ICD-10 Codes
E28.3 Primary ovarian failure. E28.31 Premature menopause.
General Information
In 1969 G. Jones described three patients with secondary hypergonadotropic amenorrhea and intact follicular apparatus. Resistant ovary syndrome also known as Savage syndrome received its name after one of the patients.
Definition and Terminology
Premature ovarian failure (POF) is a clinical syndrome associated with secondary hypergonadotropic amenorrhea in combination with low levels of estrogen, testosterone, anti-Mullerian hormone, inhibin B in women aged under 40.
This syndrome has other synonymic names: premature menopause, hypergonado-tropic amenorrhea, hypergonadotropic hypogonadism, Savage syndrome and other. "Premature ovarian failure" has been recognized as the most appropriate term as it best characterizes not only the loss of ovarian function but also the variability of clinical presentations implying a possibility of spontaneous (although quite rare) restoration of ovarian function.
Epidemiology
POF is noted in 1-3% of women; it depends on the age and ethnicity. In the age group 30-39 the prevalence is 76:100,000 of female population annually, at the age 40-44 the prevalence increases to 881:100,000.
POF is revealed in 14-18% of women with secondary amenorrhea. Familial conditions are not common: no more than 4-20% of cases. However, in 47% of patients the family history indicates primary and secondary oligoamenorrhea in first line relatives.
Etiology and Pathogenesis
The causes of premature depletion of ovarian reserve are divided in the following way:
• genetic (FMR1 transmutation, mutations of FOXL2, NR5A1, BMP15, FSHR and Gs alpha, as well as of steroidogenic enzymes);
• infectious and toxic [viral diseases (HIV, herpes infection including Epstein-Barr virus, smallpox, rubella, epidemic parotitis, tuberculosis, malaria, shigellosis];