Semin Reprod Med 2013; 31(06): 462-468
DOI: 10.1055/s-0033-1356482
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Accelerating Ovarian Age: Cancer Treatment in the Premenopausal Woman

Joseph Letourneau
1   Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California
2   Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina
,
S. W. Chan
1   Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California
,
Mitchell P. Rosen
1   Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California
› Author Affiliations
Further Information

Publication History

Publication Date:
07 October 2013 (online)

Abstract

The reproductive sequelae of cancer treatments may provide an important model of accelerated ovarian aging. Tens of thousands of women treated for cancer each year experience infertility and early menopause as a result of treatment. A spectrum of reproductive compromise commonly ranges from immediate menopause at the time of cancer treatment to the less proximate outcome of early menopause in the years to decades after treatment. A woman's reproductive lifespan can be shortened after chemotherapy or radiation because such treatments likely decrease the number of viable eggs after treatment. This acceleration in the decline of the number of follicles leads to increased rates of not only infertility and miscarriage but also early menopause, which represents the most extreme form of accelerated ovarian aging. The degree of reproductive impairment is dependent on chronologic age and the diagnosis or treatment. The variation in outcomes that persist may be partially explained by pretreatment ovarian reserve. Establishing the use of clinical predictors such as ovarian reserve markers to effectively anticipate such outcomes is an obvious and important keystone in the foundation of cancer survivorship research. An improved understanding of cancer treatment's ability to accelerate follicle death, decrease fecundability, and initiate an earlier menopause could provide a clinically relevant, time-shortened, and reproducible snapshot into the basic biology of ovarian aging.

