Spontaneous Premature Ovarian Insufficiency

Key Points

  • Spontaneous POI affects up to 4% of women aged <40 years and the cause is unknown in most women.
  • Diagnosis can be difficult/ delayed. Diagnostic criteria1 include FSH levels> 25 IU on 2 occasions at least 1 month apart following 4-6 months of amenorrhea with exclusion of secondary causes of amenorrhoea.
  • Consequences of POI include menopausal symptoms, psychological distress, infertility, and an increased risk of osteoporosis, cardiovascular disease and possibly cognitive problems.
  • MHT/HRT (unless contraindicated) is recommended until at least usual age of menopause to treat symptoms and minimize the risk of long term health problems. The OCP is an alternative option for women who are medically eligible to use an oestrogen-containing method (the usual contraindications apply).
  • Donor egg/embryo is usually required to achieve a pregnancy.

pdfAMS Spontaneous Premature Ovarian Insufficiency229.73 KB

Definitions and Epidemiology

Loss of ovarian function occurring in women younger than 40 years of age is called premature ovarian insufficiency (POI)1. POI may also be referred to as primary ovarian insufficiency, premature menopause or premature/ primary ovarian failure). POI can occur spontaneously affecting up to 4% of women and may vary with ethnicity2. POI may also occur secondary to medical treatments, including chemotherapy, radiotherapy or surgery (see AMS Information Sheet Early menopause due to chemotherapy and radiotherapy). Approximately 11% of female childhood cancer survivors developed premature ovarian insufficiency (based on hormone criteria)in one cohort although the frequency varies3. Menopause occurring between 40-45 years of age is called early menopause1, with spontaneous early menopause affecting approximately 12% of women2.

Factors associated with an earlier age at menopause include smoking, nulliparity, hysterectomy, HIV infection, low bodyweight, a family history of early menopause and adverse life events4. There is no evidence that early menopause is associated with the use of oral contraceptives, fertility drugs or artificial hormones in the environment5. Low birthweight, poor childhood growth, emotional stress at a young age, lower socioeconomic position and environmental toxins are factors identified in some but not all studies4.

Diagnosis of POI often has long term physical and psychological consequences, so women may need emotional support and ongoing medical follow-up.

Causes of POI1


What are the consequences?

Fertility issues:

Hormone Replacement Therapy:

Prevention of bone loss:

Prevention of cardiovascular disease:

Women with early menopause should minimize CVD risk by maintaining normal weight, exercising regularly, ceasing smoking, maintaining a healthy diet, controlling diabetes mellitus and high blood pressure, and preventing or treating high levels of cholesterol and triglycerides.

Further information:

September 2011, Revised August 2015, Revised September 2020


1. Webber L, Davies M, Anderson R, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016; 31(5): 926-37.

2. Golezar S, Ramezani Tehrani F, Khazaei S, Ebadi A, Keshavarz Z. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric 2019; 22(4): 403-11.

3. Chemaitilly W, Li Z, Krasin MJ, et al. Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort. The Journal of Clinical Endocrinology & Metabolism 2017; 102(7): 2242-50.

4. Mishra GD, Chung H-F, Cano A, et al. EMAS position statement: Predictors of premature and early natural menopause. Maturitas 2019; 123: 82-8.

5. Davis S, Lambrinoudaki I, Lumsden MA, et al. Menopause. Nature Reviews Disease Primers 2015; 1: 1-19.

6. Laven JS. Genetics of Early and Normal Menopause. Seminars in Reproductive Medicine 2015; 33(6): 377-83.

7. Yeganeh L, Boyle JA, Wood A, Teede H, Vincent AJ. Menopause guideline appraisal and algorithm development for premature ovarian insufficiency. Maturitas 2019; 130: 21-31.

8. Xu X, Jones M, Mishra GD. Age at natural menopause and development of chronic conditions and multimorbidity: results from an Australian prospective cohort. Human Reproduction 2020; 35(1): 203-11.

9. Anagnostis P, Siolos P, Gkekas NK, et al. Association between age at menopause and fracture risk: a systematic review and meta-analysis. Endocrine 2019; 63(2): 213-24.

10. Anagnostis P, Christou K, Artzouchaltzi AM, et al. Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis. European Journal of Endocrinology 2019; 180(1): 41-50.

11. Zhu D, Chung HF, Dobson AJ, et al. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data. Lancet Public Health 2019; 4(11): e553-e64.

12. Muka T, Oliver-Williams C, Kunutsor S, et al. Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality: A Systematic Review and Meta-analysis. JAMA Cardiology 2016; 1(7): 767-76.

13. Collaborative Group on Hormonal Factors in Breast C. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012; 13(11): 1141-51.

14. Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015; 18(4): 483-91.

15. Gazarra LBC, Bonacordi CL, Yela DA, Benetti-Pinto CL. Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives. Menopause 2020.

16. Kiriakova V, Cooray SD, Yeganeh L, Somarajah G, Milat F, Vincent AJ. Management of bone health in women with premature ovarian insufficiency: Systematic appraisal of clinical practice guidelines and algorithm development. Maturitas 2019; 128: 70-80.

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Content updated September 2020