Review Article

Primary Ovarian Insufficiency: Current Concepts

Authors: Gretchen Collins, MD, Bansari Patel, MD, Suruchi Thakore, MD, James Liu, MD

Abstract

A potential consequence of chemotherapy is the destruction of oocytes, resulting in primary ovarian insufficiency (POI) in young patients; this often results in secondary amenorrhea and necessitates hormone replacement therapy. Regardless of the etiology of POI, the chance of pregnancy is low in this patient population. Given the extent to which oocyte depletion or dysfunction is variable, there is the possibility of spontaneous ovulation on hormone replacement therapy and subsequent pregnancy, however. If pregnancy is not desired, contraception always should be discussed. In most patients, the etiology of POI will not be known, but the treatment for all patients includes estrogen and progesterone therapy, which ensures the development of secondary sex characteristics, acquisition of peak bone mass, and promotion of uterine growth and maturation. Early diagnosis, patient education, and emotional support are important to mitigate long-term sequelae.

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References

1. McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas 1992;14:103-115.
 
2. Laml T, Schulz-Lobmeyr I, Obruca A, et al. Premature ovarian failure: etiology and prospects. Gynecol Endocrinol 2000;14:292-302.
 
3. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol 1986;67:604-606.
 
4. Committee opinion no. 605: primary ovarian insufficiency in adolescents and young women. Obstet Gynecol 2014;124:193-197.
 
5. Anasti JN. Premature ovarian failure: an update. Fertil Steril 1998;70:1-15.
 
6. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009;360:606-614.
 
7. Lobo RA. Early ovarian ageing: a hypothesis. What is early ovarian ageing? Hum Reprod 2003;18:1762-1764.
 
8. Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One 2010;5:e8772.
 
9. Dang-Tan T, Franco EL. Diagnosis delays in childhood cancer: a review. Cancer 2007;110:703-713.
 
10. Afeiche MC, Bridges ND, Williams PL, et al. Dairy intake and semen quality among men attending a fertility clinic. Fertil Steril 2014;101:1280-1287.
 
11. Simpson JL, Rajkovic A. Ovarian differentiation and gonadal failure. Am J Med Genet 1999;89:186-200.
 
12. Zinn AR, Ross JL. Molecular analysis of genes on xp controlling Turner syndrome and premature ovarian failure (POF). Semin Reprod Med 2001;19:141-146.
 
13. Irvine WJ, Chan MM, Scarth L, et al. Immunological aspects of premature ovarian failure associated with idiopathic Addison' disease. Lancet 1968;2:883-887.
 
14. Alper MM, Garner PR. Premature ovarian failure: its relationship to autoimmune disease. Obstet Gynecol 1985;66:27-30.
 
15. Kim TJ, Anasti JN, Flack MR, et al. Routine endocrine screening for patients with karyotypically normal spontaneous premature ovarian failure. Obstet Gynecol 1997;89(5 Pt 1):777-779.
 
16. Karlsson FA, Kampe O, Winqvist O, et al. Autoimmune disease of the adrenal cortex, pituitary, parathyroid glands and gastric mucosa. J Intern Med 1993;234:379-386.
 
17. Ryan MM, Jones HR, Jr. Myasthenia gravis and premature ovarian failure. Muscle Nerve 2004;30:231-233.
 
18. Oktem O, Guzel Y, Aksoy S, et al. Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility. Obstet Gynecol Surv 2015;70:196-210.
 
19. Sammaritano LR. Menopause in patients with autoimmune diseases. Autoimmun Rev 2012;11:A430-A436.
 
20. Rebar RW. Premature ovarian"failure"in the adolescent. Ann N Y Acad Sci 2008;1135:138-145.
 
21. Morrison JC, Givens JR, Wiser WL, et al. Mumps oophoritis: a cause of premature menopause. Fertil Steril 1975;26:655-659.
 
22. van Kasteren YM, Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update 1999;5:483-492.
 
23. Gupta N, Sharma JB, Mittal S, et al. Genital tuberculosis in Indian infertility patients. Int J Gynaecol Obstet 2007;97:135-138.
 
24. Singh N, Dadhwal V, Sharma KA, et al. Xanthogranulomatous inflammation: a rare cause of premature ovarian failure. Arch Gynecol Obstet 2009;279:729-731.
 
25. Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964-1988 in Ontario, Canada. Am J Epidemiol 1999;150:245-254.
 
26. Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update 2001;7:535-543.
 
27. Apperley JF, Reddy N. Mechanism and management of treatment-related gonadal failure in recipients of high dose chemoradiotherapy. Blood Rev 1995;9:93-116.
 
28. Kinney A, Kline J, Kelly A, et al. Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years. Hum Reprod 2007;22:1175-1185.
 
29. Di Prospero F, Luzi S, Iacopini Z. Cigarette smoking damages women' reproductive life. Reprod Biomed Online 2004;8:246-247.
 
30. Chang SH, Kim CS, Lee KS, et al. Premenopausal factors influencing premature ovarian failure and early menopause. Maturitas 2007;58:19-30.
 
31. Mahadevan K, Murthy MS, Reddy PR, et al. Early menopause and its determinants. J Biosoc Sci 1982;14:473-479.
 
32. Pearce K, Tremellen K. Influence of nutrition on the decline of ovarian reserve and subsequent onset of natural menopause. Hum Fertil (Camb) 2016;19:173-179.
 
33. Taneri PE, Kiefte-de Jong JC, Bramer WM, et al. Association of alcohol consumption with the onset of natural menopause: a systematic review and meta-analysis. Hum Reprod Update 2016;22:516-528.
 
34. Rebar RW. Premature ovarian failure. Obstet Gynecol 2009;113:1355-1363.
 
35. Woad KJ, Watkins WJ, Prendergast D, et al. The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol 2006;46:242-244.
 
