title: Ovarian Damage During chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility.
abstract: Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency(POI) due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a) for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.
authors: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
authors: Wendy
authors: W
authors: Marder
authors: Senait
authors: S
authors: Fisseha
authors: Martha A
authors: MA
authors: Ganser
authors: Emily C
authors: EC
authors: Somers
keywords: autoimmune diseases; cyclophosphamide; fertility preservation; primary ovarian insufficiency
references: Obstet Gynecol. 1986 Apr;67(4):604-6
references: 3960433
references: Maturitas. 1996 May;24(1-2):97-106
references: 8794440
references: Ann Intern Med. 1993 Sep 1;119(5):366-9
references: 8338289
references: Arthritis Rheum. 2008 Nov 15;59(11):1639-46
references: 18975359
references: Psychooncology. 2001 May-Jun;10(3):231-41
references: 11351375
references: Semin Reprod Med. 2010 Sep;28(5):360-9
references: 20845236
references: Cochrane Database Syst Rev. 2011 Nov 09;(11):CD008018
references: 22071842
references: Ann Rheum Dis. 2012 Sep;71(9):1524-9
references: 22425941
references: Ann Rheum Dis. 1996 Apr;55(4):224-9
references: 8733438
references: Oncol Rep. 2003 Jan-Feb;10(1):151-5
references: 12469162
references: N Engl J Med. 1973 Nov 29;289(22):1159-62
references: 4754963
references: Osteoporos Int. 2002 Oct;13(10):777-87
references: 12378366
references: Hum Reprod. 2008 Nov;23(11):2506-12
references: 18664468
references: Acta Odontol Scand. 2002 Aug;60(4):208-12
references: 12222644
references: Gynecol Endocrinol. 2012 Aug;28(8):624-7
references: 22296584
references: Menopause. 2008 Sep-Oct;15(5):919-23
references: 18551082
references: J Clin Psychiatry. 2012 Jul;73(7):993-1001
references: 22687742
references: J Bone Miner Res. 2004 Jul;19(7):1172-80
references: 15177001
references: Fertil Steril. 2012 Nov;98(5):1266-70.e1
references: 22935556
references: Ann Intern Med. 2004 Nov 16;141(10):764-70
references: 15545676
references: Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S104-12
references: 22018194
references: Cancer Biol Ther. 2007 Feb;6(2):170-7
references: 17218784
references: Autoimmun Rev. 2004 Aug;3(6):423-53
references: 15351310
references: Am J Public Health. 1989 Jun;79(6):709-14
references: 2729468
references: J Clin Oncol. 2006 Aug 1;24(22):3576-82
references: 16877724
references: Fertil Steril. 2009 Aug;92(2):688-93
references: 18829005
references: J Rheumatol. 2002 Oct;29(10):2129-35
references: 12375322
references: Clin Endocrinol (Oxf). 2008 Apr;68(4):499-509
references: 17970776
references: JAMA. 2002 Jul 17;288(3):321-33
references: 12117397
references: Menopause. 2007 May-Jun;14(3 Pt 2):567-71
references: 17476146
references: Arthritis Rheum. 2009 Jun 15;61(6):822-9
references: 19479699
references: Joint Bone Spine. 2011 Jan;78(1):41-4
references: 20471889
references: Lancet. 2010 Sep 11;376(9744):911-21
references: 20708256
references: Mayo Clin Proc. 2006 Oct;81(10):1361-7
references: 17036562
references: Curr Opin Rheumatol. 2008 Mar;20(2):131-7
references: 18349741
references: N Engl J Med. 2005 Nov 24;353(21):2219-28
references: 16306519
references: Lupus. 2004;13(8):569-74
references: 15462485
references: Endocrinol Metab Clin North Am. 2003 Mar;32(1):135-57, vii
references: 12699296
references: N Engl J Med. 1989 Sep 7;321(10):641-6
references: 2488072
references: Semin Arthritis Rheum. 2011 Dec;41(3):346-52
references: 21868068
references: Osteoporos Int. 2009 Mar;20(3):427-33
references: 18600287
references: Arthritis Rheum. 2002 Aug;46(8):2121-31
references: 12209517
references: Menopause Int. 2010 Mar;16(1):38-41
references: 20424285
references: N Engl J Med. 2009 Feb 5;360(6):606-14
references: 19196677
references: JAMA. 2006 Mar 22;295(12):1374-6
references: 16551707
references: Fertil Steril. 2005 Jun;83(6):1734-41
references: 15950644
references: Drug Saf. 2005;28(5):401-16
references: 15853442
references: Maturitas. 1994 Aug;19(2):117-24
references: 7968644
references: Menopause. 2008 Jan-Feb;15(1):23-31
references: 18257141
references: Menopause. 2009 Jan-Feb;16(1):15-23
references: 19034050
references: Ann Rheum Dis. 2010 Jun;69(6):1155-7
references: 20439290
references: Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S85-92
references: 22018191
references: J Clin Endocrinol Metab. 1993 Nov;77(5):1148-51
references: 8077305
