Estrogen Significantly Inhibits Hepcidine Synthesis

[Douglas Ek]

17β-Estradiol Inhibits Iron Hormone Hepcidin Through an Estrogen Responsive Element Half-Site

”Hepcidin is the central regulatory molecule of systemic iron homeostasis (5). In this study, we found that hepcidin mRNA is inhibited in cells and in mice by nanomolar concentrations of E2 (Figs. 2 and and5),5), which is physiologically or pharmacologically relevant to young women at the preovulatory phase or those taking a contraceptive.”

According to this study, E2 affects hepcidin production. High E2 significantly inhibits hepcidin production thus leading to higher iron absorption from the diet. The connection seems clear and thus lowering/inhibiting estrogen would be beneficial for people with elevated ferritin. Also since vitamin E and aspirin seems to be able to lower iron this might be through its effect of lowering estrogen thus increasing hepcidin production. Or its a combination of things. Also, people with low estrogen might be more susceptible to get anemia. Men with low testosterone would equal low estrogen and thus might result in depletion of iron stores. Just a thought.

Same goes for estrogen and copper. Estrogen increases copper absorption. Zinc is an estrogen inhibitor and been shown to deplete both iron and copper levels.

 

[Captain_Coconut]

Anemia is more common in women and obese people though...

 

[tankasnowgod]

Anemia is more common in women and obese people though...

Well, women menstruate (at least pre-menopause), so most iron related markers are lower in women for this very reason. No big mystery there.

As for obese..... well, I don't know of anything that even suggests that. Anemia, however, can happen for all sorts of reasons, and can even happen with high body iron stores. If anemia is common in obese people, I would bet it's something like pernicious anemia, B6 deficiency anemia, or anemia of chronic disease.

 

[Captain_Coconut]

Well, women menstruate (at least pre-menopause), so most iron related markers are lower in women for this very reason. No big mystery there.

As for obese..... well, I don't know of anything that even suggests that. Anemia, however, can happen for all sorts of reasons, and can even happen with high body iron stores. If anemia is common in obese people, I would bet it's something like pernicious anemia, B6 deficiency anemia, or anemia of chronic disease.

I have reached the following opinion after reading many studies on iron and obesity, my opinion is with exception for those who simply do not consume enough calories or have a very poor diet. I think the majority of anemia cases truly are because of inflammation / disbiosis rather than from having a lack of iron in the diet. Because of bacterial overload / inflammation, and depending on how systemic it is, the body either raises or lowers hepcidin in response. Ulcers can also cause a lot of blood loss and be at play, but these are also basically a disbiosis issue. There is also the potential for gut bacteria to simply steal iron and decrease its availability to us. The blood lost during a normal period is so small it is not a real factor. What creates a difference in iron stores between men and women, is that men start storing more iron after puberty because of the effect testosterone has on iron storage. Those with normal periods cannot become anemic because of the small amount of blood lost. Kind of the same way it is hard to become anemic from daily aspirin use, which when taken the traditional way does create small blood loss. After pregnancy when women resume menses their iron stores go up... showing that iron storage in women is pretty unrelated to menses. So what causes iron disregulation, personally I think too much heme iron, too much saturated fat, too much fructose, alcohol in excess, and not enough polyphenols in the diet all are largely responsible. Having high ferritin is associated with obesity and inflammation, which also happens from a fatty liver, which also is strongly associated with obesity. A fatty liver will basically leak out ferritin throughout the body and create an inflammatory cascade. Ferritin is not really supposed to be in serum at high levels, it is an intracellular product, if you see it high in serum that indicates a high rate of cell death. I think serum ferritin may also be a source of iron for pathogens in the body. If the liver cannot store iron properly then anemia will eventually result as the available iron to bone marrow becomes too low, further the free iron from red blood cell death will not be mopped up at a good rate - furthering the free iron inflammation.

 

[tankasnowgod]

The blood lost during a normal period is so small it is not a real factor. What creates a difference in iron stores between men and women, is that men start storing more iron after puberty because of the effect testosterone has on iron storage.

