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

Abstract

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.

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…Serum estradiol levels were also lower in the same age group, but LH levels did not vary significantly in any of the age groups. Recent largescale cohort studies conducted in Australia [235][236][237][238], Norway [239], and United States [240] have provided further important insights into the overall pattern of ovarian sex steroids and gonadotropins that occur during the MT. It is reported that circulating FSH levels rise progressively during the MT and that in perimenopausal women estradiol production fluctuates with FSH and often reaches higher concentrations than those in young normal cycling women below the age of 35.…”

Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation

“…Recent data show that Asian women in the United States undergoing menopause have lower estradiol levels than Caucasian women (33,34). Adipose tissue is a major source of estradiol in postmenopausal women, and the higher estradiol levels in Caucasians may be due, in part, to the greater adiposity of Caucasian women (32,33).…”

“…Adipose tissue is a major source of estradiol in postmenopausal women, and the higher estradiol levels in Caucasians may be due, in part, to the greater adiposity of Caucasian women (32,33).…”

Further evidence that FSH causes bone loss independently of low estrogen

“…1a). During this early phase up to 5 years before the last menstrual period, estrogen levels are relatively unperturbed, whereas follicle-stimulating hormone (FSH) levels are rising to compensate for failing ovaries [6,7] (Fig. 1b).…”

“…1 Bone loss at the most rapid rate in obese (top panel) or non-obese (bottom panel) begins 2-3 years before the last menstrual period (a), during which time serum estrogen levels are stable while serum FSH is rising (b). Adapted, with permission, from refs [3] and [6] more closely using appropriate primers [26]. Furthermore, injection of FSH into mice with intact ovaries [34], or its transgenic overexpression [33], even in hpg mice, is unlikely to reveal pro-resorptive actions of FSH.…”