DHEA-S hormone linked to shorter lifespan in men, but not women
8 comments
·June 23, 2025A_D_E_P_T
derbOac
Just to add to this, I was surprised to see this because my impression of the literature is that lower DHEA-S and greater declines in DHEA-S are usually associated with greater mortality rates and shorter lifespan, not the other way around.
I guess there will always be study variability in results, but I've grown kind of jaded by MR analyses at this point.
flobosg
> Maybe I'll seriously write the editors a letter regarding this paper.
Or put a comment on PubPeer! https://pubpeer.com/publications/ABEC366688EE00BCD774A32A7CC...
aDyslecticCrow
I have no idea what half of these words mean, but my phone screen is slightly warm from the rage and disappointment in the words... it can only come from a truly disappointed researcher.
I trust this comment without a nugget of doubt.
A_D_E_P_T
There are a lot of flaws but here's the most glaring: They looked at three genes to determine whether DHEA-S affects longevity in men. But the problem is that the genes they tracked as markers for DHEA-S are also involved in lots of other stuff!
rs45446698 (CYP3A7) is also associated with testosterone, height, BMI, bone density, C‑reactive protein, estrogen, and urate. It's also heavily involved in the metabolism of drugs and exogenous chemicals in infants and neonates; it's not as widely expressed in adults: https://en.wikipedia.org/wiki/CYP3A7
rs615567 (FGF9) is associated with bone development, vision traits, blood pressure, and cardiovascular disease. Also lots of other stuff: https://en.wikipedia.org/wiki/FGF9
rs36155566 (MCM9) is a member of the mini-chromosome maintenance (MCM) protein family, and it's involved in various processes related to cell division. Reviewed here: https://www.sciencedirect.com/science/article/pii/S258900422...
These are ultra-pleiotropic genes. They do a lot. You'd be hard-pressed to pick worse genes as yardsticks. (Maybe CYP3A4, lol.)
So you simply can't look at those three -- which together explain just ~1% of DHEA-S variance -- and pin anything on DHEA-S! They didn't even attempt to measure DHEA-S in their larger cohort to bolster their findings. It's really shoddy.
cj
> Given that DHEA-s is a precursor of testosterone, our finding is consistent with a recent warning from the FDA that testosterone products may increase blood pressure in men
The bottom of the article seems to try to draw a link between high DHEA and testosterone and blood preassure.
Might be a bit of a leap, but higher DHEA -> higher testosterone -> higher blood pressure seems to be the takeaway?
This study [0] also links DHEA to higher IGF-1, and IIRC high IGF-1 is also linked to higher rates of cancer.
IGF-1, testosterone, estrogen, etc... they all seem to have optimal health benefits when in an "ideal range". Too low is bad. Too high is also bad. No free lunch it seems.
anonnon
People actually take DHEA? Aren't testosterone prohormones extremely unpredictable, with possible aromatization of testosterone into estrogen and conversion of testosterone into DHT as side effects?
nonameiguess
I have no idea if there's any way to know how common it is, but it can be recommended as an anti-aging supplement for people over 55 who have specifically tested as being low in DHEA. It's not widely discussed in any kind of fitness space I've ever looked at other than teenage SARMS users who know they need to supplement with what they usually call a "testosterone base" because taking any SARM will tank natural test production. Couple that with widespread aversion to needles, which is why they're using SARMS rather than steroids in the first place, and you might sometimes see people trying to use DHEA, which isn't going to do jack shit but they'll use it anyway.
It's also one of those dubious bullshit upsell add-ons you'll see in men's clinics that exist to give people who don't need it prescriptions for TRT.
Lifelong supplementation that would be equivalent to a genetic predisposition to making more of it naturally has to be exceedingly rare, though, probably to the point that zero people ever have done it.
Junk study. Literally everything about it is garbage. I know that I shouldn't be, but I'm astounded that this passed peer review.
The manuscript's claim that DHEA-S shortens male lifespan relies on a fundamentally flawed Mendelian randomization (MR) analysis. The core problem is extremely weak genetic instruments: Only 3 variants per sex, explaining just 1% of DHEA-S variance (!), likely inflated by a small discovery cohort. These variants are also pleiotropic (affecting multiple steroid/metabolic pathways), and thus violate a key MR assumption. With only 3 variants, standard pleiotropy tests (MR-Egger, weighted median) are useless. Under the circumstances, claims of "no pleiotropy" are completely untenable.
Critical biases compound this: Adjusting the exposure GWAS for BMI introduces collider bias. Using noisy parental lifespan as a proxy outcome injects measurement error, socio-economic confounding, and sex-discordant genetic issues. Statistical power is overstated, and multiple testing (10+ primary tests) is ignored -- the key lifespan finding wouldn't survive correction.
Also LOL(!!!) at using this junk to push policy recommendations against DHEA supplements. Is this a hatchet job funded by a private interest group?! Even if we take the most generous interpretation of their findings, MR assesses lifelong genetic exposure, not short-term supplementation in relevant populations.
And basically it's a textbook case of why so much of the scientific literature is junk. Maybe I'll seriously write the editors a letter regarding this paper.