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Hormones and Cancer

, Volume 7, Issue 3, pp 178–187 | Cite as

Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study

  • Tess V. Clendenen
  • Kathryn Hertzmark
  • Karen L. Koenig
  • Eva Lundin
  • Sabina Rinaldi
  • Theron Johnson
  • Vittorio Krogh
  • Göran Hallmans
  • Annika Idahl
  • Annekatrin Lukanova
  • Anne Zeleniuch-JacquotteEmail author
Original Paper

Abstract

Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case–control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1 = 1.59, 95 % CI = 0.96, 2.64, p = 0.08) and free testosterone (ORT3-T1 = 1.76, 95 % CI = 1.01, 3.07, p = 0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n = 51 cases; ≥55 years, n = 110 cases). Among women who were ≥55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95 % CI = 1.25, 3.44, p = 0.005) for a doubling in testosterone and 1.55 (95 % CI = 1.04, 2.31, p = 0.049) for a doubling in free testosterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged ≥55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted.

Keywords

Testosterone Androgen Endometrial Cancer Blood Donation Androstenedione 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This work was supported by the National Cancer Institute (R01 CA081212, R01 CA098661, P30 CA016087 and UM1 CA182934) and the National Institute of Environmental Health Sciences (Center grant ES000260).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12672_2016_258_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 17 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Tess V. Clendenen
    • 1
  • Kathryn Hertzmark
    • 2
  • Karen L. Koenig
    • 1
  • Eva Lundin
    • 3
  • Sabina Rinaldi
    • 4
  • Theron Johnson
    • 5
  • Vittorio Krogh
    • 6
  • Göran Hallmans
    • 7
  • Annika Idahl
    • 8
  • Annekatrin Lukanova
    • 5
  • Anne Zeleniuch-Jacquotte
    • 1
    • 9
    Email author
  1. 1.Department of Population Health, Division of Epidemiology and BiostatisticsNew York University School of MedicineNew YorkUSA
  2. 2.Department of Environmental Medicine, Division of Epidemiology and BiostatisticsNew York University School of MedicineNew YorkUSA
  3. 3.Department of Medical Biosciences, PathologyUmeå UniversityUmeåSweden
  4. 4.International Agency for Research on CancerLyonFrance
  5. 5.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)HeidelbergGermany
  6. 6.Epidemiology and Prevention UnitFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  7. 7.Department of Public Health and Clinical Medicine/Nutritional Research and Department of Biobank ResearchUmeå UniversityUmeåSweden
  8. 8.Department of Clinical Sciences, Obstetrics and GynecologyUmeå UniversityUmeåSweden
  9. 9.New York University Cancer InstituteNew YorkUSA

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