Fertility and Sterility
Volume 84, Issue 4 , Pages 958-965, October 2005

Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure

  • Vladimir K. Bakalov, M.D.

      Affiliations

    • Section on Women’s Health Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • James N. Anasti, M.D.

      Affiliations

    • Section on Women’s Health Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Karim A. Calis, Pharm.D., M.P.H.

      Affiliations

    • Clinical Research Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • ,
  • Vien H. Vanderhoof, C.R.N.P.

      Affiliations

    • Section on Women’s Health Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland
  • ,
  • Ahalya Premkumar, M.D.

      Affiliations

    • Clinical Research Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • ,
  • Shu Chen, M.D., Ph.D.

      Affiliations

    • FIRS Laboratories, RSR Ltd., Cardiff, United Kingdom
    • Drs. Shu Chen, Jadwiga Frumaniak, and Bernard Rees Smith are named inventors on a patent relating to 21 hydroxylase autoantibodies and employees of RSR Ltd., a developer and manufacturer of in vitro diagnostics including reagents for the measurement of 21 hydroxylase autoantibodies. In addition, Dr. Smith is a shareholder in RSR, Ltd.
  • ,
  • Jadwiga Furmaniak, M.D., Ph.D.

      Affiliations

    • FIRS Laboratories, RSR Ltd., Cardiff, United Kingdom
    • Drs. Shu Chen, Jadwiga Frumaniak, and Bernard Rees Smith are named inventors on a patent relating to 21 hydroxylase autoantibodies and employees of RSR Ltd., a developer and manufacturer of in vitro diagnostics including reagents for the measurement of 21 hydroxylase autoantibodies. In addition, Dr. Smith is a shareholder in RSR, Ltd.
  • ,
  • B. Rees Smith, Ph.D., D.Sc.

      Affiliations

    • FIRS Laboratories, RSR Ltd., Cardiff, United Kingdom
    • Drs. Shu Chen, Jadwiga Frumaniak, and Bernard Rees Smith are named inventors on a patent relating to 21 hydroxylase autoantibodies and employees of RSR Ltd., a developer and manufacturer of in vitro diagnostics including reagents for the measurement of 21 hydroxylase autoantibodies. In addition, Dr. Smith is a shareholder in RSR, Ltd.
  • ,
  • Maria J. Merino, M.D.

      Affiliations

    • Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • ,
  • Lawrence M. Nelson, M.D.

      Affiliations

    • Section on Women’s Health Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland
    • Corresponding Author InformationReprint requests: Lawrence M. Nelson, M.D., National Institutes of Health, CRC 1-3330, 10 Center Drive, MSC-1103, Bethesda, Maryland 20892-1103 (FAX: 301-402-0574

Received 24 November 2004; received in revised form 27 April 2005; accepted 27 April 2005.

Objective

To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis.

Design

Controlled, prospective.

Setting

Tertiary research center.

Patient(s)

Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure.

Intervention(s)

Ovarian biopsy in 10 women.

Main Outcome Measure(s)

Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers.

Result(s)

We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies (4/4 vs. 0/6). Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography (11.4 ± 5.6 mL vs. 1.5 ± 0.4 mL) (mean ± SEM). They were also more likely to have subclinical adrenal insufficiency and clinical signs of androgen deficiency (3/4 vs. 0/6). Overall, 10/266 women tested positive for adrenal cortex autoantibodies (3.8%, 95% confidence interval: 1.8%–6.5%).

Conclusion(s)

In women who present with 46,XX spontaneous premature ovarian failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologically confirmed autoimmune oophoritis.

Key Words:  Adrenal cortex autoantibodies , autoimmune oophoritis , premature ovarian failure , hypergonadotropic amenorrhea , hypergonadotropic hypogonadism , ovarian insufficiency , adrenal insufficiency , Addison disease

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PII: S0015-0282(05)02779-2

doi:10.1016/j.fertnstert.2005.04.060

Fertility and Sterility
Volume 84, Issue 4 , Pages 958-965, October 2005