Last reviewed: August 2020
Last updated: March  2018



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
More 1st investigations to order

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 DEXA scan
More investigations to consider

Treatment algorithm


Professor of Obstetrics and Gynaecology

Academic Unit of Reproductive & Developmental Medicine

The University of New South Wales




WL declares that he has no competing interests.

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 monograph. 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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