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Chemotherapy-Induced Ovarian Failure

Manifestations and Management

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Abstract

Thanks to improvements in treatment regimens, more and more patients are now surviving cancer. However, cancer survivors are faced with the serious long-term effects of the different modalities of cancer treatments. One of these adverse effects is chemotherapy-induced irreversible damage to the ovarian tissues, which leads to premature ovarian failure and its resulting consequences such as hot flashes, osteoporosis, sexual dysfunction and the risk of infertility. Chemotherapy-induced ovarian failure (or chemotherapy-induced premature menopause) affects the quality of life of female cancer survivors. Although there is no clear definition of chemotherapy-induced ovarian failure, irreversible amenorrhoea lasting for several months (>12 months) following chemotherapy and a follicle stimulating hormone level of ≥30 MIU/mL in the presence of a negative pregnancy test seems to be an appropriate characterisation. Different chemotherapy agents, alkylating cytotoxics in particular, have the potential to cause progressive and irreversible damage to the ovaries. The result of this damage is a state of premature ovarian failure, with progressive declining of estrogen levels, decreasing bone mass and an increased risk of fractures. Historically, hormonal replacement therapy (HRT) has been used to treat menopausal problems in the general population, but concerns about the potential of estrogen to increase the risk of breast cancer in women at high-risk or increase the risk of recurrence in cancer survivors, have forced physicians to utilise alternative treatments. This review discusses some of the newer therapies that are now available to provide appropriate symptom control, avoid complications such as fractures and possibly prevent infertility by making the ovarian epithelium less susceptible to cytotoxic agents.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Hewitt M, Breen N, Devesa S. Cancer prevalence and survivorship issues: analyses of the 1992 National Health Interview Survey. J Natl Cancer Inst 1999; 91: 1480–6

    Article  PubMed  CAS  Google Scholar 

  2. Birch JM, Marsden HB, Morris Jones PH, et al. Improvements in survival from childhood cancer: results of a population based survey over 30 years. BMJ 1988; 28: 1372–6

    Article  Google Scholar 

  3. Wingo PA, Ries LA, Parker SL, et al. Long-term cancer patient survival in the United States. Cancer Epidemiol Biomarkers Prev 1998; 7: 271–82

    PubMed  CAS  Google Scholar 

  4. Bookman M, Longo D, Young R. Late complications of curative treatment in Hodgkin’s disease. JAMA 1988; 260: 680–3

    Article  PubMed  CAS  Google Scholar 

  5. Meister LA, Meadows AT. Late effects of childhood cancer therapy. Curr Probl Pediatr 1993; 23: 102–31

    PubMed  CAS  Google Scholar 

  6. Blumenfeld Z, Avivi I, Ritter M, et al. Preservation of fertility and ovarian function and minimizing chemotherapy-induced gonadotoxicity in young women. J Soc Gynecol Invest 1999; 6: 229–39

    Article  CAS  Google Scholar 

  7. Chapman RM, Sutcliffe SB, Maipas JS. Cytotoxic induced ovarian failure in women with Hodgkin’s disease: I. hormonal function. JAMA 1979; 242: 1877–81

    Article  PubMed  CAS  Google Scholar 

  8. Chapman RM. Effect of cytotoxic therapy on sexuality and gonadal function. Semin Oncol 1982; 9: 84–93

    PubMed  CAS  Google Scholar 

  9. Kreuser ED, Xirus N, Hetzel WD, et al. Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy of Hodgkin’s disease. J Cancer Res Clin Oncol 1987; 113: 260–6

    Article  PubMed  CAS  Google Scholar 

  10. Rivkees SA, Crawford JD. The relationship of gonadal damage to chemotherapy. JAMA 1988; 259: 2123–5

    Article  PubMed  CAS  Google Scholar 

  11. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14: 1718–29

    PubMed  CAS  Google Scholar 

  12. Klein NA, Soules MR. Endocrine changes of the perimenopause. Clin Obstet Gynecol 1998; 41: 912–9210

    Article  PubMed  CAS  Google Scholar 

  13. Familiari GA, Caggiati A, Nottola SA, et al. Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin’s disease. Hum Reprod 1993; 8: 2080–7

    PubMed  CAS  Google Scholar 

  14. Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol 2000; 27: 123–31

    Article  Google Scholar 

  15. Ataya K, Moghissi K. Chemotherapy-induced premature ovarian failure: mechanisms and prevention. Steroids 1989; 54: 607–26

    Article  PubMed  CAS  Google Scholar 

  16. Berg G, Gottwall T, Hammar M, et al. Climacteric symptoms among women aged 60-62 in Linkoping, Sweden, in 1986. Maturitas 1988; 10: 193–9

