eMedicine Specialties > Obstetrics and Gynecology > Reproductive Endocrinology and Infertility

Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure: Follow-up

Author: Vaishali Popat, MD, MPH, Fellow in Endocrinology, National Institutes of Health
Coauthor(s): Lawrence M Nelson, MD, MBA, Head of Integrative Reproductive Medicine Unit, Investigator, Intramural Research Program on Reproductive and Adult Endocrinology, National Institutes of Child Health and Human Development, National Institutes of Health
Contributor Information and Disclosures

Updated: Jun 1, 2007

Follow-up

Further Outpatient Care

  • See Treatment.
  • Patients with ovarian failure should be seen annually to monitor their HRT.
  • Symptoms and signs of thyroid disease and adrenal insufficiency should be sought during the annual follow-up visits.
  • TSH levels should be checked every 3-5 years (every year if antiperoxidase antibody test is positive).
  • If a woman with POF/POI has positive adrenal antibodies on her initial evaluation, even if all adrenal function tests are normal, she is at high risk of developing adrenal insufficiency and should have an annual ACTH stimulation test. Whether women with initially negative adrenal antibody tests continue to carry higher than normal risk for adrenal insufficiency and whether any follow-up tests are justified is less clear. Until enough evidence is acquired, the authors suggest that an adrenal antibody test should be performed every 3-5 years.
  • Patients with secondary ovarian failure should be monitored for manifestations of the underlying hypothalamic/pituitary pathology (progression of space-occupying lesions and development/progression of hypopituitarism).

Prognosis

  • Women with spontaneous POF/POI have a low but real chance of spontaneous pregnancy. Approximately 5-10% become pregnant subsequent to the diagnosis of POF/POI. HRT does not prevent such pregnancies. Paradoxically, even oral contraceptives, which are designed for pregnancy protection of women without ovarian abnormalities, may not suppress the rare spontaneous ovulations of women with POF/POI. Therefore, patients with POF/POI should be well instructed about their reproductive situation so that they can make informed decisions regarding fertility.
  • Ovum donation remains the best current option to resolve the infertility, but patients with POF/POI should not be encouraged hastily because spontaneous pregnancy is a real possibility and ovum donation is as successful in older women as it is in younger women.

Patient Education

Miscellaneous

Special Concerns

  • Women with POF/POI who desire fertility occasionally opt for unproven treatments. Of particular concern is the tendency to regard POF/POI as an autoimmune disease that can be treated successfully with corticosteroids. Currently, no scientific proof exists that this is true. The anecdotal reports of restored ovulation or fertility after treatment with prednisone could represent reporting bias or random phenomena.
  • Corticosteroid treatment could lead to severe complications (the authors have observed 2 cases of osteonecrosis in women with presumed autoimmune POF/POI) and should be performed only as a part of review board–approved research protocols. Other unnecessary and expensive treatments or tests also should be discouraged.
 
Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Vladimir Bakalov, MD to the development and writing of this article.



More on Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure

Overview: Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure
Differential Diagnoses & Workup: Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure
Treatment & Medication: Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure
Follow-up: Spontaneous Primary Ovarian Insufficiency and Premature Ovarian Failure
References
[ CLOSE WINDOW ]

References

  1. Bardoni B, Mandel JL, Fisch GS. FMR1 gene and fragile X syndrome. Am J Med Genet. 2000;97(2):153-63. [Medline].

  2. Kim TJ, Anasti JN, Flack MR. Routine endocrine screening for patients with karyotypically normal spontaneous premature ovarian failure. Obstet Gynecol. May 1997;89(5 Pt 1):777-9. [Medline].

  3. Rebar RW, Connolly HV. Clinical features of young women with hypergonadotropic amenorrhea. Fertil Steril. May 1990;53(5):804-10. [Medline].

  4. Snowdon DA, Kane RL, Beeson WL, et al. Is early natural menopause a biologic marker of health and aging?. Am J Public Health. Jun 1989;79(6):709-14. [Medline].

  5. Nelson LM, Anasti JN, Kimzey LM, et al. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J Clin Endocrinol Metab. Nov 1994;79(5):1470-5. [Medline].