 
  • References

  • 1 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63 (1) 11-30
  • 2 Siegel R, DeSantis C, Virgo K , et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 2012; 62 (4) 220-241
  • 3 Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14 (5) 1718-1729
  • 4 Chemaitilly W, Mertens AC, Mitby P , et al. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab 2006; 91 (5) 1723-1728
  • 5 Warne GL, Fairley KF, Hobbs JB, Martin FI. Cyclophosphamide-induced ovarian failure. N Engl J Med 1973; 289 (22) 1159-1162
  • 6 Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol 2000; 169 (1-2) 123-131
  • 7 Knobf MT. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors. Oncologist 2006; 11 (2) 96-110
  • 8 Letourneau JM, Ebbel EE, Katz PP , et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer 2012; 118 (6) 1710-1717
  • 9 Patel A, Sreedevi M, Malapati R , et al. Reproductive health assessment for women with cancer: a pilot study. Am J Obstet Gynecol 2009; 201 (2) e1-e4
  • 10 Tschudin S, Bitzer J. Psychological aspects of fertility preservation in men and women affected by cancer and other life-threatening diseases. Hum Reprod Update 2009; 15 (5) 587-597
  • 11 Carter J, Rowland K, Chi D , et al. Gynecologic cancer treatment and the impact of cancer-related infertility. Gynecol Oncol 2005; 97 (1) 90-95
  • 12 Wallace WHB. Oncofertility and preservation of reproductive capacity in children and young adults. Cancer 2011; 117 (10, Suppl): 2301-2310
  • 13 Anderson RA, Wallace WHB. Antimüllerian hormone, the assessment of the ovarian reserve, and the reproductive outcome of the young patient with cancer. Fertil Steril 2013; 99 (6) 1469-1475
  • 14 Lee SJ, Schover LR, Partridge AH , et al; American Society of Clinical Oncology. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 2006; 24 (18) 2917-2931
  • 15 Rugo HS, Rosen MP. Reducing the long-term effects of chemotherapy in young women with early-stage breast cancer. JAMA 2011; 306 (3) 312-314
  • 16 Schover LR. Patient attitudes toward fertility preservation. Pediatr Blood Cancer 2009; 53 (2) 281-284
  • 17 Albright F, Smith PH, Fraser R. A syndrome characterized by primary ovarian insufficiency and decreased stature: report of 11 cases with a digression on hormonal control of axillary and pubic hair. Am J Med Sci 1942; 204: 625-648
  • 18 Letourneau JM, Melisko ME, Cedars MI, Rosen MP. A changing perspective: improving access to fertility preservation. Nat Rev Clin Oncol 2011; 8 (1) 56-60
  • 19 Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009; 360 (6) 606-614
  • 20 Chemaitilly W, Mertens AC, Mitby P , et al. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab 2006; 91 (5) 1723-1728
  • 21 Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary?. Hum Reprod Update 2012; 18 (5) 525-535
  • 22 Letourneau JM, Ebbel EE, Katz PP , et al. Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer. Cancer 2012; 118 (7) 1933-1939
  • 23 Sklar CA, Mertens AC, Mitby P , et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst 2006; 98 (13) 890-896
  • 24 Rosen MP, Sternfeld B, Schuh-Huerta SM, Reijo Pera RA, McCulloch CE, Cedars MI. Antral follicle count: absence of significant midlife decline. Fertil Steril 2010; 94 (6) 2182-2185
  • 25 Rosen MP, Johnstone E, Addauan-Andersen C, Cedars MI. A lower antral follicle count is associated with infertility. Fertil Steril 2011; 95 (6) 1950-1954 , e1
  • 26 Levi AJ, Raynault MF, Bergh PA, Drews MR, Miller BT, Scott Jr RT. Reproductive outcome in patients with diminished ovarian reserve. Fertil Steril 2001; 76 (4) 666-669
  • 27 Elter K, Kavak ZN, Gokaslan H, Pekin T. Antral follicle assessment after down-regulation may be a useful tool for predicting pregnancy loss in in vitro fertilization pregnancies. Gynecol Endocrinol 2005; 21 (1) 33-37
  • 28 Rosendahl M, Andersen CY, la Cour Freiesleben N, Juul A, Løssl K, Andersen AN. Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age. Fertil Steril 2010; 94 (1) 156-166
  • 29 Letourneau JM, Niemasik EE, McCulloch CE , et al. Temporary amenorrhea predicts future infertility in young women treated with chemotherapy. Journal of Cancer Theraputics & Research 2013; 2: 1-9
  • 30 Petrek JA, Naughton MJ, Case LD , et al. Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 2006; 24 (7) 1045-1051
  • 31 Sukumvanich P, Case LD, Van Zee K , et al. Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study. Cancer 2010; 116 (13) 3102-3111
  • 32 Kiserud CE, Fosså A, Holte H, Fosså SD. Post-treatment parenthood in Hodgkin's lymphoma survivors. Br J Cancer 2007; 96 (9) 1442-1449
  • 33 Forman EJ, Anders CK, Behera MA. A nationwide survey of oncologists regarding treatment-related infertility and fertility preservation in female cancer patients. Fertil Steril 2010; 94 (5) 1652-1656
  • 34 Loprinzi CL, Wolf SL, Barton DL, Laack NN. Symptom management in premenopausal patients with breast cancer. Lancet Oncol 2008; 9 (10) 993-1001
