Premature Ovarian Failure

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 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 by typical manifestations of climacterium: infertility associated with palpitations, heat intolerance, flushes, anxiety, depression, fatigue. POF is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Beyond infertility, hormone defects may cause severe neurological, metabolic or cardiovascular consequences and lead to the early onset of osteoporosis. Heterogeneity of POF is also reflected by the variety of possible causes, including autoimmunity, toxics, 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. Disease name and synonyms Premature ovarian failure (POF; POF1: OMIM 311360); Hypergonadotropic ovarian failure; Menopausa precoce. Included diseases POF2 (OMIM #300511); POF3 (OMIM #608996) Definition Premature ovarian failure is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles/arrested folliculogenisis before the age of 40 years (secondary amenorrhea) [1,2] Epidemiology POF affects approximately: one in 10,000 women by age 20; one in 1,000 women by age 30; one in 100 women by age 40 [3]. The familial form of POF is rare, representing 4 to 31% of all cases of POF [4-6] Etiology The causes of POF are extremely heterogeneous. Acquired forms such as those occurring after treatments for neoplastic diseases or autoimmune diseases account for many cases [1]. POF has a strong genetic component with X chromosome abnormalities playing a primary role mainly in the cases with ovarian dysgenesis [7-10]. A gene (or genes) for POF (POF1) was localised to Xq21.3–Xq27 on the basis of deletions in various patients and families. A second gene (or genes) for POF (POF2) implicated by the analysis of balanced X/autosomal translocations has been localised to