS). The present analysis comprised 224 cases (161 from the NHS/NHSII and 63 from the WHS) and 603 controls (matched at a ratio of 1:3 for the NHS/NHSII and 1:2 for the WHS), with follow-up of up to 14 years. Women ranged in age from 34 years to 72 years (mean age = 56 years). The authors did not observe any associations between plasma androgen levels and risk of ovarian cancer. For example, comparing the top quartile with the bottom quartile, the relative risk was 0.74 (95% confidence interval: 0.44, 1.25; p-trend = 0.34) for testosterone and 0.76 (95% confidence interval: 0.45, 1.30; p-trend = 0.65) for androstenedione. There was a suggestion that dehydroepiandrosterone and dehydroepiandrosterone sulfate were inversely associated with ovarian cancer risk among postmenopausal women (for top quartile vs. bottom, relative risks were 0.65 and 0.70, respectively). Overall, these results do not support a positive association between circulating androgen levels and ovarian cancer risk.

androgens; androstenedione; dehydroepiandrosterone; dehydroepiandrosterone sulfate; ovarian neoplasms; prospective studies; testosterone

Abbreviations: CI, confidence interval; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; EDTA, ethylenediaminetetraacetic acid; NHS, Nurses' Health Study; NHSII, Nurses' Health Study II; WHS, Women's Health Study


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Androgens of adrenal and ovarian origin are hypothesized to increase risk of ovarian cancer (1, 2). Experimental studies suggest that testosterone can increase ovarian cancer cell proliferation (3–6); other androgens may indirectly affect risk via conversion to testosterone (7) or have direct effects on proliferation (8, 9). Because of the paucity of prospective studies with blood samples (1), only recently have epidemiologic data become available regarding this hypothesis. Three prospective studies (comprising 31–192 cases) have examined the relation between circulating androgen levels and ovarian cancer risk, with inconclusive results (10–12). In general, no association was observed for dehydroepiandrosterone sulfate (DHEAS) or testosterone (11, 12), while a potential positive association was observed for androstenedione among either all women (10) or premenopausal women (11). However, these studies included only 355 cases combined (113 premenopausal women and 242 postmenopausal women). Given the potential importance of this pathway, we examined whether plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA), and DHEAS were associated with ovarian cancer risk in a prospective, nested case-control study conducted among women from three cohort studies: the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Women's Health Study (WHS).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Study population
The Nurses' Health Studies.
The NHS began in 1976 among 121,700 US female registered nurses aged 30–55 years, and the NHSII began in 1989 among 116,609 US female registered nurses aged 25–42 years. All women completed an initial questionnaire and have been followed biennially since.

In 1989–1990, 32,826 NHS participants (aged 43–69 years) provided blood samples and completed a short questionnaire (13); follow-up was 98 percent in 2004. Between 1996 and 1999, 29,611 NHSII participants (aged 32–54 years) provided blood samples and completed a short questionnaire (14); follow-up was 98 percent in 2003.

Overall, 161 confirmed cases of epithelial ovarian cancer or peritoneal cancer (NHS: 141, NHSII: 20) were diagnosed after blood collection and before June 1, 2004 (NHS) or June 1, 2003 (NHSII) (15). Mean time from blood drawing to diagnosis was 80 months (range, 1–174 months). Each case was matched to three controls, who had intact ovaries at the time of the case's diagnosis, on menopausal status at baseline and diagnosis, age, month of blood collection, time of day of blood drawing, fasting status, luteal day of blood collection (NHSII only), and use of postmenopausal hormones at blood drawing.

The Women's Health Study.
The WHS is a completed randomized trial that examined low-dose aspirin and vitamin E supplementation for the primary prevention of cancer and cardiovascular disease (16–18). Beginning in 1992, 39,876 US female professionals aged ≥45 years were enrolled in the trial and completed a baseline questionnaire. Blood samples were collected in ethylenediaminetetraacetic acid (EDTA) and citrate tubes from 28,345 women before randomization (15). This study included women from the treatment and placebo groups (neither treatment was associated with cancer risk (16, 17)); morbidity and mortality follow-up were 97 percent and 99 percent complete, respectively, in 2004.

