Aspirin reduces testosterone and sperm count

[Hugh Johnson]

You seem to be in perfect health, very lucky for you. Why are you on a forum for sick people? I’m honestly curious because I never would care about this forum if I was well.

Being here in perfect health would make a person very lucky and quite wise

 

[Astolfo]

Every body chemistry is different.

To be honest, with all the positive studies that get posted on here I thought i'd be seeing a lot more people who have benefitted from regular aspirin dosing, but that doesn't appear to be the case. There's definitely some but not as many as I'd expect.

Aspirin is highly regarded here but you can find other health gurus that don't think the same. It's not something you would recommend everybody to use it daily, without giving any prior warning of potential side effects. Here I am. I got permanent tinnitus from short-term daily Aspirin. And there are other people lived the same thing. This is one of a serious life long side effect of Aspirin but those are never talked here.

 

[GelatinGoblin]

Every body chemistry is different.



Aspirin is highly regarded here but you can find other health gurus that don't think the same. It's not something you would recommend everybody to use it daily, without giving any prior warning of potential side effects. Here I am. I got permanent tinnitus from short-term daily Aspirin. And there are other people lived the same thing. This is one of a serious life long side effect of Aspirin but those are never talked here.

there are talks on this forum of tinnitus definitely being reversible, you should look into it.

 

[X3CyO]

Not only necessary for sperm production, it's necessary for testosterone synthesis (leydig cells in testicles)

I find it crazy that a lot of guys on this forum recommended for years aspirin for increasing androgens while it does the exact opposite

can you provide the mechanism of action or provide a diagram of some sort? I cant find any in depth info. Just stuff on LH.

Would appreciate.

Thank you

 

[Astolfo]

there are talks on this forum of tinnitus definitely being reversible, you should look into it.

I did.

 

[GreekDemiGod]

This thread confuses me. First time I'm reading something like this.
What about the lowering of estrogen & cortisol that Aspirin offers that should indirectly be pro-Testosterone levels?

 

[StayPositive]

This thread confuses me. First time I'm reading something like this.
What about the lowering of estrogen & cortisol that Aspirin offers that should indirectly be pro-Testosterone levels?

It lowers estrogen because it reduces pge2 levels which increased aromatase activity

But it also reduces pgd2 by the same extend, and pgd2 is used by leydig cells for testosterone production

 

[StayPositive]

Hi guys, i did a lot of researches on aspirin recently.

I came to the conclusion that low dose aspirin (81mg) is anti estrogen and pro testosterone. In fact, aspirin is only a cox1 inhibitor in such doses. It has effect on cox2 too but on high doses only .

Aspirin is a very powerful cox1 inhibitor even in very small doses (as low as 20mg) but has no effects on cox2 at these dosages. Asprin is 170 times more effective at inhibiting cox1 than cox2

We all know that aspirin is anti estrogen because it reduces pge2. In fact, pge2 greatly increases aromatase expression (aromatase is the enzyme that convertes testosterone to estrogen).

Pge2 is produced from cox1 AND from cox2.

On the other hand, i think high doses aspirin are anti estrogen AND anti androgen. In fact, aspirin, at high doses, inhibits cox 1 and cox 2. Cox 2 is responsible for the formations of severals prostaglandins, in which pgd2. The problem is that pgd2 is needed for testosterone production. Pgd2 is very tied to androgens. In fact it is used by the testicles (leydig cells) for testosterone production. So if you reduce it too much (325 mg of aspirin reduces serum pgd2 by 86%), it will probably reduces testosterone.

A 81 mg pill of aspirin per day reduces serum pge2 by 45% but has no effect on cox 2 and pgd2. I think it can be a very powerful tool against estrogen at this dosage. But dont take high doses if you want to reduce estrogen and increase testosterone. Because it will reduces testosterone level too.

 

[Inaut]

Hi guys, i did a lot of researches on aspirin recently.

