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Premature Ovarian Failure

Premature ovarian failure (premature ovarian failure) is defined as cessation of menses before age 40. Premature ovarian failure presents with amenorrhea, low estrogen levels, and elevated gonadotropins. The term "premature" was coined when it was thought that affected patients had no remaining ovarian follicles. However, investigators have found evidence of ovarian function in about 60 percent of patients with premature menopause or premature ovarian failure. Some patients can spontaneously resume cyclic menstruation and even become pregnant. premature ovarian failure is thought to be a heterogeneous disorder.

The prevalence of premature menopause or premature ovarian failure in women under age 40 is estimated to be between 0.3 and 1.0 percent. In women with primary amenorrhea, the prevalence of premature ovarian failure ranges between 10 and 28 percent. In those with secondary amenorrhea, the prevalence is between 4 and 18 percent.

The causes of premature menopause or premature ovarian failure can be divided into two distinct categories: follicle depletion and follicular dysfunction. In patients with follicle depletion, either an initial deficiency in primordial follicles or

Other chromosomal abnormalities associated with premature ovarian failure include mosaicism and structural abnormalities of the sex chromosomes. Follicle depletion can also be caused by autoimmunity or surgery. Between 10 and 18 percent of patients with premature ovarian failure may have an autoimmune etiology. An increased frequency of premature ovarian failure has been noted in women with Addison's disease, myasthenia gravis, rheumatoid arthritis, and autoimmune thyroiditis. Rare causes of premature

Table 19

Classification of Premature Ovarian Failure

Ovarian follicle depletion

Deficient initial follicle number

Pure gonadal dysgenesis

Thymic aplasia/hypoplasia Idiopathic

Accelerated follicular atresia

X-chromosome related

Turner's syndrome

X mosaics

X deletions


Viral agents (e.g., mumps)

Autoimmunity latrogenic

Oocyte-specific cell-cycle regulation defect


Ovarian follicular dysfunction

Enzyme deficiencies

17-alpha hydroxylase 17-20 desmolase

Cholesterol desmolase

Galactose- I -phosphate uridyltransferase


Lymphocytic oophoritis

Gonadotropin-receptor-blocking antibodies

Antibodies to gonadotropins

Signal defects

Abnormal gonadotropins

Abnormal gonadotropin receptor

Abnormal G protein


Idiopathic (resistant ovary syndrome)

In follicular dysfunction, the oocytes/follicles fail to function despite adequate gonadotropin levels. Most causes of dysfunction are unclear, but may be related to enzyme deficiencies or signal defects.

Women with premature ovarian failure may present with primary or secondary amenorrhea. Many women with primary

Differential Diagnosis of Premature Ovarian Failure

Prodromal premature ovarian failure

Pure gonadal dysgenesis

Abnormal karyotype

Autoimmune ovarian failure

latrogenic ovarian failure

Associated with other syndromes:

Autoimmune polyglandular syndrome

Nonorgan-specific autoimmunity

Isolated immunoglobulin A deficiency


Miscellaneous causes (rare)

Perrault's syndrome


Enzyme deficiencies

17-alpha hydroxylase

17-20 desmolase

Cholesterol desmolase


Thymic disorders


DiGeorge's syndrome


Pseudo-ovarian failure

Thymic disorders

Gonadotropin-producing pituitary adenoma

Isolated gonadotropin deficiency


Gonadotropin antibodies


Therapy for premature ovarian failure depends primarily on the patient's desire for future pregnancy. Up to 20 percent of patients with premature ovarian failure ovulate spontaneously when the few remaining follicles respond to high circulating levels of 

Most reported pregnancies in patients with premature ovarian failure occur while patients are receiving hormone replacement therapy, but this does not imply a cause-and-effect relationship. It is not possible to predict the likelihood of ovulation. Pregnancy rates using donor oocytes have been reported to be between 16.8 and 30.0 percent, similar 

Treatment of women under age 40 who do not desire pregnancy is fairly straightforward. The long-term risks associated with estrogen deficiency, osteoporosis, and premature cardiovascular disease can be prevented with standard combination 

A dosage of as much as 1.25 mg of conjugated estrogen (Premarin) may be necessary to provide symptom relief in this younger patient population. Patients should be counseled regarding possible spontaneous return of ovarian function and ovulation, and, if