Confirmed cases (n = 63) were women diagnosed with invasive epithelial ovarian cancer after blood collection and before December 1, 2004. Mean time from blood drawing to diagnosis was 54 months (range, 6–120 months). Each case was matched to two controls, who had intact ovaries at the time of the case's diagnosis (except for four cases for whom only one control was identified), on menopausal status and use of postmenopausal hormones at baseline and diagnosis, age, month of blood collection, time since randomization, and fasting status.

This study was approved by the Committee on the Use of Human Subjects in Research at the Brigham and Women's Hospital (Boston, Massachusetts).

Menopausal status.
We considered a woman to be premenopausal if 1) her natural menstrual periods had not ceased or 2) she had undergone a hysterectomy with at least one ovary remaining and was ≤47 (nonsmokers) or ≤45 (smokers) years of age (NHS/NHSII) or ≤50 years of age (WHS) (19). We considered a woman to be postmenopausal if 1) her natural menstrual periods had ceased permanently or 2) she had undergone a hysterectomy with at least one ovary remaining and was ≥56 (nonsmokers) or ≥54 (smokers) years of age (NHS/NHSII) or ≥60 years of age (WHS). The remaining women, most of whom had undergone a simple hysterectomy, were considered to have an unknown menopausal status.

Laboratory assays
Testosterone and androstenedione levels were assayed in heparin (NHS/NHSII) or EDTA (WHS) plasma by liquid chromatography/mass spectrometry at Quest Diagnostics (San Juan Capistrano, California). DHEA was assayed by radioimmunoassay (Diagnostic Systems Laboratories, Webster, Texas) and DHEAS by chemiluminescent immunoassay using the Immulite autoanalyzer (Diagnostic Products Corporation, Llanberis, United Kingdom) in heparin (NHS/NHSII) or citrate plasma (WHS). Samples collected in citrate tend to have lower values due to dilution by the preservative (20). The stability of these hormones in whole blood not processed for 24–48 hours has been shown previously (21). Case-control sets and samples from the same study were assayed together, ordered randomly, and labeled to mask case-control and quality-control status. The average intraassay coefficient of variation from blinded, replicate, quality-control samples was 9.4 for androstenedione, 9.7 for DHEA, and 3.8 percent for DHEAS. For one batch of testosterone, containing 32 cases and 94 matched controls, the coefficient of variation was 40 percent; therefore, these participants were excluded from analyses of testosterone. The average coefficient of variation of the other three batches was 13.3 percent.

Statistical analysis
Only seven outliers (22) were detected and removed: for the NHS, testosterone level >208 ng/dl (n = 1) and DHEA level <0.1 ng/ml (n = 1); for the NHSII, DHEA level <0.8 ng/ml (n = 2) and DHEAS level <10 µg/ml (n = 3). We had 224 cases (11 peritoneal cancer and 213 epithelial ovarian cancer) and 603 controls for the analysis. Relative risks and 95 percent confidence intervals were determined using conditional logistic regression comparing quartiles of hormone concentrations (23). Quartile cutpoints were based on the control distribution within each study to account for differences in sample type between studies and different age ranges, since levels of some androgens decline with age (7, 24, 25). In the primary analyses, we combined premenopausal and postmenopausal women, since androgen levels are more strongly associated with age than with menopausal status (7, 24, 25).

To account for potentially differing sample types between studies, we used continuous probit scores to determine the p value for trend (26). We adjusted for a priori potential confounders, including ever use of postmenopausal hormones, parity, duration of oral contraceptive use, simple hysterectomy, tubal ligation, age at menarche, and family history of ovarian cancer. Other potential confounders, including body mass index (weight (kg)/height (m)2), age at menopause, and physical activity, did not substantially alter the results and were not included in the final models.

