Causes of POF
A variety of different underlying conditions can cause POF. A lot of these causes are still being studied and we have a long way to go in terms of fully understanding the mechanism. Often, an underlying cause cannot be found; this can be incredibly frustrating for the woman as well as her doctor. This doesn't mean that there isn't an underlying cause, it just means that we haven't discovered it yet in the scientific community.
Some of the known causes of POF are as follows:
1. Fragile X Premutation Carrier Associated POF
Women who carry a mutated form of a gene called "FMR1" on their X-chromosome are at a higher risk for going through POF. Up to 20% of carriers of this genetic disorder undergo POF, and another handful go through earlier-than-usual menopause. We don't fully know yet why carrying this genetic mutation leads to an increased risk of ovarian failure, but the newest research shows that it may relate to an increased level of slightly abnormal protein that accumulates in the ovaries (recall from the "Some Vocabulary to Know" section that genes code for creating proteins in the body, so if the gene is slightly messed up, the protein will be as well).
2. Chemotherapy/Radiation Associated POF
Chemotherapy drugs as well as radiation are the most common causes of toxin-induced ovarian failure. This is due to the fact that chemotherapy drugs and radiation kill cells that are dividing rapidly. Therefore, they kill the cancer cells but they also kill off other quickly-dividing cells in the body, such as hair follicles (hence the hair loss), and ovarian follicles. This can be a potentially devastating long-term consequence of undergoing cancer treatment. Some of the chemo drugs known to be associated with ovarian damage are as follows:
- Nitrogen mustard
- L-phenylalanine mustard
3. Autoimmune Ovarian Failure
Sometimes for unknown reasons, the body creates immune defense proteins (known as antibodies) against its own tissues. These antibodies vary depending on the type of autoimmune disorder. Up to 4% of women with POF have antibodies directed against their own ovarian cells and their adrenal glands (these are detectable in blood tests). These women can have adrenal insufficiency, ovarian insufficiency, or both.
The mumps virus has been associated with testicular failure in men and is presumed to be associated with premature ovarian failure in women, but not enough large-scale scientific studies have been performed to know for sure yet.
The majority of patients with POF have not been found to have any of the above conditions. Some toxins in the environment may have more subtle effects on ovarian function and if many are added together, these may cause POF. Some examples of these factors are cigarette smoking (lowers menopausal age), weight gain (raises menopausal age), higher socioeconomic status (raises menopausal age), and parity (aka number of pregnancies carried to a viable age; lowers menopausal age).