What is premature ovarian failure (POF)?
Health care providers use the term POF to describe a stop in normal functioning of the ovaries in a woman under the age of 40. Many women naturally experience a decline in fertility at age 40; this age may also mark the beginning of irregularities in their menstrual cycles that signal the onset of menopause. For women with POF, the fertility decline and menstrual irregularities occur before age 40, sometimes even in the teens. Some health care providers also use the term primary ovarian insufficiency to describe this condition.
In the past, health care providers called this condition premature menopause, but this term is not an accurate description of what happens in a woman with POF. A woman who has gone through natural menopause will rarely ever have another period; a woman with POF is much more likely to have periods, even though they might not come regularly. There is virtually no chance for a woman who has gone through menopause naturally to get pregnant; in some cases, a woman with POF can still get pregnant.
What causes POF?
Although researchers have a general idea of what causes POF, in most cases the exact cause remains unclear. To understand what happens in POF, you need to understand what happens in a woman's body when it's functioning normally.
The Normal Menstrual Cycle
In general, a woman's reproductive health involves her:
- Hypothalamus (pronounced high-poe-THAL-amus) - part of the brain that functions as the main control for the body's reproductive system. The hypothalamus works like a thermostat in a furnace, in that it controls the levels of different hormones and other chemicals in the body. If the hypothalamus detects that there is too little of a hormone in the body, it orders the body to make more.
- Pituitary (pronounced pitt-OO-ih-terry) gland - the body's master gland. The pituitary sends out hormones, or chemical signals to control the other glands in the body. The pituitary gets orders from the hypothalamus about what the body needs.
- Ovaries - the source of eggs in a woman's body. The ovaries have follicles, which are tiny, fluid-filled sacs that hold the eggs. The ovaries also make hormones that help to maintain a woman's health, such as estrogen, progesterone, and testosterone. The ovaries receive the chemical signals from the pituitary and respond by making certain hormones. In POF, the ovaries stop working correctly in both their egg production role, and in their hormone production role.
- Uterus - where a woman carries a baby, also called the womb.
- The uterus has different layers; its innermost layer or lining is called the endometrium - endo means inside and metrium (pronounced MEE-tree-um) means womb.
- The endometrium functions as a bed for an embryo when a woman is pregnant. If no pregnancy occurs during the cycle, then the endometrium is shed as a menstrual flow, or a period, and the cycle starts all over again.
- The hypothalamus keeps track of the level of estradiol (pronounced ess-trah-DYE-awl) in the body. Estradiol is the natural estrogen that a woman's body makes, so we'll call it estrogen from now on.
- When the level gets low, the hypothalamus sends an order to the pituitary gland telling it that the body needs more estrogen.
- The pituitary gets the order and responds by sending out follicle stimulating hormone (FSH), a hormone that causes the follicles on the ovary to grow and mature. Mature follicles make estrogen and other substances, such as inhibin. The pituitary continues to make FSH until the mature ovarian follicles make enough estrogen. If the follicles don't make enough estrogen, the level of FSH goes even higher.
- When the level of estrogen gets high enough, the hypothalamus and pituitary know that there is a mature egg in one of the follicles. To get this egg to the uterus so that it can be fertilized, the pituitary sends out a large burst of luteinizing hormone (LH). LH breaks open the mature follicle to release the egg, which allows it to move toward the uterus. The level of LH is only high during the time an egg is being released. This LH burst is the basis for home ovulation detection kits. Because LH may be high throughout much of the menstrual cycle in women who have POF, home ovulation detection kits are unreliable in these women.
- The empty follicle is then transformed into a yellowish, corpus luteum (pronounced CORE-puss loo-tee-um). Corpus means body and luteum means yellow.
- The corpus luteum makes progesterone, the hormone that prepares the uterus for pregnancy.
- Increased levels of progesterone cause the endometrium to change in preparation for pregnancy, should it occur. Once the endometrium is properly prepared, it can support an embryo and allow the embryo to grow.
- If the egg is fertilized, it sends out a hormone called HCG to let the body know that it;it's there. HCG causes the corpus luteum to continue to make progesterone, the hormone needed for pregnancy. Pregnancy tests measure the level of HCG. If HCG is present, then it's likely that a woman is pregnant.
- If there is no signal, that is, no HCG is present because the egg wasn't fertilized, the corpus luteum stops making progesterone. Without progesterone, the endometrium starts to break down, and the woman's body sheds it as her period.
What happens differently in POF?
Currently, researchers are unable to pinpoint exactly what happens in POF to stop normal function of the ovaries in most cases. Remember that the FSH levels are high when the ovaries fail to produce enough estrogen. LH levels also stay high in many cases, even during the occasional times that follicles successfully grow. Mature follicles in the ovaries make estrogen, as well as other substances, including the protein inhibin. Because women with POF have low levels of estrogen, scientists are focusing their attention on the follicles in the ovary in their study of POF.