    Article  PubMed  CAS  Google Scholar 

  17. Carpenter JS, Andrykowski MA, Cordova M, et al. Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life. Cancer 1998; 82: 1682–91

    Article  PubMed  CAS  Google Scholar 

  18. Beral V, Banks E, Reeves G. Evidence from randomized trials on the long-term effects of hormone replacement therapy. Lancet 2002; 360: 942–4

    Article  PubMed  Google Scholar 

  19. Li CI, Malone KE, Porter PL, et al. Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. JAMA 2003; 289: 3254–63

    Article  PubMed  CAS  Google Scholar 

  20. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 2003; 289: 3243–53

    Article  PubMed  CAS  Google Scholar 

  21. Rossouw JE. Effect of postmenopausal hormone therapy on cardiovascular risk. J Hypertens 2002; 20: S62–5

    CAS  Google Scholar 

  22. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288: 321–33

    Article  PubMed  CAS  Google Scholar 

  23. Stephenson J. FDA orders estrogen safety warnings: agency offers guidance for HRT use. JAMA 2003; 289: 537–8

    Article  PubMed  Google Scholar 

  24. Consensus development conference: prophylaxis and treatment of osteoporosis. Osteoporos Int 1991; 1: 114–7

    Google Scholar 

  25. van der Voort DJ, Geusens PP, et al. Risk factors for osteoporosis related to their outcome: fractures. Osteoporos Int 2001; 12: 630–8

    Article  PubMed  Google Scholar 

  26. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4: 368–81

    Article  PubMed  CAS  Google Scholar 

  27. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. JAMA 2001; 285: 785–95

  28. Bruning PF, Pit MJ, de Jong-Bakker M, et al. Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J Cancer 1990; 61: 308–10

    Article  PubMed  CAS  Google Scholar 

  29. Kanis JA, McCloskey EV, Powles T, et al. A high incidence of vertebral fracture in women with breast cancer. Br J Cancer 1999; 79: 1179–81

    Article  PubMed  CAS  Google Scholar 

  30. Saarto T, Blomqvist C, Valimaki M, et al. Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens. Br J Cancer 1997; 75: 602–5

    Article  PubMed  CAS  Google Scholar 

  31. Powles TJ, McCloskey E, Paterson AH, et al. Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer. J Natl Cancer Inst 1998; 90: 704–8

    Article  PubMed  CAS  Google Scholar 

  32. Headley JA, Theriault RL, LeBlanc AD, et al. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy. Cancer Invest 1998; 16: 6–11

    Article  PubMed  CAS  Google Scholar 

  33. Sverrisdottir A, Fornander T, Rutqvist L. Bone mineral density in premenopausal patients in a randomized trial of adjuvant endocrine therapy (ZIPP-TRIAL). San Francisco: American Society of Clinical Oncology, 2001

    Google Scholar 

  34. Favus MJ, editor. Primer on metebolic bone diseases and disorders of mineral metabolism. 4th ed. Philadelphia: Lippincott, 1999: 502

    Google Scholar 

  35. The Writing Group for the PEPI. Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions [PEPI] trial. JAMA 1996; 276: 1389–96

    Google Scholar 

  36. Prince RL. Counterpoint: estrogen effects on calcitropic hormones and calcium homeostasis. Endocr Rev 1994; 15: 301–9

    PubMed  CAS  Google Scholar 

  37. Eastell R. Management of osteoporosis due to ovarian failure. Med Pediatr Oncol 2003; 41: 222–7

    Article  PubMed  Google Scholar 

  38. Pfeilschifter J, Diel IJ. Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol 2000; 18: 1570–93

    PubMed  CAS  Google Scholar 

  39. Friedlander G, Tross R, Doganis AG. Effects of chemotherapeutic agents on bone: I. short-term methotrexate and doxorubicin [adriamycin] treatment in a rat model. J Bone Joint Surg Am 1984; 66: 602–7

    Google Scholar 

  40. Wang TM, Shih C. Study of histomorphometric changes of the mandibular condyles in neonatal and juvenile rats after administration of cyclophosphamide. Acta Anat (Basel) 1986; 127: 93–9

    Article  CAS  Google Scholar 

  41. Delmas PD, Fontana A. Bone loss induced by cancer treatment and its management. Eur J Cancer 1998; 34: 260–2

    Article  PubMed  CAS  Google Scholar 

  42. Powles TJ, Hickish T, Kanis JA, et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 1996; 14: 78–84

    PubMed  CAS  Google Scholar 

  43. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 1998; 351: 1451–67

    Google Scholar 

  44. Grey AB, Stapleton JP, Evans MC, et al. The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women. Am J Med 1995; 99: 636–41

