Summary

Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea). It is a heterogeneous disorder affecting approximately 1% of women <40 years, 1:10,000 women by age 20 and 1:1,000 women by age 30. The most severe forms present with absent pubertal development and primary amenorrhea (50% of these cases are due to ovarian dysgenesis), whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with premature follicular depletion. As in the case of physiological menopause, POF presents with typical manifestations of climacterium: infertility associated with palpitations, heat intolerance, flushes, anxiety, depression and fatigue. POF is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (luteinizing hormone, LH, and follicle stimulating hormone, FSH) (hypergonadotropic amenorrhea). In addition to infertility, hormone defects may have severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis. The heterogeneity of POF is reflected by the variety of possible causes, including autoimmunity, toxins, drugs, as well as genetic defects. POF has a strong genetic component. X chromosome abnormalities (e.g. Turner syndrome) represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

Expert reviewer(s)

• Pr Paolo BECK-PECCOZ
• Pr Luca PERSANI