Running on Empty: The Hidden Impact of Iron Deficiency in Perimenopausal Women

What Every Perimenopausal Woman Needs to Know About Getting Diagnosed

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After the last post on heavy menstrual bleeding, there were some questions about iron deficiency and how to make the diagnosis. This is an important topic because A) iron deficiency is common, B) it can cause a wide variety of symptoms (sometimes it isn’t perimenopause, it’s iron deficiency!), and C) women often struggle to get diagnosed and thus don’t get treated.

To advocate for yourself, you need to know the symptoms of iron deficiency, the causes, the tests to ask for, and how to interpret the results. So let’s get into it!

Iron Deficiency: A Primer

Iron deficiency is the most common nutritional deficiency. Many people know that low iron can lead to anemia, a condition where the body isn’t making enough red blood cells. This occurs because iron is a critical component of hemoglobin, the protein in red blood cells that carries oxygen. What is less well known is how vital iron is for many other processes in the body. Every cell requires iron to function appropriately. For example, iron is critical for mitochondria (the cell's powerhouse) to function, and is involved in DNA synthesis and repair, lipid metabolism, and drug metabolism, just to name a few vital iron-dependent processes. Like many things in the body, iron is like Goldilocks, too little is bad, but so is too much. As a result, the body has evolved mechanisms to tightly regulate how much iron is absorbed from food, how it is transported throughout the body, how it recirculates in the body, and how it is removed.

While iron deficiency anemia is an important medical condition, people can be iron deficient without anemia, and this is also a medical concern that is serious enough, even when there isn’t anemia, to warrant an investigation and treatment. Here’s a list of symptoms associated with iron deficiency.

• Absent mindedness

• Decreased cognitive function

• Decreased exercise tolerance

• Depression

• Dry skin

• Fatigue

• Headache

• Hair loss

• Joint pain

• Memory problems

• Muscle pain

• Palpitations

• Restless leg syndrome

• Sleep disturbances

• Weakness

• Weight gain

If you are thinking, “Wow, those symptoms overlap with perimenopause and menopause,” you are correct. If you have these symptoms, before you or your medical team blames perimenopause, you need to know your iron status. And of course, it can be both! Or more. Honestly, it’s like BINGO sometimes.

What Causes Iron Deficiency?

It is important to understand the cause of iron deficiency, so hopefully it can be treated. In addition, some serious medical conditions can present with iron deficiency, so making the correct diagnosis early on may improve outcomes.

Inadequate iron in the diet can contribute to iron deficiency. While some studies suggest that people who are vegan are at higher risk, because the type of iron in plants is not as well absorbed as the iron in meat, other studies show that when someone who is vegan has a well balanced diet, they are not at an increased risk. Tea, including green tea leaf supplements, can negatively affect iron absorption.

Some people don’t absorb iron from food as well as others because of medications called proton pump inhibitors, as a consequence of bariatric surgery, or because of bowel conditions, such as celiac disease and inflammatory bowel disease.

Blood loss is also a cause of iron deficiency, because the body has to make up for the extra red blood cells being lost. Menstruation is obviously a big cause for women. Blood can also be lost from the bowel from bleeding ulcers, inflammatory bowel disease, or even cancer.

Elite athletes can develop iron deficiency, because iron is lost with sweat and training increases production of red blood cells, so more iron is needed to match that need. Exercise-related inflammation can also affect how iron is absorbed from the bowel, effectively reducing intake. Interestingly, the risk of athletic-related iron deficiency is more common for women versus men.

Who Should Be Tested for Iron Deficiency?

Anyone with any of the symptoms listed above or someone at high risk for iron deficiency, so this includes people with heavy menstrual periods.

Guidelines do not specifically recommend screening people without symptoms. However, given how common iron deficiency is among women who menstruate, a case can definitely be made for testing at least once. Considering heavy bleeding is more common during perimenopause (and is under diagnosed and under treated) and many women in perimenopause have at least one of the symptoms listed above, I recommend everyone in perimenopause get their iron tested.

How to Diagnose Iron Deficiency

A complete blood count (CBC) does not diagnose iron deficiency. It is an essential test when iron deficiency is a concern because if anemia is present, it suggests the condition may be more severe and the results may also alter some of the treatment. But the key takeaway here is that a CBC is not a sufficient test for iron deficiency. Many women are told because their CBC is normal and they don’t have anemia that they can’t be iron deficient or that further testing isn’t needed, but that is not true.

