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Premature ovarian failure

  • Overview
  • Theory
  • Diagnosis
  • Management
  • Follow up
  • Resources
Last reviewed: 2 Aug 2025
Last updated: 09 Jan 2025

Summary

Definition

History and exam

Key diagnostic factors

  • age <40 years
  • family history of primary ovarian failure
  • menstrual irregularities
  • toxic exposures
Full details

Other diagnostic factors

  • hot flashes
  • sleep disturbance
  • irritability
  • vaginal dryness
  • infertility
  • vaginal atrophy
  • small uterus with nonpalpable ovaries
  • cognitive abnormalities
  • signs of thyroid dysfunction
  • signs of adrenal dysfunction
  • signs of hyperprolactinemia
  • signs of genetic syndromes
Full details

Risk factors

  • family history of POF
  • exposure to chemotherapy or radiation
  • autoimmune disease
  • family history of fragile X syndrome
  • galactosemia
  • hysterectomy
  • uterine artery embolization
  • smoking
  • lower socioeconomic status, higher education level, nulliparity
  • presence of specific genetic variants
  • ovarian surgery
Full details

Diagnostic tests

1st tests to order

  • pregnancy test
  • serum follicle-stimulating hormone (FSH) level
  • serum luteinizing hormone (LH) level
  • serum estradiol level
  • anti-Müllerian hormone (AMH) level
  • thyroid function tests
  • serum prolactin level
  • transvaginal ultrasound
Full details

Tests to consider

  • thyroid peroxidase antibody
  • serum fasting glucose level
  • electrolytes, BUN, creatinine
  • karyotype
  • fragile X premutation
  • adrenocorticotropic hormone (ACTH) stimulation test
  • serum adrenal antibodies
  • baseline dual-energy x-ray absorptiometry scan
Full details

Treatment algorithm

ACUTE

all patients

Contributors

Authors

William Ledger, MA, DPhil (Oxon), MB, ChB, FRCOG, FRANZCOG, CREI

Professor of Obstetrics and Gynaecology

Academic Unit of Reproductive & Developmental Medicine

The University of New South Wales

Sydney

Australia

Disclosures

WL is the author of one reference cited in this topic.

Rachael Rodgers, BA, BSc, MBBS, MScMed (RHHG)

Fellow in Reproductive Endocrinology

Reproductive Medicine

Royal Hospital for Women

Sydney

Australia

Disclosures

RR declares that she has no competing interests.

Acknowledgements

Dr William Ledger would like to gratefully acknowledge Dr William Hurd, Dr Rebecca Flyckt, and Dr Nichole Giannios, the previous contributors to this topic.

Disclosures

WH, RF, and NG declare that they have no competing interests.

Peer reviewers

John F. Randolph Jr., MD

Professor and Director

Division of Reproductive Endocrinology and Infertility

Department of Obstetrics and Gynecology

University of Michigan Health System

Ann Arbor

MI

Disclosures

JFR declares that he has no competing interests.

Edward Morris, MD

Consultant

Honorary Senior Lecturer and Clinical Director

Department of Obstetrics and Gynaecology

Norfolk and Norwich University Hospital

Norwich

UK

Disclosures

EM declares that he has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

North American Menopause Society. Early menopause guidebook. 6th edition. Cleveland, OH: North American Menopause Society; 2006.

Chen H, Li J, Cui T, Hu L. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev. 2011;(11):CD008018.Full text  Abstract

The North American Menopause Society Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 Jul 1;29(7):767-94. Abstract

Panzer C, Guay A. Testosterone replacement therapy in naturally and surgically menopausal women. J Sex Med. 2009 Jan;6(1):8-18. Abstract

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 Sep-Oct;5(5):483-92. Abstract

Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009 Feb 5;360(6):606-14. Abstract

Toulis KA, Tzellos T, Kouvelas D, et al. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther. 2009 Feb;31(2):221-35. Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

  • Differentials

    • Pregnancy
    • Polycystic ovary syndrome
    • Anorexia nervosa
    More Differentials

  • Guidelines

    • Guideline on premature ovarian insufficiency
    • The 2022 hormone therapy position statement of the North American Menopause Society
    More Guidelines

  • Patient information

    Menopause: should I take HRT?

    Menopause: what is it?

    More Patient information
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