Is Hydrogen Sulfide the New Estrogen?
Is Hydrogen Sulfide the New Estrogen?
A little-known study from 2020 suggests it may be.
We know sulfite, which derives from hydrogen sulfide, tanks testosterone in males. Could hydrogen sulfide also feminize men through estrogenic effects?
Could it explain “estrogen dominance” in women when estrogen levels in the blood, saliva, or urine simply don’t support that interpretation?
Maybe.
If so, this is revolutionary to our understanding.
Let’s look at some hints it may be true.
This is educational in nature and not medical or dietetic advice. See terms for additional and more complete disclaimers.
Estrogen increases hydrogen sulfide (H2S) production.
Hydrogen sulfide is a gas with many signaling roles like nitric oxide, and among those many roles they are both vasodilators. They are both absolutely essential to our physiology.
At much higher doses, hydrogen sulfide is a lethal toxin that inhibits complex IV of the respiratory chain and releases iron from ferritin, causing secondary toxicity from free iron.
It increases dramatically in pregnancy because it is an important regulator of placental function. Among its effects, it relaxes the placental vasculature, which removes restrictions on fetal growth and improves the health of the baby later in life.
Two reviews cover data suggesting it is responsible for the nausea and vomiting of pregnancy, as well as in extreme cases hallucinations and other elements of psychosis due to its conversion to sulfite, which destroys thiamin, B6, folate, and possibly other B vitamins.
Gestational malnutrition, hyperemesis gravidarum, and Wernicke's encephalopathy: What is missing?
It follows from this that any such issues that correlate with the estrogen peaks of the menstrual cycle are also likely due to hydrogen sulfide. For example, vasodilation can cause headaches and B vitamin depletion can disrupt mood.
Why does estrogen increase hydrogen sulfide?
For years I chalked this up to it playing an important role in placental function.
But, hold up.
Sure, pregnancy is the naturally occurring period of exposure to consistently high estrogen levels. But why on earth would all of its associated vasodilation and potential toxicity risk be bound up with the normal ebb and flow of the menstrual cycle?
It occurred to me that hydrogen sulfide may be estrogen’s little assistant, doing much of its bidding.
So I looked for evidence that hydrogen sulfide can by itself cause breasts to develop.
Lo and behold, injection of hydrogen sulfide into prepubescent female mice causes them to develop breasts!
Published in 2020, this paper has only been cited three times according to Google Scholar. Not that it’s an amazing paper that should have been published in Nature. No, it’s just an ok paper. But the implications of this are simply stunning, so it is crazy that it has gotten so little attention.
Low concentrations of hydrogen sulfide caused breast development, while high concentrations inhibited breast development.
Low concentrations increased estrogen levels, and high concentrations decreased estrogen levels.
However, that does not mean the breast development was caused exclusively by the estrogen spike. When mammary cells were incubated with hydrogen sulfide in vitro, it increased their viability and promoted signaling cascades associated with growth. No estrogen involved.
Now, many questions arise.
Is this a non-specific growth-promoting effect?
Does hydrogen sulfide make everyone older and thus make prepubescent mice pubescent?
Or does hydrogen sulfide just align itself with estrogen, stimulating estrogen in a positive feedback loop and helping do the things that estrogen likes to have done?
Hydrogen sulfide promotes proliferation in oral cancer cells, but then again, so does estrogen. Hydrogen sulfide promotes cell viability in the brain, which does not seem like a pro-aging effect, but it is an estrogenic effect. Hydrogen sulfide stimulates GLP-1, making it nature’s Ozempic, and estrogen synergizes with GLP-1 to enhance its suppression of food and water intake.
Hydrogen sulfide’s growth-promoting effects might, then, be related to the role of estrogen in causing endometrial hyperplasia, which is opposed by progesterone and is likely a major driver of menstrual cramps.
Estrogen and hydrogen sulfide both play essential roles in both men and women.
But could hydrogen sulfide independently mimic estrogen in some ways, leading to undesirable feminization in men or the many problems associated with excess or imbalanced estrogen in women?
It is too early to say, but this certainly deserves research!
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I had an interesting thought about the connection to migraines, but tell me if i am connecting the dots wrong here:
My gf saw a specialists for her migraines who said it is likely due to estrogen dominance which according to her can causes elevated histamine in the brain which causes/contributes to her migraines. Now i am not sure if this theory is correct but she took Calcium D Glucarate and it has been remarkably effective, more than anything else she has tried before.
Given the possible connection of Hydrogen Sulfide to estrogen as laid out here, and H2S's relationship to vasodilation which is also related to migraines, and that CoQ10 is needed to clear hydrogen sulfide as you mention in CoQ10 Deficiency Is Sulfur Toxicity, and how high doses of CoQ10 seem effective for migraines, could it be that for some types of migraines the culprit is perhaps Hydrogen Sulfide or it is H2S related or Sulfur toxicity in general?
Is the SUOX gene mutation something you ever look at in whole genome sequencing when people have high sulfite?