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Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN

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Abstract

We tested the hypothesis that higher serum osteocalcin and urinary N-telopeptide of type I collagen (NTx) concentrations would be found in women with increasing cycle irregularity or increased follicle stimulating hormone concentrations. We studied 2,375 pre- and early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), aged 42–52 years, who self-identified their race/ethnic origin as African-American (28.3%), Caucasian (49.4%), Japanese (10.5%) or Chinese (11.8%). Outcome measures were serum osteocalcin, a measure of bone formation, and NTx, a measure of bone resorption. The explanatory variables were menopausal status, based on self-reported regularity of menstrual bleeding, and circulating endogenous hormone concentrations including estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) concentrations. Additionally, we evaluated the association of the bone turnover markers with the Free Androgen Index (FAI) and the Free Estradiol Index (FEI), ratios of total testosterone and estradiol concentrations to SHBG, respectively. Higher FSH concentrations were associated with higher NTx concentrations (β=0.003, partial r 2=2.1%, p<0.0001), both before and after adjusting for other covariates (total explained variability of 9%). Higher FSH concentrations were also associated with higher osteocalcin concentrations (β=−0.216, partial r 2=4.1%, p<0.0001, total explained variability of 15.4%). There were no significant associations of the bone turnover markers with other endogenous hormones, following adjustment for covariates. Mean osteocalcin and NTx values were not significantly different in premenopausal women compared to early perimenopausal women. In these pre- and early perimenopausal women, higher FSH concentrations, but not other serum reproductive hormone concentrations, are positively associated with greater bone turnover prior to the last menstrual period.

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Acknowledgements

The Study of Women's Health Across the Nation (SWAN) was funded by the National Institute on Aging, the National Institute of Nursing Research and the Office of Research on Women's Health of the National Institutes of Health. Supplemental funding from National Institute of Mental Health, the National Institute on Child Health and Human Development, the National Center on Complementary and Alternative Medicine, the Office of Minority Health, and the Office of AIDS Research is also gratefully acknowledged. The assays for bone turnover markers were funded by DOD 96-C6118. We thank the study staff at each site and all the women who participated in SWAN.

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Authors and Affiliations

  1. Rm 2624, SPH-1, Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory Street, Ann Arbor, MI 48109-2029, USA

    M. R. Sowers & I. Bondarenko

  2. Division of Geriatrics, UCLA School of Medicine, Los Angeles, CA 90095, USA

    G. A. Greendale

  3. Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA

    J. S. Finkelstein & R. M. Neer

  4. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA

    J. A. Cauley

  5. Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94611, USA

    B. Ettinger

Authors
  1. M. R. Sowers
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  2. G. A. Greendale
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  3. I. Bondarenko
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  4. J. S. Finkelstein
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  5. J. A. Cauley
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  6. R. M. Neer
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  7. B. Ettinger
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Corresponding author

Correspondence to M. R. Sowers.

Appendix. SWAN

Appendix. SWAN

Clinical Centers

University of Michigan, Ann Arbor, MI (U01 NR04061, MaryFran Sowers, PI); Massachusetts General Hospital, Boston, MA (U01 AG12531, Joel S. Finkelstein, PI); University of California/Kaiser, Davis, CA (U01 AG12554, Ellen Gold, PI); University of California, Los Angeles, CA (U01 AG12539, Gail Greendale PI); and the University of Pittsburgh, Pittsburgh, PA (U01 AG12546, Karen Matthews, PI).

Laboratory

University of Michigan, Ann Arbor, MI (U01 AG12495, Daniel McConnell, PI) and Medical Research Laboratories (MRL), Highland Heights, KY (subcontract of U01 AG12553, Evan Stein, Director).

Coordinating Center

University of Pittsburgh (Kim Sutton-Tyrrell, PI).

Project Officers

Taylor Harden, Carole Hudgings, Marcia Ory, Sherry Sherman.

Steering Committee Chair

Jennifer L. Kelsey.

The manuscript was reviewed by the Publications and Presentations Committee of SWAN and has its endorsement.

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Sowers, M.R., Greendale, G.A., Bondarenko, I. et al. Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN. Osteoporos Int 14, 191–197 (2003). https://doi.org/10.1007/s00198-002-1329-4

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  • DOI: https://doi.org/10.1007/s00198-002-1329-4

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