Genetic aspects of premature ovarian failure: a literature review

The diagnosis of premature ovarian failure (POF) is based on the finding of amenorrhea before the age of 40 years associated with follicle-stimulating hormone levels in the menopausal range. It is a heterogeneous disorder affecting approximately 1% of women <40 years, 1:10,000 women by age 20 years and 1:1,000 women by age 30 years. POF is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea).

Review of significant articles regarding genetic causes that are associated with POF.

Heterogeneity of POF is reflected by a variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Changes at a single autosomal locus and many X-linked loci have been implicated in women with POF. X chromosome abnormalities (e.g., Turner syndrome) represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Many genes have been involved in POF development, among them BMP15, FMR1, FMR2, LHR, FSHR, INHA, FOXL2, FOXO3, ERα, SF1, ERβ and CYP19A1 genes.

Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of cases.