Well, literally every iron researcher will disagree with you on this point. Any time you loose ANY blood, you lower your body iron stores. Blood donation is the go to way to lower iron stores.

And the stats simply don't bear you out. On average, women lose 80 ml of blood during a period. On average, women get between 4-9 periods a year. Let's say 6. 6 times 80 is 480 ml of blood lost a year, which is juuuuust about the the amount taken during a blood donation, which is 470 ml. It's estimated that each donation removes 200-250 mg of iron, and drops ferritin about 30 ng/dl. So, in early 20s, a man would be expected to have about an extra gram of iron in his body compared to a woman of the same age, in the 30s, about 2 grams, and so on.

Women also lose a significant amount of blood during childbirth, along with any iron that went into making the baby.

A single period won't make all that much difference, but 6 periods a year every year certainly do. And they continue to keep iron low, until women hit menopause, when, wouldn't you know it, iron starts accumulating in women. Oh, and women who have hysterectomies in their 20s and 30s and stop mentruating? Same exact thing, they start to accumulate iron.

Any effect testosterone has is a distant second to cumulative blood loss.

 

[Captain_Coconut]

Anemia is more common in women and obese people though...

I wrote this but was thinking about raised serum ferritin in obese and not anemia, my mistake.

 

[Captain_Coconut]

And the stats simply don't bear you out. On average, women lose 80 ml of blood during a period. On average, women get between 4-9 periods a year. Let's say 6. 6 times 80 is 480 ml of blood lost a year, which is juuuuust about the the amount taken during a blood donation, which is 470 ml. It's estimated that each donation removes 200-250 mg of iron, and drops ferritin about 30 ng/dl. So, in early 20s, a man would be expected to have about an extra gram of iron in his body compared to a woman of the same age, in the 30s, about 2 grams, and so on.

On par with the blood lost from taking 2 aspirin every day. So why do we not frequently hear about aspirin using men with anemia?

 

[Captain_Coconut]

Have fun:

Low Testosterone Levels and the Risk of Anemia in Older Men and Women

Low Testosterone Levels and the Risk of Anemia in Older Men and Women

 

[tankasnowgod]

On par with the blood lost from taking 2 aspirin every day. So why do we not frequently hear about aspirin using men with anemia?

Well, I was responding to the claim specifically about iron stores. Anemia doesn't have to be driven by low iron stores, as is demonstrated by sickle cell anemia, thalessemia, and such. But much more relevant would be something like pernicious anemia, which is caused by low B12.

But, you also have to think of context. Who takes two aspirin every day Older men? What were their iron stores to begin with? Likely higher than 25 ng/dl. In fact, in the average man 20 and up, it's about 150 ng/dl.

Girls get their periods in their early teens. The age of 12 is when iron stores are lowest in both sexes, about 20 ng/ml Ferritin or so. Then, thanks to menstruation, they lose somewhere between a half pint of blood to two pints of blood a year. In some cases of hemochromatosis, after a patient is de-ironed, they may only need to donate 1-2 pints . Women are getting that by default.

So, in general, their iron stores will be low from teens to 40s, and they will have a need to make more hemoglobin..... implying a bigger need for B6, folate, and B12, among other vitamins, than their male counterparts that don't donate blood.

Older men who take 2 aspirins a day have a much higher starting ferritin level than a teen girl that first gets her period. You can jump off a step, and not get hurt, but you jump off a three story building, you should expect some serious damage. Yeah, in both examples you are "jumping." But the distance of the fall is a key difference.

If those same women adopt a low meat diet, as many women that age do, they would be getting less of all those vitamins.

So, again to recap, you would expect young women in general to have low iron, and low-ish stores of B12, Folate, and B6. Low levels of those vitamins and the mineral iron would again mean anemia is more likely.

Or, more to the point of TLR- Because men don't start using 2 aspirin a day when they are twelve and keep on using it for 30 years until they hit their forties. That's the only way you could have an accurate comparison to menstruating women.