In secondary analyses, we excluded cases diagnosed within 2 or 4 years of blood collection and evaluated associations among epithelial ovarian, invasive, and serous cancer cases. We stratified results by age at diagnosis (<55 years vs. ≥55 years), menopausal status at blood drawing or diagnosis (premenopausal vs. postmenopausal), body mass index (<25 vs. ≥25), and use of postmenopausal hormones (among postmenopausal women; never/past use vs. current use). We employed the p value for heterogeneity to compare the slopes from the continuous probit hormone score for each stratum, using a Wald test. These analyses used unconditional logistic regression adjusting for matching factors, including age at blood drawing, fasting status, time of blood drawing, month of blood drawing, menopausal status at blood drawing and diagnosis, and study.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
At blood collection, women in the NHS/NHSII ranged in age from 34 years to 69 years (mean = 56 years) and women in the WHS ranged in age from 45 years to 72 years (mean = 56 years) (table 1). In general, characteristics of the participants were similar between the studies. Median androgen levels did not differ between cases and controls within either the NHS/NHSII or the WHS (for all hormones, p-difference ≥ 0.08).


View this table:
[in this window]
[in a new window]

  		TABLE 1. Characteristics (mean, median, or %) at blood collection of cases and matched controls from the Nurses' Health Studies and the Women's Health Study

 
We did not observe any associations between plasma androgen levels and risk of ovarian cancer (table 2). The adjusted relative risk comparing the top quartile with the bottom quartile was 0.74 (95 percent confidence interval (CI): 0.44, 1.25; p-trend = 0.34) for testosterone, 0.76 (95 percent CI: 0.45, 1.30; p-trend = 0.65) for androstenedione, 0.72 (95 percent CI: 0.44, 1.19; p-trend = 0.28) for DHEA, and 0.79 (95 percent CI: 0.47, 1.33; p-trend = 0.32) for DHEAS. There was no significant heterogeneity between studies (p ≥ 0.11). With one exception, results were similar when we excluded cases diagnosed within 2 or 4 years of blood collection or when we examined only epithelial ovarian, invasive, or serous cancer cases (data not shown); for DHEA, we observed a significant inverse trend (p-trend = 0.05) after excluding cases diagnosed within 2 years of blood collection.


View this table:
[in this window]
[in a new window]

  		TABLE 2. Relative risk of ovarian cancer by quartile of plasma androgen concentrations among women in the Nurses' Health Studies and the Women's Health Study

 
We observed some nearly statistically significant interactions of DHEA and DHEAS levels with age at diagnosis/reference date and menopausal status at blood collection (table 3). Specifically, there was little or no association between DHEA or DHEAS levels and ovarian cancer risk among women diagnosed before age 55 years or women who were premenopausal at blood collection. However, levels of both appeared inversely associated with risk among women who were diagnosed at age ≥55 years or were postmenopausal at blood collection. Among women diagnosed at age ≥55 years, the relative risk for the top quartile of DHEA compared with the bottom quartile was 0.58 (95 percent CI: 0.34, 1.01; p-trend = 0.07); the comparable relative risk for postmenopausal women was 0.65 (95 percent CI: 0.36, 1.19; p-trend = 0.04). We did not observe other interactions for the hormones studied (data not shown).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Relative risk* of ovarian cancer by age at diagnosis and menopausal status at baseline, according to plasma androgen concentrations, among women from the Nurses' Health Studies and the Women's Health Study

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
In a large prospective, nested case-control study, we did not observe associations between circulating androgen levels and risk of ovarian cancer. There was a suggestive inverse association between DHEA or DHEAS and ovarian cancer risk, particularly among older women; however, given the limited sample size in this subgroup, these results should be interpreted with caution. We also did not observe any associations when excluding women diagnosed either 2 or 4 years after blood collection, thus minimizing the possibility that levels could be influenced by subclinical disease.