    Article  PubMed  CAS  Google Scholar 

  45. Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992; 326: 852–6

    Article  PubMed  CAS  Google Scholar 

  46. Resch A, Biber E, Seifert M, et al. Evidence that tamoxifen preserves bone density in late postmenopausal women with breast cancer. Acta Oncol 1998; 37: 661–4

    Article  PubMed  CAS  Google Scholar 

  47. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371–88

    Article  PubMed  CAS  Google Scholar 

  48. Love RR, Mazess RB, Tormey DC, et al. Bone mineral density in women with breast cancer treated with adjuvant tamoxifen for at least two years. Breast Cancer Res Treat 1988; 12: 297–302

    Article  PubMed  CAS  Google Scholar 

  49. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators: mechanisms of action and application to clinical practice. N Engl J Med 2003; 348: 618–29

    Article  PubMed  CAS  Google Scholar 

  50. Benson JR, Pitsinis V. Update on clinical role of tamoxifen. Curr Opin Obstet Gynecol 2003; 15: 13–23

    Article  PubMed  Google Scholar 

  51. Yoneda K, Tanji Y, Ikeda N, et al. Influence of adjuvant tamoxifen treatment on bone mineral density and bone turnover markers in postmenopausal breast cancer patients in Japan. Cancer Lett 2002; 186: 223–30

    Article  PubMed  CAS  Google Scholar 

  52. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282: 637–45

    Article  PubMed  CAS  Google Scholar 

  53. O’Regan RM, Jordan VC. Tamoxifen to raloxifene and beyond. Semin Oncol 2001; 28: 260–73

    Article  PubMed  Google Scholar 

  54. Delmas PD, Ensrud KE, Adachi JD, et al. For the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. Efficacy of Raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002; 87: 3609–17

    Article  PubMed  CAS  Google Scholar 

  55. Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet 2002; 359: 2131–9

    Article  PubMed  CAS  Google Scholar 

  56. Cohen MH, Johnson JR, Li N, et al. Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer. Clin Cancer Res 2002; 8: 665–9

    PubMed  CAS  Google Scholar 

  57. Harper-Wynne CL, Sacks NP, Shenton K, et al. Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer. J Clin Oncol 2002; 20: 1026–35

    Article  PubMed  CAS  Google Scholar 

  58. Bajetta E, Ferrari L, Celio L, et al. The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. J Steroid Biochem Mol Biol 1997; 63: 261–7

    Article  PubMed  CAS  Google Scholar 

  59. Eastell R HR. Effect of anastrozole on bone density and bone turnover: results of the arimidex (Anastrozole), tamoxifen, alone or in combination (ATAC) study. Programs and Proceedings of the 24th Annual Meeting of the American Society for Bone and Mineral Research; San Antonio (TX) 2002

    Google Scholar 

  60. Lindsay R, Cosman F. Estrogen in prevention and treatment of osteoporosis. Ann N Y Acad Sci 1990; 592: 326–33

    Article  PubMed  CAS  Google Scholar 

  61. Riis BJ, Overgaard K, Christiansen C. Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy. Osteoporos Int 1995; 5: 276–80

    Article  PubMed  CAS  Google Scholar 

  62. Lindsay R, Hart DM, MacLean A, et al. Bone response to termination of oestrogen treatment. Lancet 1978; I: 1325–7

    Article  Google Scholar 

  63. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992; 327: 1637–42

    Article  PubMed  CAS  Google Scholar 

  64. Reid IR, Ames RW, Evans MC, et al. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Am J Med 1995; 98: 331–5

    Article  PubMed  CAS  Google Scholar 

  65. Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337: 670–6

    Article  PubMed  CAS  Google Scholar 

  66. Licata AA. Bisphosphonate therapy. Am J Med Sci 1997; 31: 17–22

    Article  Google Scholar 

  67. Reszka AA, Rodan GA. Bisphosphonate mechanism of action. Curr Rheumatol Rep 2003; 5: 65–74

    Article  PubMed  Google Scholar 

  68. Flanagan AM, Chambers TJ. Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone. Calcif Tissue Int 1991; 49: 407–15

    Article  PubMed  CAS  Google Scholar 

  69. Pataki A, Muller K, Green JR, et al. Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment. Anat Rec 1997; 249: 458–68

    Article  PubMed  CAS  Google Scholar 

  70. Rogers MJ, Frith JC, Luckman SP, et al. Molecular mechanisms of action of bisphosphonates. Bone 1999; 24: 73S–9S

    Article  PubMed  CAS  Google Scholar 

  71. Tumber A, Morgan HM, Meikle MC, et al. Human breast-cancer cells stimulate the fusion, migration and resorptive activity of osteoclasts in bone explants. Int J Cancer 2001; 91: 665–72

