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Published in final edited form as: Maturitas. 2009 Sep 5;65(2):161. doi: 10.1016/j.maturitas.2009.08.003

Premature menopause or early menopause: long-term health consequences

Lynne T Shuster a, Deborah J Rhodes b, Bobbie S Gostout c, Brandon R Grossardt d, Walter A Rocca e,f
PMCID: PMC2815011  NIHMSID: NIHMS144160  PMID: 19733988

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.

Keywords: Premature menopause, Early menopause, Estrogen, Bilateral oophorectomy, Mortality, Morbidity

1. 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].

2. 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 natural menopause at younger ages. In addition, we combined graphically some results from the Mayo Clinic Cohort Study of Oophorectomy and Aging pertaining to women who were younger than age 45 years at the time of oophorectomy [2].

3. 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 under age 40 years [6,7] and spontaneous early menopause is reported to affect approximately 5% of women between ages 40 and 45 years [5].

POF has been found to be associated with intermittent ovarian function in nearly half of the women affected [3]. While spontaneous or induced return of ovarian function is possible, most women with POF experience sustained sex steroid deficiency for longer periods compared with women who experienced spontaneous menopause around the median age. Thus, POF and other causes of premature spontaneous menopause are generally classified together when evaluating long-term health outcomes.

Women with premature spontaneous menopause (including POF) are at increased risk for low bone density, earlier onset osteoporosis and fractures [8], impaired endothelial function [9], earlier onset of coronary heart disease [10], and increased cardiovascular mortality and total mortality [11–16]. Women with POF have been reported to have diminished general and sexual well-being and are less satisfied with their sexual lives [17]. In addition, women with POF have been reported to have more anxiety, depression, somatization, sensitivity, hostility, and psychological distress than women with normal ovaries [17]. POF is frequently associated with autoimmunity, and women with autoimmune POF are at increased risk for adrenal insufficiency, hypothyroidism, diabetes, myasthenia gravis, rheumatoid arthritis, and systemic lupus erythematosus [4,18].

4. 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 outcomes following induced menopause is starting to accumulate.

4.1. Induced menopause following cancer therapy

Ovarian damage from cancer therapy depends on the age at treatment and on the type of treatment. Women younger than age 40 years and children are at lower risk for ovarian failure than older women; however, exposure to higher doses of alkylating agents and higher doses of radiation to the ovary are more likely to induce ovarian failure [20]. Based on the Childhood Cancer Survivor Study (CCSS), a cohort study of survivors of childhood cancer treated at 25 cancer centers throughout North America between 1970 and 1986, approximately 6% of childhood cancer survivors experienced acute ovarian failure (AOF) during cancer treatment or shortly after completing cancer treatment [21]. Another 8% retained ovarian function during treatment but later developed premature menopause [21]. This is believed to be an underestimate of the true population incidence of premature menopause because the median age attained in this group at the time of analysis was only 29 years [22].

Follow-up of childhood cancer survivors has identified an increase in miscarriages, an increase in small for gestational age offspring, and a reduction in live births [21]. Longer term health outcomes, beyond cancer free survival, are not yet available; however, these subjects are expected to be at increased risk for osteoporosis, cardiovascular disease, psychosexual dysfunction, and decreased quality of life [22].

Approximately 25% of breast cancer cases occur in premenopausal women, and breast cancer accounts for one third of cancers in reproductive-age women [23]. Adjuvant chemotherapy and endocrine therapies are now standard, resulting in ovarian insufficiency and sex steroid suppression among many women with a history of breast cancer. Approximately two-thirds of premenopausal women become amenorrheic after starting the chemotherapy regimen most commonly used for breast cancer [24]; however, the overall risk of inducing menopause depends on the type and dose of chemotherapy and on the age of the woman. Several, but not all, studies have reported improved cancer-free survival in women who developed amenorrhea after chemotherapy [25]. Consequences of induced ovarian failure include premature menopause, infertility, vasomotor symptoms, vaginal dryness, dyspareunia, weight gain, and osteoporosis [26,27].

