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Primary Ovarian Insufficiency: Get the Facts About Treatment

What is primary ovarian insufficiency (POI)?

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

What are the symptoms of primary ovarian insufficiency?

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:

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

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    How is primary ovarian insufficiency diagnosed?

    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
    • 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

    Are there associated disorders or conditions associated with primary ovarian insufficiency?

    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

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    What are the treatments for primary ovarian insufficiency?

    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.

    Hormone replacement therapy (HRT)

    HRT is the most common treatment for women with POI. It gives the body the
    estrogen and other hormones that the ovaries are not making. HRT improves sexual
    health and decreases the risks for cardiovascular disease (including
    attacks, stroke, and high blood pressure) and osteoporosis.17

    If a woman with POI begins HRT, she is expected to start having regular
    periods again. In addition, HRT is expected to reduce other symptoms, such as
    hot flashes and night sweats, and help maintain bone health.1,13,17,26 HRT
    will not prevent pregnancy, and evidence suggests it might improve pregnancy
    rates for women with POI by lowering high levels of luteinizing hormone – which
    stimulates ovulation – to normal in some women.19

    HRT is usually a combination of an estrogen and a progestin. A progestin is a
    form of progesterone. Sometimes, the combination might also include
    testosterone, although this approach is controversial.11 HRT
    comes in several forms: pills, creams, gels, patches that stick onto the skin,
    an intrauterine device, or a vaginal ring.14 Estradiol
    is the natural form of human estrogen. The optimal method of providing estradiol
    to women with POI is by a skin patch or vaginal ring. These methods are linked
    with a lower risk of potentially fatal blood clots developing. Most women
    require a dose of 100 micrograms of estradiol per day. It is important to take a
    progestin along with estradiol to balance out the effect of estrogen on the
    lining of the womb. Women who do not take a progestin along with estradiol are
    at increased risk of developing
    endometrial cancer. The progestin with the best
    evidence available to support use in women with POI is 10 mg of
    medroxyprogesterone acetate by mouth per day for the first 12 calendar days of
    each month.

    A health care provider may suggest that a woman with POI take HRT until she
    is about 50 years old, the age at which menopause usually begins.

    After that time, she should talk with her health care provider about stopping
    the treatment because of risks associated with using this type of therapy in the
    years after the normal age of menopause.4

    Is it safe for women with POI to take HRT?

    In general, HRT treatment for women with POI is safe and is associated with
    only minimal side effects. Women with POI take HRT to replace hormones their
    bodies would normally be making if they didn’t have POI.

    The HRT taken by women with POI is different from the hormone therapies taken
    by women who are going through or have gone through natural menopause, which are
    often called menopausal or post-menopausal hormone therapy (PMHT).

    A large, long-term study – called the Women’s Health Initiative – examined the
    effects of a specific type of PMHT, taken for more than 5 years, by women ages
    50 to 79 who had already gone through menopause. This study showed that PMHT was
    associated with an increased risk of stroke, blood clots, heart disease, heart
    attacks, and breast cancer in these women.20

    These results do not apply to young women with POI who take HRT.4,14
    The type and amount of HRT prescribed to women with POI is different from the
    PMHT taken by older women.4

    A woman should talk to her health care provider if she has questions about
    HRT as a treatment for POI. Also, she should tell her health care provider about
    any side effects she experiences while taking HRT. There are many different
    types of HRT. Women should work with their health care providers to find out the
    best type of treatment.

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    Calcium and vitamin D supplements

    Because women with POI are at higher risk for osteoporosis, they should get
    at least 1,200 to 1,500 mg of elemental calcium and 1000 IU (international
    units) of vitamin D, which helps the body absorb calcium, every day.21
    These nutrients are important for bone health.14
    A health care provider may do a bone mineral density test to check for bone

    Regular physical activity and healthy body weight

    Weight-bearing physical activity, such as walking,
    jogging, and stair
    climbing, helps build bone strength and prevents osteoporosis.14
    Maintaining a healthy body weight and getting regular physical activity are also
    important for reducing the risk of heart disease. These factors can affect
    cholesterol levels, which in turn can change the risk for heart disease.22

    Treatments for associated conditions

    POI is associated with other health conditions, including (but not limited
    to) Addison’s disease,
    Fragile X permutation, thyroid dysfunction, depression, anxiety, and
    certain other genetic, metabolic, and autoimmune disorders.

    Women who have POI as well as one of these associated conditions will require
    additional treatment for the associated condition. In some cases, treatment
    involves medication or hormone therapy. Other types of treatments might also be

    Emotional support

    For many women who experience infertility, including those with POI, feelings
    of loss are common. In one study, almost 9 out of 10 women reported feeling
    moderate to severe emotional distress when they learned of their POI diagnosis.14,
    ​ Several organizations offer help finding these types of professionals.

    POI in teens

    Receiving a diagnosis of POI can be emotionally difficult for teenagers and
    their parents. A teen may have a similar emotional experience as an adult who
    receives the diagnosis, but there are many aspects of the experience that are
    unique to being a teenager. It is important for parents, the teenager, and
    health care providers to work closely together to ensure that the teenager gets
    the right treatment and maintains her emotional and physical health in the long
    term. There are resources to provide advice and support for parents, teenagers,
    and health care providers.25


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