Early Menopause is an Inherited Condition

abstract& commentary

Synopsis: Fifty percent of women who have menopause before the age of 45 have a familial pattern consistent with either a dominant X-linked or autosomal inheritance.

Source: Tibiletti MG, et al. Human Reprod 1999;14: 2731-2734.

Tibiletti and colleagues from milan inves- tigated 36 women with menopause between the ages of 40 and 45. Of these 36 women, 30 had no obvious explanation for their early menopause. Fifteen of these 30 had evidence of familial early menopause. Analysis of the families indicated a dominant pattern of inheritance through either maternal or paternal relatives. This pattern of inheritance is similar to that observed in 81 women with premature ovarian failure previously described by the same authors. These results suggest that the age of menopause is controlled by genes, probably located on the X-chromosome. Deletions or mutations of these genes would explain premature ovarian failure as well as early age of onset of menopause.

COMMENT BY LEON SPEROFF, MD

Evidence indicates that the average age of menopause (approximately 51) has not changed throughout recorded history. It is estimated that 10% of women have menopause younger than the age of 45, and only 1%, at most 2%, experience premature ovarian failure, defined as menopause younger than the age of 40. In a previous report by this Italian group, one-third of patients with premature ovarian failure have been found to have an inherited family pattern consistent with a dominant transmission either through the maternal or paternal line.1 Studies have indicated that a critical region of the X-chromosome plays a role in premature ovarian failure. These studies have identified the region q21 on the X-chromosome as the site of a critical gene.2

The belief that a significant portion of early menopause may be genetically determined was strengthened by reports that significant relationships exist between the menopausal age of mothers and daughters and in twins. The cytogenetic studies indicate that there is a genetic relationship between early menopause and premature ovarian failure in a significant number of women who experience these conditions. Thus, somewhere from 30-50% of women who experience early menopause do so for genetic reasons and, therefore, a family history of early menopause or premature ovarian failure significantly increases the risk for an individual to have a similar experience.

It is important to note that, in these studies, those individuals with early menopause, and even with premature ovarian failure, had respectable pregnancy rates. Of course, in individuals with this familial condition, delaying pregnancy until late in life carries with it the risk of experiencing menopause prior to achieving pregnancy. Also of interest in the analysis of these patients was that there was no increased rate of miscarriage.

These results raise the possibility of eventually being able to establish the presence or absence of an abnormality on the X-chromosome that would predict the age of menopause. Of course, this would be extremely helpful in counseling regarding fertility.

References

1. Vegetti W, et al. Human Reprod 1998;13:1796-1800.

2. Bione S, et al. Amer J Human Genetics 1998;50: 533-541.

The following statements are true regarding early menopause and premature ovarian failure except:

a. As many as 50% of women with early menopause have an inherited condition as the etiology.

b. The most likely critical site that determines the age of menopause is located on the long arm of the X-chromosome.

c. Patients with premature ovarian failure have a different genetic mutation compared with patients with early menopause.

d Patients with an inherited condition for early menopause do not have an increased risk of spontaneous miscarriage.