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Change in Estradiol and Follicle-Stimulating Hormone across the Early Menopausal Transition: Effects of Ethnicity and Age

Department of Obstetrics and Gynecology, School of Medicine (J.F.R.), and Departments of Epidemiology (MF.S., I.V.B., S.D.H.) and Biostatistics (R.J.L.), School of Public Health, University of Michigan, Ann Arbor, Michigan 48109; and Department of Obstetrics and Gynecology (J.L.L.), Rush University Medical Center, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: John F. Randolph, Jr., M.D., L4228 Women’s Hospital, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0276. E-mail: jfrandol{at}med.umich.edu.

Serum reproductive hormone concentrations were measured longitudinally in a community-based, multiethnic population of midlife women to assess whether ethnic differences exist in the patterns of change in estradiol (E2) and FSH and, if so, whether these differences are explained by host characteristics. We studied 3257 participants from seven clinical sites in the Study of Women’s Health Across the Nation (SWAN) who were aged 42–52 yr at baseline and self-identified as African American (28.2%), Caucasian (47.1%), Chinese (7.7%), Hispanic (8.4%), or Japanese (8.6%). E2 and FSH were assayed in serum collected primarily in the early follicular phase of a spontaneous menstrual cycle in three consecutive annual visits. The primary explanatory variables included in repeated-measures regression analyses were race/ethnicity, menopausal status, age, body mass index (BMI), day of the cycle, smoking, parity, socioeconomic status, study site, and the self-report of diabetes at baseline.

At the baseline visit, 46.2% of the women were classified as being early perimenopausal, with the remaining being premenopausal. By the second follow-up visit, 5.5% of the women in that cohort were postmenopausal, 66.8% were early perimenopausal, 8.3% were late perimenopausal, and 19.4% remained premenopausal.

Serum E2 concentrations decreased significantly with age, with a steeper decline at higher ages. FSH concentrations increased significantly with age, with a steeper increase at higher ages. Similar patterns in the decline of E2 and the increase in FSH with age were found across ethnic groups, but the levels of these hormones differed by race/ethnicity. Specifically, over time, Chinese and Japanese women had lower E2 concentrations but similar FSH levels, compared with Caucasian women, and African American women had higher FSH concentrations but comparable E2 levels with those of Caucasian women. These ethnic differences in E2 and FSH were independent of menopausal status. The effect of BMI on serum E2 and FSH levels varied by menopausal status. Increasing BMI was associated with decreasing concentrations of E2 among premenopausal and early perimenopausal women but was associated with increasing concentrations of E2 among late perimenopausal and postmenopausal women. Increasing BMI was associated with decreasing concentrations of FSH, with the effect of BMI becoming larger as women transitioned through menopause.

We conclude that serum E2 levels decrease and FSH concentrations increase with increasing age in midlife women, that ethnic differences in E2 over time differ from ethnic differences in FSH and suggest ethnic differences in the pituitary-ovarian relationship, and that the effect of BMI on E2 and FSH concentrations varies by menopausal status.

The Study of Women’s Health Across the Nation (SWAN) was funded by the National Institute on Aging, National Institute of Nursing Research, and Office of Research on Women’s Health of the National Institutes of Health. Supplemental funding from the National Institute of Mental Health, National Institute on Child Health and Human Development, National Center on Complementary and Alternative Medicine, Office of Minority Health, and Office of AIDS Research is also gratefully acknowledged.

Clinical Centers: University of Michigan, Ann Arbor, Michigan (U01 NR04061, MaryFran Sowers, PI); Massachusetts General Hospital, Boston, Massachusetts (U01 AG12531, Joel Finkelstein, PI); Rush University, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois (U01 AG12505, Lynda Powell, PI); University of California, Davis/Kaiser, California (U01 AG12554, Ellen Gold, PI); University of California, Los Angeles, California (U01 AG12539, Gail Greendale, PI); University of Medicine and Dentistry/New Jersey Medical School, Newark, New Jersey (U01 AG12535, Gerson Weiss, PI); and the University of Pittsburgh, Pittsburgh, Pennsylvania (U01 AG12546, Karen Matthews, PI).

Laboratory: University of Michigan, Ann Arbor, Michigan (U01 AG12495, Central Ligand Assay Satellite Services, Daniel McConnell, PI) and Medical Research Laboratories, Highland Heights, Kentucky (subcontract of U01 AG12553, Evan Stein, Director).

Coordinating Center: University of Pittsburgh, Pittsburgh, Pennsylvania (Kim Sutton-Tyrrell, PI).

Project Officers: Janice Phillips, Sherry Sherman.

Steering Committee Chair: Susan Johnson.

Abbreviations: BMI, Body mass index; E2, estradiol; SWAN, Study of Women’s Health Across the Nation.

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