In Reply Our study1 showed that the early onset of menopause is associated with an increased risk of cardiovascular disease and mortality. We agree with Hayes et al as well as Mascitelli and Goldstein that elevated iron levels observed after menopause can be a potential mechanism linking the early onset of menopause with adverse cardiometabolic health. Iron is one of the most abundant metals in the human body and is required as an essential cofactor in many important biological processes, such as oxygen transport, DNA synthesis, energy production, and regulation of cell growth and differentiation.2
However, because of its propensity to participate in oxidation-reduction reactions that generate harmful free radicals, iron can be toxic to cells and lead to alterations in organ function when present at high concentrations.2 An elevated concentration of plasma ferritin, an iron-binding blood plasma glycoprotein, has been associated with adverse cardiometabolic profile and increased risk of cardiovascular disease in women, as well with other long-term diseases associated with early-onset menopause, such as osteoporosis.3- 6 Emerging evidence shows that serum levels of ferritin increase with aging in women and that iron accumulation is a common process in postmenopausal women.7 For women of reproductive age, because of menstruation, endogenous iron is excreted through blood loss, resulting in reduced levels of ferritin and iron storage.3 Following menopause, iron is no longer lost through menstruation, and the metal ion increasingly accumulates in the body.3 Thus, early menopause might be detrimental to cardiovascular health in women because of the early exposure to elevated levels of iron. Perhaps in the near future, other studies will examine the therapeutic potential of the manipulation of iron levels for treating cardiovascular disease in women with early onset of menopause.
Corresponding Author: Taulant Muka, MD, MPH, PhD, Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, Dr Molewaterplein 50, Office NA29-14, 3000 CA Rotterdam, the Netherlands (email@example.com).
Published Online: January 4, 2017. doi:10.1001/jamacardio.2016.5084
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Muka T, Chowdhury R, Franco OH. Effect of Iron Levels on Women After Premature or Early-Onset Menopause—Reply. JAMA Cardiol. Published online January 04, 2017. doi:10.1001/jamacardio.2016.5084