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Vol. 33, No. 1, 2009
Issue release date: May 2009
Free Access
Neuroepidemiology 2009;33:32–40
(DOI:10.1159/000211951)

Increased Mortality for Neurological and Mental Diseases following Early Bilateral Oophorectomy

Rivera C.M.a · Grossardt B.R.b · Rhodes D.J.a · Rocca W.A.c, d
Divisions of aPreventive and Occupational Medicine, Department of Internal Medicine, bBiomedical Statistics and Informatics and cEpidemiology, Department of Health Sciences Research, and dDepartment of Neurology, College of Medicine, Mayo Clinic, Rochester, Minn., USA
email Corresponding Author

Abstract

Background: The effects of oophorectomy on brain aging remain uncertain. Methods: We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.


 goto top of outline Key Words

  • Oophorectomy
  • Neurological diseases
  • Mental diseases
  • Mortality
  • Cohort study

 goto top of outline Abstract

Background: The effects of oophorectomy on brain aging remain uncertain. Methods: We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd: Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074–1083.
  2. Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd: Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology 2008;70:200–209.
  3. Rocca WA, Grossardt BR, Maraganore DM: The long-term effects of oophorectomy on cognitive and motor aging are age dependent. Neurodegener Dis 2008;5:257–260.
  4. Shuster LT, Gostout BS, Grossardt BR, Rocca WA: Prophylactic oophorectomy in premenopausal women and long-term health. Menopause Int 2008;14:111–116.
  5. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH: Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 2004;291:2947–2958.
  6. 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.
  7. Porta MS, International Epidemiological Association: A Dictionary of Epidemiology, ed 5. Oxford, Oxford University Press, 2008.
  8. Rocca WA, Grossardt BR, Geda YE, Gostout BS, Bower JH, Maraganore DM, de Andrade M, Melton LJ 3rd: Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy. Menopause 2008;15:1050–1059.
  9. Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, Melton LJ 3rd: Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Womens Health (London) 2009;5:39–48.
  10. Melton LJ 3rd, Bergstralh EJ, Malkasian GD, O’Fallon WM: Bilateral oophorectomy trends in Olmsted County, Minnesota, 1950–1987. Epidemiology 1991;2:149–152.
  11. Melton LJ 3rd, Crowson CS, Malkasian GD, O’Fallon WM: Fracture risk following bilateral oophorectomy. J Clin Epidemiol 1996;49:1111–1115.
  12. 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.
  13. Beard CM, Crowson CS, Malkasian GD, O’Fallon WM, Melton LJ 3rd: Cardiovascular disease and cancer risk following bilateral oophorectomy: a population-based study in Rochester, Minnesota. J Womens Health 1995;4:133–141.

