Biomarkers of Menopause

Abstract

Menopause is defined as the permanent cessation of menstruation resulting from loss of ovarian follicular activity, occurring between the late 40s and early 50s in a woman’s life. However, the age of onset of menopause shows considerable individual variation. As women approach the age for menopause, they experience a decline in fertility. Moreover, a high number of women develop climacteric symptoms caused by hormonal changes during perimenopause. Therefore, accurate assessments of late reproductive age and the menopausal transition are very important in healthcare as well as when applying reproductive techniques. In this chapter, the hormonal changes occurring around menopause are described, while focusing on four major hormones – estradiol (E2), follicle-stimulating hormone (FSH), inhibin B, and anti-Müllerian hormone (AMH). Among the hormones, the levels of inhibin B and AMH exhibit significant changes in early menopausal transition, during which an apparent decline in fertility already occurs. However, individual differences in AMH levels decreased as the women entered the late menopausal transition stage. Moreover, the proportion of women with undetectable AMH levels had increased when they approached late menopausal transition. These trends in the levels were more apparent for AMH than for inhibin B. These observations indicate that AMH is the first hormone to exhibit a change in level and is a reliable biomarker of ovarian function during menopausal transition. In addition, the FSH levels gradually increase during early menopausal transition without any accompanying decline in E2 levels. Furthermore, the initiation of a rapid increase in FSH levels and decline in E2 levels was found to occur between 2 years before the final menstrual period and 2 years after the final menstrual period, after which these levels remain stable.