    Article  PubMed  CAS  Google Scholar 

  72. Hall DG, Stoica G. Effect of the bisphosphonate risedronate on bone metastases in a rat mammary adenocarcinoma model system. J Bone Miner Res 1994; 9: 221–30

    Article  PubMed  CAS  Google Scholar 

  73. Cummings SR, Eckert S, Krueger KA, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280: 2077–82

    Article  PubMed  CAS  Google Scholar 

  74. Karpf DB, Shapiro DR, Seeman E, et al. Prevention of nonvertebral fractures by alendronate: a meta-analysis. Alendronate Osteoporosis Treatment Study Groups. JAMA 1997; 277: 1159–64

    Article  PubMed  CAS  Google Scholar 

  75. Black DM, Cummings SR, Karpf DB, et al. Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996; 348: 1535–41

    Article  PubMed  CAS  Google Scholar 

  76. Hosking D, Chilvers CE, Christiansen C, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age: Early Postmenopausal Intervention Cohort Study Group. N Engl J Med 1998; 338: 485–92

    Article  PubMed  CAS  Google Scholar 

  77. Liberman UA, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 1995; 333: 1437–43

    Article  PubMed  CAS  Google Scholar 

  78. Stock JL, Bell NH, Chesnut CH, et al. Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women. Am J Med 1997; 103: 291–7

    Article  PubMed  CAS  Google Scholar 

  79. Pavlakis N, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2002; (1): CD003474

  80. Zolendronate [zometa]. Med Lett Drugs Ther 2001; 43: 110–1

  81. CGP 42446 Protocol 007 [data on file]. Novartis Pharmaceuticals, 1998

  82. Berenson J. Phase II trial of Zoledronate vs Pamidronate in Multiple Myeloma and Breast Cancer Patients with Osteolytic Lesions. Montreal, Canada: Second North American Symposium on Skeletal Complications of Malignancy. 1999

    Google Scholar 

  83. Kanis JA, Powles T, Paterson AH, et al. Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone 1996; 19: 663–7

    Article  PubMed  CAS  Google Scholar 

  84. Delmas PD, Balena R, Confravreux E, et al. Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study. J Clin Oncol 1997; 15: 955–62

    PubMed  CAS  Google Scholar 

  85. Hillner BE, Ingle JN, Berenson JR, et al. Pamidronate in prevention of bone complications in metastatic breast cancer: a costeffectiveness analysis. J Clin Oncol 2000; 18: 72–9

    PubMed  CAS  Google Scholar 

  86. Downs Jr RW, Bell NH, Ettinger MP, et al. Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab 2000; 85: 1783–8

    Article  PubMed  CAS  Google Scholar 

  87. Barni S, Mondin R. Sexual dysfunction in treated breast cancer patients. Ann Oncol 1997; 8: 149–53

    Article  PubMed  CAS  Google Scholar 

  88. Ganz PA, Rowland JH, Meyerowitz BE, et al. Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors. Recent Results Cancer Res 1998; 152: 396–411

    Article  PubMed  CAS  Google Scholar 

  89. Schover LR, Yetman RJ, Tuason LJ, et al. Partial mastectomy and breast reconstruction: a comparison of their effects on psychosocial adjustment, body image, and sexuality. Cancer 1995; 75: 54–64

    Article  PubMed  CAS  Google Scholar 

  90. Ganz PA, Desmond KA, Belin TR, et al. Predictors of sexual health in women after a breast cancer diagnosis. J Clin Oncol 1999; 17: 2371–80

    PubMed  CAS  Google Scholar 

  91. Young-McCaughan S. Sexual functioning in women with breast cancer after treatment with adjuvant therapy. Cancer Nurs 1996; 19: 308–19

    Article  PubMed  CAS  Google Scholar 

  92. Ganz PA, Kwan L, Stanton AL, et al. Quality of life at the end of primary treatment of breast cancer: first results from the moving beyond cancer randomized trial. J Natl Cancer Inst 2004; 96: 376–87

    Article  PubMed  Google Scholar 

  93. Thors CL, Broeckel JA, Jacobsen PB. Sexual functioning in breast cancer survivors. Cancer Control 2001; 8: 442–8

    PubMed  CAS  Google Scholar 

  94. Fallowfield LJ, Hall A, Maguire GP, et al. Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial. BMJ 1990; 301: 575–80

    Article  PubMed  CAS  Google Scholar 

  95. Ganz PA, Coscarelli A, Fred C, et al. Breast cancer survivors: psychosocial concerns and quality of life. Breast Cancer Res Treat 1996; 38: 183–99

