The menopausal transition--endocrinology.

INTRODUCTION

The Melbourne Women's MidLife Health Project (MWMHP) and related studies have yielded valuable information regarding the endocrine changes of the menopausal transition, which are summarized in this review.

AIM

To describe the endocrinology of the menopause transition.

MAIN OUTCOME MEASURES

Includes changes in inhibins A and B, follicle stimulating hormone (FSH), and estradiol, cross-sectionally in regularly cycling volunteers, and longitudinally (including testosterone) in women passing through the menopause transition.

METHODS

Early follicular phase hormone concentrations were measured by well-characterized immunoassays in normal volunteers aged 20-50 years, and in 438 subjects initially recruited between ages 45 and 55 for a longitudinal study of the menopause transition, the MWMHP, in which annual blood samples were obtained. The data summarized here includes the first 6 years of follow-up. These volunteers also recorded menstrual cycle data and responded to detailed annual questionnaires.

RESULTS

In regularly cycling female volunteers aged more than 40 years, it was established that inhibin B is a significant determinant of circulating FSH levels. From the MWMHP, the central endocrine event marking the onset of menstrual irregularity was shown to be a fall in follicular phase inhibin B concentrations, with a nonsignificant rise in FSH and no change in estradiol or inhibin A. Cross-sectional analysis of data from women in the early stages of the MWMHP showed a wide variation in circulating FSH levels, irrespective of menopausal status, indicating that single FSH measurements provide little useful information regarding menopausal status. Based on the prospective determination of the date of final menses (FMP), it was shown that estradiol levels begin to fall and FSH levels to rise about 2 years before FMP. At the time of FMP, FSH levels were approximately 50% of those ultimately reached postmenopausally, while estradiol had fallen by approximately 50% from reproductive age levels. Despite a major decline in sexual function, as women transited the menopause, there was no significant decline in circulating testosterone levels, the decline in sexual function being correlated with the decline in estradiol, not testosterone. Analysis of data from related studies showed that endocrinologically normal ovulatory cycles could be observed in women who had already experienced cycle irregularity, even more than 3 months of amenorrhea, and could occur close to or at the time of FMP.

CONCLUSIONS

An extensive database on the endocrinology of the menopause transition, including both cross-sectional and longitudinal information, has been obtained.