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Abstract
This scoping review synthesizes existing research on two major transitions in females' lives: puberty and perimenopause. These two periods of vast physiological change demarcate the beginning and the end of the reproductive life cycle and are associated with major neuroendocrine reorganization across two key systems, the hypothalamic-pituitary-gonadal (HPG) axis the hypothalamus-pituitary-adrenal (HPA) axis. Despite growing evidence suggesting that the timing and experience of puberty and perimenopause are related to various physical and mental health outcomes (e.g., mood disorders, metabolism, cardiovascular health, autoimmune conditions, and cancer), these two processes are rarely examined together. In this paper, we bridge these disparate literatures to highlight similarities, isolate inconsistencies, and identify important areas for future research in women's health.
Introduction
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?
Section snippets
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.
References (167)
Oestrogen window hypothesis of the aetiology of breast cancer
Lancet
(1980)
- R.C. Kessler
Epidemiology of women and depression
J. Affect. Disord.
(2003)
- R. Kaltiala-Heino et al.
Early puberty is associated with mental health problems in middle adolescence
Soc. Sci. Med.
(2003)
- A. Herva et al.
Age at menarche and depression at the age of 31 years: findings from the Northern Finland 1966 Birth Cohort Study
J. Psychosom. Res.
(2004)
- B. Harlow et al.
Factors associated with early menopause
Maturitas
(2000)
- G.
Hale et al.
Hormonal changes and biomarkers in late reproductive age, menopausal transition, and menopause
Best Pract. Res. Clin. Obstet. Gynaecol.
(2009)
- G. Greendale et
al.
The menopause
Lancet
(1999)
- J. Graber et al.
Is psychopathology associated with the timing of pubertal development?
J. Am. Acad. Child Adolesc. Psychiatry
(1997)
- E. Gold
The timing of the age at which natural menopause occurs
Obstet. Gynecol. Clin. N. Am.
(2011)
- K.K. Davison et al.
Why are early maturing girls less active? Links between pubertal development, psychological well-being, and physical activity among girls at ages 11 and 13
Soc. Sci. Med. (1982)
(2007)
Corticotropin-releasing factor, corticosteroids, stress, and sugar: energy balance, the brain, and behavior
Horm. Brain Behav.
(2002)
The menopausal transition – endocrinology
J. Sex. Med.
(2008)
Autoimmune diseases and reproductive aging
Clin. Immunol.
(2013)
Childhood adversity and pubertal timing: understanding the origins of adulthood cardiovascular risk
Biol. Psychol.
(2013)
Advanced pubertal status at age 11 and lower physical activity in adolescent girls
J. Pediatr.
(2007)
Transactions among adolescent trait and state emotion and diurnal and momentary cortisol activity in naturalistic settings
Psychoneuroendocrinology
(2006)
Growth patterns and the risk of breast cancer in women
N. Engl. J. Med.
(2004)
The effects of body mass index on age at menopause
Int. J. Obes.
(2002)
Overweight and obese teenagers: why is adolescence a critical period?
Pediatr. Obes.
(2012)
Estradiol and pubertal growth in girls
Horm. Res. Paediatr.
(2012)
The menopause and breast cancer
J. Epidemiol. Community Health
(1987)
Pubertal changes in hormone levels and depression in girls
Psychol. Med.
(1999)
Puberty and depression: the roles of age, pubertal status and pubertal timing
Psychol. Med.
(1998)
Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood
Int. J. Cancer
(1989)
Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles
J. Clin. Endocrinol. Metab.
(1983)
Pubertal processes and physiological growth in adolescence
Scoping studies: towards a methodological framework
Int. J. Soc. Res. Methodol.
(2005)
Scoping the scope’of a cochrane review
J. Public Health
(2011)
Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis
Menopause
(2006)
Reproductive factors, smoking, and the risk for rheumatoid arthritis
Epidemiology
(1990)
The distance between genes and culture
J. Anthropol. Res.
(1984)
Childhood experience, interpersonal development, and reproductive strategy: an evolutionary theory of socialization
Child. Dev.
(1991)
Family rearing antecedents of pubertal timing
Child. Dev.
(2007)
A life course approach to chronic disease epidemiology: conceptual models, empirical challenges and interdisciplinary perspectives
Int. J. Epidemiol.
(2002)
Pubertal timing, androgens, and obesity phenotypes in women at midlife
J. Clin. Endocrinol. Metab.
(2012)
Socioeconomic status in relation to early menarche among black and white girls
Cancer Causes Control
(2009)
Does risk for anxiety increase during the menopausal transition? Study of women's health across the nation
Menopause
(2013)
A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project
Hum. Reprod. Update
(2007)
Nomenclature and endocrinology of menopause and perimenopause
Expert Rev. Neurother.
(2007)
Menopausal transition and psychological distress in a nationally representative sample: Is menopause associated with psychological distress?
J. Aging Health
(1994)
Individual differences are accentuated during periods of social change: the sample case of girls at puberty
J. Personal. Soc. Psychol.
(1991)
Early stress predicts age at menarche and first birth, adult attachment, and expected lifespan
Hum. Nat.
(2005)
A healthy body in a healthy mind—and vice versa—the damaging power of “uncontrollable” stress
J. Clin. Endocrinol. Metab.
(1998)
Age at menarche and racial comparisons in US girls
Pediatrics
(2003)
Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression
Menopause
(2007)
Risk for new onset of depression during the menopausal transition: the Harvard Study of Moods and Cycles
Arch. General Psychiatry
(2006)
Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118,964 women with breast cancer from 117 epidemiological studies
Lancet Oncol.
(2012)
Hormonal and reproductive risk factors for development of systemic lupus erythematosus: results of a population-based, case–control study
Arthritis Rheum.
(2002)
Reproductive and menopausal factors and risk of systemic lupus erythematosus in women
Arthritis Rheum.
(2007)
Adolescent onset of the gender difference in lifetime rates of major depression: a theoretical model
Arch. General Psychiatry
(2000)
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