The test for iron deficiency is a ferritin level. This is not an iron level, which is a fairly inaccurate test as iron levels fluctuate significantly throughout the day. Ferritin is a protein that stores iron, so a ferritin level is a good reflection of the amount of iron in the body. Think of ferritin as a bank account for iron, storing excess that is not in use and dispensing when it is needed. Ferritin helps keeps the iron in cells in the “just right” Goldilocks zone. When ferritin levels are low, that means the iron stores are low. In our bank analogy that means your account is running low of cash.

Iron deficiency occurs when someone has symptoms and their ferritin level is less than 30 μg/L (or < 30 ng/ml), but it’s important to understand that this isn’t a hard and fast rule, because some research suggests that some people may have symptoms of iron deficiency when ferritin levels are between 30 and 50 μg/L. In addition, with restless leg syndrome, treating with iron when ferritin levels are ≤ 75 μg/L can be helpful. It’s important to put the ferritin level in perspective with the symptoms.

The World Health Organization definition of iron deficiency is < 15 μg/L, and by this definition, 7.4% of women ages 25 and older are iron deficient (if the level is raised to 25 μg/L, then 15.3% have iron deficiency). The WHO level trips some people up, because they think treatment is only warranted when levels are below 15 μg/L. Another confusing factor is the lab that is used may indicate the lower level of the normal for ferritin is 22 μg/L, 20 μg/L, or even 15 μg/L, leading people to erroneously conclude that their iron is normal because they have a ferritin of 24 μg/L (for example). What the lab is reporting here is a reference range, which is the expected range of results for a healthy population. There is also some variation in reference ranges lab to lab. But when someone has symptoms, the clinical cut off for iron deficiency is < 30 μg/L (and possibly < 50 μg/L depending on their symptoms). When someone has a ferritin between 15-30 μg/L and no symptoms, they probably have iron deficiency, but the decision to treat is more individual. Given how common many of the symptoms of iron deficiency are (who doesn’t have fatigue or dry skin?), and that ferritin levels < 30 μg/L can affect the body’s ability to produce red blood cells, and symptoms like fatigue can come on gradually, and people might not appreciate how badly they felt until after they are treated, I usually recommend treatment. Also, with treatment of iron deficiency we usually aim to get the ferritin levels to > 100 μg/L, so it seems a like a mixed message to think that 20 or 25 μg/L is just fine.

There is an important caveat regarding ferritin levels. Ferritin can be elevated in situations with chronic inflammation, such as metabolic syndrome, chronic alcohol use, diabetes, and cancer. Meaning ferritin levels can rise and it doesn’t reflect an increase in iron stores. For people with inflammatory conditions, a ferritin level of < 100 μg/L is considered iron deficient. In addition, people can have what is called functional iron deficiency, meaning there is enough iron in storage (their ferritin levels are over 30), but it can’t be used. This can also occur in situations where there is chronic inflammation or after gastric bypass.

For people with inflammatory conditions or who have had gastric bypass, when their ferritin level is in the normal range, we don’t know if the there is really enough iron in the body and all the cells are receiving iron as they should be, or if there is iron, but it can’t be used. In these cases, it’s like getting account balance from the bank and not knowing if it’s accurate and not knowing if your account is frozen. To get around this issue, a test called transferrin saturation or TSAT can help.

Transferrin is a protein that transports iron, and a level of 20% or higher means enough spots that carry iron are filled, which means sufficient iron is being transported around the body. To stay with our money analogy, the TSAT tells us if your money is being transferred when you are making payments. When TSAT levels are < 20%, as far as the your body/the merchant is is concerned, there isn’t enough iron/money to transfer. A high ferritin and low TSAT levels means the diagnosis is functional iron deficiency, which tells us that your body can’t move enough iron around to meet its needs, and so as far as your body is concerned it’s as if your iron stores are low.

Understanding inflammation and function iron deficiency is important, because ferritin levels can be 200 μg/L and someone can still have functional iron deficiency!

Putting it All Together

Here is a handy graphic. (and no, I won’t be giving up my day job to do graphic design.)

When there is uncertainty, a TSAT level can be helpful.

If someone has chronic inflammation or had bariatric surgery, then ordering a TSAT along with a CBC and ferritin makes sense. If you are trying to save money and/or resources and there are no conditions that would cause the ferritin level to go up, then starting with a CBC and ferritin is fine.

Hopefully that answers questions about being tested for iron deficiency!

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