Premature Ovarian Failure

PREMATURE OVARIAN FAILURE

The diagnosis of premature ovarian failure applies to the approximately 1% of women who experience menopause before the age of 40 years. The diagnosis should be suspectedin a young woman with hot flushes and other symptoms of hypo-estrogenism and secondary amenorrhea (e.g., a woman seeking treatment for infertility). The diagnosis is confirmed by lab-oratory findings of menopausal FSH levels. Interestingly, hot flushes are not as common as might be expected in this group of patients. The diagnosis has profound emotional implications for most patients, especially if their desires for childbearing have not been fulfilled, as well as metabolic and constitutional implications. There are many causes of premature loss of oocytes and premature menopause; some of the more common causes are discussed below. Given its potential dramatic impact, premature ovarian failure demands a careful workup in order to identify the under-lying cause and permit appropriate management.

Genetic Factors

Several factors influence a woman’s reproductive life span. Genetic information that determines the length of a woman’s reproductive life is carried on the distal long arm of the X chromosome. Partial deletion of the long arm of one X chromosome results in premature ovarian failure. Total loss of the long arm of the X chromosome, as seen in Turner syndrome, results in ovarian failure at birth or in early childhood. When suspected, these diagnoses can be established by careful mapping of the X chromosome.

Gonadotropin-Resistant Ovary Syndrome (Savage Syndrome)

Some women with premature ovarian failure have an ade-quate number of ovarian follicles, yet these follicles are resistant to FSH and LH. A number of pregnancies have been reported in women with the gonadotropin-resistant ovary syndrome during the administration of exogenous estrogen. This fact supports a role for estrogens in stimu-lating FSH receptors in the ovarian follicles.

Autoimmune Disorders

Some women develop autoantibodies against thyroid, adrenal, and ovarian endocrine tissues. These autoantibod-ies may cause ovarian failure. Occasionally these women respond to hormone therapy with subsequent resumption of ovulation. 

Smoking

Women who smoke tobacco can undergo ovarian failure some 3 to 5 years earlier than the expected time of menopause. It is estab-lished that women who smoke metabolize estradiol primar-ily to 2-hydroxyestradiol. The 2-hydroxylated estrogens are termed catecholestrogens because of their structural sim-ilarity to catecholamines. The catecholestrogens act as anti-estrogens and block estrogen action. The mechanism for premature ovarian failure in smokers is unknown. However, the effects of smoking should be considered in smokers who are experiencing symptoms of estrogen deficiency.

Alkylating Cancer Chemotherapy

Alkylating cancer chemotherapeutic agents affect the membrane of ovarian follicles and hasten follicular atre-sia. One of the consequences of cancer chemotherapy in reproductive-age women is loss of ovarian function. Young women being treated for malignant neoplasms should be counseled of this possibility and advised that they may be candidates for follicular retrieval and cryopreservation as a means for attempting future pregnancy.

Hysterectomy

Surgical removal of the uterus (hysterectomy) in repro-ductive-age women is associated with menopause some 3 to 5 years earlier than the expected age. The mechanism for this occurrence is unknown. It is likely to be associated with alteration of ovarian blood flow resulting from the surgery.