Diseases

Because POI results in lower levels of certain hormones, women with POI are at greater risk for a number of health conditions, including:

• Osteoporosis. The hormone estrogen helps keep bones strong. Without enough estrogen, women with POI often develop osteoporosis. Osteoporosis is a bone disease that causes weak, brittle bones that are more likely to break and fracture.1
• Low thyroid function. This problem also is called hypothyroidism (pronounced hahy-puh-THAHY-roi-diz-uhm). The thyroid is a gland that makes hormones that control your body's metabolism and energy level. Low levels of the hormones made by the thyroid can affect your metabolism and can cause very low energy and mental sluggishness. Cold feet and constipation are also features of low thyroid function. Researchers estimate that between 14% and 27% of women with POI also have low thyroid function.4
• Anxiety and depression. Hormonal changes caused by POI can contribute to anxiety or lead to depression.16 Women diagnosed with POI can be shy, anxious in social settings, and may have low self-esteem more often than women without POI.4 It is possible that depression may contribute to POI.16
• Cardiovascular (heart) disease. Lower levels of estrogen, as seen in POI, can affect the muscles lining the arteries and can increase the buildup of cholesterol in the arteries. Both factors increase the risk of atherosclerosis (pronounced ath-uh-roh-skluh-ROH-sis) - or hardening of the arteries - which can slow or block the flow of blood to the heart. Women with POI have higher rates of illness and death from heart disease than do women without POI.1,6,11
• Dry eye syndrome and ocular (eye) surface disease. Some women with POI have one of these conditions, which cause discomfort and may lead to blurred vision.4 If not treated, these conditions can cause permanent eye damage.

Addison's disease is also associated with POI. Addison's disease is a life-threatening condition that affects the adrenal glands, which produce hormones that help the body respond to physical stress, such as illness and injury. These hormones also affect ovary function.14 About 3% of women with POI have Addison's disease.15

The key signs of POI are:

• Missed or irregular periods for 4 months, typically after having had regular periods for a while
• High levels of follicle-stimulating hormone (FSH)
• Low levels of estrogen4,6,13

If a woman is younger than age 40 and begins having irregular periods or stops having periods for 4 months or longer, her health care provider may take these steps to diagnose the problem:

• Do a pregnancy test. This test will rule out an unexpected pregnancy as the reason for missed periods.4
• Do a physical exam. During the physical exam, the health care provider looks for signs of other disorders. In some cases, the presence of these other disorders will rule out POI. Or, if the other disorders are associated with POI, such as Addison's disease, a health care provider will know that POI may be present.4
• Collect blood. The health care provider will collect your blood and send it to a lab, where a technician will run several tests, including:
  • Follicle-Stimulating Hormone (FSH) test. FSH signals the ovaries to make estrogen, sometimes called the "female hormone" because women need high levels of it for fertility and overall health. If the ovaries are not working properly, as is the case in POI, the level of FSH in the blood increases. The health care provider may do two FSH tests, at least a month apart. If the FSH level in both tests is as high as it is in women who have gone through menopause, then POI is likely.4
  • Luteinizing (pronounced LOO-tee-uh-nahyz-ing) hormone (LH) test. LH signals a mature follicle to release an egg. Women with POI have high LH levels, more evidence that the follicles are not functioning normally.1
  • Estrogen test. In women with POI, estrogen levels are usually low, because the ovaries are not functioning properly in their role as estrogen producers.1,6
  • Karyotype (pronounced KAR-ee-uh-tahyp) test. This test looks at all 46 of your chromosomes to check for abnormalities. The karyotype test could reveal genetic changes in the structure of chromosomes that might be associated with POI and other health problems.1,4
• Do a pelvic ultrasound. In this test, the health care provider uses a sound wave (sonogram) machine to create and view pictures of the inside of a woman's pelvic area. A sonogram can show whether or not the ovaries are enlarged or have multiple follicles.4,11

The health care provider will also ask questions about a woman's medical history. He or she may ask about:

• A blood relative with POI or its symptoms
• A blood relative with Fragile X syndrome or an unidentified intellectual or developmental disability
• Ovarian surgery
• Radiation or chemotherapy treatment
• Pelvic Inflammatory Disease or other sexually transmitted infections
• An endocrine disorder, such as diabetes4

If they do not do tests to rule out POI, some health care providers might assume missed periods are related to stress.4 However, this approach is problematic because it will lead to a delay in diagnosis; further evaluation is needed.4

