Early Menopause and Premature Ovarian Insufficiency (POI)
What is Premature Ovarian Insufficiency (POI) ?
Premature ovarian insufficiency (POI) is a condition in which the ovaries spontaneously stop functioning normally in people who are younger than 40 years.
The average age of natural menopause is age 50 to 51, but menopause anytime between the ages of 45 and 55 is considered normal. Menopause is when a person stops having monthly periods and the ovaries stop releasing eggs and stop making the hormones oestrogen, progesterone and testosterone.
The term "early menopause" is when menopause occurs between age 40 and 45.
In most cases, is not clear why this happens. In people with POI, both of the following occur:
●The ovaries stop releasing eggs ("ovulation") or release them only intermittently.
●The ovaries stop producing the hormones oestrogen, progesterone and testosterone or produce them only intermittently.
Periods either stop or they are intermittent.
Because the ovaries are not working consistently, a women with POI is unlikely to be able to get pregnant naturally. However, some people continue to have intermittent periods for some time, during which it may be possible to get pregnant. Sometimes people use the term "premature menopause" to describe POI, but this is not entirely accurate since the ovaries may continue to work intermittently for some time.
Being diagnosed with POI can be emotionally devastating, especially for people who were planning or hoping to become pregnant in the future. If that is true for you, it's important to take care of your emotional health, get support from others, and learn about your options.
Causes of Premature Ovarian Insufficiency (POI)
We often do not know why primary ovarian insufficiency (POI) occurs. Many cases of the condition will likely be explained by genetic changes, exposure to certain "toxins" (e.g., some drugs or chemicals), or autoimmune disorders.
However, Most cases are "idiopathic," meaning they have no known cause. Even so, it is important to be tested for the known causes of POI. Some of the known causes may be associated with other effects on your health or the health of your family members.
Genetic causes — Genetic causes of POI may be due to abnormal chromosomes or changes in individual genes:
●Turner syndrome – The biological sex of a person is determined by their X and Y chromosomes. Females normally have two X chromosomes, while males have one X chromosome and one Y chromosome. Females with Turner syndrome have only one X chromosome; the other one is missing. This is the most common chromosomal defect in humans. It causes abnormalities throughout the reproductive system and can cause POI. Missing a specific portion of one X chromosome can also cause POI.
●Fragile X syndrome – Fragile X syndrome is the most common cause of intellectual disability worldwide. People with fragile X have an abnormal gene on the X chromosome. Those who have the abnormal gene do not always have intellectual disability, but the genetic abnormality can worsen with each successive generation. In other words, if a person with POI caused by a change in the fragile X gene gets pregnant, they are at risk of having a baby with intellectual disability. For this reason, females who are "carriers" for the abnormality in the fragile X gene are advised to have genetic counselling before trying to get pregnant.
●Other chromosomal and genetic causes – A number of other chromosomal and genetic abnormalities can lead to POI.
Toxic causes — The most common causes of "toxin-induced" ovarian insufficiency are chemotherapy drugs and radiation therapy, both of which are used to treat cancer by killing cancer cells. Chemotherapy drugs are also often used to treat other diseases, such as severe rheumatoid arthritis.
Autoimmune causes — When it is working properly, the body's immune system identifies and destroys foreign or abnormal cells that can cause infection, cancer, or other problems. When a person has an "autoimmune" disorder, the immune system instead attacks the body's normal, healthy cells. In some cases of POI, the immune system mistakenly attacks hormone-producing (endocrine) organs, including not only the ovaries but also the adrenal glands, the thyroid glands, and other structures.
People whose ovarian insufficiency is caused by an autoimmune disorder should have blood tests to evaluate their adrenal and thyroid function. If the adrenal glands are affected, it can cause a very serious and potentially life-threatening condition called "primary adrenal insufficiency" (Addison's disease).
Symptoms of POI
Symptoms of primary ovarian insufficiency (POI) can include menstrual and hormonal changes, infertility, and emotional symptoms.
Menstrual changes — Most people with POI go through normal puberty and have regular periods before their ovaries stop working normally. They most often seek medical attention when their period becomes irregular or infrequent.
