ReviewPremature menopause or early menopause: Long-term health consequences
Introduction
Premature menopause refers to menopause that occurs before age 40 years, and early menopause refers to menopause that occurs at or before age 45 years, both ranges being well below the median age of natural menopause (age 51 years) [1]. Premature menopause or early menopause can be spontaneous or induced; if induced, it can be due to medical interventions such as chemotherapy or surgical interventions such as bilateral oophorectomy. Regardless of cause, women who experience estrogen deficiency at an age well before the median age of natural menopause are now recognized to be at increased risk for premature morbidity and mortality.
In this review, we present the evidence regarding long-term health outcomes following different types of early menopause. While the hormonal milieu is quite different for women with spontaneous premature ovarian failure compared with women who experienced induced menopause due to bilateral oophorectomy or to cancer treatment, both conditions are associated with long-term health risks. Estrogen replacement appears to mitigate some but not all long-term health consequences of premature menopause or early menopause. Thus, other hormonal mechanisms are likely involved [2].
Section snippets
Methods
Using the Medline database, we conducted a comprehensive literature search of publications related to premature or early menopause, using the keywords “premature menopause”, “early menopause”, “surgical menopause”, “induced menopause”, “ovarian failure”, “ovarian insufficiency”, and “bilateral oophorectomy”. We considered observational studies reporting outcomes for women who reached menopause before the age of 45 years and studies comparing health outcomes following induced compared with
Spontaneous premature ovarian failure (POF) or early menopause
Premature ovarian failure (POF), also now referred to as primary ovarian insufficiency [3] or primary ovarian dysfunction [4], is a syndrome of amenorrhea, low sex steroid levels, and elevated gonadotropin levels among women younger than age 40 years. POF is most frequently idiopathic but may also be due to autoimmune disorders, genetic causes, infections or inflammatory conditions, enzyme deficiencies, or metabolic syndromes [1], [3], [5]. POF is reported to affect approximately 1% of women
Induced premature menopause or early menopause
Induced menopause may result from premenopausal bilateral oophorectomy or from cancer treatments including chemotherapy and radiation. Premature menopause from these causes has increased over time because of the improved success in the treatment of cancer in children, adolescents, and reproductive-age women. Similarly, the practice of prophylactic bilateral oophorectomy at the time of hysterectomy has increased over time [19]. However, evidence for the long-term risks and adverse health
Discussion
Premature menopause and early menopause, whether spontaneous or induced, are associated with long-term health risks which may include premature death, cardiovascular disease, neurologic disease, osteoporosis, psychosexual dysfunction, and mood disorders. Estrogen mitigates some but not all of these consequences.
The most common interpretation of these findings is that premature or early menopause is the first step in a chain of causality leading to tissue or organ dysfunctions and lesions via
Competing interests
The authors report no conflicts of interest.
Contributors
Study concept and design: Shuster, Rocca; acquisition of data: Grossardt, Rocca; analysis and interpretation of data: Grossardt, Rocca; drafting of manuscript: Shuster; critical review of manuscript for intellectual content: Shuster, Rhodes, Gostout, Grossardt, Rocca; statistical analysis: Grossardt, Rocca; study supervision: Shuster, Rocca.
Provenance
Commissioned and externally peer reviewed.
Funding
The Mayo Clinic Cohort Study of Oophorectomy and Aging was funded by NIH grant R01 NS033978 from the National Institute of Neurological Disorders and Stroke and was made possible by the NIH grant R01 AR030582 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Acknowledgements
The authors thank Ms. Barbara J. Balgaard for her secretarial assistance.
References (54)
- et al.
Management of premature ovarian failure
Best Pract Res Clin Obstet Gynaecol
(2009) - et al.
Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study
J Clin Epidemiol
(1999) - et al.
Age at natural menopause and mortality
Ann Epidemiol
(1998) Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century
Am J Med
(2005)- et al.
The influence of endocrine treatments for breast cancer on health-related quality of life
Cancer Treat Rev
(2008) - et al.
Survival patterns after oophorectomy in premenopausal women: a population-based cohort study
Lancet Oncol
(2006) - et al.
The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy
Maturitas
(2006) Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women
Psychoneuroendocrinology
(1988)- et al.
Effects of estrogen on memory function in surgically menopausal women
Psychoneuroendocrinology
(1992) - et al.
Prophylactic oophorectomy at elective hysterectomy. Effects on psychological well-being at 1-year follow-up and its correlations to sexuality
Maturitas
(2005)
A prospective study of quality of life among women undergoing risk-reducing salpingo-oophorectomy versus gynecologic screening for ovarian cancer
Gynecol Oncol
A controlled study of mental distress and somatic complaints after risk-reducing salpingo-oophorectomy in women at risk for hereditary breast ovarian cancer
Gynecol Oncol
Hypoactive sexual desire disorder in menopausal women: a survey of Western European women
J Sex Med
Prevention of spinal osteoporosis in oophorectomised women
Lancet
Menopause practice: a clinician's guide
Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging
Womens Health (Lond Engl)
Clinical practice. Primary ovarian insufficiency
N Engl J Med
Mechanisms of premature ovarian failure
Ann Endocrinol (Paris)
Incidence of premature ovarian failure
Obstet Gynecol
Premature menopause in a multi-ethnic population study of the menopause transition
Hum Reprod
Effect of early menopause on bone mineral density and fractures
Menopause
Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy
J Clin Endocrinol Metab
Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis
Menopause
Menopause
Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women
Am J Epidemiol
Age at natural menopause and cause-specific mortality
Am J Epidemiol
Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women
Am J Epidemiol
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