A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project

Abstract

The menopause, defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity, marks the end of natural female reproductive life. It is preceded by a period of menstrual cycle irregularity, the menopausal transition, which usually begins in the mid-40s and is conventionally divided into early and late phases. The endocrine changes, which underlie the transition, are predominantly the consequence of a marked decline in ovarian follicle numbers. The most significant changes include a decrease in early cycle inhibin B and in anti-Mullerian hormone (AMH) levels. The decline in inhibin B results in an increase in FSH, which appears to be an important factor in the maintenance of estradiol (E2) concentrations until late in reproductive life. In the post-menopause, FSH levels are markedly raised, E2 levels are low, whereas inhibin B and AMH are undetectable. The menopausal transition is a time of marked hormonal instability. The Melbourne Women's Midlife Health Project has been an extremely productive study in which it has been possible to describe longitudinal changes in hormone levels throughout the menopause transition and to separate the effects of hormone change from the effects of ageing on a number of endpoints. This review provides the background for an accompanying manuscript in which a novel approach to modelling the hormonal changes during the transition is described.

Hormone levels and cognitive function in postmenopausal midlife women

“…As estradiol levels (Burger et al, 2007) -but not testosterone levels (Burger et al, 2000;Davison et al, 2005) -decline dramatically across the natural menopausal transition, the ratio of testosterone to estradiol will increase. In our study, high levels of testosterone relative to estradiol were negatively associated with both semantic memory and verbal episodic memory.…”

“…Circulating levels of estradiol decline as women enter the menopausal transition and drop to a low, steady level during the early postmenopause (Burger et al, 2007). In contrast, although testosterone declines during a woman's reproductive years, levels are generally unaffected by the natural menopausal transition (Burger et al, 2000;Davison et al, 2005).…”

Impact of a premature menopause on cognitive function in later life

“…Endocrine changes accompanying the menopause include a gradual albeit erratic decline in estrogen levels over several years, 1 which drop to a low level in the postmenopause. 2 These changes in estrogen levels have been speculated to account for the increased reporting of memory complaints during this period. 3,4 In support of this, experimental evidence indicates that estrogen has neuroprotective and neurotrophic effects 5 and, after the menopause, brain atrophy in women accelerates at a faster rate than in men.…”

Chemotherapy-Related Amenorrhea in Breast Cancer: Review of the Main Published Studies, Biomarkers of Ovarian Function and Mechanisms Involved in Ovarian Toxicity

“…The average age of menopause in women of Caucasian/European origin is around 51 years Bines et al (1996); Burger et al (2007); Gracia et al (2005); Welt et al (2006). Pituitary gonadotrophins stimulate ovarian steroid hormone production (estrogens, progesterone and androgens).…”