references: J Bone Miner Res. 1994 Mar;9(3):311-5
references: 8191923
references: J Rheumatol. 2003 Jul;30(7):1508-12
references: 12858449
references: Oncologist. 2008 May;13(5):613-4; author reply 615-7
references: 18581656
references: Ann N Y Acad Sci. 2000;900:393-402
references: 10818427
references: Arthritis Rheum. 1999 May;42(5):882-90
references: 10323443
references: Maturitas. 2010 Feb;65(2):161-6
references: 19733988
references: Am J Epidemiol. 2003 May 15;157(10):923-9
references: 12746245
references: Menopause. 2004 Nov-Dec;11(6 Pt 2):766-77
references: 15543028
references: Womens Health (Lond). 2009 Sep;5(5):565-76
references: 19702455
references: Lupus. 2000;9(6):401-5
references: 10981642
references: J Autoimmun. 2009 Nov-Dec;33(3-4):197-207
references: 19819109
references: Ann Epidemiol. 1998 May;8(4):229-35
references: 9590601
references: Ann N Y Acad Sci. 2010 Sep;1205:254-61
references: 20840281
references: Joint Bone Spine. 2011 Jan;78(1):23-30
references: 20471897
references: Arch Gynecol Obstet. 2005 Nov;273(1):17-9
references: 16007508
references: CA Cancer J Clin. 2012 Jul-Aug;62(4):220-41
references: 22700443
references: Am J Epidemiol. 2005 Dec 1;162(11):1089-97
references: 16221806
references: Maturitas. 2006 Jan 20;53(2):226-33
references: 15955642
references: Fertil Steril. 1997 Jul;68(1):95-102
references: 9207591
references: Menopause. 2008 Nov-Dec;15(6):1086-94
references: 18791485
references: Arch Intern Med. 1999 May 24;159(10):1061-6
references: 10335682
references: Am J Epidemiol. 2000 Mar 15;151(6):620-3
references: 10733044
references: Gynecol Oncol. 2009 Mar;112(3):594-600
references: 19141360
references: J Womens Health (Larchmt). 2009 Mar;18(3):311-9
references: 19281314
references: PLoS One. 2010 Feb 16;5(2):e9193
references: 20169063
references: J Psychosom Obstet Gynaecol. 2000 Sep;21(3):167-74
references: 11076338
references: Arthritis Care Res (Hoboken). 2012 Jan;64(1):2-8
references: 22213721
references: Lancet. 1994 Jul 2;344(8914):23-7
references: 7912297
references: Osteoporos Int. 2003 Jul;14(6):525-30
references: 12730751
references: Semin Reprod Med. 2011 Jul;29(4):328-41
references: 21969267
references: Ann Intern Med. 2005 Apr 19;142(8):620-6
references: 15838068
references: Arthritis Rheum. 2005 Sep;52(9):2761-7
references: 16142702
references: J Rheumatol. 2005 Jun;32(6):967-70
references: 15940751
references: Hum Reprod Update. 1999 Sep-Oct;5(5):483-92
references: 10582785
references: BJOG. 2012 Jun;119(7):810-6
references: 22531019
references: Endocrinol Metab Clin North Am. 2011 Jun;40(2):409-17, ix
references: 21565675
references: Br Med J. 1973 May 12;2(5862):325-8
references: 4704517
references: Menopause. 2012 Mar;19(3):257-71
references: 22367731
references: Am J Epidemiol. 2001 May 1;153(9):865-74
references: 11323317
references: Fertil Steril. 2010 May 1;93(7):2321-9
references: 19243752
references: Lupus. 2012 Aug;21(9):953-8
references: 22438026
references: Arthritis Res Ther. 2011 Jul 28;13(4):235
references: 21861862
references: Am J Epidemiol. 1997 Mar 1;145(5):408-15
references: 9048514
references: Bone. 1990;11(1):1-5
references: 2331425
references: Curr Opin Ophthalmol. 2000 Dec;11(6):478-83
references: 11141645
references: Fertil Steril. 1990 May;53(5):804-10
references: 2110072
references: Arthritis Rheum. 2006 Jun 15;55(3):420-6
references: 16739208
references: Acta Anat (Basel). 1986;127(2):93-9
references: 3788461
references: Hypertension. 2009 May;53(5):805-11
references: 19332659
references: Drug Saf. 2007;30(10):861-81
references: 17867724
references: Ann Oncol. 2010 May;21(5):983-7
references: 19828559
references: Otolaryngol Clin North Am. 2010 Aug;43(4):753-68
references: 20599080
references: Arthritis Rheum. 1998 May;41(5):831-7
references: 9588734
references: Neurology. 2008 Jan 15;70(3):200-9
references: 17761549
references: Isr Med Assoc J. 2009 Aug;11(8):486-91
references: 19891237
references: Clin Endocrinol (Oxf). 2010 Dec;73(6):707-14
references: 20738314
references: Eur J Clin Invest. 1999 Oct;29(10):877-85
references: 10583430
references: Fam Cancer. 2001;1(3-4):149-56
references: 14574171
references: Neurology. 2007 Sep 11;69(11):1074-83
references: 17761551
references: J Clin Oncol. 2000 Apr;18(7):1570-93
references: 10735906
references: N Engl J Med. 2010 Jul 15;363(3):221-32
references: 20647199
references: Ann Oncol. 2012 Jul;23(7):1818-25
references: 22228451
references: J Clin Oncol. 2008 Feb 10;26(5):753-8
references: 18258983