Primary ovarian insufficiency (POI) happens when the ovaries stop functioning normally before the age of 40 years. POI is also known as premature ovarian insufficiency, premature ovarian failure, or premature ovarian insufficiency syndrome. [1]
Women with POI have ovaries that stop releasing eggs at ovulation, or do so rarely. Additionally, the ovaries stop producing estrogen and progesterone, or if these hormones are produced, it happens intermittently. [1] [2]
POI is not the same as premature menopause, as it is still possible to become pregnant.
Premature menopause occurs before the age of 40 and pregnancy is no longer possible.
With POI, the ovaries may work intermittently and pregnancy is rare but possible. Natural menopause happens after a woman hasn’t had a period for 12 months. The average age of women experiencing menopause is 51 years.[2] [7] [5] [6] [3]
POI is a chronic disorder, and there is a range of impaired ovarian function. Approximately 76% of women with POI have normal, regular periods during puberty and early adulthood, but then menstrual cycles become irregular, and for most women, they cease completely. However, 5% to 10% percent of women may achieve a spontaneous pregnancy because it’s possible to sporadically ovulate with POI. [1] [6]
The chances of POI decrease the younger you are, affecting [1][9]:
1 in
0women younger than 40 years old
1 in
0women younger than 30 years old
1 in
0women younger than 20 years old
As well, women with primary ovarian insufficiency have a two-year lower life expectancy than those without POI. This is because POI has a significant negative influence on mental and cognitive health, fertility, bone health, and cardiovascular health.[1] [9]
The prevalence and incidence rates for POI also differ across ethnicities. One study demonstrated that there are significantly higher incidence rates in Hispanic and African American women compared to Japanese and Chinese women. [9]
Because the body eventually produces little or no estrogen, women with POI can experience symptoms of menopause before they reach the age of perimenopause.
Some symptoms of menopause that women with POI might experience include: [2] [1]
- ▢ hot flashes
▢ night sweats
▢ mood swings
▢ fatigue
▢ sleep issues
▢ lack of libido
▢ brain fog
▢ joint pain
▢ depression
▢ anxiety
▢ vaginal dryness
▢ urinary incontinence
▢ irritability
Women with POI are also more likely to have dry eye syndrome, and they have a higher lifetime risk of osteopenia and osteoporosis, cardiovascular and neurocognitive disorders. [5] [7]
Autoimmune Diseases
Autoimmune Diseases
In some cases of POI, the immune system mistakenly attacks hormone-producing (endocrine) organs, damaging the ovaries but also potentially the adrenal glands, and the thyroid glands. Signs of this occurring include:
-
▢ patchy loss of skin pigmentation
▢ premature graying of hair
▢ spot baldness
Women experiencing POI from autoimmune disorders may also experience signs of adrenal insufficiency, where the adrenal glands (located on top of the kidneys) do not produce enough hormones. Signs and symptoms include:
-
▢ patches of dark skin
▢ cravings for salt
▢ anorexia
▢ abdominal pain
▢ loss of hair under the arms and in the pubic area
There may also be symptoms of thyroid disease, including:
-
▢ bulging eyes
▢ goiter
▢ increased or decreased heart rate
[1] [7] [11]
Genetic Causes
Genetic Causes
Women with POI have a 10% – 20% chance of having an affected female family member indicating a possible genetic link for this condition. The most common genetic disorders that can lead to POI include: [1]
Turner syndrome – Females with Turner syndrome have only one X chromosome (compared to two X chromosomes in healthy females), causing problems with the reproductive system including POI. Missing a portion of one X chromosome, instead of the whole chromosome can also cause POI. Turner syndrome is the most common genetic cause of POI. [7]
Fragile X syndrome – Fragile X syndrome happens when there is an abnormal gene on the X chromosome that causes intellectual challenges. Women who carry this abnormal gene (which may not be expressed, so there may be no intellectual disability), have a 20% chance of developing POI.
Other genetic causes include the presence of some Y chromosome material, even though Y chromosomes are supposed to appear only in males. Having this as a cause of POI is rare but possible. [2]
Infectious Diseases
Infectious Diseases
Infectious Diseases that can damage the ovaries may cause POI. The most likely infectious diseases to have this impact are mumps, tuberculosis and malaria [1]
Cancer Treatments
Cancer Treatments
Cancer treatments, including chemotherapy and radiation therapy are the most common reasons for ‘toxin-induced’ POI. These therapies treat cancer by killing individual cancer cells. [1] [2]
Diagnosing Primary Ovarian Insufficiency
POI is diagnosed if you are under the age of 40, experience irregular periods, and have elevated levels of follicle-stimulating hormone (FSH), one of the reproductive hormones. FSH works by stimulating follicles containing eggs to grow and prepare for ovulation, or release from the ovary. [2]
Tests that your healthcare provider will run to diagnose and then identify the cause of POI include:
Blood Tests
Blood Tests
Blood tests are used to check estrogen and FSH levels. If they are higher than 25 mIU/mL when measured four weeks apart in women younger than 40 years, this will give a diagnosis of POI. [1] [7]
A blood test for thyroid-stimulating hormone can determine if autoimmune thyroid disease is the cause of POI. As well, blood tests for adrenal hormones can identify if the cause is an autoimmune adrenal disease.
