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Male Fertility Requires Progesterone And Antagonism Of A PUFA Metabolite

haidut

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Ray has written many times on progesterone's role in both female and male health. This study discovered that sperm actually has a progesterone "receptor" on its tail, and it is the activation of this "receptor" by progesterone that allows sperm to make the final push into the egg and perform the fertilization. Without the activity of that "receptor", it seems males would be infertile.
In addition to highlighting the importance of progesterone (and by association vitamin E) for male fertility, this study also suggests that drugs like RU486 (if it is indeed a progesterone antagonist) can be used as both male and female contraceptives. This also probably explains why endocrine disruptors like BPA are so bad for male fertility - i.e. in addition to being thyroid antagonists and estrogen agonists, those chemicals are also progesterone antagonists.
Furthermore, the mechanism of action of progesterone to increase sperm motility is to displace a chemical called 2AG. The 2AG stands for 2-arachidonoylglycerol and, you guessed it, is a metabolite of arachidonic acid. This suggests that PUFA (arachidonic acid) has a a role in suppressing male fertility. In addition, since 2AG is an agonist of the cannabinoid "receptor" is may suggest that other agonists like THC from marijuana have similar effects. At least one study has found that high levels of THC in the blood lower sperm motility. This may be why Peat has repeatedly cautioned against excess marijuana use saying it is "anti-androgenic and anti-fertility".

Preventing sperm’s ‘power kick’ could be key to unisex contraceptive
"...UC Berkeley biologists have discovered the switch that triggers the power kick sperm use to penetrate and fertilize a human egg, uncovering a possible source of male infertility but also a potential target for contraceptives that work in both men and women. The switch is a protein receptor that responds to the female sex hormone progesterone, which is released by the egg or oocyte, the ultimate goal toward which sperm swim. Thousands of these receptors sit on the surface of a sperm’s tail and when the sperm gets close to the egg, the hormone activates the receptor and triggers a cascade of changes that make the tail snap like a whip, powering the sperm into and hopefully through the cells protecting the egg. “If the receptor protein doesn’t recognize progesterone, you would be infertile,” said Melissa Miller, a postdoctoral fellow at both UC Berkeley and UC San Francisco and the first author of a paper reporting the discovery. “This gives us an understanding of another pathway that is involved in human sperm activity.” A drug that inactivates this newly discovered receptor, however, might make a good “unisex” contraceptive – one that could be used by either sexual partner."

"...That proved to be the case. They showed that progesterone actually binds to a previously mysterious enzyme called ABHD2, which is found at high levels in sperm. Once progesterone binds to the enzyme, which sits on the surface of the sperm, it removes a lipid (2AG) that has been inhibiting the calcium channel. Released of inhibition, CatSper opens the gate to calcium ions and eventual sperm activation."
 

jaa

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Cool. This is the first time I've seen Ray's framework shed cannabis in a negative light outside the smoking increases estrogen perspective.

Do you think taking a progesterone supplement be the best way to combat occasional (2-3 times/week) edible cannabis consumption for a male? Or could supplementing pregnenolone, dhea, vit adek achieve a similar or better result?
 

haidut

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Cool. This is the first time I've seen Ray's framework shed cannabis in a negative light outside the smoking increases estrogen perspective.

Do you think taking a progesterone supplement be the best way to combat occasional (2-3 times/week) edible cannabis consumption for a male? Or could supplementing pregnenolone, dhea, vit adek achieve a similar or better result?

I think Ray spoke against it only in the context of being used every day and being smoked. When drank as a tea and if it is occasional, it is probably fine.
Progesterone supplement is probably only needed if there is evidence THC has harmed fertility.
 

FredSonoma

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I think Ray spoke against it only in the context of being used every day and being smoked. When drank as a tea and if it is occasional, it is probably fine.
Progesterone supplement is probably only needed if there is evidence THC has harmed fertility.
Does marijuana decrease progesterone? What about tobacco?
 

jaa

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I think Ray spoke against it only in the context of being used every day and being smoked. When drank as a tea and if it is occasional, it is probably fine.
Progesterone supplement is probably only needed if there is evidence THC has harmed fertility.

The way you use the forum as a platform to sell your supplements is downright shameful! :D

Thanks for the info.
 

haidut

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The way you use the forum as a platform to sell your supplements is downright shameful! :D

Thanks for the info.

I know, right? I push them every chance I get :)
 

haidut

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So progesterone is not just a female hormone?

Nope, it's actually the main antagonist of estrogen in the body. So, both men and women need it. Same with DHEA - it is the main antagonist to cortisol and it is released primarily with the goal of ultimately converting to DHT. See this.
DHT production depends on stress
So, progesterone and DHEA/DHT are the main steroid protective factors that the body tries to synthesize to combat stress. So, with aging these abilities decline and estrogen / cortisol rule unopposed. Like I said in another post of mine, progesterone and DHT are probably the only two hormones worth supplementing with either through direct supplementation or using pro-hormones like pregnenolone and DHEA.
 

tca300

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Nope, it's actually the main antagonist of estrogen in the body. So, both men and women need it. Same with DHEA - it is the main antagonist to cortisol and it is released primarily with the goal of ultimately converting to DHT. See this.
DHT production depends on stress
So, progesterone and DHEA/DHT are the main steroid protective factors that the body tries to synthesize to combat stress. So, with aging these abilities decline and estrogen / cortisol rule unopposed. Like I said in another post of mine, progesterone and DHT are probably the only two hormones worth supplementing with either through direct supplementation or using pro-hormones like pregnenolone and DHEA.
I've searched alot recently but cant find any good evidence on how many milligrams of progesterone a healthy male would produce in a day. Have you run into any good information on that? Thanks!
 

haidut

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I've searched alot recently but cant find any good evidence on how many milligrams of progesterone a healthy male would produce in a day. Have you run into any good information on that? Thanks!

Progesterone levels are the same in both male and female children before puberty. So, if you can find the reference range for children that would be the level I would try to optimize for.
 

Jsaute21

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Can any men on here share either experimental or research based knowledge on thyroid supplementation's effect on fertility? I am thinking about purchasing tyromix due to slightly low t3 & t4 levels, but feel strange supplementing foreign hormones when i am not in a dire situation. Would be regretful down the line if my fertility was impacted.
 

Orion

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^ any thoughts on above?

RP mentioned that you would want cholesterol above 200 to take thyroid. Adequate vitamin A, thyroid and cholesterol are required to manufacture pregnenolone, pregesterone, and DHEA the protective steroids, which also enhance fertility. Without adequate calories/nutrition thyroid could cause stress reactions, so raise cortisol/adrenaline/estrogen, so down regulate fertility. Sucrose, honey, juices, fruit, OJ, will raise cholesterol.

RP also mentions that vitamin E is very helpful for fertility, helps protect against lipid perioxidation of eaten/stored PUFA.
 
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