Last reviewed: 18 Apr 2021
Last updated: 15 Oct 2020



History and exam

Key diagnostic factors

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

Other diagnostic factors

  • hot flushes
  • sleep disturbance
  • irritability
  • vaginal dryness
  • infertility
  • vaginal atrophy
  • small uterus with non-palpable ovaries
  • cognitive abnormalities
  • signs of thyroid dysfunction
  • signs of adrenal dysfunction
  • signs of hyperprolactinaemia
  • signs of genetic syndromes

Risk factors

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

Diagnostic investigations

1st investigations to order

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

Investigations to consider

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

Treatment algorithm


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.

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 reviewersVIEW ALL

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.


Honorary Senior Lecturer and Clinical Director

Department of Obstetrics and Gynaecology

Norfolk and Norwich University Hospital




EM declares that he has no competing interests.

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