  6. Kalantaridou SN, Calis KA, Vanderhoof VH, Bakalov VK, Corrigan EC, Troendle JF. Testosterone deficiency in young women with 46,XX spontaneous premature ovarian failure. Fertil Steril. Nov 2006;86(5):1475-82. [Medline].

  7. Anasti JN. Premature ovarian failure: an update. Fertil Steril. Jul 1998;70(1):1-15. [Medline].

  8. Anasti JN, Adams S, Kimzey LM, et al. Karyotypically normal spontaneous premature ovarian failure: evaluation of association with the class II major histocompatibility complex. J Clin Endocrinol Metab. Mar 1994;78(3):722-3. [Medline].

  9. Bannatyne P, Russell P, Shearman RP. Autoimmune oophoritis: a clinicopathologic assessment of 12 cases. Int J Gynecol Pathol. 1990;9(3):191-207. [Medline].

  10. Belvisi L, Bombelli F, Sironi L, Doldi N. Organ-specific autoimmunity in patients with premature ovarian failure. J Endocrinol Invest. Dec 1993;16(11):889-92. [Medline].

  11. Betterle C, Rossi A, Dalla Pria S, et al. Premature ovarian failure: autoimmunity and natural history. Clin Endocrinol (Oxf). Jul 1993;39(1):35-43. [Medline].

  12. Betterle C, Volpato M. Adrenal and ovarian autoimmunity. Eur J Endocrinol. Jan 1998;138(1):16-25. [Medline].

  13. Biscotti CV, Hart WR, Lucas JG. Cystic ovarian enlargement resulting from autoimmune oophoritis. Obstet Gynecol. Sep 1989;74(3 Pt 2):492-5. [Medline].

  14. Bondy CA, Nelson LM, Kalantaridou SN. The genetic origins of ovarian failure. J Womens Health. Dec 1998;7(10):1225-9. [Medline].

  15. Byrne J. Infertility and premature menopause in childhood cancer survivors. Med Pediatr Oncol. Jul 1999;33(1):24-8. [Medline].

  16. Check JH, Nowroozi K, Chase JS, et al. Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril. May 1990;53(5):811-6. [Medline].

  17. Chen S, Sawicka J, Betterle C, et al. Autoantibodies to steroidogenic enzymes in autoimmune polyglandular syndrome, Addison''s disease, and premature ovarian failure. J Clin Endocrinol Metab. May 1996;81(5):1871-6. [Medline].

  18. Christin-Maitre S, Vasseur C, Portnoi MF, Bouchard P. Genes and premature ovarian failure. Mol Cell Endocrinol. Oct 25 1998;145(1-2):75-80. [Medline].

  19. Conway GS, Kaltsas G, Patel A, et al. Characterization of idiopathic premature ovarian failure. Fertil Steril. Feb 1996;65(2):337-41. [Medline].

  20. Coope J. Hormonal and non-hormonal interventions for menopausal symptoms. Maturitas. Mar 1996;23(2):159-68. [Medline].

  21. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. Apr 1986;67(4):604-6. [Medline].

  22. Davis SR. Premature ovarian failure. Maturitas. Feb 1996;23(1):1-8. [Medline].

  23. Fenichel P, Sosset C, Barbarino-Monnier P, et al. Prevalence, specificity and significance of ovarian antibodies during spontaneous premature ovarian failure. Hum Reprod. Dec 1997;12(12):2623-8. [Medline].

  24. Finer N, Fogelman I, Bottazzo G. Pregnancy in a woman with premature ovarian failure. Postgrad Med J. Dec 1985;61(722):1079-80. [Medline].

  25. Fiumara A, Sorge G, Toscano A, et al. Perrault syndrome: evidence for progressive nervous system involvement. Am J Med Genet. Jul 30 2004;128A(3):246-9. [Medline].

  26. Garguillo AR, Hill JA. Autoimmune endocrinopathies in female reproductive dysfunction. In: Volpe R, ed. Contemporary Endocrinology: Autoimmune Endocrinopathies. Totowa, NJ: Humana Press; 1999:365-91.

  27. Hagerman RJ, Leavitt BR, Farzin F, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet. May 2004;74(5):1051-6. [Medline].

  28. Hoek A, Schoemaker J, Drexhage HA. Premature ovarian failure and ovarian autoimmunity. Endocr Rev. Feb 1997;18(1):107-34. [Medline].