4.2. Induced menopause following prophylactic bilateral oophorectomy

Approximately 1 in 9 women aged 35–45 years has undergone hysterectomy, with 40 percent undergoing bilateral oophorectomy at the same time, resulting in the abrupt onset of menopause [19]. The practice of prophylactic oophorectomy has increased over time and more than doubled between 1965 and 1990 [19]. Meanwhile, reports now link induced menopause from bilateral oophorectomy with serious health consequences including premature death, cardiovascular and neurologic disease, and osteoporosis, in addition to menopausal symptoms, psychiatric symptoms, and impaired sexual function.

4.2.1. Mortality and cardiovascular disease

The Mayo Clinic Cohort Study of Oophorectomy and Aging involved a population-based sample of 4,780 women and reported increased all-cause mortality in women who underwent prophylactic bilateral oophorectomy before age 45 years [28]. The increased mortality was mainly observed in women who did not take estrogen after the surgery and up until age 45 years (HR 1.93, 95% CI 1.25–2.96). Cardiovascular mortality was also increased in the women who underwent bilateral oophorectomy before age 45 years and did not take estrogen [29].

The Danish Nurse Cohort Study, a prospective cohort study of nearly 20 000 women, reported an increased risk of ischemic heart disease among women who underwent bilateral oophorectomy before age 40 years compared to after age 45 years. There was a smaller increased risk for ischemic heart disease among women who experienced natural menopause before age 40 years. Among the women who experienced menopause as a result of bilateral oophorectomy, estrogen therapy was associated with significant protection against ischemic heart disease. The benefit from estrogen was most pronounced for current users and for women who started treatment within 1 year after surgery [30].

In 2009, Parker and colleagues reported results from the Nurses’ Health Study cohort of 30 000 women who underwent hysterectomy for benign disease, comparing outcomes following ovarian conservation versus bilateral oophorectomy [31]. Hysterectomy with bilateral oophorectomy before age 45 years was associated with an increased risk for coronary heart disease, even when analyses were adjusted for known cardiovascular risk factors and for use of estrogen therapy. Oophorectomy at any age was associated with an increased risk of death, including coronary heart disease and lung cancer deaths.

In summary, data consistently show an increased risk for cardiovascular disease in women who undergo bilateral oophorectomy inducing premature menopause or early menopause. Estrogen replacement proximate to bilateral oophorectomy appears to be particularly important for reducing premature coronary heart disease and death in this group of women.

4.2.2. Neurologic outcomes

Women in the Mayo Clinic Cohort Study of Oophorectomy and Aging who underwent bilateral oophorectomy before the onset of natural menopause had an increased risk of cognitive impairment or dementia when compared with referent women, and the risk increased with younger age at oophorectomy [2]. The increased risk among these women was restricted to those who did not take estrogen after surgery and until at least age 50 years. Thus, it is suggested that estrogen treatment following oophorectomy protected against the increased risk. The Mayo Clinic Cohort Study of Oophorectomy and Aging also showed that women who underwent bilateral oophorectomy before menopause were at increased risk of parkinsonism, and the risk increased with younger age at time of oophorectomy [2].

Other studies have evaluated cognitive function and memory function in surgically menopausal women, but age-specific data are limited. Nappi and colleagues reported that women who underwent surgical menopause following bilateral oophorectomy underperformed on certain memory tasks [32]. Scores among the surgically menopausal women tended to be lower when the oophorectomy occurred at younger ages. In a longitudinal study in Egypt, women who underwent surgical menopause had significantly decreased global cognitive functioning scores and memory scale scores 3 to 6 months after oophorectomy compared with premenopausal controls [33]. Lower performance correlated with lower estradiol levels.

Sherwin evaluated 50 women before and after hysterectomy with bilateral oophorectomy or ovarian conservation and found a reduction in cognitive function in the women who underwent bilateral oophorectomy (mean age 45.4 years) if no hormone therapy was given [34]. Women who underwent hysterectomy with ovarian conservation and women with bilateral oophorectomy who were given estrogen, androgens, or both, experienced no declines in cognitive function [34]. These short-term clinical trials suggested that cognitive and memory functions correlate with sex steroid hormone levels, and that estrogen maintained at physiologic levels improves cognitive functions [35].