Genetic Tests
Genetic Tests
Karyotyping is a type of genetic test that maps a person’s complete set of chromosomes. A karyotype will be requested for all women experiencing POI without a known cause, especially if the woman is younger than 30 years.
If the karyotype doesn’t show abnormalities (like Turner syndrome), further genetic testing for Fragile X syndrome will be recommended. There will also be screening for other genetic abnormalities that may impact the X chromosomes. [1]
Honor your feelings of grief, especially if you have not had children yet and were planning on it. Natural pregnancy and delivery is possible, but rare. [2]
Talk to someone you trust. While talking to someone isn’t going to change the reality, having a trusted friend or partner hear your concerns can be a huge relief.
Take care of your physical body. Eating well, getting sufficient exercise, and having good quality sleep will make you feel better in your day to day life.
Practice meditation and/or breathing exercises. These practices help calm your mind and may give you some relief as you process and come to accept your diagnosis.
Journal your thoughts and feelings. Keeping a journal is a proven way to self-reflect and practice self-care. Take the time to journal things that are good as well, to give yourself a boost when you need it!
Join a support group or a peer group. Your healthcare provider can give you a recommendation for a support group or point you to specialty care organizations.
Therapy & Counselling
Therapy & Counselling
Therapy and counselling is needed to help women with the psychological impacts of this diagnosis. This is especially true for women being diagnosed later and who haven’t had children yet as learning they are unlikely to get pregnant naturally can be devastating.
Hormone Replacement Therapy
HRT
Hormone replacement therapy (HRT) will likely be prescribed to support and mimic normal estrogen levels until the average age of natural menopause, around 51 years old.
In Vitro Fertilization
IVF
In vitro fertilization (IVF) is a possibility for women with POI who are interested in having children. Donor eggs may be needed as POI typically reduces or even eliminates the likelihood of healthy eggs from the mother.
Birth Control
Birth Control
Birth control may be prescribed if you do not want to become pregnant. Although rare, it is possible to conceive and carry a pregnancy with POI.
Calcium & Vitamin D
Calcium & Vitamin D Supplements
Because women with POI are at higher risk for osteoporosis, you should take calcium and vitamin D every day.[2] [4]
The Science
Primary ovarian insufficiency (POI) is associated with follicle problems. Follicles are small fluid-filled sacs in the ovaries, each one containing one immature egg. Normally there are thousands of follicles contained in each ovary.
During the menstrual cycle, one egg from one follicle will mature and be released from the ovary where it travels through the fallopian tube towards the uterus. If the egg is fertilized it will implant in the uterine wall and continue developing throughout pregnancy.
Women are born with all of their follicles in place and natural menopause happens when all follicles have been depleted. One problem with POI is when there are not enough follicles, meaning there will not be enough eggs to be released throughout your reproductive years.
Another problem with POI is when there are sufficient follicles but they do not work properly, so either they are empty or they do not release eggs during ovulation. In some cases, the follicle itself will degenerate and disappear. [7]
False
It is rare, but possible, to get pregnant with POI. About 5% – 10% of women with POI have spontaneous and successful pregnancies.
False.
In premature menopause, the ovaries are depleted of follicles so pregnancy cannot occur. In POI, there are problems with the follicles, but it is possible for an egg to be released and pregnancy to occur.
References
[1] https://www.medicinenet.com/how_common_is_primary_ovarian_insufficiency/article.htm
[2] https://www.uptodate.com/contents/primary-ovarian-insufficiency-beyond-the-basics
[3] https://www.nichd.nih.gov/health/topics/poi/conditioninfo
[4] https://medlineplus.gov/primaryovarianinsufficiency.html
[5] https://www.endocrine.org/patient-engagement/endocrine-library/primary-ovarian-insuffiency
[6] https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-primary-ovarian-insufficiency-premature-ovarian-failure
[7] Chon Seung Joo , Umair Zobia , Yoon Mee-Sup. Premature Ovarian Insufficiency: Past, Present, and Future. Frontiers in Cell and Developmental Biology 9, 2021https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.672890 DOI=10.3389/fcell.2021.672890
[8] Nie, L., Wang, X., Wang, S. et al. Genetic insights into the complexity of premature ovarian insufficiency. Reprod Biol Endocrinol 22, 94 (2024). https://doi.org/10.1186/s12958-024-01254-2
[9] Federici Silvia , Rossetti Raffaella , Moleri Silvia , Munari Elisabetta V. , Frixou Maria , Bonomi Marco , Persani Luca. Primary ovarian insufficiency: update on clinical and genetic findings. Frontiers in Endocrinology 15, 2024. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1464803 DOI=10.3389/fendo.2024.1464803 ISSN=1664-2392
[10] https://fragilex.org/understanding-fragile-x/info-series
[11] Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, Grymowicz M, Smolarczyk K, Kostrzak A, Smolarczyk R, Rudnicka E, Meczekalski B. Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge. Int J Mol Sci. 2021 Mar 5;22(5):2594. doi: 10.3390/ijms22052594. PMID: 33807517; PMCID: PMC7961833.
Original content, last updated January 30, 2025.
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