Endocrinology it Is Generally Assumed That Iron

Endocrinology

It is generally assumed that iron stores increase during menopausal transition (Kim et al. 2012). However, no longitudinal studies have been conducted to ascertain this. Some women undergoing menopause experience increased insulin resistance and other cardiovascular conditions, which are not attributable to changes in adiposity or sex hormones. Iron is known to be a strong pro-oxidant, which catalyzes reactions tending to raise oxidative stress. This, in turn, is a risk factor for insulin resistance. Increased measures of iron during menopause may then contribute to insulin resistance at this period (Kim et al.).

In response, the Study of Women's Health across the Nation or SWAN was designed and conducted to determine and investigate biologic and sociologic changes during and after menopause (Kim et al. 2012). The researchers measured several iron markers at pre-menopause and post-menopause to find out if 1) iron measures increase from pre-menopause to post-menopause longitudinally; 2) there are an increase in insulin resistance and glucose level from pre-menopause to post-menopause longitudinally; and 3) pre-menopausal measures of iron and changes in these measures during and after menopause are in any way connected with changes in insulin resistance and glucose levels, in addition to other factors associated with insulin resistance. These include changes in adiposity, inflammation, and sex hormone-binding globulin (Kim et al.).

Participants and Methods

Participants to this multi-site longitudinal cohort study were 70 community-based female respondents aged 42-52 (Kim et al. 2012). They had intact uterus with at least one ovary and did not take estrogen or similar medications, which could have affect ovarian function. They all had at least menstrual period in the three months preceding the study. They were enrolled in one of the 7 identified clinic sites, one in Detroit. This report emanated from the Michigan SWAN site and approved by the University of Michigan Institutional Review Board. The inclusion criteria for the choice of respondents were natural menopause as differentiated from that resulting from hysterectomy or oophorectomy and the last known menstrual period. They were selected according to estimated differences in ferritin derived from observations in cross-section studies between pre-menopausal and post-menopausal women (Kim et al.).

Post-menopausal women were those who ceased to menstruate for 12 months or more (Kim et al. 2012). Those on estrogen or progestin therapy at the pre-menopausal or post-menopausal visit or reported diabetes from any examination were excluded. Changes in insulin resistance and glucose levels could be affected by subsequent medications and behavioral changes. They were chosen at random, had similar age, came from same race or ethnicity, and were of anthropometric size as compared with those of Michigan SWAN without diabetes and who had entered natural menopause (Kim et al.).

Discussion and Conclusion

Discussion

Tests found that ferritin increased and sTfR:ferritin decreased from pre-menopause to post-menopause (Kim et al. 2012). This occurrence was consistent with an increase in iron stores. Insulin resistance and glucose levels likewise increase during the transition. The largest changes in iron stores also had the strongest link between iron and changes in HOMA-IR. Their measures of iron were lower during pre-menopause and highly increased over the menopausal transition (Kim et al.).

To the best of the authors' knowledge, this is the only longitudinal study on such changes and the only investigation ever conducted on the connection with insulin resistance in a community-based sample. This suggests another pathway through which menopausal women may develop insulin resistance beyond inappropriate lifestyle changes and the increasing ratio of androgen: estrogen during menopause. Earlier cross-sectional studies revealed that women of reproductive age have lower iron indicators than middle-aged or elderly women. One population-based study reported the prevalence of iron deficiency at 11% in those aged 20-49 years and 5% in those 50-69 years old. Those increases in iron stores could have been due to the termination of menstrual bleeding among the pre-menopausal Danish women. The primary basis of iron levels were merely self-reported duration of absorption and could be different from those reported in pre-menopausal women. Lastly, ferritin and other iron indicators were connected with elevated liver function tests, especially alanine animotransferase. This suggests non-alcoholic fatty liver disease and an increased probability of insulin resistance. Thus, fatty liver disease may also confound or mediate the connection between iron and insulin resistance (Kim et al.).

The study also established the significant link between iron measures and HOMA-IR when iron was represented by sTfR but not by ferritin or transferrin alone (Kim et al. 2012). Two nested case-control studies earlier investigated a single measure of sTfR ferritin and found the connection with oncoming diabetes. This present research did not yield large changes in the serum sTfR levels between pre-menopause and post-menopause. This suggested that the aspect of iron metabolism that could have changed from pre-menopause to post-menopause was not erythropoiesis alone (Kim et al.).

Merits of this investigation can include its random selection from a longitudinal community-based study (Kim et al. 2012). Its sample size is a limitation. It used proxy measures for iron and iron stores had no bone marrow biopsy confirmation. SWAN likewise used proxy measures for insulin resistance, like HOMA-IR, and this is usual in large epidemiologic studies instead of insulin clamp measurements. The cohort respondents were somewhat young. It is possible that as they age and their time since menopause increases, their iron stores correspondingly increase much more. It is also possible that iron associations with HOMA_IR may become more pronounced (Kim et al.).