Follicles in the ovaries start out as microscopic seeds, called primordial (pronounced prime-OR-dee-ul) follicles. These seeds are not yet follicles, but can grow into them. In general, a woman is born with about two million primordial follicles, which should be enough to last her until she goes through menopause. But this may not be the case for a woman with POF. Women with POF may fall into one of two groups.
A woman with follicle depletion has no responsive follicles left in her ovaries. There is no way for the body to make more primordial follicles. And, currently, there is no way for scientists to make primordial follicles. Although scientists haven't identified all the causes of follicle depletion, some known causes include:
- Chemotherapy or radiation therapy - strong treatments for cancer
- An abnormal or missing X chromosome - the X chromosome stores genetic material that helps build a person. It also helps to determine whether a person is a male or a female. Females need two normal X chromosomes to make enough primordial follicles, and to use them properly. If a critical part of either X chromosome is missing, or if an entire X chromosome is missing, the body may not make enough primordial follicles to begin with, or it may use them up too quickly. This problem is the cause of POF in 2 percent to 3 percent of women with the condition.
- Even when it appears that all a woman's follicles are depleted, it is possible that a very small number of surviving follicles can, without warning, begin to function on their own. This spontaneous function can cause ovulation or a menstrual period; if insemination occurs, this function could lead to pregnancy, although such a situation is uncommon. Currently, health care providers can't predict which women with POF will experience this recovery of ovarian function.
A woman with follicle dysfunction still has follicles in her ovaries, but for unknown reasons they are not working properly. Currently, scientists do not have a safe and effective way to make follicles start working normally again. Although they have yet to identify all the causes of follicle dysfunction, some known causes include:
- An autoimmune attack - the immune system normally protects the body from invading bacteria and viruses. In some women, though, for reasons researchers donitdon't understand, the immune system attacks developing follicles, which prevents the follicles from working the way they should. Current research suggests that this type of problem occurs in 5 percent of women with POF.
- A low number of follicles - even though only one mature follicle releases an egg each month, that follicle usually has less mature follicles developing along with it. Scientists don't understand exactly how, but these supporting follicles seem to play a role in helping the mature follicle function normally. If these extra follicles are missing, the dominant follicle becomes luteinized and will not mature and release an egg properly. Current research estimates that this problem may occur in up to 60 percent of women with POF, but this is not a definite number.
Research also shows that 10 percent to 20 percent of women with POF have a family history of the condition, which could mean that some cases of POF have a genetic component. But, inheritance patterns show that POF is not a purely genetic disorder. Research into the causes of POF is ongoing, in hopes that knowing why it occurs will also help in developing treatments for the disorder.
How many women have POF?
POF affects approximately:
- One in 10,000 women by age 20
- One in 1,000 women by age 30
- One in 250 women by age 35
- One in 100 women by age 40
What are the symptoms of POF?
The most common first symptom of POF is having irregular periods. Health care providers sometimes dismiss irregular or skipped periods (sometimes called amenorrhea - pronounced AY-men-or-ee-uh) as being related to stress; but a woman's monthly cycle is actually an important sign of her health, in the same way that blood pressure or temperature are signs of health. If you have irregular periods or skip periods, you should tell your health care provider, so that he or she can begin to determine the cause of these problems.
Some women with POF also experience other symptoms with POF. These symptoms are similar to those experienced by women who are going through natural menopause and include (but are not limited to):
- Hot flashes
- Night sweats
- Poor concentration
- Decreased interest in sex
- Pain during sex
- Drying of the vagina
How do I know if I have POF?
One of the most common signs of POF is having irregular periods. Women should pay close attention to their menstrual cycles, so that they can alert their health care provider when changes occur in their periods.
If you are under age 40 and your periods are irregular, or if you miss your period altogether for three months or more, your health care provider may measure the level of FSH in your blood, to determine if you have primary ovarian insufficiency in its early stages, or possibly even fully developed POF. Remember that FSH signals the ovaries to make estrogen. If the ovaries are not working properly, as is the case in POF, the level of FSH in the blood increases. A higher level of FSH in the blood is a strong sign of POF. But, irregular periods alone are not a sure sign that you have POF - research shows that fewer than 10 percent of women who have irregular or skipped periods have high FSH levels and POF.
To do an FSH test, your health care provider will collect some of your blood and send it to a laboratory. At the lab, a technician will check the level of FSH. If the level of FSH is in the menopausal range, it is likely that you have POF.
Source: National Institutes of Health
Updated: September 2003
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