Overall, there are no clear patterns of association between various androgens and ovarian cancer risk across the four prospective studies published to date (table 4). No investigators observed an association with testosterone in premenopausal or postmenopausal women or overall (10–12). In two smaller studies, a suggestive increased risk with higher levels of androstenedione was reported (10, 11); however, Lukanova et al. (11) observed this association only in premenopausal women (44 cases). Results are inconsistent for DHEAS, with a suggestive positive association being observed by Helzlsouer et al. (10) but a potentially inverse association being observed in our study.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Results from prospective nested case-control studies published to date examining the relation between androgens and risk of ovarian cancer

 
Experimental evidence supports a role of androgens in ovarian cancer etiology, through increasing cell proliferation (3–6, 8, 9). It is possible that studies of circulating androgen levels have not observed clear associations because they do not adequately reflect exposure at the tissue level. Ovarian epithelium has limited vasculature, and therefore paracrine sources of androgens may be more important than endocrine sources (1, 3). For example, DHEAS, which is completely derived from the adrenal glands (1, 3), has not shown a clear association in any prospective studies to date (10–12), including our own. Androstenedione, which is approximately 50 percent ovary-derived (1, 3), was associated with an increased risk in two of four studies (10–12 and the current study). However, it will be necessary to carry out larger studies and combine the existing published data before these relations can be completely understood.

Our study had several limitations. First, the NHS/NHSII and the WHS collected different types of blood samples (heparin vs. EDTA/citrate); however, we used study-specific cutpoints to reduce the influence of this issue. Second, we had only one blood sample per person, and a single blood sample may not reflect exposure over 14 years of follow-up. However, the intraclass correlation over 3 years for these androgens ranged from 0.56 to 0.94 in premenopausal women (27) and from 0.66 to 0.88 in postmenopausal women (28), suggesting that one sample is representative of longer-term levels. Third, we were only able to match on day of the luteal phase at blood collection for NHSII women (~30 percent of premenopausal participants). However, androgen levels do not vary substantially by menstrual phase (7, 24, 25), and in the one study that did match on this factor (12), no association was observed.

Strengths of this study include its long follow-up period, with blood samples being collected prior to disease diagnosis. We identified 224 cases, thus increasing the total number of prospectively collected cases in published studies by approximately 50 percent.

In conclusion, our study, in conjunction with existing prospective epidemiologic studies (with a total of approximately 580 ovarian cancer cases worldwide), does not support the hypothesis that circulating androgen concentrations are a risk factor for ovarian cancer in premenopausal or postmenopausal women. Current data suggest that there are no overall associations between circulating androgen levels and risk of ovarian cancer; however, associations in some subgroups warrant additional evaluation.


   ACKNOWLEDGMENTS
 
Financial support for this project was obtained from National Institutes of Health grants P01 CA87969, R01 CA49449, R01 CA67262, R01 CA50385, P50 CA105009, HL43851, and CA47988.