I came to the conclusion that low dose aspirin (81mg) is anti estrogen and pro testosterone. In fact, aspirin is only a cox1 inhibitor in such doses and has effect on cox2 too but on high doses.

Aspirin is a very powerful cox1 inhibitor even in very small doses (as low as 20mg) but has no effects on cox2 at these dosages. Asprin is 170 times more effective at inhibiting cox1 than cox2

We all know that aspirin is anti estrogen because it reduces pge2. In fact, pge2 greatly increases aromatase expression (aromatase is the enzyme that convertes testosterone to estrogen).

Pge2 is produced from cox1 AND from cox2.

On the other hand, i think high doses aspirin are anti estrogen AND anti androgen. In fact, aspirin, at high doses, inhibits cox 1 and cox 2. Cox 2 is responsible for the formations of severals prostaglandins, in which pgd2. The problem is that pgd2 is needed for testosterone production. Pgd2 is very tied to androgens. In fact it is used by the testicles (leydig cells) for testosterone production. So if you reduce it too much (325 mg of aspirin reduces serum pgd2 by 86%), it will probably reduces testosterone.

A 81 mg pill of aspirin per day reduces pge2 by 45% but has no effect on cox 2 and pgd2. I think it can be a very powerful tool against estrogen at this dosage. But dont take high doses if you want to reduce estrogen and increase testosterone. Because it will reduces testosterone level too.

Thanks @StayPositive . I needed a positive spin on this aspirin thread!

 

[grithin]

I wonder if the spiking has anything to do with it. Compare a high single dose that spikes blood vs multiple lessor doses that maintain elevated blood aspirin.

Then I wonder, considering that the half life of aspirin increases as the dose increases (for humans), large doses would potentially lead to a constant supply of aspirin in the body.
From Pharmacokinetic Study of Aspirin in Healthy Female Volunteers , it appears there is a constant clearing rate, such that (clearing rate)/(blood concentration) is lower as blood concentration is higher (making the half life larger with higher doses).

I don't know the clearing rate in mice. I imagine that the mouse high metabolism might lead to a faster clearance of aspirin, such that, even with a high relative dose, the dose is cleared and there is not much of a constant elevation of aspirin in the body.
Based on the study in the link I presented, it looks like it takes 700 minutes (~12hr) to (nearly) entirely clear 600mg of aspirin. A single 1.2g dose might lead to a constant supply of aspirin in the blood for 24hr.


@StayPositive

I don't think the COX1 vs COX2 inhibition matters. COX1 is still needed for PGE2 production:

[COX-1] -> PGG2 -> [COX-2] -> PGH2 -> [tissue] -> PGE2

Is there an online resource that models this system? Just the above linkage took me a bit of time going through wikipedia.

To clarify the model a bit:

PGE2 -> stimualtes release of luteinizing hormone-releasing hormone (LHRH) (The actions of prostaglandin E2, naloxone and testosterone on starvation-induced suppression of luteinizing hormone-releasing hormone and luteinizing-hormone secretion. In vitro and in vivo studies - PubMed) (Gonadotropin-releasing hormone - Wikipedia)
LHRH (GnRH) -> LH

wiki: LH binds to LH receptors on the membrane surface of Leydig cells. Binding to this receptor causes an increase in cyclic adenosine monophosphate (cAMP), a secondary messenger, which allows cholesterol to translocate into the mitochondria. Within the mitochondria, cholesterol is converted to pregnenolone by CYP11A1

LH -> pregnenolone -> DHEA -> androstenedione -> testosterone

How much pregnenolone in the blood ends up as testosterone? As in, if pregnenolone were obtained apart from leydig cells responding to LHRH, could a normal testosterone level be reached if LHRH were suppressed?