In summary, some cohort studies reported an increased risk for neurologic impairment following bilateral oophorectomy, with a suggestion of increased risk when surgical menopause occurs at a younger age, and reduced risk when estrogen replacement was given. By contrast, two other studies reported limited or no memory and cognitive differences among women with bilateral oophorectomy versus hysterectomy or natural menopause [36,37]. However, there was no delineation in these studies of the subgroup of women who might be at greatest risk – i.e., women undergoing bilateral oophorectomy before age 45 years.

4.2.3. Mood and sexual function

Bilateral prophylactic oophorectomy seems to be associated with an increased long-term risk of de novo anxiety symptoms, as evidenced by the Mayo Clinic Cohort Study of Oophorectomy and Aging [2]. Women in this study who underwent bilateral oophorectomy at younger ages (before age 49 years) were at greater risk for anxiety, and treatment with estrogen did not modify the risk. An increase in depressive symptoms diagnosed by a physician was also found in this study, but the association was weaker [2].

The link between oophorectomy and depression has been recognized for many years, but age-specific data are limited. In one study, women who underwent oophorectomy along with hysterectomy had significantly greater anxiety and depression, and less positive well-being than the women whose ovaries had been conserved [38]. Oophorectomized women taking estrogen reported less anxiety and depression, and their psychological well-being was similar to women whose ovaries had been conserved. Oophorectomized women also reported more impaired sexual function compared to women with intact ovaries; however, these sexual symptoms were not ameliorated by taking estrogen [38].

In contrast, a more recent prospective study of 323 women evaluated psychological well-being and sexual function at baseline and one year after simple hysterectomy versus hysterectomy with oophorectomy. The changes between baseline and follow-up in psychological well-being and in reported sexual function did not vary between the two groups [39].

Several studies reported negative psychosocial and sexual consequences of prophylactic oophorectomy performed in women at increased risk for breast cancer or ovarian cancer, such as women with a family history of breast cancer or ovarian cancer or with a BRCA mutation. Madalinska and colleagues compared the quality of life in women with prophylactic oophorectomy versus women with periodic gynecologic screening (846 women aged 30–59 years). The most common adverse effects of bilateral oophorectomy were increased hot flashes, night sweats, vaginal dryness, dyspareunia, weight gain, and a loss of interest in sex [40]. Estrogen therapy reduced but did not eliminate vasomotor symptoms, and was associated with an increase in vaginal dryness and dyspareunia.

Fang and colleagues prospectively compared the quality of life in 75 women at increased risk for ovarian cancer who received prophylactic oophorectomy versus gynecologic screening [41]. The women who underwent oophorectomy (mean age 46 years) experienced poorer physical functioning, greater pain, less vitality, poorer social functioning, greater discomfort and less satisfaction with sexual activities at one month; however, many of the symptoms improved by 6 months except hot flashes and sexual impairment. Overall, women who underwent prophylactic oophorectomy were more likely to experience hot flashes, dyspareunia, and less satisfaction with sexual intercourse.

In a study of 503 Norwegian women at increased risk of breast cancer or ovarian cancer, women who underwent prophylactic bilateral oophorectomy at a mean age of 48.5 years experienced more palpitations, constipation, pain, stiffness, osteoporosis, and musculoskeletal disease following surgery compared with population controls, even after adjustment for use of hormone therapy [42]. However, prophylactic bilateral oophorectomy was associated with lower levels of depression and mental distress after surgery, probably because of reduced concerns about cancer risk.

Dennerstein and colleagues compared findings among surgically or naturally menopausal women, using validated measures of female sexual function in the Women’s International Study of Health and Sexuality (WISHeS) [43]. Women who underwent hysterectomy with bilateral oophorectomy were more likely to have low sexual desire, less likely to be sexually active, and more likely to be dissatisfied with their sex life and partner relationships. Women younger than age 50 years (mean age 44 years) who had undergone bilateral oophorectomy were twice as likely to have low sexual desire compared with premenopausal women; however, the likelihood of low desire was significantly reduced with hormone therapy.

