This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Santoro, N. Articles by Weiss, G. Search for Related Content PubMed PubMed Citation Articles by Santoro, N. Articles by Weiss, G.

Body Size and Ethnicity Are Associated with Menstrual Cycle Alterations in Women in the Early Menopausal Transition: The Study of Women’s Health across the Nation (SWAN) Daily Hormone Study

Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Women’s Health (N.S.), Albert Einstein College of Medicine, New York, New York 10461; University of Medicine and Dentistry of New Jersey-New Jersey Medical School (N.S., G.W.), Newark, New Jersey 07103; Department of Population Health and Reproductive Medical Sciences (B.L.) and Epidemiology and Preventive Medicine (E.B.G.), University of California at Davis, and Kaiser Permanente, Davis, California 95616; Central Ligand Assay Satellite Services (D.M., R.M.) and Department of Epidemiology (M.F.S.), University of Michigan, Ann Arbor, Michigan 48109; Department of Community Health (J.A., S.C.), Brown University, Providence, Rhode Island 02912; New England Research Institutes (J.A., S.C.), Watertown, Massachusetts 02472; Division of Preventive and Behavioral Medicine, Department of Medicine (S.C., J.K.), University of Massachusetts Medical Center, Worcester, Massachusetts 02155; Endocrine Unit, Department of Medicine (J.S.F.), Massachusetts General Hospital, Boston, Massachusetts 02114; Departments of Epidemiology (G.A.G., M.S.) and Medicine (S.K.), Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California 90095; Division of Epidemiology, Department of Health Research and Policy (J.K.), Stanford University School of Medicine, Stanford, California 94305-5405; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility (J.L.L.) and Epidemiology (L.P.), Rush Presbyterian-St. Luke’s Medical Center, Chicago, Illinois 60612; and Department of Psychiatry (K.M.) and Epidemiology and Data Coordinating Center (J.S.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Address all correspondence and requests for reprints to: Nanette Santoro, M.D., Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Mazer 316, Bronx, New York 10461. E-mail: glicktoro{at}aol.com.

The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women.

The Study of Women’s Health across the Nation (SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42–52 yr at baseline. All participants are seen annually to assess a variety of endpoints. A subcohort of 848 women undergoes further investigation of their daily patterns of reproductive hormones in the Daily Hormone Study (DHS). DHS enrollees annually complete a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 d (whichever comes first). Chemiluminescent assays measured urinary LH and FSH, as well as metabolites of estradiol [estrone conjugates (E1c)] and progesterone [pregnanediol glucuronide (Pdg)]. Cycles were assessed for evidence of luteal activity and day of luteal transition using previously developed algorithms. Midreproductive-aged women who underwent similar daily urinary analyses served as historical controls. Correlates of cycle features were identified.

Eight hundred thirty-three cycles were evaluable and had complete data on covariates. Six hundred seventy-four (80.9%) cycles had evidence of luteal activity, and 159 (19.1%) did not. Women who were at least 49 yr old were less likely to have cycles with luteal activity and had more variable cycle length, higher total-cycle FSH, and lower total-cycle Pdg. Compared with heavier women, those with body mass index less than 25 kg/m² had shorter cycles and higher total-cycle LH, FSH, and Pdg but not E1c. Chinese- and Japanese-American women had overall lower adjusted total-cycle E1c excretion. Smoking was not significantly associated with cycle length or hormones. When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition.

In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve.

The Study of Women’s Health across the Nation (SWAN) was funded by the National Institute on Aging (Grants 12535 to G.W., 12554 to E.B.G., 12495 to D.M., 12531 to J.S.F., 12539 to G.A.G., 12505 to L.P., and 12546 to K.M.); the National Institute of Nursing Research Grants U01 NR04061 (to M.F.S.); and the Office of Research on Women’s Health of the National Institutes of Health. Supplemental funding from the National Institute of Mental Health, the National Institute on Child Health and Human Development (Grants 02759 to J.S.F. and 41978 to N.S.), the National Center on Complementary and Alternative Medicine, the Office of Minority Health, and the Office of AIDS Research is also gratefully acknowledged.

Project Officers: Taylor Harden, Carole Hudgings, Marcia Ory, and Sheryl Sherman. Steering Committee Chair: Jennifer L. Kelsey, Ph.D., and Susan Johnson, M.D.

Abbreviations: BMI, Body mass index; Cr, creatinine; DHS, Daily Hormone Study; DLT, day of luteal transition; E1c, estrone conjugates; ELA, evidence of luteal activity; Pdg, pregnanediol glucuronide; SWAN, Study of Women’s Health across the Nation.