Wiki Pregnenolone
`Pregnenolone is synthesized from cholesterol.[14] This conversion involves hydroxylation of the side chain at the C20 and C22 positions, with cleavage of the side chain.[14] The enzyme performing this task is cytochrome P450scc, located in the mitochondria, and controlled by anterior pituitary trophic hormones, such as adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone, in the adrenal glands and gonads.[citation needed]`

"most circulating pregnenolone is derived from the adrenal cortex"

What additional hormones, besides those consequent to LRHR, result in pregnenolone production?

 

[StayPositive]

I wonder if the spiking has anything to do with it. Compare a high single dose that spikes blood vs multiple lessor doses that maintain elevated blood aspirin.

Then I wonder, considering that the half life of aspirin increases as the dose increases (for humans), large doses would potentially lead to a constant supply of aspirin in the body.
From Pharmacokinetic Study of Aspirin in Healthy Female Volunteers , it appears there is a constant clearing rate, such that (clearing rate)/(blood concentration) is lower as blood concentration is higher (making the half life larger with higher doses).

I don't know the clearing rate in mice. I imagine that the mouse high metabolism might lead to a faster clearance of aspirin, such that, even with a high relative dose, the dose is cleared and there is not much of a constant elevation of aspirin in the body.
Based on the study in the link I presented, it looks like it takes 700 minutes (~12hr) to (nearly) entirely clear 600mg of aspirin. A single 1.2g dose might lead to a constant supply of aspirin in the blood for 24hr.


@StayPositive

I don't think the COX1 vs COX2 inhibition matters. COX1 is still needed for PGE2 production:

[COX-1] -> PGG2 -> [COX-2] -> PGH2 -> [tissue] -> PGE2

Is there an online resource that models this system? Just the above linkage took me a bit of time going through wikipedia.

To clarify the model a bit:

PGE2 -> stimualtes release of luteinizing hormone-releasing hormone (LHRH) (The actions of prostaglandin E2, naloxone and testosterone on starvation-induced suppression of luteinizing hormone-releasing hormone and luteinizing-hormone secretion. In vitro and in vivo studies - PubMed) (Gonadotropin-releasing hormone - Wikipedia)
LHRH (GnRH) -> LH

wiki: LH binds to LH receptors on the membrane surface of Leydig cells. Binding to this receptor causes an increase in cyclic adenosine monophosphate (cAMP), a secondary messenger, which allows cholesterol to translocate into the mitochondria. Within the mitochondria, cholesterol is converted to pregnenolone by CYP11A1

LH -> pregnenolone -> DHEA -> androstenedione -> testosterone

How much pregnenolone in the blood ends up as testosterone? As in, if pregnenolone were obtained apart from leydig cells responding to LHRH, could a normal testosterone level be reached if LHRH were suppressed?


Wiki Pregnenolone
`Pregnenolone is synthesized from cholesterol.[14] This conversion involves hydroxylation of the side chain at the C20 and C22 positions, with cleavage of the side chain.[14] The enzyme performing this task is cytochrome P450scc, located in the mitochondria, and controlled by anterior pituitary trophic hormones, such as adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone, in the adrenal glands and gonads.[citation needed]`

"most circulating pregnenolone is derived from the adrenal cortex"

What additional hormones, besides those consequent to LRHR, result in pregnenolone production?

"[COX-1] -> PGG2 -> [COX-2] -> PGH2 -> [tissue] -> PGE2"

This model is false. Cox1 and Cox2 produce prostaglandins independently

Cox 2 produces pgd2, pge2, pgf2a

Cox1 produces pge1, pge2, pgi2 and txa2

 

[grithin]

Yeah, somehow I missed that COX 1-2 are mostly identical and can both produce PGG2.

But, there are still a lot of holes.

Why is it taken that pgd2 is something positive?

From my quick search, I find:

[The effect of prostaglandin D2 on rat testicular testosterone levels](https://pubmed.ncbi.nlm.nih.gov/2591605/)

These results suggest that PGD2 may play an inhibitory action on LH action in androgen synthesis in the rat testis.