    Article  PubMed  CAS  Google Scholar 

  96. Joly F, Espie M, Marty M, et al. Long-term quality of life in premenopausal women with node-negative localized breast cancer treated with or without adjuvant chemotherapy. Br J Cancer 2000; 83: 577–82

    Article  PubMed  CAS  Google Scholar 

  97. Mortimer JE, Boucher L, Baty J, et al. Effect of tamoxifen on sexual functioning in patients with breast cancer. J Clin Oncol 1999; 17: 1488–92

    PubMed  CAS  Google Scholar 

  98. Ganz PA, Rowland JH, Desmond K, et al. Life after breast cancer: understanding women’s health-related quality of life and sexual functioning. J Clin Oncol 1998; 16: 501–14

    PubMed  CAS  Google Scholar 

  99. Berglund G, Nystedt M, Bolund C, et al. Effect of endocrine treatment on sexuality in premenopausal breast cancer patients: a prospective randomized study. J Clin Oncol 2001; 19: 2788–96

    PubMed  CAS  Google Scholar 

  100. Ganz PA, Schag AC, Lee JJ, et al. Breast conservation versus mastectomy: is there a difference in psychological adjustment or quality of life in the year after surgery? Cancer 1992; 69: 1729–38

    Article  PubMed  CAS  Google Scholar 

  101. Wapnir IL, Cody RP, Greco RS, Subtle differences in quality of life after breast cancer surgery. Ann Surg Oncol 1999; 6: 359–66

    Article  PubMed  CAS  Google Scholar 

  102. Dorval M, Maunsell E, Deschenes L, et al. Type of mastectomy and quality of life for long term breast carcinoma survivors. Cancer 1998; 83: 2130–8

    Article  PubMed  CAS  Google Scholar 

  103. Kiebert GM, de Haes JC, van de Velde CJ. The impact of breast-conserving treatment and mastectomy on the quality of life of early-stage breast cancer patients: a review. J Clin Oncol 1991; 9: 1059–70

    PubMed  CAS  Google Scholar 

  104. Moyer A. Psychosocial outcomes of breast-conserving surgery versus mastectomy: a meta-analytic review. Health Psychol 1997; 16: 284–98

    Article  PubMed  CAS  Google Scholar 

  105. Greendale GA, Petersen L, Zibecchi L, et al. Factors related to sexual function in postmenopausal women with a history of breast cancer. Menopause 2001; 8: 111–9

    Article  PubMed  CAS  Google Scholar 

  106. Ganz PA, Greendale GA, Petersen L, et al. Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. J Natl Cancer Inst 2000; 92: 1054–64

    Article  PubMed  CAS  Google Scholar 

  107. Nachtigall LE. Comparative study: replens versus local estrogen in menopausal women. Fertil Steril 1994; 61: 178–80

    PubMed  CAS  Google Scholar 

  108. Loprinzi CL, Abu-Ghazaleh S, Sloan JA, et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. J Clin Oncol 1997; 15: 969–73

    PubMed  CAS  Google Scholar 

  109. Greendale GA, Reboussin BA, Hogan P, et al. Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial. Obstet Gynecol 1998; 92: 982–8

    Article  PubMed  CAS  Google Scholar 

  110. Rioux JE, Devlin C, Gelfand MM, et al. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause 2000; 7: 156–61

    Article  PubMed  CAS  Google Scholar 

  111. Davis SR, Tran J. Testosterone influences libido and well being in women. Trends Endocrinol Metab 2001; 12: 33–7

    Article  PubMed  CAS  Google Scholar 

  112. Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000; 343: 682–8

    Article  PubMed  CAS  Google Scholar 

  113. Simon JA. Safety of estrogen/androgen regimens. J Reprod Med 2001; 46: 281–90

    PubMed  CAS  Google Scholar 

  114. Stein KD, Jacobsen PB, Hann DM, et al. Impact of hot flashes on quality of life among postmenopausal women being treated for breast cancer. J Pain Symptom Manage 2000; 19: 436–45

    Article  PubMed  CAS  Google Scholar 

  115. Finck G, Barton DL, Loprinzi CL, et al. Definitions of hot flashes in breast cancer survivors. J Pain Symptom Manage 1998; 16: 327–33

    Article  PubMed  CAS  Google Scholar 

  116. Roberts J, Chambers LF, Blake J, et al. Psychosocial adjustment in post-menopausal women. Can J Nurs Res 1992; 24: 29–46

    PubMed  CAS  Google Scholar 

  117. Daly E, Gray A, Barlow D, et al. Measuring the impact of menopausal symptoms on quality of life. BMJ 1993; 307: 836–40

