X chromosome defects and premature ovarian failure

X chromosome defects and premature ovarian failure wo articles in this issue of the Journal by Driscoll et al.,' and McAuley et aLY2T describe patients with premature ovarian failure (POF) with associated defects on the X chromosome which offer insights into the aetiology of this complex disorder.POF is characterised by secondary amenorrhoea, hypoestrogenism, and elevated gonadotrophins in women under the age of 40 years.It is a common condition and occurs in 1% of women under the age of 40 years, and will affect 0.1% of women before the age of 30 years.' POF is becoming a challenging issue for couples, particularly as women delay having families until later in life.Two significant consequences of POF are the loss of fertility, and the clinical effects of hypoestrogenism.Low levels of oestrogen from a young age appear to increase the risk of osteoporosis and coronary heart disea~e.~POF is clearly a heterogeneous disorder, and only a few causes can be identified.4dIatrogenic agents, such as chemotherapy or radiotherapy, are known to reduce follicle numbers and cause POF.Although autoimmune diseases are seen in 10- 20% of women with POF, the role of autoimmunity remains controversial.*Infections, such as mumps, have also been suggested to cause oophritis resulting in ovarian failure.Other minor causes include galactosaemia, enzyme deficiencies and defects of gonadotrophin signalling.For most of these known causes, the pathway of molecular events leading to the development of ovarian failure is still unclear.At a physiological level, POF is most likely to have arisen from either a decreased number of oocytes being formed during development, or an increased rate of oocyte atresia during reproductive life.It is likely that the various identified causes will affect one of these physiological processes, for example, to increase the rate of oocyte atresia.It is clear that there is a genetic basis for POF.The familial aggregation of POF implies that