36. Nelson SM. Biomarkers of ovarian response: current and future applications. Fertil Steril 2013;99:963-969.
 
37. Alzubaidi NH, Chapin HL, Vanderhoof VH, et al. Meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure. Obstet Gynecol 2002;99(5 Pt 1):720-725.
 
38. Murray A, Schoemaker MJ, Bennett CE, et al. Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency. Genet Med 2014;16:19-24.
 
39. Wittenberger MD, Hagerman RJ, Sherman SL, et al. The FMR1 premutation and reproduction. Fertil Steril 2007;87:456-465.
 
40. Bachelot A, Rouxel A, Massin N, et al. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur J Endocrinol 2009;161:179-187.
 
41. Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis 2006;1:9.
 
42. Tao XY, Zuo AZ, Wang JQ, et al. Effect of primary ovarian insufficiency and early natural menopause on mortality: a meta-analysis. Climacteric 2016;19:27-36.
 
43. Bakalov VK, Vanderhoof VH, Bondy CA, et al. Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure. Hum Reprod 2002;17:2096-2100.
 
44. Betterle C, Volpato M, Rees Smith B, et al. I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison' disease. J Clin Endocrinol Metab 1997;82:932-938.
 
45. Anasti JN, Kalantaridou SN, Kimzey LM, et al. Bone loss in young women with karyotypically normal spontaneous premature ovarian failure. Obstet Gynecol 1998;91:12-15.
 
46. Uygur D, Sengul O, Bayar D, et al. Bone loss in young women with premature ovarian failure. Arch Gynecol Obstet 2005;273:17-19.
 
47. Atsma F, Bartelink ML, Grobbee DE, et al. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause 2006;13:265-279.
 
48. Menning BE. The emotional needs of infertile couples. Fertil Steril 1980;34:313-319.
 
49. Mahlstedt PP. The psychological component of infertility. Fertil Steril 1985;43:335-346.
 
50. Stanton AL, Tennen H, Affleck G, et al. Cognitive appraisal and adjustment to infertility. Women Health 1991;17:1-15.
 
51. Groff AA, Covington SN, Halverson LR, et al. Assessing the emotional needs of women with spontaneous premature ovarian failure. Fertil Steril 2005;83:1734-1741.
 
52. Weber L, Davies M, Anderson R, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016;31:926-937.
 
53. Ankarberg-Lindgren C, Kristrom B, Norjavaara E. Physiological estrogen replacement therapy for puberty induction in girls: a clinical observational study. Horm Res Paediatr 2014;81:239-244.
 
54. Cisternino M, Nahoul K, Bozzola M, et al. Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism. J Endocrinol Invest 1991;14:481-488.
 
55. Steingold KA, Matt DW, DeZiegler D. Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. J Clin Endocrinol Metab 1991;72:275-280.
 
56. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of transsexual persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2009;94:3132-3154.
 
57. Taboada M, Santen R, Lima J, et al. Pharmacokinetics and pharmacodynamics of oral and transdermal 17β estradiol in girls with Turner syndrome. J Clin Endocrinol Metab 2011;96:3502-3510.
 
58. Jospe N, Orlowski CC, Furlanetto RW. Comparison of transdermal and oral estrogen therapy in girls with Turner' syndrome. J Pediatr Endocrinol Metab 1995;8:111-116.
 
59. Afeiche MC, Gaskins AJ, Williams PL, et al. Processed meat intake is unfavorably and fish intake favorably associated with semen quality indicators among men attending a fertility clinic. J Nutr 2014;144:1091-1098.
 
60. Cartwright B, Robinson J, Seed PT, et al. Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab 2016;101:3497-3505.
 
61. Shapiro AG, Rubin A. Spontaneous pregnancy in association with hypergonadotropic ovarian failure. Fertil Steril 1977;28:500-501.
 
62. Shangold MM, Turksoy RN, Bashford RA, et al. Pregnancy following the"insensitive ovary syndrome."Fertil Steril 1977;28:1179-1181.
 
63. Starup J, Philip J, Sele V. Oestrogen treatment and subsequent pregnancy in two patients with severe hypergonadotrophic ovarian failure. Acta Endocrinol (Copenh) 1978;89:149-157.
 
64. Polansky S, De Papp EW. Pregnancy associated with hypergonadotropic hypogonadism. Obstet Gynecol 1976;47:47S-51S.
 
65. Szlachter BN, Nachtigall LE, Epstein J, et al. Premature menopause: a reversible entity? Obstet Gynecol 1979;54:396-398.
 
66. Wright CS, Jacobs HS. Spontaneous pregnancy in a patient with hypergonadotrophic ovarian failure. Br J Obstet Gynaecol 1979;86:389-392.
 
67. Jeppsson S, Ljungberg O, Rannevik G. Hypergonadotrophic hypogonadism with preserved fertility-a new syndrome? Acta Endocrinol (Copenh) 1980;95:388-392.
 
68. Check JH, Chase JS. Ovulation induction in hypergonadotropic amenorrhea with estrogen and human menopausal gonadotropin therapy. Fertil Steril 1984;42:919-922.
 
69. Alper MM, Jolly EE, Garner PR. Pregnancies after premature ovarian failure. Obstet Gynecol 1986;67(3 Suppl):59S-62S.
 
70. Chen X, Chen SL, Ye DS, et al. Retrospective analysis of reproductive outcomes in women with primary ovarian insufficiency showing intermittent follicular development. Reprod Biomed Online 2016;32:427-433.
 
71. Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol 2016;28:217-222.
 
72. Cordeiro CN, Christianson MS, Selter JH, et al. In vitro activation: a possible new frontier for treatment of primary ovarian insufficiency. Reprod Sci 2016;23:429-438.