  29. Kalantaridou SN, Braddock DT, Patronas NJ, Nelson LM. Treatment of autoimmune premature ovarian failure. Hum Reprod. Jul 1999;14(7):1777-82. [Medline].

  30. Kalantaridou SN, Davis SR, Nelson LM. Premature ovarian failure. Endocrinol Metab Clin North Am. Dec 1998;27(4):989-1006. [Medline].

  31. Kalantaridou SN, Naka KK, Papanikolaou E, et al. Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy. J Clin Endocrinol Metab. Aug 2004;89(8):3907-13. [Medline].

  32. Koh JM, Kim CH, Hong SK. Primary ovarian failure caused by a solvent containing 2-bromopropane. Eur J Endocrinol. May 1998;138(5):554-6. [Medline].

  33. LaBarbera AR, Miller MM, Ober C. Autoimmune etiology in premature ovarian failure. Am J Reprod Immunol Microbiol. Mar 1988;16(3):115-22. [Medline].

  34. Lonsdale RN, Roberts PF, Trowell JE. Autoimmune oophoritis associated with polycystic ovaries. Histopathology. Jul 1991;19(1):77-81. [Medline].

  35. Luborsky JL, Visintin I, Boyers S. Ovarian antibodies detected by immobilized antigen immunoassay in patients with premature ovarian failure. J Clin Endocrinol Metab. Jan 1990;70(1):69-75. [Medline].

  36. Meyers CM, Boughman JA, Rivas M. Gonadal (ovarian) dysgenesis in 46,XX individuals: frequency of the autosomal recessive form. Am J Med Genet. Jun 28 1996;63(4):518-24. [Medline].

  37. Miller ME, Chatten J. Ovarian changes in ataxia telangiectasia. Acta Paediatr Scand. Sep 1967;56(5):559-61. [Medline].

  38. Namnoum AB, Merriam GR, Moses AM, Levine MA. Reproductive dysfunction in women with Albright''s hereditary osteodystrophy. J Clin Endocrinol Metab. Mar 1998;83(3):824-9. [Medline].

  39. Nelson LM, Anasti JN, Flack MR. Premature ovarian failure. In: Adashi E, ed. Reproductive Endocrinology, Surgery, and Technology. Philadelphia, Pa: Raven Press; 1996:1394-410.

  40. Nelson LM, Anasti JN, Kimzey LM, Defensor RA, Lipetz KJ, White BJ. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J Clin Endocrinol Metab. Nov 1994;79(5):1470-5. [Medline].

  41. Nelson LM, Bakalov VK. Mechanisms of follicular dysfunction in 46,XX spontaneous premature ovarian failure. Endocrinol Metab Clin North Am. Sep 2003;32(3):613-37. [Medline].

  42. Nelson LM, Kimzey LM, White BJ. Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial. Fertil Steril. Jan 1992;57(1):50-5. [Medline].

  43. Novosad JA, Kalantaridou SN, Tong ZB, Nelson LM. Ovarian antibodies as detected by indirect immunofluorescence are unreliable in the diagnosis of autoimmune premature ovarian failure: a controlled evaluation. BMC Womens Health. Mar 17 2003;3(1):2. [Medline].

  44. Prueitt RL, Zinn AR. A fork in the road to fertility. Nat Genet. Feb 2001;27(2):132-4. [Medline].

  45. Rebar RW, Cedars MI. Hypergonadotropic forms of amenorrhea in young women. Endocrinol Metab Clin North Am. Mar 1992;21(1):173-91. [Medline].

  46. Rebar RW, Morandini IC, Erickson GF, Petze JE. The hormonal basis of reproductive defects in athymic mice: diminished gonadotropin concentrations in prepubertal females. Endocrinology. Jan 1981;108(1):120-6. [Medline].

  47. Rosen GF, Stone SC, Yee B. Ovulation induction in women with premature ovarian failure: a prospective, crossover study. Fertil Steril. Feb 1992;57(2):448-9. [Medline].

  48. Schwartz CE, Dean J, Howard-Peebles PN, et al. Obstetrical and gynecological complications in fragile X carriers: a multicenter study. Am J Med Genet. Jul 15 1994;51(4):400-2. [Medline].