DEFINE_ME

As shown recently, cyclooxygenase 2 (COX2), the inducible key enzyme for the prostaglandin (PG) biosynthetic
pathway, is abundantly present in interstitial cells of testes
of men suffering from different forms of impaired spermatogenesis and sub- or infertility, while it is absent in human
testes with normal spermatogenesis

These would seemingly indicate that PDG2 elevation is a sign of dysfunction/inflammation, and that, perhaps aspirin lowering PDG2 is a positive sign.
This would correspond with the fact COX-2 is inducible (by cytokine), whereas COX-1 is constitutive.

And again, any one have an online model for these things? I've noticed wikipedia has added pathways (Glycolysis - Wikipedia) but I find the software very lacking.

 

[Peaterpeater]

So what is the consensus? Aspirin bad? Aspirin good? I hate this thread because I can’t understand it!

 

[X3CyO]

I wonder if the spiking has anything to do with it. Compare a high single dose that spikes blood vs multiple lessor doses that maintain elevated blood aspirin.

Then I wonder, considering that the half life of aspirin increases as the dose increases (for humans), large doses would potentially lead to a constant supply of aspirin in the body.
From Pharmacokinetic Study of Aspirin in Healthy Female Volunteers , it appears there is a constant clearing rate, such that (clearing rate)/(blood concentration) is lower as blood concentration is higher (making the half life larger with higher doses).

I don't know the clearing rate in mice. I imagine that the mouse high metabolism might lead to a faster clearance of aspirin, such that, even with a high relative dose, the dose is cleared and there is not much of a constant elevation of aspirin in the body.
Based on the study in the link I presented, it looks like it takes 700 minutes (~12hr) to (nearly) entirely clear 600mg of aspirin. A single 1.2g dose might lead to a constant supply of aspirin in the blood for 24hr.


@StayPositive

I don't think the COX1 vs COX2 inhibition matters. COX1 is still needed for PGE2 production:

[COX-1] -> PGG2 -> [COX-2] -> PGH2 -> [tissue] -> PGE2

Is there an online resource that models this system? Just the above linkage took me a bit of time going through wikipedia.

To clarify the model a bit:

PGE2 -> stimualtes release of luteinizing hormone-releasing hormone (LHRH) (The actions of prostaglandin E2, naloxone and testosterone on starvation-induced suppression of luteinizing hormone-releasing hormone and luteinizing-hormone secretion. In vitro and in vivo studies - PubMed) (Gonadotropin-releasing hormone - Wikipedia)
LHRH (GnRH) -> LH

wiki: LH binds to LH receptors on the membrane surface of Leydig cells. Binding to this receptor causes an increase in cyclic adenosine monophosphate (cAMP), a secondary messenger, which allows cholesterol to translocate into the mitochondria. Within the mitochondria, cholesterol is converted to pregnenolone by CYP11A1

LH -> pregnenolone -> DHEA -> androstenedione -> testosterone

How much pregnenolone in the blood ends up as testosterone? As in, if pregnenolone were obtained apart from leydig cells responding to LHRH, could a normal testosterone level be reached if LHRH were suppressed?


Wiki Pregnenolone
`Pregnenolone is synthesized from cholesterol.[14] This conversion involves hydroxylation of the side chain at the C20 and C22 positions, with cleavage of the side chain.[14] The enzyme performing this task is cytochrome P450scc, located in the mitochondria, and controlled by anterior pituitary trophic hormones, such as adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone, in the adrenal glands and gonads.[citation needed]`

"most circulating pregnenolone is derived from the adrenal cortex"

What additional hormones, besides those consequent to LRHR, result in pregnenolone production?

Yeah, somehow I missed that COX 1-2 are mostly identical and can both produce PGG2.

But, there are still a lot of holes.

Why is it taken that pgd2 is something positive?

