Menopause Transition: Annual Changes in Serum Hormonal Patterns over the Menstrual Cycle in Women during a Nine-Year Period Prior to Menopause

Abstract

To examine the hormonal characteristics of menstrual cycles in healthy women approaching menopause, serum hormone profiles were investigated annually in this longitudinal study of 13 healthy women between 4 and 9 yr before menopause and the year of the menopause. Serum FSH, LH, estradiol, progesterone, total inhibin, inhibins A and B, and prolactin were determined in blood samples collected annually three times weekly for 4 wk beginning with the onset of menses. Menstrual bleeding diaries covering this 4- to 9-yr period were also collected allowing the prospective identification of the final menstrual period. A change in serum hormone patterns was observed in cycles approaching menopause, exemplified by an increasing number of cycles of prolonged length with a prolonged follicular phase resulting in a failure to detect a luteal phase rise in serum progesterone within the 4-wk collection period. These prolonged cycles (designated B cycles based on a previous work) were analyzed separately and compared with the remaining ovulatory (D) cycles. No B cycles were identified in any women earlier than 27 cycles from menopause. The proportion of B cycles increased as menopause approached, reaching 62% in the last 10 cycles. The proportion of D cycles decreased accordingly. The B cycles during the initial 4-wk collection period were characterized by elevated FSH, LH, FSH/inhibin A and FSH/inhibin B ratios, and longer duration, although cycle length/subject was not significantly different presumably due to the small number of B cycles. The D cycles showed no changes in hormonal profiles over the 4- to 9-yr time period. These data indicate that there is a time-related change in the character of menstrual cycles as menopause approaches, with an increasing proportion of cycles observed with prolonged follicular phases that may either be delayed ovulatory cycles or anovulatory cycles. The increase in the proportion of B cycles with elevated early follicular phase FSH levels and low inhibin/FSH ratios toward menopause provides a basis for the apparent early increase in serum FSH and decrease in serum inhibins observed previously in studies of the menopause transition based on sampling confined to the follicular phase only. The data amplify and clarify current concepts of the endocrine basis of the menopause transition.

Reproductive ageing in women

“…It has been suggested that the resulting reduced negative feedback from inhibins on pituitary FSH secretion could be responsible for the observed elevated serum FSH levels in women of advanced reproductive age [76][77][78][79][80][81]. Longitudinal prospective studies have also shown age-related decline in serum inhibin B levels with advancing age during the menopausal transition [88,89].…”

Predicting the menopause: the role of inhibin B

“…Prospective studies have helped define the pattern and timing of the rise in FSH, and falls in oestradiol and the inhibins. [5][6][7] These studies have demonstrated that FSH rises and inhibin A and B fall two to three years before the menopause, while oestradiol production is maintained. The fall in inhibin A was similar to that of inhibin B but lagged it by a year.…”

“…A more detailed analysis of cycle parameters in women approaching the menopause 6 showed that ovulatory cycles occurred right up to the final menstrual period, although cycles were increasingly likely to be prolonged and anovulatory. The hormonal characteristics of the ovulatory cycles were normal, however, without elevated FSH concentrations and with normal patterns of inhibin and oestradiol production.…”

Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany

“…There is uncertainty of the menopausal status when using interview data on cessation of menses. Hormonal patterns might be more promising predictors of the menopausal status [44,45]. Biologically, cessation of menses is mainly due to the loss of ovarian follicular activity accompanied by a decrease in ovarian hormonal secretions (for review Ottolenghi et al, 2004) [46].…”