This article has been cited by other articles:

				H. Kang, S. K. Lee, M.-H. Kim, J. Song, S. J. Bae, N. K. Kim, S.-H. Lee, and K. Kwack Parathyroid hormone-responsive B1 gene is associated with premature ovarian failure Hum. Reprod., June 1, 2008; 23(6): 1457 - 1465. [Abstract] [Full Text] [PDF]

				S. C. Kent, C. L. Gnatuk, A. R. Kunselman, L. M. Demers, P. A. Lee, and R. S. Legro Hyperandrogenism and Hyperinsulinism in Children of Women with Polycystic Ovary Syndrome: A Controlled Study J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1662 - 1669. [Abstract] [Full Text] [PDF]

				N. Santoro, S. L. Crawford, W. L. Lasley, J. L. Luborsky, K. A. Matthews, D. McConnell, J. F. Randolph Jr., E. B. Gold, G. A. Greendale, S. G. Korenman, et al. Factors Related to Declining Luteal Function in Women during the Menopausal Transition J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1711 - 1721. [Abstract] [Full Text] [PDF]

				E. B. Gold, B. Lasley, S. L. Crawford, D. McConnell, H. Joffe, and G. A. Greendale Relation of Daily Urinary Hormone Patterns to Vasomotor Symptoms in a Racially/Ethnically Diverse Sample of Midlife Women: Study of Women's Health Across the Nation Reproductive Sciences, December 1, 2007; 14(8): 786 - 797. [Abstract] [PDF]

				G. E. Hale, X. Zhao, C. L. Hughes, H. G. Burger, D. M. Robertson, and I. S. Fraser Endocrine Features of Menstrual Cycles in Middle and Late Reproductive Age and the Menopausal Transition Classified According to the Staging of Reproductive Aging Workshop (STRAW) Staging System J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3060 - 3067. [Abstract] [Full Text] [PDF]

				A. Jain, A. J. Polotsky, D. Rochester, S. L. Berga, T. Loucks, G. Zeitlian, K. Gibbs, H. N. Polotsky, S. Feng, B. Isaac, et al. Pulsatile Luteinizing Hormone Amplitude and Progesterone Metabolite Excretion Are Reduced in Obese Women J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2468 - 2473. [Abstract] [Full Text] [PDF]

				A. H. Eliassen, S. A. Missmer, S. S. Tworoger, D. Spiegelman, R. L. Barbieri, M. Dowsett, and S. E. Hankinson Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst, October 4, 2006; 98(19): 1406 - 1415. [Abstract] [Full Text] [PDF]

				J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]

				K.A. O'Connor, E. Brindle, R.C. Miller, J.B. Shofer, R.J. Ferrell, N.A. Klein, M.R. Soules, D.J. Holman, P.K. Mansfield, and J.W. Wood Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method Hum. Reprod., June 1, 2006; 21(6): 1442 - 1452. [Abstract] [Full Text] [PDF]

				K. A. Matthews, N. Santoro, B. Lasley, Y. Chang, S. Crawford, R. C. Pasternak, K. Sutton-Tyrrell, and M. Sowers Relation of Cardiovascular Risk Factors in Women Approaching Menopause to Menstrual Cycle Characteristics and Reproductive Hormones in the Follicular and Luteal Phases J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1789 - 1795. [Abstract] [Full Text] [PDF]

				G. M. Lambert-Messerlian and B. L. Harlow The Influence of Depression, Body Mass Index, and Smoking on Serum Inhibin B Levels in Late Reproductive-Aged Women J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1496 - 1500. [Abstract] [Full Text] [PDF]

				H. M. Kravitz, I. Janssen, N. Santoro, J. T. Bromberger, M. Schocken, S. A. Everson-Rose, K. Karavolos, and L. H. Powell Relationship of Day-to-day Reproductive Hormone Levels to Sleep in Midlife Women Arch Intern Med, November 14, 2005; 165(20): 2370 - 2376. [Abstract] [Full Text] [PDF]

				M. K. Melby, M. Lock, and P. Kaufert Culture and symptom reporting at menopause Hum. Reprod. Update, September 1, 2005; 11(5): 495 - 512. [Abstract] [Full Text] [PDF]

				G. Weiss, J. H. Skurnick, L. T. Goldsmith, N. F. Santoro, and S. J. Park Menopause and Hypothalamic-Pituitary Sensitivity to Estrogen JAMA, December 22, 2004; 292(24): 2991 - 2996. [Abstract] [Full Text] [PDF]