    External Resources

  14. Melton LJ 3rd: History of the Rochester Epidemiology Project. Mayo Clin Proc 1996;71:266–274.
  15. Commission on Professional and Hospital Activities: H-ICDA, Hospital Adaptation of ICDA, ed 2. Ann Arbor, 1973.
  16. Therneau TM, Grambsch PM: Modeling Survival Data: Extending the Cox Model. New York, Springer, 2000.
  17. Armstrong K, Schwartz JS, Randall T, Rubin SC, Weber B: Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis. J Clin Oncol 2004;22:1045–1054.
  18. Weisskopf MG, O’Reilly EJ, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A: Prospective study of military service and mortality from ALS. Neurology 2005;64:32–37.
  19. Buckley J, Warlow C, Smith P, Hilton-Jones D, Irvine S, Tew JR: Motor neuron disease in England and Wales, 1959–1979. J Neurol Neurosurg Psychiatry 1983;46:197–205.
  20. Chio A, Magnani C, Oddenino E, Tolardo G, Schiffer D: Accuracy of death certificate diagnosis of amyotrophic lateral sclerosis. J Epidemiol Community Health 1992;46:517–518.
  21. Hoffman PM, Brody JA: The reliability of death certificate reporting for amyotrophic lateral sclerosis. J Chronic Dis 1971;24:5–8.
  22. Smith R, Studd JW: A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. J R Soc Med 1992;85:612–613.
  23. Holmqvist P, Wallberg M, Hammar M, Landtblom AM, Brynhildsen J: Symptoms of multiple sclerosis in women in relation to sex steroid exposure. Maturitas 2006;54:149–153.
  24. Voskuhl RR: Hormone-based therapies in MS. Int MS J 2003;10:60–66.
  25. Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR: Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 2002;52:421–428.
  26. Houtchens MK: Pregnancy and multiple sclerosis. Semin Neurol 2007;27:434–441.
  27. Morrison JH, Brinton RD, Schmidt PJ, Gore AC: Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci 2006;26:10332–10348.
  28. Gibbs RG: Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging 2000;21:107–116.
  29. Webber KM, Casadesus G, Marlatt MW, Perry G, Hamlin CR, Atwood CS, Bowen RL, Smith MA: Estrogen bows to a new master: the role of gonadotropins in Alzheimer pathogenesis. Ann N Y Acad Sci 2005;1052:201–209.
  30. Singh M: Progesterone-induced neuroprotection. Endocrine 2006;29:271–274.
  31. Singh M, Sumien N, Kyser C, Simpkins JW: Estrogens and progesterone as neuroprotectants: what animal models teach us. Front Biosci 2008;13:1083–1089.
  32. Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J: Progesterone receptors: form and function in brain. Front Neuroendocrinol 2008;29:313–339.
  33. Bialek M, Zaremba P, Borowicz KK, Czuczwar SJ: Neuroprotective role of testosterone in the nervous system. Pol J Pharmacol 2004;56:509–518.
  34. Beard CM, Melton LJ 3rd, Cedel SL, Richelson LS, Riggs BL: Ascertainment of risk factors for osteoporosis: comparison of interview data with medical record review. J Bone Miner Res 1990;5:691–699.
  35. Coulam CB, Adamson SC, Annegers JF: Incidence of premature ovarian failure. Obstet Gynecol 1986;67:604–606.
  36. Marks NF, Shinberg DS: Socioeconomic status differences in hormone therapy. Am J Epidemiol 1998;148:581–593.
  37. Grodstein F, Clarkson TB, Manson JE: Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 2003;348:645–650.
  38. Lynch JW, Kaplan GA, Cohen RD, Tuomilehto J, Salonen JT: Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction? Am J Epidemiol 1996;144:934–942.

 goto top of outline Author Contacts

Dr. Walter A. Rocca
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic
200 First Street SW
Rochester, MN 55905 (USA)
Tel. +1 507 284 3568; Fax +1 507 284 1516; E-Mail rocca@mayo.edu


 goto top of outline Article Information

Received: August 2, 2008
Accepted: February 1, 2009
Published online: April 8, 2009
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 3, Number of References : 38


 goto top of outline Publication Details

Neuroepidemiology

Vol. 33, No. 1, Year 2009 (Cover Date: May 2009)

Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)

For additional information: http://www.karger.com/NED


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: The effects of oophorectomy on brain aging remain uncertain. Methods: We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.



 goto top of outline Author Contacts

Dr. Walter A. Rocca
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic
200 First Street SW
Rochester, MN 55905 (USA)
Tel. +1 507 284 3568; Fax +1 507 284 1516; E-Mail rocca@mayo.edu


 goto top of outline Article Information

Received: August 2, 2008
Accepted: February 1, 2009
Published online: April 8, 2009
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 3, Number of References : 38


 goto top of outline Publication Details

Neuroepidemiology

Vol. 33, No. 1, Year 2009 (Cover Date: May 2009)

Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)

For additional information: http://www.karger.com/NED


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd: Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074–1083.
  2. Rocca WA, Bower JH, Maraganore DM, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ 3rd: Increased risk of parkinsonism in women who underwent oophorectomy before menopause. Neurology 2008;70:200–209.
  3. Rocca WA, Grossardt BR, Maraganore DM: The long-term effects of oophorectomy on cognitive and motor aging are age dependent. Neurodegener Dis 2008;5:257–260.
  4. Shuster LT, Gostout BS, Grossardt BR, Rocca WA: Prophylactic oophorectomy in premenopausal women and long-term health. Menopause Int 2008;14:111–116.
  5. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH: Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 2004;291:2947–2958.
  6. 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.
  7. Porta MS, International Epidemiological Association: A Dictionary of Epidemiology, ed 5. Oxford, Oxford University Press, 2008.
  8. Rocca WA, Grossardt BR, Geda YE, Gostout BS, Bower JH, Maraganore DM, de Andrade M, Melton LJ 3rd: Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy. Menopause 2008;15:1050–1059.
  9. Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, Melton LJ 3rd: Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Womens Health (London) 2009;5:39–48.
  10. Melton LJ 3rd, Bergstralh EJ, Malkasian GD, O’Fallon WM: Bilateral oophorectomy trends in Olmsted County, Minnesota, 1950–1987. Epidemiology 1991;2:149–152.
  11. Melton LJ 3rd, Crowson CS, Malkasian GD, O’Fallon WM: Fracture risk following bilateral oophorectomy. J Clin Epidemiol 1996;49:1111–1115.
  12. 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.
  13. Beard CM, Crowson CS, Malkasian GD, O’Fallon WM, Melton LJ 3rd: Cardiovascular disease and cancer risk following bilateral oophorectomy: a population-based study in Rochester, Minnesota. J Womens Health 1995;4:133–141.

