What causes premature menopause?

Premature menopause often happens unexpectedly and remains a very mysterious condition. It may sometimes be caused by certain medical treatments. Smoking has been associated with an earlier menopause but does not typically cause premature menopause. A number of different genetic mutations have been associated with POI but in most cases, the underlying cause is unknown.

Surgery on the ovaries:
Ovaries may be intentionally removed, for instance, to reduce the risk of cancer related to an inborn genetic risk (e.g. BRCA1/2 gene mutation). In some cases, ovaries may become severely damaged due to surgery on the ovaries (e.g. for treating ovarian cysts or extensive endometriosis).

Cancer treatment:
Another very important cause of damage to ovaries is treatment for cancer such as chemotherapy. Chemotherapy blocks the survival of cancer cells by causing damage to their genetic material (or DNA). Unfortunately, eggs in the ovary are also very sensitive to the damaging effects of chemotherapy. Some chemotherapy drugs (e.g. the alkylating agents) are especially dangerous to the ovaries. For these reasons, prior to undergoing cancer treatment, reproductive-aged women should be referred to a fertility specialist to discuss options for fertility preservation.

Genetic and unknown causes:
In most cases, the underlying cause for premature menopause is unknown.
In rare instances, females may be born with genetic changes that predispose to the early loss of eggs. In extreme cases, like most instances of Turner syndrome (these girls are born with only one X chromosome instead of two), the ovaries may not have any eggs from birth. In other instances, there may be eggs at birth, but they then undergo an early decline leading to premature menopause.
Some medical conditions and a number of genetic mutations have been found to be associated with an early decline in egg numbers. Some examples are Galactosemia, the Fragile X premutation and BPES (Blepharophimosis-Ptosis-Epicanthus inversus Syndrome).