Primary ovarian insufficiency (POI) is a condition that occurs when a person stops ovulating regularly before the age of 40 years. It causes irregular or absent menstrual periods, which can make it more difficult to get pregnant naturally.

POI is different than early menopause. While menopause is a normal process that can occur earlier than average in some people, POI occurs due to the ovaries not working as they should.

In this article, we look at POI in more detail, including its symptoms, causes, and treatments, as well as its effects on fertility.

A note about sex and gender

Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.

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POI is a medical condition that causes the ovaries to stop working as they typically do before a person reaches the age of 40 years. It can develop as early as puberty but can also start in someone’s 20s or 30s. Another name for the condition is premature ovarian insufficiency.

When they are working correctly, the ovaries release an egg during the menstrual cycle. This process is known as ovulation. The egg travels from the ovaries down the fallopian tubes and into the uterus, where it attaches to the womb lining. If the egg becomes fertilized, it stays there and begins to grow. If not, the womb lining sheds, causing a period.

However, people with POI do not ovulate often. As a result, they also have very few periods, or none at all. The ovaries also stop producing as much estrogen and other female sex hormones.

POI is not the same as early menopause. Menopause refers to the transition that everyone with female reproductive organs goes through at some point. In the United States, this happens at an average age of 52 years, but in some people, the transition naturally begins sooner, at 40–45 years.

Menopause causes a decline in fertility. Periods start to become less regular before eventually stopping entirely. After this point, it is no longer possible to get pregnant.

Early menopause and POI sound similar, but POI occurs below the age of 40 years and for different reasons. Researchers believe that POI happens due to a problem in the ovary follicles, which are where eggs grow and mature. Although this affects fertility, getting pregnant is uncommon rather than impossible.

The main symptom of POI is irregular or missed periods. People may also notice the signs if they are trying to get pregnant but are having trouble conceiving naturally. Having difficulty getting pregnant is often the reason why people with POI first visit a doctor.

Some individuals with POI also experience other symptoms, such as:

Scientists are not completely sure how POI develops, but they believe that it occurs due to problems with the follicles inside the ovaries. Follicles are tiny sacs in which eggs grow.

Most females have a finite number of follicles that mature and release eggs up until menopause, by which time there are none left. However, if there is an early decrease in the number of working follicles, or the follicles are not functioning as they should, this may cause POI.

In many cases, doctors cannot identify a reason why this might have happened. However, POI does have some risk factors. These include:

  • Genetics: About 10–20% of people with POI have a family member who also has the condition, which suggests that genetics are an important factor in POI. Several genetic mutations and medical conditions are associated with POI, including fragile X syndrome and Turner syndrome. About 28% of people with POI have one of these genetic differences.
  • Autoimmune disorders: Autoimmune conditions occur when the body’s immune system attacks its own healthy tissue. A 2019 study estimates that autoimmunity may account for 4–30% of all POI cases. Thyroiditis and Addison’s disease appear to be more common among those with POI than among the general population.
  • Exposures: Chemotherapy, radiation therapy, and toxins can damage follicles in the ovaries and stop them from working. Toxins are substances that are harmful to humans. Examples of toxins that may contribute to POI include cigarette smoke and pesticides.
  • Metabolic disorders: Metabolism controls how the body uses energy. Most females with a metabolic disorder known as galactosemia also have POI.

If someone has irregular or absent periods for at least 4 months and they are under the age of 40 years, a doctor can perform tests to diagnose or rule out POI. They will usually begin by taking someone’s medical and family history and then perform a physical examination. Next, they may order tests, such as:

  • a pregnancy test to rule out unexpected pregnancy
  • blood tests to assess the levels of follicle stimulating hormone, luteinizing hormone, and estrogen
  • a karyotype test, which can detect genetic differences and conditions
  • a pelvic ultrasound, which can show the condition of the ovaries
  • tests for other conditions that may explain absent or irregular periods

There is no cure for POI, so the goal of treatment is to reduce any symptoms and prevent complications. Treatment typically involves a combination of medication and dietary or lifestyle adjustments.

Many of the potential symptoms and complications of POI are related to a lack of hormones, particularly estrogen. Restoring normal levels of estrogen can help improve quality of life and reduce the risk of the following conditions:

Hormone replacement therapy (HRT)

HRT can replace some of the hormones that the ovaries are no longer producing. People can take it as an oral tablet, apply it to the skin as a cream or patch, or use a vaginal ring or intrauterine device (IUD), which a doctor places inside the uterus.

A 2016 study found that HRT use in menopause was associated with a higher risk of stroke, blood clots, heart disease, heart attacks, and breast cancer. However, the doses of HRT that people with POI take are much lower than this and are not linked to an increased risk of these conditions.

People with POI can keep taking HRT until they reach menopause, when hormone levels would usually decline.

Hormonal birth control

For people who do not want to get pregnant, a doctor may prescribe a combined hormonal form of birth control instead of HRT. This contraception also replaces lost hormones but protects more effectively against pregnancy.

Some people may wish to use a progesterone-only form of hormonal birth control. For example, those who experience migraine with aura cannot take estrogen, so they may need to use a progesterone-only alternative, such as an IUD, implant, or pill.

Bone health supplements

As POI increases the risk of osteoporosis, a doctor may recommend taking calcium and vitamin D supplements. Both of these nutrients are important for bone health.

Treating related conditions

If a person has a condition that may be related to POI, such as an autoimmune disease, then treating or managing it is also important.

In addition to medical treatments, people can modify their lifestyle to lower the risk of POI-related complications. Ways to reduce the risk include:

  • maintaining a moderate weight
  • eating a balanced diet that contains adequate calcium
  • getting more vitamin D from safe sunlight exposure
  • using weight-bearing exercises, such as stair climbing or weightlifting, to build bone strength
  • engaging in regular aerobic exercise to benefit cardiovascular health

Many people with POI will find it difficult to conceive naturally. Only 5–10% of these individuals can conceive without fertility treatments. Ovulation is still a possibility, but many people will require additional help.

In vitro fertilization (IVF) with donor eggs is an effective way for a person with POI to become pregnant. During IVF, a doctor takes eggs from someone else’s ovary, fertilizes them with sperm in a laboratory, and then places the embryos into the recipient’s uterus. Using multiple embryos increases the chances of implantation.

The person receiving the embryo will need to take hormones to support the process. IVF does have some risks, such as a higher likelihood of pregnancy-related high blood pressure. People may need to try IVF multiple times, which can be expensive, and many insurance companies do not cover IVF procedures.

Anyone with POI who does not wish to get pregnant should speak with a doctor about birth control options.

POI is a condition in which the ovaries do not function as they usually would, causing irregular or missed periods. Doctors diagnose it in people below the age of 40 years who have missed at least four periods.

POI can cause significant difficulty getting pregnant, as well as disruptive symptoms and an increased risk of certain conditions. Doctors often use HRT to reduce the symptoms and the risk of complications. Although some people with POI conceive naturally, many require fertility treatments if they wish to become pregnant.