Biological processes such as puberty and menopause are

Puberty is initiated in late childhood through a cascade of neuroendocrine changes that results in extensive physical growth, sexual maturation, and reproductive capability. Pubertal maturation consists of two associated but independent processes: adrenarche, the reappearance of adrenal androgen production (around ages 6–8); and gonadarche, the pubertal reactivation of the hypothalamic-pituitary-gonadal (HPG) axis a few years later (Grumbach, 2004). Menarche, the initiation of the menstrual cycle, occurs toward the end of puberty, around the ages of 12–13 in most developed countries (Patton and Viner, 2007).

Perimenopause is defined as the period immediately preceding menopause when endocrinological, biological, and clinical features of approaching menopause commence (Hale and Burger, 2009; Prior, 1998). Women typically begin the shift from a reproductive state to non-reproductive state during their mid-to late 40s, and they remain in this transitory state for approximately 4–5 years before reaching menopause (Burger et al., 2007b; Prior and Hitchcock, 2011). Perimenopause culminates with menopause, when menses have ceased for a period of at least 12 consecutive months (Burger, 2008).

The neuroendocrine system presides over the significant hormonal changes occurring in the HPG axis during puberty and perimenopause (see Table 1 for a summary). In particular, both of these periods are characterized by major changes in the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which together regulate ovarian follicle growth and ovulation, and estradiol, the most abundant form of endogenous estrogen (Albin et al., 2012, Archibald et al., 2003, Burger, 2008, Burger et al., 2007a, Burger et al., 2007a, Nelson, 2008; Prior and Hitchcock, 2011; Prior, 2006). Mean levels of estradiol increase across pubertal development until menarche, when estradiol levels stabilize and then cycle regularly through the menstrual cycle each month. During late perimenopause, concentration of estradiol falls markedly from its elevated levels present during early perimenopause and eventually begins to stabilize (see Fig. 1).

In addition to the HPG axis changes related to puberty and perimenopause, another set of endocrine changes occur in the hypothalamus-pituitary-adrenal (HPA) axis. Levels of cortisol, the major hormonal output of the HPA system, vary throughout the day based on: (1) a strong circadian rhythm (i.e., basal pattern with high morning levels, low evening levels, and a strong negative slope), and (2) experiences of stress or challenge (i.e., cortisol reactivity) (McEwen et al., 1997). A growing body of research suggests that the overall basal activity of the HPA axis increases with sexual maturation in girls (i.e., higher average levels of cortisol across the day) (Adam, 2006, Gunnar et al., 2009, Legro et al., 2003, Netherton et al., 2004, Schiefelbein and Susman, 2006, Shirtcliff et al., 2005, Stroud et al., 2009). Initial research also suggests that girls experience increased cortisol reactivity (i.e., hypercortisolism) to stressful tasks across puberty (Gunnar et al., 2009, Stroud et al., 2009, Stroud et al., 2004).

Although comparatively less is known about the HPA axis changes during perimenopause, some studies have found an increase in cortisol levels as women transition from an early to late menopausal transition stage (Woods et al., 2006, Woods et al., 2009). Other research suggests that estrogen regulates corticotropin-releasing hormone gene expression, resulting in elevated cortisol levels (Vamvakopoulos and Chrousos, 1993). Therefore, as women approach menopause, increasing levels of FSH stimulate ovarian follicles to produce excess estrogen, which may influence cortisol levels (Santoro et al., 1996). There is also some evidence for greater HPA reactivity among postmenopausal women, with older women showing higher cortisol in response to challenge compared to both younger women and similarly-aged males (Seeman et al., 2001). Importantly, HPA activity is involved in regulating many physiological processes relevant to health including cardiovascular activity, blood pressure, and immune and inflammatory functioning (Chrousos and Gold, 1998).

The years surrounding both the initiation and completion of the female reproductive cycle are associated with major neuroendocrine reorganization that is distinct from other periods of the life course. In particular, dramatic changes occur across two key systems: the HPG axis—including fluctuations of LH, FSH, and estradiol— and hyperactivation of the HPA axis. By exploring the shared biological processes and associated health outcomes related to both puberty and perimenopause, we sought to answer: (1) What chronic diseases show a discontinuous increase in prevalence across both transitions? (2) Independent of the experience of these transitions, what is the association of pubertal and perimenopausal timing on health and disease?

Methods

To examine the extent, range, and nature of these literatures, we conducted a comprehensive scoping review to summarize a breadth of evidence on chronic diseases and conditions related to puberty and perimenopause. Following methodological guidelines for this type of literature review (Arksey and O'Malley, 2005, Armstrong et al., 2011, Levac et al., 2010) we defined our research focus as links between reproductive transitions and health outcomes. We included all literature presenting

Association of pubertal and perimenopausal transitions with health outcomes

Biological, behavioral, environmental, and social influences across the life span continuously interact to affect health of both individuals and populations (Ben-Shlomo and Kuh, 2002, Halfon et al., 2014). Central to the life course framework is the idea that health trajectories may be altered more readily during certain windows of rapid development or biological reorganization, also termed “critical” or “sensitive periods.” Whereas exposures acting in critical periods affect health in such a

Discussion

The aim of this article was to review the dramatic physiological changes occurring during the beginning and end of women's reproductive lives and how they are linked to later life health outcomes and mortality. We presented evidence using the sensitive periods model to suggest that events occurring during puberty and perimenopause—as well as their timing—are correlated with or influence risk for some of the leading causes of morbidity and mortality in women. We do not deny that other life

Acknowledgements

The authors received financial support from the Robert Wood Johnson Foundation Health & Society Scholars Program (Hoyt) and the National Institute of Child Health and Human Development, grant # T32-HD007275 (Falconi). The authors wish to thank Dr. Jerilynn Prior, for permission to include a figure from her previously published work, and Dr. Nancy Adler, for helpful comments on a previous draft of the paper.

Cited by (50)

Recommended articles (6)