Estimates suggest that about 1% of women and teenage girls in the United States have POI.1 Researchers estimate that, categorized by age, POI affects:

• 1 in 10,000 women by age 20
• 1 in 1,000 women by age 30
• 1 in 250 women by age 35
• 1 in 100 women by age 408

Several factors can affect a woman's risk for POI:

• Family history. Women who have a mother or sister with POI are more likely to have the disorder. About 10% to 20% of women with POI have a family history of the condition.8
• Genes. Some changes to genes and genetic conditions put women at higher risk for POI. Research suggests that these disorders and conditions cause as much as 28% of POI cases.9 For example:
  • Women who carry a variation of the gene for Fragile X syndrome are at higher risk for Fragile X-Associated POI (FXPOI). 10 Fragile X syndrome is the most common inherited form of intellectual and developmental disability, but women with FXPOI do not have Fragile X syndrome itself. Instead, they have a change or mutation in the same gene that causes Fragile X syndrome, and this change is linked to FXPOI.
  • Most women who have Turner syndrome develop POI. Turner syndrome is a condition in which a girl or woman is partially or completely missing an X chromosome. Most women are XX, meaning they have two X chromosomes. Women with Turner syndrome are X0, meaning one of the X chromosomes is missing.
• Other factors. Autoimmune diseases, viral infections, chemotherapy, and other treatments also may put a woman at higher risk of POI.8

The first sign of POI is usually menstrual irregularities or missed periods,2 which is sometimes called amenorrhea (pronounced ey-men-uh-REE-uh or uh-men-uh-REE-uh). In addition, some women with POI have symptoms similar to those experienced by women who are going through natural menopause, including:

• Hot flashes
• Night sweats
• Irritability
• Poor concentration
• Decreased sex drive
• Pain during sex
• Vaginal dryness1,5

For many women with POI, trouble getting pregnant or infertility is the first symptom they experience and is what leads them to visit their health care provider. This is sometimes called "occult" (hidden) or early POI.6

Currently, there is no proven treatment to restore normal function to a woman's ovaries.1,2 But there are treatments for some of the symptoms of POI, as well as treatments and behaviors to reduce health risks and conditions associated with POI. It is also important to note that between 5% and 10% of women with POI get pregnant without medical intervention after they are diagnosed with POI. Some research suggests that these women go into what is known as "spontaneous remission" of POI, meaning that the ovaries begin to function normally on their own. When the ovaries are working properly, fertility is restored and the women can get pregnant.

In about 90% of cases, the exact cause of POI is a mystery.4,6,11 Research shows that POI is related to problems with the follicles (pronounced FOL-i-kulz)—the small sacs in the ovaries in which eggs grow and mature.6 Follicles start out as microscopic seeds called primordial (pronounced prahy-MAWR-dee-uhl) follicles. These seeds are not yet follicles, but they can grow into them. Normally, a woman is born with approximately 2 million primordial follicles,12 typically enough to last until she goes through natural menopause, usually around age 50.4 For a woman with POI, there are problems with the follicles:1

• 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.6

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.6,8,12
• 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. Recent studies suggest that about 20% of women with POI have an autoimmune disease.4,13
  • Thyroiditis (pronounced thahy-roi-DAHY-tis) is the autoimmune disorder most commonly associated with POI.13 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.14 About 3% of women with POI have Addison's disease.15
• Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells.2,6,11
• Metabolic disorders. These disorders affect the body's ability to create, store, and use the energy it needs. For example, galactosemia (pronounced guh-lak-tuh-SEE-mee-uh) affects how your body processes galactose (guh-LAK-tohs), a type of sugar. More than 80% of women and girls with galactosemia also have POI.13
• Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion. In addition, viruses have been shown to affect follicle function.4,12

Health care providers use the term POI when a woman's ovaries stop working normally before she is 40 years of age.1,2 Many women naturally experience reduced fertility when they are around 40 years old. This age may mark the start of irregular menstrual periods that signal the onset of menopause. For women with POI, irregular periods and reduced fertility occur before the age of 40, sometimes as early as the teenage years.3,4 In the past, POI used to be called "premature menopause" or "premature ovarian failure," but those terms do not accurately describe what happens in a woman with POI. A woman who has gone through menopause will never have another normal period and cannot get pregnant. A woman with POI may still have periods, even though they might not come regularly, and she may still get pregnant.2,4