4.2.4. Osteoporosis

Numerous studies have shown that bone loss accelerates following menopause. The earlier in life that menopause occurs, the lower bone density will be later in life [8]. Therefore, oophorectomy before age 45 years is a well-established risk-factor for osteoporosis. Even in women who undergo bilateral oophorectomy after natural menopause, the risk of osteoporotic fracture may be increased compared with women with intact ovaries [44]. Estrogen therapy prevents bone loss and reduces fracture risk following oophorectomy [45]; however, the long-term use of estrogen therapy – which would be needed for bone protection in these women at increased risk – has declined after the publication of results from the Women’s Health Initiative clinical trials [2].

5. 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 hormonal mechanisms [2]. However, before discussing this interpretation more extensively, we also mention the alternative hypothesis that premature or early menopause is the result of an accelerated aging process determined by genetic or non-genetic causes and involving all tissues and organs throughout the body, including the ovaries [46]. Under this hypothesis, the hormonal changes following premature or early menopause have no causal role in the development of premature death, cardiovascular disease, neurologic disease, osteoporosis, psychosexual dysfunction, and mood disorders. The evidence in support of this hypothesis is limited.

Whether different types of premature menopause or early menopause result in different long-term health consequences remains unknown. Their hormonal milieus differ because the postmenopausal ovary is hormonally active, producing small amounts of estradiol and estrone, as well as androgens including testosterone, androstenedione, and dehydroepiandrosterone [47]. Following bilateral oophorectomy in premenopausal women, estradiol levels drop, testosterone levels drop by 40–50%, and follicle-stimulating hormone levels rise abruptly. Women undergoing bilateral oophorectomy continue to have lower levels of androgens than naturally menopausal women even beyond 65 years of age [48].

With POF, follicle-stimulating hormone levels are elevated and estradiol levels are low, but sporadic increases in estradiol may occur [49]. Ovarian androgens remain age-appropriate in these women [50]. Ovarian failure caused by cancer therapy, when permanent, is associated with elevated follicle-stimulating hormone levels and reduced estradiol levels similar to natural menopause; androgen function has not been well-characterized. Overall, different consequences from the different types of menopause may relate to the extent of disruption of the hypothalamic-pituitary-ovarian axis as much as to the reduced levels of circulating sex steroid hormones [2].

Concern about the risks of hormone therapy following publication of results from the Women’s Health Initiative clinical trials may be inappropriate if applied to women with premature menopause or early menopause who typically need estrogen in adequate replacement doses for a duration of time long enough to reduce the consequences of prolonged estrogen deficiency. It is important that clinicians not withhold health-promoting estrogen replacement for these women.

Professional organizations including the North American Menopause Society, the British Menopause Society, and the International Menopause Society recommend estrogen replacement therapy for women with premature menopause or premature ovarian failure [51–53]. There is some evidence, although not from randomized controlled clinical trials, that restoring pathologically low estrogen levels will reduce the later development of cardiovascular disease, osteoporosis, and possibly dementia. This leads to the general recommendation that estrogen be continued in women who experience premature menopause or early menopause until at least around the median age of natural menopause (approximately age 51 years).

The health benefits of prophylactic bilateral oophorectomy for reducing the risk of breast, ovarian, and fallopian tube cancers in women known to be at increased risk, such as BRCA1 or BRCA2 mutation carriers, is well-established [54]. However, for those women not known to be at increased risk of cancer, early spontaneous menopause or early induced menopause may result in more risks than benefits, and should be accompanied by estrogen replacement. Even in women with BRCA1 or BRCA2 mutations who undergo risk-reducing prophylactic bilateral oophorectomy before age 45 years, short-term estrogen replacement is an option [54]. The age of onset of estrogen deficiency appears to be an important determinant of long-term health [2].

Figure 1.

Figure 1

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The effects of bilateral oophorectomy increased with younger age at the time of oophorectomy for several outcomes investigated by the Mayo Clinic Cohort Study of Oophorectomy and Aging [2,28,29]. Risk was expressed using hazard ratios and 95% confidence intervals. The age strata on the x-axis are slightly different for overall mortality and cardiovascular mortality versus cognitive impairment or dementia and parkinsonism.

Acknowledgements

The authors thank Ms. Barbara J. Balgaard for her secretarial assistance. 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.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Competing interests (including funding information)

The authors report no conflicts of interest.

List of contributors and their role in the paper

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.