  49. Sedmak DD, Hart WR, Tubbs RR. Autoimmune oophoritis: a histopathologic study of involved ovaries with immunologic characterization of the mononuclear cell infiltrate. Int J Gynecol Pathol. 1987;6(1):73-81. [Medline].

  50. Sharf M, Israeli I, Graff G. The value of ovarian biopsy in the diagnosis and treatment of amenorrhea-related sterility. Obstet Gynecol. Jan 1972;39(1):89-94. [Medline].

  51. Simpson JL, Rajkovic A. Ovarian differentiation and gonadal failure. Am J Med Genet. Dec 29 1999;89(4):186-200. [Medline].

  52. Sklar C. Reproductive physiology and treatment-related loss of sex hormone production. Med Pediatr Oncol. Jul 1999;33(1):2-8. [Medline].

  53. Smith JA, Vitale S, Reed GF, et al. Dry eye signs and symptoms in women with premature ovarian failure. Arch Ophthalmol. Feb 2004;122(2):151-6. [Medline].

  54. Taylor AE, Adams JM, Mulder JE, et al. A randomized, controlled trial of estradiol replacement therapy in women with hypergonadotropic amenorrhea. J Clin Endocrinol Metab. Oct 1996;81(10):3615-21. [Medline].

  55. Tong ZB, Nelson LM. A mouse gene encoding an oocyte antigen associated with autoimmune premature ovarian failure. Endocrinology. Aug 1999;140(8):3720-6. [Medline].

  56. Tung KS, Lu CY. Immunologic basis of reproductive failure. Monogr Pathol. 1991;(33):308-33. [Medline].

  57. van Kasteren YM, Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update. Sep-Oct 1999;5(5):483-92. [Medline].

  58. Yan G, Schoenfeld D, Penney C, et al. Identification of premature ovarian failure patients with underlying autoimmunity. J Womens Health Gend Based Med. Apr 2000;9(3):275-87. [Medline].

  59. Zarate A, Karchmer S, Gomez E, Castelazo-Ayala L. Premature menopause. A clinical, histologic, and cytogenetic study. Am J Obstet Gynecol. Jan 1 1970;106(1):110-4. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

ovaries, reproductive organs, premature ovarian failure, primary ovarian failure, premature menopause, primary ovarian insufficiency, POF, anovulation, endocrine failure

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Vaishali Popat, MD, MPH, Fellow in Endocrinology, National Institutes of Health
Vaishali Popat, MD, MPH is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, American Medical Association, and Endocrine Society
Disclosure: Nothing to disclose.

Coauthor(s)

Lawrence M Nelson, MD, MBA, Head of Integrative Reproductive Medicine Unit, Investigator, Intramural Research Program on Reproductive and Adult Endocrinology, National Institutes of Child Health and Human Development, National Institutes of Health
Lawrence M Nelson, MD, MBA is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Endocrine Society, and Society for Experimental Biology and Medicine
Disclosure: Nothing to disclose.

Medical Editor

Thomas Michael Price, MD, Associate Professor of Reproductive Endocrinology, Director of Reproductive Fellowship Training Program, Duke University Medical Center
Thomas Michael Price, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Endocrine Society, Phi Beta Kappa, Society for Gynecologic Investigation, and South Carolina Medical Association
Disclosure: Clinical Advisors Group Consulting fee Consulting; MEDA Corp Consulting Consulting fee Consulting; Gerson Lehrman Group Advisor  Consulting fee Consulting; Roche/GSK Spokesperson  Consulting fee Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

A David Barnes, MD, PhD, MPH, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital, Mammoth Lakes, California, Pioneer Valley Hospital, Salt Lake City, Utah, Warren General Hospital, Warren, Pennsylvania and Mountain West Hospital, Tooele, Utah
A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Bryan D Cowan, MD, Professor and Chairman, Department of Obstetrics and Gynecology, University of Mississippi College of Medicine; Consulting Staff, Department of Obstetrics and Gynecology, Veterans Affairs Medical Center; Medical Director, Wiser Hospital for Women, University of Mississippi Medical Center
Bryan D Cowan, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Gynecological and Obstetrical Society, American Medical Association, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Endocrine Society, Sigma Xi, Society for Assisted Reproductive Technologies, Society for Gynecologic Investigation, Society for the Study of Reproduction, and Society of Laparoendoscopic Surgeons
Disclosure: Galil None Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.