Familial form of idiopathic premature and early menopause

Introduction - Mean age at menopause is over 45 in 88% of women, under 45 in 9.7% (early menopause-EM), and under 40 years in only 1.9% (premature ovarian failure-POF). Although there have been some reports of familial POF, very little is known about the incidence and inheritance pattern of the idiopathic form of premature and early menopause. Patients and Methods - 98 patients with idiopathic POF and 28 with idiopathic EM were studied. Family members were traced back three generations in order to assess the presence of other cases showing early or premature menopause. Results - 32 patients with POF (32.7%) had family members showing the disorder, while 12 patients with EM (42.9%) had relatives with either POF or EM. This high incidence of family history strongly suggests that the disorder is a recognizable hereditary entity. The pedigree analysis showed a dominant maternal and/or paternal transmission with incomplete penetrance. Preliminary results obtained with the use of a haplotype-sharing analysis suggest an X-linked mode of inheritance. Interestingly, pedigree analysis on the EM population revealed the same dominant maternal or paternal pattern of inheritance observed in POF families. An Xq deletion was found in one family. Conclusion - There is a family history in many idiopathic POF and EM patients. A proportion of POF and EM conditions differs only in the age of menopause onset, and may represent variable expression of the same genetic disease. The different phenotypes can be explained by genetic heterogeneity and/or different environmental factors.