    Article  PubMed  CAS  Google Scholar 

  118. Greendale GA, Lee NP, Arriola ER. The menopause. Lancet 1999; 353: 571–80

    Article  PubMed  CAS  Google Scholar 

  119. McKinlay SM, Jefferys M. The menopausal syndrome. Br J Prev Soc Med 1974; 28: 108–15

    PubMed  CAS  Google Scholar 

  120. Casper RF, Yen SS. Neuroendocrinology of menopausal flushes: an hypothesis of flush mechanism. Clin Endocrinol [Oxf] 1985; 22: 293–312

    Article  CAS  Google Scholar 

  121. Rosenberg J, Larsen SH. Hypothesis: pathogenesis of postmenopausal hot flush. Med Hypotheses 1991; 35: 349–50

    Article  PubMed  CAS  Google Scholar 

  122. Kronenberg F, Downey JA. Thermoregulatory physiology of menopausal hot flashes: a review. Can J Physiol Pharmacol 1987; 65: 1312–24

    Article  PubMed  CAS  Google Scholar 

  123. Staropoli CA, Flaws JA, Bush TL, et al. Predictors of menopausal hot flashes. J Womens Health 1998; 7: 1149–55

    Article  PubMed  CAS  Google Scholar 

  124. Rabin DS, Cipparrone N, Linn ES, et al. Why menopausal women do not want to take hormone replacement therapy. Menopause 1999; 6: 61–7

    Article  PubMed  CAS  Google Scholar 

  125. Notelovitz M, Lenihan JP, McDermott M, et al. Initial 17betaestradiol dose for treating vasomotor symptoms. Obstet Gynecol 2000; 95: 726–31

    Article  PubMed  CAS  Google Scholar 

  126. Lobo RA, McCormick W, Singer F, et al. Depo-medroxyprogesterone acetate compared with conjugated estrogens for the treatment of postmenopausal women. Obstet Gynecol 1984; 63: 1–5

    PubMed  CAS  Google Scholar 

  127. Garg PP, Kerlikowske K, Subak L, et al. Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a metaanalysis. Obstet Gynecol 1998; 92: 472–9

    Article  PubMed  CAS  Google Scholar 

  128. Coughlin SS, Giustozzi A, Smith SJ, et al. A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer. J Clin Epidemiol 2000; 53: 367–75

    Article  PubMed  CAS  Google Scholar 

  129. Riman T, Dickman PW, Nilsson S, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst 2002; 94: 497–504

    Article  PubMed  CAS  Google Scholar 

  130. Smith DC, Prentice R, Thompson DJ, et al. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 1975; 293: 1164–7

    Article  PubMed  CAS  Google Scholar 

  131. McDonald TW, Malkasian GD, Gaffey TA, Endometrial cancer associated with feminizing ovarian tumor and polycystic ovarian disease. Obstet Gynecol 1977; 49: 654–8

    PubMed  CAS  Google Scholar 

  132. Hoibraaten E, Qvigstad E, Arnesen H, et al. Increased risk of recurrent venous thromboembolism during hormone replacement therapy: results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial [EVTET]. Thromb Haemost 2000; 84: 961–7

    PubMed  CAS  Google Scholar 

  133. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000; 132: 689–96

    PubMed  CAS  Google Scholar 

  134. Barrett-Connor E, Grady D. Hormone replacement therapy, heart disease, and other considerations. Annu Rev Public Health 1998; 19: 55–72

    Article  PubMed  CAS  Google Scholar 

  135. Hulley S, Furberg C, Barrett-Connor E, et al. HERS Research Group. Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up [HERS II]. JAMA 2002; 288: 58–66

    Article  PubMed  CAS  Google Scholar 

  136. Chen CL, Weiss NS, Newcomb P, et al. Hormone replacement therapy in relation to breast cancer. JAMA 2002; 287: 734–41

    Article  PubMed  CAS  Google Scholar 

  137. Lacey Jr JV, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002; 288: 334–41

    Article  PubMed  CAS  Google Scholar 

  138. Vastag B. Hormone replacement therapy falls out of favor with expert committee. JAMA 2002; 287: 1923–4

    Article  PubMed  Google Scholar 

  139. Tanis BC, van den Bosch MA, Kemmeren JM, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med 2001; 345: 1787–93

    Article  PubMed  CAS  Google Scholar 

  140. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study [HERS] Research Group. JAMA 1998; 280: 605–13

    Article  PubMed  CAS  Google Scholar 

  141. Grady D, Herrington D, Bittner V, et al. HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up [HERS II]. JAMA 2002; 288: 49–57

    Article  PubMed  Google Scholar 

  142. Weiss LK, Burkman RT, Cushing-Haugen KL, et al. Hormone replacement therapy regimens and breast cancer risk. Obstet Gynecol 2002; 100: 1148–58