References

  • 1.North American Menopause Society. Menopause Practice: A Clinician's Guide. 3rd ed. Cleveland, OH: North American Menopause Society; 2007. [Google Scholar]
  • 2.Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, 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;5:39–48. doi: 10.2217/17455057.5.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360:606–614. doi: 10.1056/NEJMcp0808697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Panay N, Kalu E. Management of premature ovarian failure. Best Pract Res Clin Obstet Gynaecol. 2009;23:129–140. doi: 10.1016/j.bpobgyn.2008.10.008. [DOI] [PubMed] [Google Scholar]
  • 5.Santoro N. Mechanisms of premature ovarian failure. Ann Endocrinol (Paris) 2003;64:87–92. [PubMed] [Google Scholar]
  • 6.Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67:604–606. [PubMed] [Google Scholar]
  • 7.Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N. Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod. 2003;18:199–206. doi: 10.1093/humrep/deg005. [DOI] [PubMed] [Google Scholar]
  • 8.Gallagher JC. Effect of early menopause on bone mineral density and fractures. Menopause. 2007;14:567–571. doi: 10.1097/gme.0b013e31804c793d. [DOI] [PubMed] [Google Scholar]
  • 9.Kalantaridou SN, Naka KK, Papanikolaou E, Kazakos N, Kravariti M, Calis KA, et al. Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy. J Clin Endocrinol Metab. 2004;89:3907–3913. doi: 10.1210/jc.2004-0015. [DOI] [PubMed] [Google Scholar]
  • 10.Atsma F, Bartelink ML, Grobbee DE, van der Schouw YT. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause. 2006;13:265–279. doi: 10.1097/01.gme.0000218683.97338.ea. [DOI] [PubMed] [Google Scholar]
  • 11.NAMS Continuing Medical Education Activity. Menopause. 2007;14:555. [Google Scholar]
  • 12.Jacobsen BK, Knutsen SF, Fraser GE. Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study. J Clin Epidemiol. 1999;52:303–307. doi: 10.1016/s0895-4356(98)00170-x. [DOI] [PubMed] [Google Scholar]
  • 13.de Kleijn MJ, van der Schouw YT, Verbeek AL, Peeters PH, Banga JD, van der Graaf Y. Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. Am J Epidemiol. 2002;155:339–345. doi: 10.1093/aje/155.4.339. [DOI] [PubMed] [Google Scholar]
  • 14.Mondul AM, Rodriguez C, Jacobs EJ, Calle EE. Age at natural menopause and cause-specific mortality. Am J Epidemiol. 2005;162:1089–1097. doi: 10.1093/aje/kwi324. [DOI] [PubMed] [Google Scholar]
  • 15.Cooper GS, Sandler DP. Age at natural menopause and mortality. Ann Epidemiol. 1998;8:229–235. doi: 10.1016/s1047-2797(97)00207-x. [DOI] [PubMed] [Google Scholar]
  • 16.Jacobsen BK, Heuch I, Kvale G. Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Am J Epidemiol. 2003;157:923–929. doi: 10.1093/aje/kwg066. [DOI] [PubMed] [Google Scholar]
  • 17.van der Stege JG, Groen H, van Zadelhoff SJ, Lambalk CB, Braat DD, van Kasteren YM, et al. Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure. Menopause. 2008;15:23–31. doi: 10.1097/gme.0b013e3180f6108c. [DOI] [PubMed] [Google Scholar]
  • 18.Hoek A, Schoemaker J, Drexhage HA. Premature ovarian failure and ovarian autoimmunity. Endocr Rev. 1997;18:107–134. doi: 10.1210/edrv.18.1.0291. [DOI] [PubMed] [Google Scholar]
  • 19.Keshavarz H, Hillis SD, Kieke BA, Marchbanks PA. Surveillance Summaries, July 12, 2002. Vol. 51. MMWR; 2002. Hysterectomy Surveillance — United States, 1994–1999; pp. 1–8. [PubMed] [Google Scholar]
  • 20.Sklar C. Maintenance of ovarian function and risk of premature menopause related to cancer treatment. J Natl Cancer Inst Monogr. 2005:25–27. doi: 10.1093/jncimonographs/lgi018. [DOI] [PubMed] [Google Scholar]