From my quick search, I find:

[The effect of prostaglandin D2 on rat testicular testosterone levels](https://pubmed.ncbi.nlm.nih.gov/2591605/)

DEFINE_ME

These would seemingly indicate that PDG2 elevation is a sign of dysfunction/inflammation, and that, perhaps aspirin lowering PDG2 is a positive sign.
This would correspond with the fact COX-2 is inducible (by cytokine), whereas COX-1 is constitutive.

And again, any one have an online model for these things? I've noticed wikipedia has added pathways (Glycolysis - Wikipedia) but I find the software very lacking.

Thanks for the clarifications.

So is that the mechanism? Or just a response to the stimulus?

 

[grithin]

Inhibition of COX 1, which produces PGE2, could be the mechanism, since
PGE2 -> stimualtes release of luteinizing hormone-releasing hormone (LHRH)

However, in dysfuntional leydig cells, PDG2 is also used to instigate sperm production, and that could be where COX 2 inhibition by higher doses of aspirin plays a part.

 

[JKX]

Hi guys, i did a lot of researches on aspirin recently.

I came to the conclusion that low dose aspirin (81mg) is anti estrogen and pro testosterone. In fact, aspirin is only a cox1 inhibitor in such doses. It has effect on cox2 too but on high doses only .

Aspirin is a very powerful cox1 inhibitor even in very small doses (as low as 20mg) but has no effects on cox2 at these dosages. Asprin is 170 times more effective at inhibiting cox1 than cox2

We all know that aspirin is anti estrogen because it reduces pge2. In fact, pge2 greatly increases aromatase expression (aromatase is the enzyme that convertes testosterone to estrogen).

Pge2 is produced from cox1 AND from cox2.

On the other hand, i think high doses aspirin are anti estrogen AND anti androgen. In fact, aspirin, at high doses, inhibits cox 1 and cox 2. Cox 2 is responsible for the formations of severals prostaglandins, in which pgd2. The problem is that pgd2 is needed for testosterone production. Pgd2 is very tied to androgens. In fact it is used by the testicles (leydig cells) for testosterone production. So if you reduce it too much (325 mg of aspirin reduces serum pgd2 by 86%), it will probably reduces testosterone.

A 81 mg pill of aspirin per day reduces serum pge2 by 45% but has no effect on cox 2 and pgd2. I think it can be a very powerful tool against estrogen at this dosage. But dont take high doses if you want to reduce estrogen and increase testosterone. Because it will reduces testosterone level too.

Prostaglandins are required for testosterone production? No they are not and if you believe so you've missed out a huge chunk of Ray's work. PGs are a sign of stress, just like elevated estrogen, just like elevated FFA. They slow metabolism to spare the organism under stress. With regard to aspirin I'd recommend:

Aspirin, brain, and cancer

Ray Peat

raypeat.com

Steroid pathways are many and complex. The basics for T for example:

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. ...

www.ncbi.nlm.nih.gov

Looking at substances in isolation is a little blinkered. As is looking at the formation of substances in isolation and looking at the formation of substances through singular pathways.

If your T reduced using aspirin (which I would question. Any blood tests before and after?) then you are probably hypothyroid and hypogonadal (again, blood tests?). Shutting off stress based pathways may very well reveal hypothyroidism. Try adding some pregnenolone with it.

 

[StayPositive]

Prostaglandins are required for testosterone production? No they are not and if you believe so you've missed out a huge chunk of Ray's work. PGs are a sign of stress, just like elevated estrogen, just like elevated FFA. They slow metabolism to spare the organism under stress. With regard to aspirin I'd recommend:

Aspirin, brain, and cancer

Ray Peat

raypeat.com

Steroid pathways are many and complex. The basics for T for example:

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. ...

www.ncbi.nlm.nih.gov

Looking at substances in isolation is a little blinkered. As is looking at the formation of substances in isolation and looking at the formation of substances through singular pathways.