    External Resources

  14. Melton LJ 3rd: History of the Rochester Epidemiology Project. Mayo Clin Proc 1996;71:266–274.
  15. Commission on Professional and Hospital Activities: H-ICDA, Hospital Adaptation of ICDA, ed 2. Ann Arbor, 1973.
  16. Therneau TM, Grambsch PM: Modeling Survival Data: Extending the Cox Model. New York, Springer, 2000.
  17. Armstrong K, Schwartz JS, Randall T, Rubin SC, Weber B: Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis. J Clin Oncol 2004;22:1045–1054.
  18. Weisskopf MG, O’Reilly EJ, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A: Prospective study of military service and mortality from ALS. Neurology 2005;64:32–37.
  19. Buckley J, Warlow C, Smith P, Hilton-Jones D, Irvine S, Tew JR: Motor neuron disease in England and Wales, 1959–1979. J Neurol Neurosurg Psychiatry 1983;46:197–205.
  20. Chio A, Magnani C, Oddenino E, Tolardo G, Schiffer D: Accuracy of death certificate diagnosis of amyotrophic lateral sclerosis. J Epidemiol Community Health 1992;46:517–518.
  21. Hoffman PM, Brody JA: The reliability of death certificate reporting for amyotrophic lateral sclerosis. J Chronic Dis 1971;24:5–8.
  22. Smith R, Studd JW: A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. J R Soc Med 1992;85:612–613.
  23. Holmqvist P, Wallberg M, Hammar M, Landtblom AM, Brynhildsen J: Symptoms of multiple sclerosis in women in relation to sex steroid exposure. Maturitas 2006;54:149–153.
  24. Voskuhl RR: Hormone-based therapies in MS. Int MS J 2003;10:60–66.
  25. Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR: Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 2002;52:421–428.
  26. Houtchens MK: Pregnancy and multiple sclerosis. Semin Neurol 2007;27:434–441.
  27. Morrison JH, Brinton RD, Schmidt PJ, Gore AC: Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci 2006;26:10332–10348.
  28. Gibbs RG: Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging 2000;21:107–116.
  29. Webber KM, Casadesus G, Marlatt MW, Perry G, Hamlin CR, Atwood CS, Bowen RL, Smith MA: Estrogen bows to a new master: the role of gonadotropins in Alzheimer pathogenesis. Ann N Y Acad Sci 2005;1052:201–209.
  30. Singh M: Progesterone-induced neuroprotection. Endocrine 2006;29:271–274.
  31. Singh M, Sumien N, Kyser C, Simpkins JW: Estrogens and progesterone as neuroprotectants: what animal models teach us. Front Biosci 2008;13:1083–1089.
  32. Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J: Progesterone receptors: form and function in brain. Front Neuroendocrinol 2008;29:313–339.
  33. Bialek M, Zaremba P, Borowicz KK, Czuczwar SJ: Neuroprotective role of testosterone in the nervous system. Pol J Pharmacol 2004;56:509–518.
  34. Beard CM, Melton LJ 3rd, Cedel SL, Richelson LS, Riggs BL: Ascertainment of risk factors for osteoporosis: comparison of interview data with medical record review. J Bone Miner Res 1990;5:691–699.
  35. Coulam CB, Adamson SC, Annegers JF: Incidence of premature ovarian failure. Obstet Gynecol 1986;67:604–606.
  36. Marks NF, Shinberg DS: Socioeconomic status differences in hormone therapy. Am J Epidemiol 1998;148:581–593.
  37. Grodstein F, Clarkson TB, Manson JE: Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 2003;348:645–650.
  38. Lynch JW, Kaplan GA, Cohen RD, Tuomilehto J, Salonen JT: Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction? Am J Epidemiol 1996;144:934–942.