    Article  PubMed  CAS  Google Scholar 

  143. Hlatky MA, Boothroyd D, Vittinghoff E, et al. Heart and Estrogen/Progestin Replacement Study [HERS] Research Group. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study [HERS] trial. JAMA 2002; 287: 591–7

    Article  PubMed  CAS  Google Scholar 

  144. Loprinzi CL. Tamoxifen-induced hot flashes. Clin Breast Cancer 2000; 1: 52–6

    Article  PubMed  CAS  Google Scholar 

  145. Ganz PA. Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life. J Natl Cancer Inst Monogr 2001; 30: 130–4

    Article  PubMed  Google Scholar 

  146. Ganz PA, Desmond KA, Leedham B, et al. Quality of life in long-term, disease-free survivors of breast cancer: a follow-up study. J Natl Cancer Inst 2002; 94: 39–49

    Article  PubMed  Google Scholar 

  147. Mourits MJ, De Vries EG, Willemse PH, et al. Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol 2001; 97: 855–66

    Article  PubMed  CAS  Google Scholar 

  148. Loprinzi CL, Goldberg RM, O’Fallon JR, et al. Transdermal clonidine for ameliorating post-orchiectomy hot flashes. J Urol 1994; 151: 634–6

    PubMed  CAS  Google Scholar 

  149. Loprinzi CL, Michalak JC, Quella SK, et al. Megestrol acetate for the prevention of hot flashes. N Engl J Med 1994; 331: 347–52

    Article  PubMed  CAS  Google Scholar 

  150. Barton DL, Loprinzi CL, Quella SK, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16: 495–500

    PubMed  CAS  Google Scholar 

  151. Quella SK, Loprinzi CL, Barton DL, et al. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J Clin Oncol 2000; 18: 1068–74

    PubMed  CAS  Google Scholar 

  152. Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 2002; 20: 1578–83

    Article  PubMed  CAS  Google Scholar 

  153. Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 2000; 356: 2059–63

    Article  PubMed  CAS  Google Scholar 

  154. Van Patten CL, Olivotto IA, Chambers GK, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 2002; 20: 1449–55

    Article  PubMed  Google Scholar 

  155. Vincent A, Fitzpatrick LA. Soy isoflavones: are they useful in menopause? Mayo Clin Proc 2000; 75: 1174–84

    Article  PubMed  CAS  Google Scholar 

  156. Upmalis DH, Lobo R, Bradley L, et al. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 2000; 7: 236–42

    Article  PubMed  CAS  Google Scholar 

  157. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause 2000; 7: 105–11

    Article  PubMed  CAS  Google Scholar 

  158. Albertazzi P, Pansini F, Bottazzi M, et al. Dietary soy supplementation and phytoestrogen levels. Obstet Gynecol 1999; 94: 229–31

    Article  PubMed  CAS  Google Scholar 

  159. Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998; 91: 6–11

    Article  PubMed  CAS  Google Scholar 

  160. Han KK, Soares Jr JM, Haidar MA, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002; 99: 389–94

    Article  PubMed  CAS  Google Scholar 

  161. Stearns V, Isaacs C, Rowland J, et al. A pilot trial assessing the efficacy of paroxetine hydrochloride [Paxil] in controlling hot flashes in breast cancer survivors. Ann Oncol 2000; 11: 17–22

    Article  PubMed  CAS  Google Scholar 

  162. Stearns V, Isaacs C, Henry-Tillman A, et al. Paroxetine is an effective therapy for hot flashes: results from a prospective randomized clinical trial. Proc Am Soc Clin Oncol 2003; 22: 731

    Google Scholar 

  163. Beebe K, Stearns V, Iyengar M. A randomized, double-blind study assessing controlled-release paroxetine [Paroxetine CR, Paxil] in the treatment of hot flashes associated with menopause. The US Psychiatric & Mental Health Congress; Las Vegas (NV) 2002

    Google Scholar 

  164. Guttuso Jr T, Kurlan R, McDermott MP, et al. Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2003; 101: 337–45

    Article  PubMed  CAS  Google Scholar 

  165. Loprinzi L, Barton DL, Sloan JA, et al. Pilot evaluation of gabapentin for treating hot flashes. Mayo Clin Proc 2002; 77: 1159–63

    Article  PubMed  CAS  Google Scholar 

  166. David A, Don R, Tajchner G, et al. Veralipride: alternative antidopaminergic treatment for menopausal symptoms. Am J Obstet Gynecol 1988; 158: 1107–15

    PubMed  CAS  Google Scholar 

  167. Vercellini P, Vendola N, Colombo A, et al. Veralipride for hot flushes during gonadotropin-releasing hormone agonist treatment. Gynecol Obstet Invest 1992; 34: 102–4

