To the Editor Muka et al1 found a higher risk of adverse cardiovascular outcomes in women who experience premature or early-onset menopause. This detrimental association is usually thought to be associated with the early loss of the ovarian function through menopause. However, the estrogen hypothesis is not consistent with epidemiological findings that premenopausal hysterectomy essentially cancels the protection even in patients with preserved functioning ovaries.2 Of note, healthy premenopausal women are largely protected from coronary heart disease; remarkably, so are women with heterozygous familial hypercholesterolemia.3 Despite a genetically determined, grossly unfavorable lipid phenotype, cardiovascular protection suggests not only that the protective factor is powerful but also that it does not operate through a lipid-related mechanism. Therefore, it has been proposed that an intact uterus has an important role in the protection of premenopausal women, and this is likely associated with the beneficial effect of iron depletion in menstruating women, ie, the iron hypothesis suggested by Sullivan4 in 1981.
Mascitelli L, Goldstein MR. Effect of Iron Levels on Women After Premature or Early-Onset Menopause. JAMA Cardiol. 2017;2(4):458. doi:10.1001/jamacardio.2016.5083