  • 35 Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004; 10 (3) 251-266
  • 36 Amir E, Freedman O, Allen L, Colgan T, Clemons M. Defining ovarian failure in amenorrheic young breast cancer patients. Breast 2010; 19 (6) 545-548
  • 37 Di Cosimo S, Alimonti A, Ferretti G , et al. Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer. Ann Oncol 2004; 15 (7) 1065-1071
  • 38 Partridge A, Gelber S, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Winer E. Age of menopause among women who remain premenopausal following treatment for early breast cancer: long-term results from International Breast Cancer Study Group Trials V and VI. Eur J Cancer 2007; 43 (11) 1646-1653
  • 39 Luciano AM, Franciosi F, Lodde V , et al. Oocytes isolated from dairy cows with reduced ovarian reserve have a high frequency of aneuploidy and alterations in the localization of progesterone receptor membrane component 1 and aurora kinase B. Biol Reprod 2013; 88 (3) 58
  • 40 Schuh-Huerta SM, Johnson NA, Rosen MP, Sternfeld B, Cedars MI, Reijo Pera RA. Genetic markers of ovarian follicle number and menopause in women of multiple ethnicities. Hum Genet 2012; 131 (11) 1709-1724
  • 41 van Dorp W, van den Heuvel-Eibrink MM, Stolk L , et al. Genetic variation may modify ovarian reserve in female childhood cancer survivors. Hum Reprod 2013; 28 (4) 1069-1076
  • 42 De Vos M, Devroey P, Fauser BCJM. Primary ovarian insufficiency. Lancet 2010; 376 (9744) 911-921
  • 43 Anderson RA, Cameron DA. Pretreatment serum anti-müllerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. J Clin Endocrinol Metab 2011; 96 (5) 1336-1343
  • 44 Decanter C, Morschhauser F, Pigny P, Lefebvre C, Gallo C, Dewailly D. Anti-Müllerian hormone follow-up in young women treated by chemotherapy for lymphoma: preliminary results. Reprod Biomed Online 2010; 20 (2) 280-285
  • 45 Brougham MFH, Crofton PM, Johnson EJ, Evans N, Anderson RA, Wallace WH. Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study. J Clin Endocrinol Metab 2012; 97 (6) 2059-2067
  • 46 Gracia CR, Sammel MD, Freeman E , et al. Impact of cancer therapies on ovarian reserve. Fertil Steril 2012; 97 (1) 134-140 , e1
  • 47 Grynnerup AG-A, Lindhard A, Sørensen S. The role of anti-Müllerian hormone in female fertility and infertility - an overview. Acta Obstet Gynecol Scand 2012; 91 (11) 1252-1260
  • 48 Kevenaar ME, Meerasahib MF, Kramer P , et al. Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology 2006; 147 (7) 3228-3234
  • 49 Appt SE, Clarkson TB, Chen H , et al. Serum antimüllerian hormone predicts ovarian reserve in a monkey model. Menopause 2009; 16 (3) 597-601
  • 50 Velentgas P, Daling JR, Malone KE , et al. Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 1999; 85 (11) 2424-2432
  • 51 Rippy EE, Karat IF, Kissin MW. Pregnancy after breast cancer: the importance of active counselling and planning. Breast 2009; 18 (6) 345-350
  • 52 Overbeek A, van den Berg MH, Kremer LC , et al; DCOG LATER-VEVO study group. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges. BMC Cancer 2012; 12: 363
  • 53 Reulen RC, Zeegers MP, Wallace WH , et al; British Childhood Cancer Survivor Study. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009; 18 (8) 2239-2247
  • 54 Blakely LJ, Buzdar AU, Lozada JA , et al. Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence. Cancer 2004; 100 (3) 465-469
  • 55 Schover LR, Brey K, Lichtin A, Lipshultz LI, Jeha S. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. J Clin Oncol 2002; 20 (7) 1880-1889
  • 56 Schover LR. Motivation for parenthood after cancer: a review. J Natl Cancer Inst Monogr 2005; 2005 (34) 2-5
  • 57 Niemasik EE, Letourneau J, Dohan D , et al. Patient perceptions of reproductive health counseling at the time of cancer diagnosis: a qualitative study of female California cancer survivors. J Cancer Surviv 2012; 6 (3) 324-332
  • 58 Behringer K, Breuer K, Reineke T , et al; German Hodgkin's Lymphoma Study Group. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol 2005; 23 (30) 7555-7564
  • 59 Anderson RA, Themmen APN, Al-Qahtani A, Groome NP, Cameron DA. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 2006; 21 (10) 2583-2592
  • 60 Tham Y-L, Sexton K, Weiss H, Elledge R, Friedman LC, Kramer R. The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am J Clin Oncol 2007; 30 (2) 126-132
  • 61 Whitehead E, Shalet SM, Blackledge G, Todd I, Crowther D, Beardwell CG. The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease. Cancer 1983; 52 (6) 988-993
  • 62 TeVelde E, Pearson P. The variability of female reproductive ageing. Hum Reprod Update 2002; 8 (2) 141-154
  • 63 Decanter C, Morschnauser F, Pigny P , et al. Anti-mullerian hormone follow-up in young women treated by chemotherapy for lymphoma preliminary results. Reprod Biomed Online 2010; 20 (2) 280-285
  • 64 Garcia C, Samuel M, Freeman E , et al. Impact of cancer therapies on ovarian reserve. Fertil Steril 2012; 97 (1) 134-140. e1