What causes POI?

In most cases, the exact cause of POI is unknown.1,2,3

Research shows that POI is related to problems with the follicles—the small sacs in the ovaries in which eggs grow and mature.3

Follicles start out as microscopic seeds called primordial follicles. These seeds are not yet follicles, but they can grow into them. Normally, a woman is born with approximately 2 million primordial follicles,4 typically enough to last until she goes through natural menopause, usually around age 50.2

For a woman with POI, there are problems with the follicles:5

  • Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles.
  • Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again.3

Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified:

  • Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion.3,4,6
  • Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Even though only one mature follicle releases an egg each month, less mature follicles usually develop along with that mature follicle and egg. Scientists don't understand exactly why this happens, but these "supporting" follicles seem to help the mature follicle function normally. If these extra follicles are missing, the main follicle will not mature and release an egg properly.
  • Autoimmune diseases. Typically, the body's immune cells protect the body from invading bacteria and viruses. However, in autoimmune diseases, immune cells turn on healthy tissue. In the case of POI, the immune system may damage developing follicles in the ovaries. It could also damage the glands that make the hormones needed for the ovaries and follicles to work properly. Several studies suggest that about one-fifth of with POI have an autoimmune disease.2,7
    • Thyroiditis is the autoimmune disorder most commonly associated with POI.7 It is an inflammation of the thyroid gland, which makes hormones that control metabolism, or the pace of body processes.
    • Addison's disease is also associated with POI. Addison's disease affects the adrenal glands, which produce hormones that help the body respond to physical stress, such as illness and injury; the hormones also affect ovary function.8 A small percentage of women with POI have Addison's disease.
  • Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells.1,3
  • Metabolic disorders. These disorders affect the body's ability to create, store, and use the energy it needs. For example, galactosemia affects how your body processes galactose, a type of sugar. A majority of women with galactosemia also have POI.7
  • Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion. In addition, viruses have been shown to affect follicle function.2,4


  1. 1. Kodaman, P. H. (2010). Early menopause: Primary ovarian insufficiency and surgical menopause. Seminars in Reproductive Medicine, 28, 360–369. https://pubmed.ncbi.nlm.nih.gov/20845236/
  2. Nelson, L. M. (2009). Primary ovarian insufficiency. New England Journal of Medicine, 360, 606–614. https://pubmed.ncbi.nlm.nih.gov/19196677/
  3. De Vos, M., Devroey, P., & Fauser, B. C. (2010). Primary ovarian insufficiency. Lancet, 376, 911–921. https://pubmed.ncbi.nlm.nih.gov/20708256/
  4. Welt, C. K. (2008). Primary ovarian insufficiency: A more accurate term for premature ovarian failure. Clinical Endocrinology, 68, 499–509. https://pubmed.ncbi.nlm.nih.gov/17970776/
  5. American Congress of Obstetricians and Gynecologists Committee Opinion of Primary Ovarian Insufficiency. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/07/primary-ovarian-insufficiency-in-adolescents-and-young-women external link
  6. Cordts, E. B., Christofolini, D. M., Dos Santos, A. A., Bianco, B., & Barbosa, C. P. (2011). Genetic aspects of premature ovarian failure: A literature review. Archives of Gynecology and Obstetrics, 283, 635–643. https://pubmed.ncbi.nlm.nih.gov/21188402/
  7. Rebar, R. W. (2009). Premature ovarian failure. Obstetrics and Gynecology, 113, 1355–1363. https://pubmed.ncbi.nlm.nih.gov/19461434/
  8. National Center for Biotechnical Information. (2009). Addison's disease. Retrieved January 12, 2012, from https://medlineplus.gov/addisondisease.html
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