The authors thank Marilyn Chown and Jeanne Sparrow for data management support.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Lukanova A, Kaaks R. Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev (2005) 14:98–107.[Abstract/Free Full Text]
  2. Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst (1998) 90:1774–86.[Abstract/Free Full Text]
  3. Godwin AK, Perez RP, Johnson SW, et al. Growth regulation of ovarian cancer. Hematol Oncol Clin North Am (1992) 6:829–41.[Web of Science][Medline]
  4. Sawada M, Terada N, Wada A, et al. Estrogen- and androgen-responsive growth of human ovarian adenocarcinoma heterotransplanted into nude mice. Int J Cancer (1990) 45:359–63.[CrossRef][Web of Science][Medline]
  5. Ahonen MH, Zhuang YH, Aine R, et al. Androgen receptor and vitamin D receptor in human ovarian cancer: growth stimulation and inhibition by ligands. Int J Cancer (2000) 86:40–6.[CrossRef][Web of Science][Medline]
  6. Syed V, Ulinski G, Mok SC, et al. Expression of gonadotropin receptor and growth responses to key reproductive hormones in normal and malignant human ovarian surface epithelial cells. Cancer Res (2001) 61:6768–76.[Abstract/Free Full Text]
  7. Strauss JF, Barbieri RL. Yen and Jaffe's reproductive endocrinology. (2004) Philadelphia, PA: Elsevier/WB Saunders Company.
  8. Parshad RK, Batth BK. Cystogenesis of antral follicles induced by dehydroepiandrosterone (DHEA) stimulates mast cell proliferation and maturation in the house rat (Rattus rattus) ovary. Indian J Exp Biol (1999) 37:933–5.[Medline]
  9. Anderson E, Lee GY, O'Brien K. Polycystic ovarian condition in the dehydroepiandrosterone-treated rat model: hyperandrogenism and the resumption of meiosis are major initial events associated with cystogenesis of antral follicles. Anat Rec (1997) 249:44–53.[CrossRef][Medline]
  10. Helzlsouer KJ, Alberg AJ, Gordon GB, et al. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA (1995) 274:1926–30.[Abstract/Free Full Text]
  11. Lukanova A, Lundin E, Akhmedkhanov A, et al. Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer (2003) 104:636–42.[CrossRef][Web of Science][Medline]
  12. Rinaldi S, Dossus L, Lukanova A, et al. Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Epidemiol Biomarkers Prev (2007) 16:23–9.[Abstract/Free Full Text]
  13. Hankinson SE, Willett WC, Manson JE, et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst (1998) 90:1292–9.[Abstract/Free Full Text]
  14. Tworoger SS, Sluss P, Hankinson SE. Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res (2006) 66:2476–82.[Abstract/Free Full Text]
  15. Tworoger SS, Lee IM, Buring J, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev (2007) 16:783–8.[Abstract/Free Full Text]
  16. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer. The Women's Health Study: a randomized controlled trial. JAMA (2005) 294:47–55.[Abstract/Free Full Text]
  17. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. The Women's Health Study: a randomized controlled trial. JAMA (2005) 294:56–65.[Abstract/Free Full Text]
  18. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med (2005) 352:1293–304.[Abstract/Free Full Text]
  19. Hankinson SE, Willett WC, Michaud DS, et al. Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst (1999) 91:629–34.[Abstract/Free Full Text]
  20. Palmer-Toy DE, Szczepiorkowski ZM, Shih V, et al. Compatibility of the Abbott IMx homocysteine assay with citrate-anticoagulated plasma and stability of homocysteine in citrated whole blood. Clin Chem (2001) 47:1704–7.[Free Full Text]
  21. Hankinson SE, London SJ, Chute CG, et al. Effect of transport conditions on the stability of biochemical markers in blood. Clin Chem (1989) 35:2313–16.[Abstract/Free Full Text]
  22. Rosner B. Percentage points for a generalized ESD many-outlier procedure. Technometrics (1983) 25:165–72.[CrossRef][Web of Science]
  23. Rosner B. Fundamentals of biostatistics. (1993) Belmont, CA: Wadsworth Publishing Company.
  24. Longcope C, Franz C, Morello C, et al. Steroid and gonadotropin levels in women during the peri-menopausal years. Maturitas (1986) 8:189–96.[CrossRef][Web of Science][Medline]
  25. Rannevik G, Jeppsson S, Johnell O, et al. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density. Maturitas (1995) 21:103–13.[CrossRef][Web of Science][Medline]
  26. Hosmer DW, Lemeshow S. Applied logistic regression. (1989) New York, NY: John Wiley and Sons, Inc.
  27. Missmer SA, Spiegelman D, Bertone-Johnson ER, et al. Reproducibility of plasma steroid hormones, prolactin, and insulin-like growth factor levels among premenopausal women over a 2- to 3-year period. Cancer Epidemiol Biomarkers Prev (2006) 15:972–8.[Abstract/Free Full Text]
  28. Hankinson SE, Manson JE, Spiegelman D, et al. Reproducibility of plasma hormone levels in postmenopausal women over a 2–3-year period. Cancer Epidemiol Biomarkers Prev (1995) 4:649–54.[Abstract]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
167/2/211    most recent
kwm278v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tworoger, S. S.
Right arrow Articles by Hankinson, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tworoger, S. S.
Right arrow Articles by Hankinson, S. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?