Reference limits for haemoglobin and ferritin

Authors� reply

Heath et al acknowledge that women should be iron replete, and the evidence we presented suggests that a large proportion of menstruating women are not. We have unpublished data showing that to maintain a ferritin concentration above 70 µg/l (99% confidence interval for iron staining in the bone marrow ⁽¹⁾), in menstruating women with chronic telogen effluvium (increased scalp hair shedding that affects one in three women), a daily iron intake of 48 mg is required. The potential benefits of a female population that is iron replete far outweigh the possible overload affecting a very small proportion of women, in whom monitoring may be employed.⁽²⁾ ⁽³⁾

The work of Zhu and Haas does nothing to support the argument of Heath et al.⁽⁴⁾ They say that this study was too short and that both tissue iron status and body iron stores were still improving simultaneously and had not yet reached a steady state. It was no surprise therefore to see an increase in the ferritin concentration and no rise in the haemoglobin concentration.

The efforts of Morison and Ferguson are welcomed, but their analysis of the data is flawed. They considered the female population to be iron replete, but the first data set was uncontrolled for the presence of chronic infection or inflammatory disease, and the subjects were unmatched for age or weight. In the second set, they chose a lower ferritin concentration than in the first. The differences in haemoglobin concentrations were substantially lower, but not significant, in women compared with men. They agree that sex specific cut off points for ferritin are inappropriate. In young people the median values only begin to diverge as menses exerts its effect (table).⁽⁵⁾

Median plasma ferritin concentrations (mg/l) in young people⁵

Sex	Age (years)
	4-6	7-10	11-14	15-18
Male	28	29	28	44
Female	27	32	28	23

We believe that a similar case exists for equality of lower haemoglobin values. Hobbs showed 40 years ago that the frequency distribution of haemoglobin concentration in response to iron supplementation in women paralleled that of men (figure).⁽⁶⁾ He concluded that the normal female range is not physiological and that iron should be given to all patients with a haemoglobin concentration below 13.6 g/100 ml (136 g/l).

(F1)� Frequency distribution of haemoglobin concentrations in response to iron treatment in anaemic men and women compared with "normal" women (reproduced with permission⁽⁵⁾)

Neither Heath et al nor Morison and Ferguson present any data to address the fact that no other mammals (including menstruating non-human primates) exhibit a sex difference for haemoglobin and red blood cell count (ferritin is not assessed in veterinary medicine). They also do not explain why these variables approximate in postmenopausal women and aged matched men, or why there are no significant differences in children. A healthy, iron replete, 30 year old woman has the same haem synthesis as one aged 60.⁽⁷⁾ What biological evidence is there to employ different reference limits for pre- and postmenopausal women, other than widespread iron deficiency due to menses?

Our aim was to highlight the scale of the underestimation of iron deficiency in menstruating women and the deleterious effects on women�s health.⁽²⁾ The practicalities of ensuring that women are iron replete are a separate issue.

Hugh Rushton

honorary senior lecturer

rushton{at}btinternet.com

School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT

Michael J Norris
senior lecturer

Robin Dover
clinical research officer

Imperial Cancer Research Fund, London WC2A 3PX

Anthony W Sainsbury
senior veterinary officer

Institute of Zoology, Zoological Society of London, London NW1 4RY

Jeremy J H Gilkes
consultant dermatologist

Ian D Ramsay
consultant endocrinologist
Lister Hospital, London SW1W 8RH

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