The relationship of bleeding patterns to daily reproductive hormones in women approaching menopause

Abstract

OBJECTIVE: To discover early hormonal predictors of menopause and the stages of the menopausal transition and to understand the hormonal basis behind the bleeding abnormalities common in the menopausal transition. METHODS: A cohort of 804 women aged 42-52 collected first void urine samples daily for one complete menstrual cycle or 50 days (whichever came first) once a year for 3 years. Urine was assayed for excreted levels of follicle-stimulating hormone, luteinizing hormone, estrogen metabolites, and progesterone metabolites, which were normalized for creatinine concentration. Anovulation was defined by an algorithm based on progesterone secretion. Menstrual bleeding parameters were derived from daily calendars. Correlations among bleeding characteristics, hormone concentrations, and other potential clinical predictors were analyzed using multivariable logistic regression models. RESULTS: An ethnically diverse population of women (mean age of 47) with a majority in the early perimenopause was studied. Approximately 20% of all cycles were anovulatory. Short cycle intervals (fewer than 21 days) were common early in the menopause transition and were associated with anovulation (44%). Long cycle intervals (more than 36 days) also were associated with anovulatory cycles (65%). Both short (1-3 days) and long (more than 8 days) duration of menstrual bleeding were associated with anovulation (18% and 23%, respectively). Women with anovulatory cycles were less likely to report heavy menstrual bleeding as compared with those with ovulatory cycles. Heavy bleeding was not associated with steroid hormone concentrations but was associated with obesity and with the self-reported presence of leiomyomata. CONCLUSIONS: Among women in the early menopause transition, abnormalities in timing of menstrual bleeding (cycle intervals or bleeding duration) have a hormonal basis and are frequently associated with anovulation. In contrast, abnormally heavy periods do not appear to have a steroid hormonal basis and are less likely after anovulatory cycles. Heavy periods are associated with obesity and leiomyomata. LEVEL OF EVIDENCE: II.