  • 21.Green DM, Sklar CA, Boice JD, Jr, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27:2374–2381. doi: 10.1200/JCO.2008.21.1839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Chen WY, Manson JE. Premature ovarian failure in cancer survivors: new insights, looming concerns. J Natl Cancer Inst. 2006;98:880–881. doi: 10.1093/jnci/djj276. [DOI] [PubMed] [Google Scholar]
  • 23.Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 doi: 10.3322/caac.20006. [DOI] [PubMed] [Google Scholar]
  • 24.Minton SE, Munster PN. Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant treatment for breast cancer. Cancer Control. 2002;9:466–472. doi: 10.1177/107327480200900603. [DOI] [PubMed] [Google Scholar]
  • 25.Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol. 2006;24:5769–5779. doi: 10.1200/JCO.2006.07.2793. [DOI] [PubMed] [Google Scholar]
  • 26.Ganz PA. Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century. Am J Med. 2005;118:136–141. doi: 10.1016/j.amjmed.2005.09.047. [DOI] [PubMed] [Google Scholar]
  • 27.Buijs C, de Vries EG, Mourits MJ, Willemse PH. The influence of endocrine treatments for breast cancer on health-related quality of life. Cancer Treat Rev. 2008;34:640–655. doi: 10.1016/j.ctrv.2008.04.001. [DOI] [PubMed] [Google Scholar]
  • 28.Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ., 3rd Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol. 2006;7:821–828. doi: 10.1016/S1470-2045(06)70869-5. [DOI] [PubMed] [Google Scholar]
  • 29.Rivera CM, Grossardt BR, Rhodes DJ, Brown RD, Jr, Roger VL, Melton LJ, 3rd, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause. 2009;16:15–23. doi: 10.1097/gme.0b013e31818888f7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Lokkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT. The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas. 2006;53:226–233. doi: 10.1016/j.maturitas.2005.04.009. [DOI] [PubMed] [Google Scholar]
  • 31.Parker WH, Broder MS, Chang E, Feskanich D, Farquhar C, Liu Z, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses' Health Study. Obstet Gynecol. 2009;113:1027–1037. doi: 10.1097/AOG.0b013e3181a11c64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Nappi RE, Sinforiani E, Mauri M, Bono G, Polatti F, Nappi G. Memory functioning at menopause: impact of age in ovariectomized women. Gynecol Obstet Invest. 1999;47:29–36. doi: 10.1159/000010058. [DOI] [PubMed] [Google Scholar]
  • 33.Farrag AK, Khedr EM, Abdel-Aleem H, Rageh TA. Effect of surgical menopause on cognitive functions. Dement Geriatr Cogn Disord. 2002;13:193–198. doi: 10.1159/000048652. [DOI] [PubMed] [Google Scholar]
  • 34.Sherwin BB. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology. 1988;13:345–357. doi: 10.1016/0306-4530(88)90060-1. [DOI] [PubMed] [Google Scholar]
  • 35.Phillips SM, Sherwin BB. Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology. 1992;17:485–495. doi: 10.1016/0306-4530(92)90007-t. [DOI] [PubMed] [Google Scholar]
  • 36.Kritz-Silverstein D, Barrett-Connor E. Hysterectomy, oophorectomy, and cognitive function in older women. J Am Geriatr Soc. 2002;50:55–61. doi: 10.1046/j.1532-5415.2002.50008.x. [DOI] [PubMed] [Google Scholar]
  • 37.Kok HS, Kuh D, Cooper R, van der Schouw YT, Grobbee DE, Wadsworth ME, et al. Cognitive function across the life course and the menopausal transition in a British birth cohort. Menopause. 2006;13:19–27. doi: 10.1097/01.gme.0000196592.36711.a0. [DOI] [PubMed] [Google Scholar]
  • 38.Nathorst-Boos J, von Schoultz B, Carlstrom K. Elective ovarian removal and estrogen replacement therapy--effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynaecol. 1993;14:283–293. doi: 10.3109/01674829309084451. [DOI] [PubMed] [Google Scholar]
