Menopause: Cause or Consequence

Vera Bittner, M.D., F.A.C.C.




The number of postmenopausal women worldwide is projected to increase from 467 million in 1990 to 1,200 million in 2030.[1] Understanding the determinants of menopause and its health consequences is thus becoming increasingly important. Menopausal age is in part genetically determined.[2,3,4] Among health behaviors and environmental factors only smoking has been consistently associated with an earlier age at menopause.[5] The menopausal transition is associated with metabolic changes reminiscent of the metabolic syndrome[6], but the impact of menopause on subsequent cardiovascular disease remains controversial, in large part because it is exceedingly difficult to disentangle adverse effects of aging from potential adverse effects of menopause.[7,8,9] Clinical trials of postmenopausal hormone therapy designed to correct the estrogen deficiency of the menopausal state have not shown any reductions in cardiovascular morbidity or mortality.[10,11,12]

Kok and colleagues suggest in their provocative paper ( that cardiovascular risk factors strongly determine menopausal age, either through direct damage to the ovarian vasculature or indirectly through an adverse impact on the endocrine system.[13] While the investigators have very accurate data on the age at cessation of menopause, it is unknown whether women who experienced cessation of menstruation at an early age were truly menopausal or may have had other endocrine disturbances such as secondary amenorrhea of varying etiologies or hypothalamic hypoestrogenemia, a condition which has been associated with angiographic coronary artery disease in a cohort of women who underwent diagnostic coronary angiography for suspected myocardial ischemia.[14] Hormonal changes which could potentially influence cardiovascular risk factor levels begin in the late reproductive stage and precede menopause by several years.[15] It is not known whether risk factors measured in the current study were already influenced by early changes in the reproductive hormonal milieu. Confounding of the analysis by underlying diseases and conditions which could influence menopausal age is also a concern, since a substantial proportion of women in the current study had unexplained improvements in cardiovascular risk factors over time despite advancing age. If cardiovascular risk factors were a strong determinant of age at menopause, one would expect substantial variation in menopausal age across different cardiovascular risk environments. Such variation has not been documented in contemporary cross-cultural comparisons and some authors have suggested that menopausal age has not changed since antiquity.[16,17,18,19]

Long-term longitudinal investigations with detailed assessments of reproductive hormones and cardiovascular risk factors beginning during the reproductive stage and carried forward through the menopausal transition to the postmenopausal stages are clearly needed to follow-up on the intriguing hypothesis put forward in the current study.

For a related article,


Figure 1. Strengths of the Study


Figure 2 Some Questions (1)


Figure 3. Some Questions (2)


Figure 4. Stages of Reproductive Aging Workshop (STRAW)


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