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!
Stay tuned for more information on understanding sulfur metabolism and how to deal with it.
In the mean time, if you missed it, check out my other writings about sulfur:
Chris, could indole-3-carbinole or DIM, mainly found in cruciferous vegetables, which have a higher sulfate content, play the main role here? I-3-C and DIM lower estrogen and convert some of the bad estrogen into to better 2-hydroxy estrogen. However, they also slightly reduce testosterone.
But what are the sources of hydrogen sulfide and how are we exposed to it?