Premature Ovarian Failure – A Review
DEFINITION
Premature ovarian failure (POF) is the loss of ovarian function before the age of 40. Usually a woman’s ovaries supply eggs until the age of 51, which is the natural age of menopause. However, with premature ovarian failure, complete loss of ovarian function can occur from the teenage years through age 40. This condition is associated with infertility and often occurs before the traditional age of child bearing. Women who have been diagnosed with POF have very often not had the opportunity to have children, and for this reason this condition has a devastating impact. It is also associated with loss of bone mass due to absence of estrogen. Premature ovarian failure is also associated with an increased incidence of heart disease, hypothyroidism, adrenal insufficiency, and other autoimmune disorders. Approximately 1% of women will experience premature ovarian failure.
HORMONAL CHANGES
Because the ovaries have stopped functioning normally, this condition is associated with severely decreased levels of estrogen. In addition, the pituitary hormone that controls the ovaries, follicle-stimulating hormone (FSH) is markedly elevated. The lack of estrogen often results in vaginal dryness, vasomotor flushes, and bladder symptoms. These hormonal changes mimic what happens at the time of natural menopause, although the symptoms are usually more severe in patients with premature ovarian failure.
CAUSES
Although the cause of premature ovarian failure is usually not clear (idiopathic), it may be caused by genetic or autoimmune disorders. Chemotherapy or radiation treatments for cancer can also cause premature ovarian failure. Multiple surgeries on the ovaries may also result in decreased ovarian volume and eventually cause premature ovarian failure. Severe pelvic infections or endometriosis may also result in destructive changes within the ovaries and cause POF.
Removal of the uterus may result in diminished blood supply to the ovaries and may result in premature failure of the ovaries. Uterine artery embolization, a procedure used to treat uterine fibroids, may result in occlusion of the arterial blood supply to the ovaries, resulting in POF.
There are two types of premature ovarian failure. In one type, there are few follicles remaining in the ovaries. This is the more common type caused by genetic disorders, autoimmune damage, chemotherapy, radiation, surgery, endometriosis, or infection. In the other type, while the growing follicles have been largely destroyed but the deeper resting follicles remain intact. The serum anti-mullerian hormone level may differentiate the two types of POF from each other, which is much higher in patients with resting follicles intact.
In some situations FSH may bind to the ovarian receptor sites but be inactive. When this is the explanation for POF, estrogen, (ethinyl estradiol) can be used to suppress the circulating FSH levels. Then, stimulation of the ovaries may be achieved through the use of synthetic FSH. The percentage of patients who may be treated successfully with this approach is limited.
DIAGNOSIS
Typically, serum FSH levels may be used to establish the diagnosis of POF. Two FSH levels above 40 mIU/ml within one month establishes the diagnosis.
FERTILITY
Approximately 5-10% of women with POF may spontaneously become pregnant. However, at the present time there is no known consistent, effective, fertility treatment for POF. Generally, patients with this condition are offered egg donation or adoption.
There has been some preliminary research suggesting that DHEA (dehydroepiandrosterone) may improve fertility potential and decrease miscarriage rates in POF patients.
HORMONAL REPLACEMENT
Patients with premature ovarian failure are at risk for developing osteoporosis, vasomotor flushes, and vaginal dryness due to estrogen deficiency. Therefore, estrogen supplementation should be implemented shortly after the diagnosis of POF is made, and should be continued until the age of natural menopause. Estrogen supplementation may be through oral or transdermal administration. These patients should also be treated with periodic progesterone administration to prevent pre-malignant changes in the uterine lining due to continuous estrogen treatment.
