Hormone replacement therapy affects iron status more than endometrial bleeding in older US women: A role for estrogen in iron homeostasis?

Miller, Elizabeth M.

doi:10.1016/j.maturitas.2016.03.014

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…On the other hand, in the study from Miller [210], hormone replacement therapy was associated with lower iron stores in post-reproductive women in the absence of uterine blood loss, indicating potential homeostatic hormonal control of the iron status. Namely, higher serum iron in post-menopause has traditionally been attributed to reduced menstrual bleeding and lack of iron loss that women experience with menopause, in addition to estrogen deficiency [210]. With findings from studies on the levels of ferritin and sex hormones, it can be concluded that as women age, their serum levels of estrogen decrease, while serum ferritin levels increase [211].…”

Section: Iron and Strokementioning

confidence: 85%

Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Kezele

Ćurko-Cofek

2020

Nutrients

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Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.

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Section: Iron and Strokementioning

confidence: 85%

Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Kezele

Ćurko-Cofek

2020

Nutrients

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“…Out of Caucasian, mixed ancestry and black African participants the latter had the highest incidence of IDA, followed by mixed ancestry and Caucasians (with IDA prevalence of 26.1%, 14% and 4.2% respectively). Similarly, Miller (Miller, 2016) noted that Hb was significantly higher in Caucasian women (aged 50 years and over) when compared to Hispanic and non-Hispanic black women within the same age group. However, ferritin was significantly lower in white women when compared non-Hispanic black women.…”

Section: What Is the Size Of The Problem?mentioning

confidence: 87%

“…In the study conducted by Miller, the women who were on hormone replacement therapy had significantly lower ferritin levels while their Hb levels were unchanged. The author also noted that ferritin levels were significantly higher in women who had undergone hysterectomy when compared to women that had not (Miller, 2016).…”

Section: Aetiology Including Physiological Age-related Changes That mentioning

confidence: 95%

“…need for establishing a consensus regarding cut-offs for iron and vitamin B12 biomarkers of status for diagnosing anemia in the elderly. Miller (2016) investigated if hormone replacement therapy in 1,066 post-menopausal women aged 50 and over had any effect on their iron status (Hb and ferritin). Results from animal models and cell studies showed that oestrogen plays a part in the regulation of iron homeostasis through hepcidin expression (Hou et al, 2012;Ikeda et al, 2012) and ferroportin signalling (Qian et al, 2015).…”

Section: Aetiology Including Physiological Age-related Changes That mentioning

confidence: 99%

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Iron status in the elderly: A review of recent evidence

Wawer

Jennings

Fairweather‐Tait

2018

Mechanisms of Ageing and Development

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A comprehensive literature review of iron status in the elderly was undertaken in order to update a previous review (Fairweather-Tait et al, 2014); 138 summarised papers describe research on the magnitude of the problem, aetiology and age-related physiological changes that may affect iron status, novel strategies for assessing iron status with concurrent health conditions, hepcidin, lifestyle factors, iron supplements, iron status and health outcomes (bone mineral density, frailty, inflammatory bowel disease, kidney failure, cancer, cardiovascular, and neurodegenerative diseases). Each section of this review concludes with key points from the relevant papers. The overall findings were that disturbed iron metabolism plays a major role in a large number of conditions associated with old age. Correction of iron deficiency/overload may improve disease prognosis, but diagnosis of iron deficiency requires appropriate cut-offs for biomarkers of iron status in elderly men and women to be agreed. Iron deficiency (with or without anemia), anemia of inflammation, and anemia of chronic disease are all widespread in the elderly and, once identified, should be investigated further as they are often indicative of underlying disease. Management options should be reviewed and updated, and novel therapies, which show potential for treating anemia of inflammation or chronic disease, should be considered.

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“…Indeed, NCOA4 is involved in regulating hormone responses (via its action as a nuclear receptor coactivator for androgen and estrogen receptors [ 16 , 17 , 32 ]) in addition to its novel role as a mediator of intracellular iron levels (as a ferritinophagic mediator [ 28 , 29 ]); we propose that NCOA4 may be involved in OVCA biology by both mechanisms of action. Prior data identifies links between estrogen/androgen levels (hormones) and iron signaling; for example, there is an inverse relationship between estrogen and body iron levels in post-menopausal women [ 59 ]. Furthermore, estrogen is well-established to regulate FPN by binding to estrogen response elements (ERE) within its promoter region [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Expression and function of nuclear receptor coactivator 4 isoforms in transformed endometriotic and malignant ovarian cells

2017

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Iron is proposed to contribute to the transition from endometriosis to specific subtypes of ovarian cancers (OVCAs). Regulation of intracellular iron occurs via a ferritinophagic process involving NCOA4 (Nuclear Receptor Coactivator 4), represented by two major isoforms (NCOA4α and NCOA4β), whose contribution to ovarian cancer biology remains uninvestigated. We thus generated transformed endometriotic cells (via HRASV12A, c-MYCT58A, and p53 inactivation) whose migratory potential was increased in response to conditioned media from senescent endometriotic cells. We identified elevated NCOA4 mRNA in transformed endometriotic cells (relative to non-transformed). Knockdown of NCOA4 increased ferritin heavy chain (FTH1) and p21 protein which was accompanied by reduced cell survival while NCOA4β overexpression reduced colony formation. NCOA4α and NCOA4β mRNA were elevated in malignant versus non-malignant gynecological cells; NCOA4α protein was increased in the assessed malignant cell lines as well as in a series of OVCA subtypes (relative to normal adjacent tissues). Further, NCOA4 protein expression was regulated in a proteasome- and autophagy-independent manner. Collectively, our results implicate NCOA4 in ovarian cancer biology in which it could be involved in the transition from precursors to OVCA.

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Hormone replacement therapy affects iron status more than endometrial bleeding in older US women: A role for estrogen in iron homeostasis?

Cited by 11 publications

References 27 publications

Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Iron status in the elderly: A review of recent evidence

Expression and function of nuclear receptor coactivator 4 isoforms in transformed endometriotic and malignant ovarian cells

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