Association between ovulation induction and early menopause—a cohort effect?

Abstract

We read the article by Pines et al., in which the interesting issue was addressed whether hormonal therapy for infertility influences age at menopause [1]. In this article it was suggested that women undergoing induction of ovulation might suffer an early menopause. However, I have serious concerns about the validity of this study. Participants in this study were postmenopausal women visiting a menopause clinic. Women with a history of ovulation induction (n=31) were compared with women who never experienced infertility treatment (control group) (n=200). The mean age at menopause was 46.4 years in the ovulation induction group and 50.0 years in the control group. However, such a comparison is only valid if women in both groups have had equal opportunity to reach menopause. To illustrate this point let us compare the mean age at menopause of women in the birth cohort 1948–1953 with women in the birth cohort 1942–1947. If we use questionnaire data from 1999, the (spurious) result will be that women in the younger birth cohort have a lower mean age at menopause than women in the older birth cohort. This artifact arises from the fact that women in the younger birth cohort are 46–51 years of age in 1999 and only those who have reached menopause before 51 years will be able to report age at menopause. Women with a later age at menopause did not yet have the opportunity to reach (and report) menopause. The older birth cohort consists of women who are 52–57 years of age in 1999 and includes also women who have (and are able to report) a later age at menopause.