Iron-deficiency is not something you get just for being a lady

When I was thirteen years old, I got my period. Soon after, I remember going with my mother to the nurse practitioner's office -- her name was Debbie. Debbie told me that once girls got their periods, they were more likely to be anemic, and I would have to watch out for it. She suggested I start to take an iron supplement.

Something about that conversation irked me, even when I discovered that I was slightly anemic a few years later. I disliked the implication that one could be pathological just by being female. And I didn't understand how it was that menses, which is only about thirty milliliters of blood loss per menses, could have such a profound impact on women's iron status.

When I was in college, I studied this in a bit more depth in my undergraduate thesis. I discovered two important studies:

First, most people assume that the sex difference in iron stores in males and females, which begins at puberty, is due to the onset of the period and looks like this:

Figure 1. Made-up data to demonstrate the assumed way the sex difference in hemoglobin is produced.

However, the sex difference in iron status in males and females derives from an increase in male iron stores at puberty, not a decrease in female iron stores. This has to do with oxygen transport and testosterone (Bergstrom et al 1995). This means that the difference that occurs at puberty actually looks like this:

Figure 2. Made-up data to demonstrate the actual way the sex difference in hemoglobin is produced.

Second, the main culprit for iron-deficiency anemia (IDA) in men is upper-gastrointestinal bleeding, so when men present with IDA the first thing they do is an endoscopy. When women present with IDA they give her iron supplements and tell her to go home because it's just her ladybusiness. Kepczyk et al (1999) decided to actually do endoscopies on women for whom a gynecological source was diagnosed by a specialist for their IDA. They found a whopping eighty-six percent of these women had a gastrointestinal disease that was likely causing their IDA. Therefore, menses likely had nothing to do with their IDA, and the assumption that menses made them pathological actually obstructed a correct diagnosis.

The majority of the women in that study were bleeding internally, and no one had figured it out until then because they had periods.

When I went to graduate school, I wanted to study menstrual and endometrial functioning because the assumption that it inherently causes disease seems to lead to a life of frustration with the medical system for many women. I figured it would be good for us to better understand variation in this part of the body... so that's what I did. I went to rural Poland, where my colleague Dr. Grazyna Jasienska has a lovely field site perfect for testing my questions about the endometrium: I wanted a non-industrial population, but couldn't choose one so remote that I didn't have access to a hospital, since the women would need to do ultrasounds for me to image their endometria. Then, I didn't set out to test specific questions about IDA, but Dr. Jasienska wanted to do some blood tests on my subjects for a related study, and happened to do a full work-up on them.

Without meaning to, I ended up with two very useful pieces of evidence: measurements of their endometrial thickness, and their iron status. I also knew their dietary iron intake since I did 24-hour diet recalls. I realized that I had the evidence in front of me to test the relationship between menstruation and anemia directly, rather than indirectly like other studies I had read.

It was a matter of some simple correlations (Clancy et al 2006):

Figure 3. Red blood cells (RBC) and hemoglobin (Hg) are positively correlated with endometrial thickness (from Clancy et al 2006). Click to embiggen!

Take a look at the p-values for the relationship between endometrial thickness (ET) and red blood cells (RBC), and ET and hemoglobin (Hg): both are statistically significant. What's more, the relationships are positive. That means that the thicker the endometria, the better the iron status. I'll admit, when I ran these stats my hypothesis was simply that there would be no relationship, likely meaning that the effect of ET on iron status was at most neutral. But a positive effect? At least in this test, there is no support for the prevailing medical assumption that menses is correlated with IDA.

I was reminded of this study of mine recently, because it was cited by someone else studying something a bit different (vanity Google Scholaring will get you that). Elizabeth Miller, a graduate student (though she may have since defended) at the University of Michigan, wrote a very interesting paper on maternal hemoglobin depletion, which is the situation where pregnancy and lactation deplete iron stores. Miller (2010) studied this phenomenon in two populations in northern Kenya, a settled population and a more pastoral one, as a way to understand the differential impact of interbirth interval, energetic constraint, and dietary iron intake on maternal depletion. I'm going to focus just on the part of this study related to issues of menses and IDA.

Miller found that iron stores slowly increase in lactating mothers with months since birth, but also that the more children these women had, the lower their hemoglobin. This makes sense in terms of where iron needs to be allocated during pregnancy and lactation, and how women with many children might not have enough time or resource to replete their iron before having their next kid.

But the really cool finding, to me, was that resumption of menses after pregnancy was positively associated with hemoglobin. Resumption of periods after pregnancy is highly variable, and largely dependent on energy availability and lactation practices. These results, that iron stores increase once you start getting your period again, indicate again that menses is not having a negative effect on iron stores. So this is the second study I know of to show a positive relationship between menses and iron status.

Ladies, unless you are menorrhagic (bleeding more than 120 milliliters each cycle) your period is not doing you wrong. If you have iron-deficiency anemia and your doctor is insisting it's because you slough off your endometrium from time to time without doing a single test to confirm it, you may want to insist on an endoscopy. It could save your life.

References

Bergström E, Hernell O, Persson LA, & Vessby B (1995). Serum lipid values in adolescents are related to family history, infant feeding, and physical growth. Atherosclerosis, 117 (1), 1-13 PMID: 8546746

Clancy, K., Nenko, I., & Jasienska, G. (2006). Menstruation does not cause anemia: Endometrial thickness correlates positively with erythrocyte count and hemoglobin concentration in premenopausal women American Journal of Human Biology, 18 (5), 710-713 DOI: 10.1002/ajhb.20538

Kepczyk, M. (1999). A prospective, multidisciplinary evaluation of premenopausal women with iron-deficiency anemia The American Journal of Gastroenterology, 94 (1), 109-115 DOI: 10.1016/S0002-9270(98)00661-3

Miller EM (2010). Maternal hemoglobin depletion in a settled northern Kenyan pastoral population. American journal of human biology : the official journal of the Human Biology Council, 22 (6), 768-74 PMID: 20721981