Ferritin Levels – Redefining Normality in Women

Medicine must improve because we want to treat the sick better and because we need to keep up with the new diagnoses being created that turn healthy people into patients. Today, Julie Laurence takes us through the coming public health crisis of “low ferritin without anemia.” Not only is ferritin unreliable at diagnosing iron deficiency, but low ferritin without anemia is usually asymptomatic.

Adam Cifu

The American Society of Hematology (ASH) recommends raising the lower limit of normal for ferritin to 30 μg/L for men and women alike. ASH is also proposing a new diagnosis: Iron deficiency without anemia. This diagnosis would be based solely on ferritin values. This follows a trend we see across medicine of turning healthy people into patients.

Increasing the lower limit of normal from 25 to 30 in men won’t change much, but going from 15 to 30 in women and labeling low ferritin as a pathological state would be an important change. According to population prevalence in North America, up to 38% of menstruating women could be defined as having the new condition, iron deficiency without anemia.

ASH has not released screening recommendations, but other hematology associations and experts are already advocating for screening menstruating women, given the high prevalence of this condition. Some labs are already flagging ferritin levels below 30 as abnormal.

We are at a turning point in the overdiagnosis of iron deficiency because ferritin is not a perfect test for it, and iron deficiency without anemia is probably unimportant.

First, the flaws of using ferritin to diagnose iron deficiency. A Cochrane review from 2021 found insufficient evidence to recommend ferritin as a screening tool for iron deficiency in healthy populations. Ferritin is an indirect marker of iron deficiency. To assess true iron deficiency, bone marrow sampling is required. Original studies on ferritin show us how poorly ferritin performs as a test for iron deficiency. In young healthy women specifically, iron depletion with bone marrow staining correlated with a median ferritin level of 9 µg/L – well below the new recommended threshold of 30 µg/L. Furthermore, up to 25% of women were iron replete at a ferritin level of 27 µg/L. Many women would thus be misdiagnosed as iron-deficient using ferritin in this context, especially given the new threshold.

Ferritin levels also fluctuate in young women with menses and with iron-rich food intake. Labeling normal ebbs as a disease state contributes to overmedicalizing normality.

Then there is the issue that treating iron deficiency without anemia has not been shown to be beneficial. Low ferritin levels are poorly correlated with reported symptoms in the absence of anemia – hair loss and restless leg syndrome are the only symptoms that reach statistical significance in a well-designed study. Most notably, reported fatigue does not seem to make the cut. Do we know what we are treating then? How can we measure treatment efficacy in the absence of reliable symptoms?

I’m not minimizing the symptoms or the burden of iron deficiency anemia. Are iron deficiency and anemia prevalent in menstruating women? Yes. Should we treat symptomatic women presenting for care? Absolutely. Should we screen for and treat iron deficiency in the absence of anemia? I’m not so sure.

Ferritins should be ordered and interpreted when there is suspicion of symptomatic iron deficiency anemia (or iron overload). Iron deficiency without anemia should not be a new diagnosis for which healthy women are tested.

Defining ferritin below 30 as being ‘abnormal’ while it is found in 38% of people seems aberrant.

So then, what should normal ferritin levels be? Normal values should be normal by definition, i.e. ‘’occurring naturally’’, ‘’approximating the statistical average or norm’’, or by scientific definition, normals should be the lower and higher limits of a bell curve of what is found in a sample of the general, otherwise healthy, population.

Let’s not make ferritin what it’s not.

Julie Laurence is a registered adult care nurse practitioner in Montreal who specializes in internal medicine at a community hospital outpatient clinic. She is affiliated with the Choosing Wisely campaign and trains future nurse practitioners at both the Université de Montréal and McGill University.

Photo Credit: Filip Mroz