Premature Ovarian Failure (POF) (cont.)

What happens differently in premature ovarian failure?

Currently, researchers are unable to pinpoint exactly what happens in premature ovarian failure 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 premature ovarian failure have low levels of estrogen, scientists are focusing their attention on the follicles in the ovary in their study of premature ovarian failure.

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 premature ovarian failure. Women with premature ovarian failure may fall into one of two groups.

Follicle Depletion

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 premature ovarian failure 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 premature ovarian failure will experience this recovery of ovarian function.

Follicle Dysfunction

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 don'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 premature ovarian failure.

  • 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 premature ovarian failure, but this is not a definite number.

Research also shows that 10 percent to 20 percent of women with premature ovarian failure have a family history of the condition, which could mean that some cases of premature ovarian failure have a genetic component. But, inheritance patterns show that premature ovarian failure is not a purely genetic disorder. Research into the causes of premature ovarian failure is ongoing, in hopes that knowing why it occurs will also help in developing treatments for the disorder.


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