Some people first notice changes in their periods when they stop taking oral contraceptive pills. This does not mean that the pills caused POI, just that the hormones in the pills "masked" it.
Infertility — With POI, the ovaries eventually stop working, making it impossible to get pregnant naturally. Some people learn that they have POI when they get an evaluation after being unable to conceive for some time.
Despite the odds being low, between 5 and 10 percent of people with the condition are able to conceive and carry a pregnancy. This is because the ovaries sometimes work intermittently for some time before they stop working completely. Other people are able to become pregnant through in vitro fertilization (IVF) using donor eggs.
Menopause symptoms — Because the body eventually produces little or no oestrogen, people with POI can also have symptoms of menopause, like hot flushes, night sweats, sleep disturbances, mood changes, brain fog to name a few.
As the condition progresses, some people may also develop urinary frequency, vaginal dryness, thinning of the vaginal walls, which can make sex painful. There are treatments that can help with these symptoms.
Diagnosis of premature ovarian insufficiency (POI) and hormone blood tests
If you are younger than 40 years and have not had a regular period for three months or longer, we recommended investigating POI.
Even if you do not want to get pregnant, primary ovarian insufficiency (POI) can affect your overall health. People with POI who do not take hormone replacement (oestrogen) are at increased risk for osteoporosis, heart disease and cognitive decline. It's important that the condition is detected early and managed appropriately.
To determine the cause of your irregular, absent, or unusually light periods, we will ask whether:
●You have symptoms besides changes to your period – Some people with POI have menopausal symptoms which indicate the ovaries are not working.
●You have had surgery on your ovaries, chemotherapy, or radiation therapy – These things all damage ovarian tissue.
●You or any of your family members have any autoimmune diseases – Examples include hypothyroidism, hyperthyroidism, or Addison's disease.
●You have any symptoms of adrenal insufficiency – These include decreased appetite, weight loss, vague abdominal pain, weakness, fatigue, salt craving, or darkening of the skin. These symptoms are important, because roughly 3 percent of people with POI develop adrenal insufficiency.
●Any of your family members have POI – Approximately 10 percent of cases of ovarian insufficiency run in families.
●You have a family history of fragile X syndrome, intellectual disability, or developmental delay – A family history of these conditions suggests that fragile X syndrome could be involved in your diagnosis.
To be diagnosed with POI, you must be under age 40, have irregular periods, and have elevated levels of a hormone called follicle-stimulating hormone (FSH). High levels of FSH indicate that your brain is trying to stimulate the ovaries, but the ovaries are not responding. Two FSH levels are taken 4-6 weeks apart.
If blood tests confirm that you have POI, your health care provider should then look for a potential cause. Tests used to determine the cause of the disorder might include:
●Karyotyping, which determines whether any chromosomal abnormalities exist.
●Testing for antibodies against the adrenal gland, which determines if you have a specific type of ovarian autoimmunity.
●Testing for the gene mutation that causes fragile X syndrome.
Treatment of POI
National guidelines recommending replacing hormones at least until the average natural age of the menopause, 51 years or beyond.
Hormone replacement — One of the main goals of POI treatment is replacing the oestrogen that the ovaries have stopped producing. That's important because oestrogen is vital to certain normal processes. The bones, for example, need oestrogen stimulation to stay strong and resistant to fracture. Without oestrogen, people with POI are at risk of developing osteoporosis (a disease in which the bones are weaker than normal).
There is also evidence that a lack of oestrogen before the age of 45 years can increase the risk of heart disease. This can also cause symptoms of menopause, including hot flushes, night sweats, sleep disturbance, and vaginal dryness HRT aims to prevent or relieve all of these consequences of oestrogen deficiency. Most people cannot take oestrogen alone; they must combine it with a form of progesterone to prevent a condition that could lead to overgrowth of the uterine lining and possible cancer of the uterus. People who do not have a uterus (i.e., have had a hysterectomy) can take oestrogen alone.
Combined oral contraceptives — People with POI often experience intermittent ovarian function and occasional ovulation. This means pregnancy is unlikely but possible. If you wish to avoid pregnancy, you can take contraceptive pills rather than HRT. The pill contains higher doses of hormones that are necessary to prevent pregnancy.