  • 39.Aziz A, Bergquist C, Nordholm L, Moller A, Silfverstolpe G. Prophylactic oophorectomy at elective hysterectomy. Effects on psychological well-being at 1-year follow-up and its correlations to sexuality. Maturitas. 2005;51:349–357. doi: 10.1016/j.maturitas.2004.08.018. [DOI] [PubMed] [Google Scholar]
  • 40.Madalinska JB, van Beurden M, Bleiker EM, Valdimarsdottir HB, Hollenstein J, Massuger LF, et al. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol. 2006;24:3576–3582. doi: 10.1200/JCO.2005.05.1896. [DOI] [PubMed] [Google Scholar]
  • 41.Fang CY, Cherry C, Devarajan K, Li T, Malick J, Daly MB. A prospective study of quality of life among women undergoing risk-reducing salpingo-oophorectomy versus gynecologic screening for ovarian cancer. Gynecol Oncol. 2009;112:594–600. doi: 10.1016/j.ygyno.2008.11.039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Michelsen TM, Dorum A, Dahl AA. 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;113:128–133. doi: 10.1016/j.ygyno.2008.12.024. [DOI] [PubMed] [Google Scholar]
  • 43.Dennerstein L, Koochaki P, Barton I, Graziottin A. Hypoactive sexual desire disorder in menopausal women: a survey of Western European women. J Sex Med. 2006;3:212–222. doi: 10.1111/j.1743-6109.2006.00215.x. [DOI] [PubMed] [Google Scholar]
  • 44.Melton LJ, 3rd, Khosla S, Malkasian GD, Achenbach SJ, Oberg AL, Riggs BL. Fracture risk after bilateral oophorectomy in elderly women. J Bone Miner Res. 2003;18:900–905. doi: 10.1359/jbmr.2003.18.5.900. [DOI] [PubMed] [Google Scholar]
  • 45.Lindsay R, Hart DM, Forrest C, Baird C. Prevention of spinal osteoporosis in oophorectomised women. Lancet. 1980;2:1151–1154. doi: 10.1016/s0140-6736(80)92592-1. [DOI] [PubMed] [Google Scholar]
  • 46.Snowdon DA, Kane RL, Beeson WL, Burke GL, Sprafka JM, Potter J, et al. Is early natural menopause a biologic marker of health and aging? Am J Public Health. 1989;79:709–714. doi: 10.2105/ajph.79.6.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ. Ovarian androgen production in postmenopausal women. J Clin Endocrinol Metab. 2007;92:3040–3043. doi: 10.1210/jc.2007-0581. [DOI] [PubMed] [Google Scholar]
  • 48.Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab. 2005;90:3847–3853. doi: 10.1210/jc.2005-0212. [DOI] [PubMed] [Google Scholar]
  • 49.Kalantaridou SN, Nelson LM. Premature ovarian failure is not premature menopause. Ann N Y Acad Sci. 2000;900:393–402. doi: 10.1111/j.1749-6632.2000.tb06251.x. [DOI] [PubMed] [Google Scholar]
  • 50.Santoro N. Research on the mechanisms of premature ovarian failure. J Soc Gynecol Investig. 2001;8:S10–S12. doi: 10.1016/s1071-5576(00)00097-6. [DOI] [PubMed] [Google Scholar]
  • 51.Utian WH, Archer DF, Bachmann GA, Gallagher C, Grodstein F, Heiman JR, et al. Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause. 2008;15:584–602. doi: 10.1097/gme.0b013e31817b076a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Pitkin J, Rees MC, Gray S, Lumsden MA, Marsden J, Stevenson JC, et al. Management of premature menopause. Menopause Int. 2007;13:44–45. doi: 10.1258/175404507780456719. [DOI] [PubMed] [Google Scholar]
  • 53.Board of the International Menopause S. Pines A, Sturdee DW, Birkhauser MH, Schneider HP, Gambacciani M, et al. IMS updated recommendations on postmenopausal hormone therapy. Climacteric. 2007;10:181–194. doi: 10.1080/13697130701361657. [DOI] [PubMed] [Google Scholar]
  • 54.Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–87. doi: 10.1093/jnci/djn442. [DOI] [PMC free article] [PubMed] [Google Scholar]

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