Elsevier

Maturitas

Volume 65, Issue 2, February 2010, Pages 161-166
Maturitas

Review
Premature menopause or early menopause: Long-term health consequences

https://doi.org/10.1016/j.maturitas.2009.08.003Get rights and content

Abstract

Objective

To review and summarize current evidence on the health consequences of premature menopause and early menopause.

Methods

We reviewed existing literature and combined graphically some results from the Mayo Clinic Cohort Study of Oophorectomy and Aging.

Results

Premature menopause or early menopause may be either spontaneous or induced. Women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae. The risk of adverse outcomes increases with earlier age at the time of menopause. Some of the adverse outcomes may be prevented by estrogen treatment initiated after the onset of menopause. However, estrogen alone does not prevent all long-term consequences, and other hormonal mechanisms are likely involved.

Conclusions

Regardless of the cause, women who experience hormonal menopause and estrogen deficiency before reaching the median age of natural menopause are at increased risk for morbidity and mortality. Estrogen treatment should be considered for these women, but may not eliminate all of the adverse outcomes.

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)

  • C.Y. Fang et al.

    A prospective study of quality of life among women undergoing risk-reducing salpingo-oophorectomy versus gynecologic screening for ovarian cancer

    Gynecol Oncol

    (2009)
  • T.M. Michelsen et al.

    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

    (2009)
  • L. Dennerstein et al.

    Hypoactive sexual desire disorder in menopausal women: a survey of Western European women

    J Sex Med

    (2006)
  • R. Lindsay et al.

    Prevention of spinal osteoporosis in oophorectomised women

    Lancet

    (1980)
  • North American Menopause Society

    Menopause practice: a clinician's guide

    (2007)
  • W.A. Rocca et al.

    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)

    (2009)
  • L.M. Nelson

    Clinical practice. Primary ovarian insufficiency

    N Engl J Med

    (2009)
  • N. Santoro

    Mechanisms of premature ovarian failure

    Ann Endocrinol (Paris)

    (2003)
  • C.B. Coulam et al.

    Incidence of premature ovarian failure

    Obstet Gynecol

    (1986)
  • J.L. Luborsky et al.

    Premature menopause in a multi-ethnic population study of the menopause transition

    Hum Reprod

    (2003)
  • J.C. Gallagher

    Effect of early menopause on bone mineral density and fractures

    Menopause

    (2007)
  • S.N. Kalantaridou et al.

    Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy

    J Clin Endocrinol Metab

    (2004)
  • F. Atsma et al.

    Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis

    Menopause

    (2006)
  • NAMS Continuing Medical Education Activity

    Menopause

    (2007)
  • M.J. de Kleijn et al.

    Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women

    Am J Epidemiol

    (2002)
  • A.M. Mondul et al.

    Age at natural menopause and cause-specific mortality

    Am J Epidemiol

    (2005)
  • B.K. Jacobsen et al.

    Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women

    Am J Epidemiol

    (2003)
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