    Article  PubMed  CAS  Google Scholar 

  168. Wesel S, Bourguignon RP, Bosuma WB. Veralipride versus conjugated oestrogens: a double-blind study in the management of menopausal hot flushes. Curr Med Res Opin 1984; 8: 696–700

    Article  PubMed  CAS  Google Scholar 

  169. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001; 19: 2739–45

    PubMed  CAS  Google Scholar 

  170. Davis SR, Briganti EM, Chen RQ, et al. The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women: a randomized controlled trial. Med J Aust 2001; 174: 68–71

    PubMed  CAS  Google Scholar 

  171. Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002; 177: 440–3

    PubMed  Google Scholar 

  172. Goodwin J, Freeman JH, Freman DH, et al. Double blind phase III trial of placebo (P) vs. megestrol acetate (MA) 20mg vs. MA 40mg as treatment for symptoms of ovarian failure in breast cancer survivors: initial results of Southwest Oncology Group S9626. San Antonio Breast Cancer Symposium; 2001

    Google Scholar 

  173. Quella SK, Loprinzi CL, Sloan JA, et al. Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes. Cancer 1998; 82: 1784–8

    Article  PubMed  CAS  Google Scholar 

  174. Barton D, Loprinzi C, Quella SK, et al. Depomedroxyprogesterone acetate for hot flashes. J Pain Symptom Manage 2002; 24: 603–7

    Article  PubMed  CAS  Google Scholar 

  175. Bertelli G, Venturini M, Del Mastro L, et al. Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study. Ann Oncol 2002; 13: 883–8

    Article  PubMed  CAS  Google Scholar 

  176. Byrne J, Mulvihill JJ, Myers MH, et al. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med 1987; 317: 1315–21

    Article  PubMed  CAS  Google Scholar 

  177. Radford JA, Shalet SM, Lieberman BA. Fertility after-treatment for cancer. BMJ 1999; 319: 935–6

    Article  PubMed  CAS  Google Scholar 

  178. Ortin TT, Shostak CA, Donaldson SS. Gonadal status and reproductive function following treatment for Hodgkin’s disease in childhood: the Stanford experience. J Radiat Oncol Biol Phys 1990; 19: 873–80

    Article  CAS  Google Scholar 

  179. Ataya KM, McKanna JA, Weintraub AM, et al. Prevention of chemotherapy-induced ovarian follicular loss in rats. Cancer Res 1985; 45: 3651–6

    PubMed  CAS  Google Scholar 

  180. Glode LM, Robinson J, Gould SF. Protection from cyclophosphamide induced testicular damage with an analogue of gonadotropin-releasing hormone. Lancet 1981; 23: 1132–4

    Article  Google Scholar 

  181. Ataya K, Moghissi K. Chemotherapy-induced premature ovarian failure: mechanisms and prevention. Steroids 1989; 54: 607–26

    Article  PubMed  CAS  Google Scholar 

  182. Ataya K, Rao LV, Lawrence E, et al. Luteinizing hormone-releasing agonist inhibits cyclophosphamide induced ovarian follicular depletion in Rhesus monkeys. Biol Reprod 1995; 52: 86–92

    Article  Google Scholar 

  183. Blumenfeld Z, Dann E, Avivi I, et al. Fertility after treatment for Hodgkin’s disease. Ann Oncol 2002; 13: 138–47

    Article  PubMed  Google Scholar 

  184. Meirow D, Lewis H, Nugent D, et al. Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool. Hum Reprod 1999; 14: 1903–7

    Article  PubMed  CAS  Google Scholar 

  185. Cox SL, Shaw J, Jenkin G. Transplantation of cryopreserved fetal ovarian tissue to adult recipients in mice. J Reprod Fertil 1996; 107: 315–22

    Article  PubMed  CAS  Google Scholar 

  186. Gosden RG, Baird DT, Wade JC, et al. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at −196 degrees C. Hum Reprod 1994; 9: 597–603

    PubMed  CAS  Google Scholar 

  187. Baird DT, Webb R, Campbell BK, et al. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at −196°C. Endocrinology 1999; 140: 462–71

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Julian R. Molina was supported by a generous grant from The Charles Oswald Foundation. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA

    Julian R. Molina, Debra L Barton &  Charles L. Loprinzi

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  1. Julian R. Molina
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Correspondence to Charles L. Loprinzi.

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Molina, J.R., Barton, D.L. & Loprinzi, C.L. Chemotherapy-Induced Ovarian Failure. Drug-Safety 28, 401–416 (2005). https://doi.org/10.2165/00002018-200528050-00004

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