Aspirin on testosterone, dopamine and sexual function

Here is why every alpha energy male should try out aspirin.

I’ll be covering how aspirin influences testosterone, dopamine, cortisol, estrogen, serotonin and sexual function.

Let’s dive in.

How aspirin works

It works mainly by blocking the COX-2 enzyme, thus reducing the production of pro-inflammatory mediators (prostaglandins) from polyunsaturated fat (PUFA). The more PUFA we eat, the more pro-inflammatory prostaglandins we produce, unless we ingest food/supplements that block COX-2, like aspirin.

Aspirin a.k.a. acetylsalicylic acid, is salicylic acid (found in high amounts in white willow bark) combined with acetic anhydride. Decomposition of aspirin yields salicylic acid and acetic acid (as found in vinegar)

This special combination allows it to powerfully acylate (irreversibly inhibit) the COX enzymes, thus reducing the production of pro-inflammatory compounds. On top of that, aspirin then also changes the function of COX, converting the enzyme’s activity from a prostaglandin-forming cyclooxygenase to a lipoxygenase-like enzyme.

This modified version of COX then produces specialized pro-resolving mediators such as aspirin-triggered lipoxins, aspirin-triggered resolvins, and aspirin-triggered maresins. 

What Does Aspirin Have to Do with Testosterone Levels?

The Leydig cells are where testosterone is produced. COX-2 is found in the Leydig cells and its expression increases with age.

This suggests that COX-2 is involved in age-related reductions in testosterone production. This is supported by the observation that long-term treatment of aged rats with COX-2 antagonists can partially reverse the drop in testosterone levels (R).

Specifically, COX2 inhibits Leydig cell steroidogenesis and the expression of the steroidogenic acute regulatory protein (StAR; the rate-limited enzyme for transporting cholesterol into the mitochondria where it’s converted to pregnenolone).

This study found that in rats, the expression of COX-2 in the Leydig cells increase by 346% from the age of 3 to 30 months. This coincided with a decrease in StAR protein expression by 33% and a drop in blood testosterone concentration and testosterone synthesis in Leydig cells to 41 and 33%, respectively (R).

In short: more COX-2 = less testosterone.

Aspirin on Testosterone Levels

In animals

There are multiple animal studies showing that aspirin lowers testosterone.

In mice, just 50mg/kg aspirin (equivalent to roughly 400mg for a 100kg guy) reduced testosterone by almost half (R).

In rats, 50mg/kg aspirin (equivalent to roughly 800mg for a 100kg guy) increased testosterone after 8 days, but then lowered it again after 15 days (R).

In another rat study, aspirin decreased testosterone, but this decrease was reversed by sprint training (R).

They conclude that the possible reason for this is that aspirin inhibits prostaglandin synthesis (via COX-2) which stimulates steroidogenesis (R, R).

However, the results are the opposite for humans.

In humans

800mg x2 daily for 10 days increased testosterone and lowered cortisol. Only 50% experienced an increase in testosterone (from 24.1 ± 3.9 nmol/L to 28.1 ± 8.2 nmol/L on average), whereas 4 of them had a very significant boost. The cortisol response was more varied (similar to placebo) (R).

In another human study, using aspirin dropped PDE2 (product of COX-2) from 86 +/- 5 to 11 +/- 2 micrograms/mL without affecting testosterone production or GnRH-stimulated LH production (R).

A third human study found that there is no strong association between NSAID use (including aspirin) and hormone levels in men. However, prescription NSAIDs may decrease levels of certain estrogens and androgens in obese and inactive men (R).

The potential beneficial mechanisms of aspirin on testosterone in humans are by:

• Inhibiting COX-2 and prostaglandin production
• Increasing lipoxygenase (LOX) (inhibiting LOX inhibited LH and cAMP stimulated steroid production in rat Leydig cells) (R)
• Producing pro-resolvins
• Increasing GnRH release suppressed by opioids. Opioids inhibit GnRH by producing prostaglandin and aspirin inhibits this. Natural opioids are frequently elevated by stress. Gluten and dairy also contain strong natural opioids that might lower testosterone.

…or all of the above.

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Aspirin on cortisol

The COX-2 product prostaglandin E2 (PDE2) stimulates the release of CRH, which stimulates the pituitary to release ACTH and then the adrenals to release cortisol.

This is normal since cortisol is released short-term to blunt inflammation. However, chronically, this will keep you in a high cortisol state.

Aspirin can help to reduce excess cortisol and improve the testosterone-to-cortisol ratio.

🔥How to lower excess cortisol

Aspirin on estrogen

COX-2 is a major promotor of aromatase expression and activity. High COX-2 activity will lead to high estrogen production and a high estradiol-to-testosterone ratio (R).

🔥How to inhibit aromatase

Aspirin on dopamine

Dopamine helps with focus, motivation, drive, energy, feeling alive and just “adding” more color to life.

Aspirin has been shown to:

• Increase tyrosine hydroxylase (rate limit step in dopamine synthesis) (R)
• Prevent dopamine depletion
• Protect against neuron toxicity (R, R)
• Prevent dopamine desensitization Stress promotes the release of dopamine, which over time can cause desensitization. Also, long-term stress is neurotoxic and can deplete dopamine production.

Aspirin use definitely helps to put me in a higher dopamine state when I feel a bit low or flat.

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Aspirin on serotonin

Although serotonin has its place and functions in the body, too much is not a good thing. Excess serotonin can contribute to brain fog, anhedonia, sexual dysfunction, zero motivation, poor sleep, fatigue, etc.

Overactivation of the serotonin receptor 5-HT2A has been shown to worsen depression and antagonizing it helps against depression.

Aspirin has been shown to:

• Lower TPH1 (tryptophan hydroxylase 1; the enzyme that synthesizes serotonin) (R)
• Decrease 5-HT2 receptors in certain areas of the brain (R, R)
• Increase serotonin turnover.
• Inhibit the aromatase (R) as excess estrogen desensitizes 5-HT1A, lowers SERT (the enzyme that clears serotonin from the synapsis) and increases 5-HT2 and serotonin synthesis (TPH).
• Inhibit excess lipolysis. Elevated free fatty acids induced by excess lipolysis increase free tryptophan which is then used for serotonin synthesis. Free tryptophan is the rate-limited factor in serotonin synthesis, and not actually the speed of TPH.

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Aspirin on sexual function

Aspirin has been shown to improve erectile function.

A recent 2020 meta-analysis found that people who took aspirin had a significant improvement in erectile function compared to non-users (R).

Aspirin helps improve erectile function by inhibiting platelet aggregation activity and stimulating the activity of endothelial NO synthase to increase the production of NO for smooth muscle relaxation.

They even concluded in the study that aspirin needs to be considered by practitioners when prescribing drugs for vasculogenic ED.

Summary

Aspirin can help to:

• Increase testosterone
• Increase dopamine
• Improve mood (R)
• Lower excess serotonin
• Lower elevated cortisol
• Lower excess estrogen
• Improve blood flow and erectile function

It’s important to note that the available studies are small and more research is needed to fully understand the relationship between aspirin and testosterone.

If testosterone optimization is the goal, I’d definitely add aspirin to the stack.

When I use aspirin, I almost always feel better; lighter, clear-headed, stress-resilient, happy, etc. All of my clients who use it as well also report many benefits when using it.

Lastly, if you have a salicylate sensitivity or it irritates your gut (stomach pains), then it likely has more downsides than upsides. But if you tolerate it fine, it’s a good addition to the toolbox for managing stress, inflammation and cortisol.