If your T reduced using aspirin (which I would question. Any blood tests before and after?) then you are probably hypothyroid and hypogonadal (again, blood tests?). Shutting off stress based pathways may very well reveal hypothyroidism. Try adding some pregnenolone with it.

There are dozens of studies showing aspirin reduces testosterone. Did you read the studies i posted on this thread?

 

[StayPositive]

Testosterone production is tied to PGD2. More researches are needed

PGD2 is produced by and acts on leydig cells​

Freshly isolated hamster Leydig cells constitutively express both COX2 (
2), and as we found, secrete PGD2 (150 fmol/106 Leydig per 3 hours). In accordance with previous results (
2), treatment of hamster Leydig cells with PGD2 (10 μM for 3 hours) resulted in a significant stimulatory effect on basal testosterone production in four experiments (P<.05 Student-Neuman-Keuls test; data not shown).
To our knowledge, this is the first report describing a “PGD2-DP system” in human testis. This system appears to be of special relevance to testes of infertile men with deranged spermatogenesis, in which COX2 is also expressed. Thus, COX2 action may initiate a chain of events, which include formation of PGD and its action on Leydig cells.
Although reasons for spermatogenic defects in the patients examined in this study are likely heterogeneous and karyotypes and endocrine profiles were not recorded, COX2 and PG synthesis appear to be common in testes of patients with different types and degrees of derangements of spermatogenesis (
1), implying a general mechanism.
Our results indicate two potential sources for PGD2 in human testes: Leydig cells, as evidenced by expression of lipocalin type PGD2 synthetase, and mast cells, which express hematopoietic type of PGD2 synthetase. As COX2, the key enzyme of PG synthesis, and PGD2 synthetases are concomitantly expressed in interstitial cells of men with impaired spermatogenesis, one must assume that formation of PGD2 in these cases occurs in the interstitial compartment. Production of PGD2 was indeed proven in freshly isolated hamster Leydig cells (
2), which also respond to PGD2 by increased testosterone production.

DEFINE_ME

 

[JKX]

There are dozens of studies showing aspirin reduces testosterone. Did you read the studies i posted on this thread?

Sure, but using a nocturnal rodant study or two to prove your point perhaps isnt the best way.

The study above doesnt prove cox or pg to be required for T synthesis. Its a terrible study which took samples of male testicular cells, looked at varying parameters such as pgd2 and co, noted they were present, but then used a hamster study to draw a conclusion!. Thoroughly despicable behaviour and representative of everything wrong with modern science.

The study mearly shows that hamster leydig cells appeared to express increased T in response to application of pgd. The authors then appear to miraculously apply this assertion to human testis with absolutely no right to do so. Hamsters are nocturnal. Their expression of hormones such as cortisol is almost the opposite of humans. Why wasn't this taken into account?

Cox is also expressed in human testicular tumors by the way... as referenced within that study. Still think thats a good thing?

I see no evidence that Cox and pg are required for T synthesis. They do increase estrogen synthesis though.

 

[StayPositive]

Sure, but using a nocturnal study or two to prove your point perhaps isnt the best way.

The study above doesnt prove cox or pg to be required for T synthesis. Its a terrible study which took samples of male testicular cells, looked at varying parameters such as pgd2 and co, noted they were present, but then used a hamster study to draw a conclusion!. Thoroughly despicable behaviour and representative of everything wrong with modern science.

The study mearly shows that hamster leydig cells appeared to express increased T in response to application of pgd. The authors then appear to miraculously apply this assertion to human testis with absolutely no right to do so. Hamsters are nocturnal. Their expression of hormones such as cortisol is almost the opposite of humans. Why wasn't this taken into account?

Cox is also expressed in human testicular tumors by the way... as referenced within that study. Still think thats a good thing?

I see no evidence that Cox and pg are required for T synthesis. They do increase estrogen synthesis though.

DEFINE_ME

This study i posted previously in this thread and done on humans shows aspirin reduces sperm production and semen volume.