Premature ovarian failure

Last reviewed: 26 Aug 2023
Last updated: 14 Apr 2023



History and exam

Key diagnostic factors

  • age <40 years
  • family history of primary ovarian failure
  • menstrual irregularities
  • toxic exposures
More key diagnostic factors

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
Other diagnostic factors

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
More risk factors

Diagnostic investigations

1st investigations 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
More 1st investigations to order

Investigations 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
More investigations to consider

Treatment algorithm


all patients



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




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




RR declares that she has no competing interests.


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


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



JFR declares that he has no competing interests.

Edward Morris, MD


Honorary Senior Lecturer and Clinical Director

Department of Obstetrics and Gynaecology

Norfolk and Norwich University Hospital




EM declares that he has no competing interests.

  • Differentials

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  • Guidelines

    • The 2022 hormone therapy position statement of the North American Menopause Society
    • The British Menopause Society and Women's Health Concern recommendations on the management of women with premature ovarian insufficiency
    More Guidelines
  • Patient leaflets

    Menopause: should I take HRT?

    Menopause: what is it?

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