Associations of reproductive hormones with transition to menopause in women age 35–47

Abstract

Objective: To describe the shapes of the trajectory of reproductive hormones over the study interval and determine the associations between hormone trajectory and fluctuations or heterogeneity (square root of variability) with menstrual cycle status in women approaching the menopause. Design: Prospective Cohort Materials/Methods: Data are from the ongoing study of ovarian aging (Penn Ovarian Aging Study). Subjects in this population-based cohort participated in 6 follow-up assessment periods at 8-month intervals over 4 years. Blood samples were obtained in the first 6 days of the menstrual cycle in 2 consecutive cycles in each assessment, for a maximum of 12 hormone values. Hormone trajectories were developed for each subject with subject’s age as the metric for time. Subject heterogeneity was defined as the square root of the residual variance (mean squared error) from the subject regression model. Menstrual cycle status was defined using the new consensus definitions from STRAW (Soules et. al., 2001). Status was assessed from observed cycles from daily symptom diaries, along with recalled information on the subjects bleeding patterns between assessments. “Late transitional” menstrual status was defined as 60 days or more of amenorrhea. Logistic regression models were developed to examine associations between hormone trajectory and variability of hormones with menstrual status controlling for other clinical variables Results: The mean age of the cohort at the sixth assessment period was 44.6 years (sd 3.5). Of the 333 women, 26.4% still had normal menstrual cycles. More than half the women (53.6%) had reported 1 or more cycles with a greater than 7 day change for their baseline cycle lengths. These two groups were compared to the 20% of the subjects who had amenorrhea for 2 or more months, which included 11 subjects who had reported 12 or more months without menses. Increased heterogeneity (variability) in estradiol (E2) and luteinizing hormone (LH) were both associated with late transitional menstrual cycle status. For a 1 standardized unit increase in the variability in E2, the odds of transitioning into late perimenopause was 2.37 (95% CI: 2.00, 2.74), and 1.58 for each unit increase in heterogeneity of LH (95% CI: 1.27, 1.90). Models were adjusted for ethnicity (African American or Caucasian), age at enrollment, education, income, and current assessments of body mass, alcohol and smoking. Conclusions: Fluctuations in hormones are important predictor of early menstrual cycle status changes in women 35–47. Supported by: NIH grant R01AG12745.