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Testosterone, a key hormone in the context of Covid-19 pandemic (nih.gov)
93 points by sebastianconcpt 22 days ago | hide | past | web | favorite | 77 comments

This isn't a study, it's a summary of reasons why testosterone might be related (positively OR negatively) to Covid19 outcomes in males. The intent seems to be to solicit funding for actual studies.

I really don't see much reason to be linking papers which are this early in the scientific process here. It just creates confusion. HN readers often don't read the links completely or at all, and are prone to overestimate how conclusive papers are. At the time I'm writing this, literally every single comment on this thread is misunderstanding what this paper is.

If you think HN commenters are bad, wait until the media gets wind of this, strips all nuance and goes "ALL MEN ARE GOING TO FUCKING DIE OF THE RONA" or a variation thereof.

HN is the media then, because a lot of these comments really do "strip all nuance". We seem to have entered an era where we're all a part of the hysteria.

Kerkeslager is right, we should all take time to actually read what this paper is saying. But obviously, most people don't, and that causes issues. Which, I imagine, is why kerkeslager advocated not even informing people until conclusive data exists. But this strategy, of course, runs into the problem that Seneca identified long ago, "A lie can make it around the world before the truth can get its shoes on."

It's just the nature of a social media based world. Not sure there is much we can do about it other than educate. To keep reminding people that they need to be skeptical, and read carefully. Even that seems not to work very well, as most people tend to believe anything that aligns with their world view, and disbelieve anything that doesn't.

It's just a tough problem. But the most dangerous thing we can do intellectually is to assume that we don't have the problem, only everyone else does.

> Which, I imagine, is why kerkeslager advocated not even informing people until conclusive data exists. But this strategy, of course, runs into the problem that Seneca identified long ago, "A lie can make it around the world before the truth can get its shoes on."

Well, the problem is that posting this sort of thing for a general audience isn't informing people. It's actually misleading people. I wouldn't call it a "lie" because the intent isn't to deceive, but it's certainly spreading untruth if what you communicate to people is what is being said in this thread.

"A lie can make it around the world ..."


Seems unlikely. Jonathan Swift has an early variant, from 1710:


Though there's: "We should always allow some time to elapse, for time discloses the truth."


And some influencer will read “RONA” as “RONI” and start picketing of pizza shops as pepperoni is killing us.

Given the rates of obesity and it's effect on people, they should.

Obesity also has a weak correlation to COVID mortality, though like all of the other studies coming out it's hard to say if that's a direct relation or if it's something that correlates with other vulnerabilities.

Have you looked at the male/female stats?


So? That doesn't prove anything to do with testosterone. There are at least a dozen other possible reasons that men might have higher infection rates and worse outcomes than women, which have nothing to do with testosterone.

And just to be clear, the paper doesn't say that testosterone his associated with worse Covid19 outcomes.

Let me summarize: good health protects from viruses.

I see in the article

"It is well established that plasma testosterone concentration is reduced by age and comorbidities like obesity, diabetes and obstructive sleep apnea (OSA) [7], all comorbidities highly prevalent in COVID-19 patients."

but I never see any discussion of people who are without those comorbidities. I know they are asking for more research to be done, but at this point, and unless there's evidence presented to the contrary, I think it's probably safe to assume it's general unhealthiness.

That is not the takeaway I get from the paper. I read it as establishing that because testosterone levels has an well established impact on muscles growth, low testosterone should thus impact respiratory muscles size at the point of getting the infection which in turn impact outcomes for people with respiratory disease. However this logic also imply that men should have an overall better outcome to respiratory disease than women, as men has on average more and larger muscles than women, but research into this tend to be more complex than that.

Low testosterone has also been linked in research with increased inflammation response. One of the causes for deadly outcomes of Covid-19 is an over inflammatory response, thus the paper argue there could be a link between low testosterone levels and increase mortality for Covid-19 patients.

The paper also mention a potential risk for people with high testosterone levels because a related gene which biological function of is unknown but which is connected to the function of prostate cancer cells. There seems to be indications that this gene can also modulate covid-19, and if we would inhibit the gene the theory is that it may reduce the effect of the virus. Clinic studies will have to show if it helps, do nothing or makes things worse, because right now its just a theory based on a gene which from my reading we don't know much about.

> good health protects from viruses

Does it? Good health may increase the odds of a good outcome for some viral infection, but it's a bit of a platitude in general. The reasons why measles, polio or HIV are so dangerous is not because of the poor health of their victims prior to infection.

And specifically, being at a heathy weight. It seems everyone's dancing around the elephant in the room, talking about "low testosterone" or "type II diabetes" as being co-morbidities.

See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955331/ for one of many sources for the link between obesity and low testosterone. Obesity just cost our nation several trillion dollars.

People on Hacker News don't like to talk about this, either, because the Computer Programmer community is also affected by obesity.

The lockdown might prevent some infections, but this sounds like it also potentially causes more severe outcomes due to less activity at home.

You control weight primary by food intake.

If you're already overweight you should combine control of calorie intake with exercise. The only way fat leaves the body (besides surgery) is by exhaling it as CO2

True, but you're always exhaling CO2, even when you're not exercising. Exercise simply doesn't create a very large increase the amount of calories you burn.

Consider: a person at my height/weight burns approximately 2500 calories/day just by resting metabolic rate. According to this calculator[1], a person of my weight running a mile at an 8 minute pace burns 136 calories. In other words, running a 5k every day would only increase my calories burned by 17%. And running 8 minute miles is one of the more efficient ways to burn calories--if you're doing some other exercise, your calories burned are likely much lower.

Compare the effort involved in running a 5k with drinking two less cans of cola (about equivalent in calories) and you'll quickly see how diet has a much larger effect on weight loss than exercise. There's a reason they say abs are made in the kitchen not in the gym.

[1] https://www.runnersworld.com/training/a20801301/calories-bur...

I ride my bike 20-50 miles for fun. At 50 calories per mile, that definitely adds up.

Folks who exercise for aerobic reasons, you know, 20 minutes of brisk walking around the park, are getting benefits. But not weight-loss benefits. There's a 10:1 difference in possible exercise regimines. It all depends where you're at in that spectrum. Broad generalities are useless.

> I ride my bike 20-50 miles for fun. At 50 calories per mile, that definitely adds up.

You're literally talking about exercising for 1-5 hours depending on pace.

Perhaps broad generalities are useless, but in the context of talking about weight loss, I don't think it's unreasonable to assume that the average person embarking on a weight loss journey is going to jump in and start doing 50 mile bike rides.

It's much more likely that they'll be doing something like a 10 mile bike ride, at a much slower pace, in which case the numbers are back into a range where diet is going to play a much larger role in their success or failure.

Sure. But my whole family does this; my boys and their spouses; their cousins and so on. Its not as uncommon as all that. But yes, we are bicycle-obsessed people.

And how many of these people are concerned about losing weight?

Ha! None of them. All lean and strong.

> In other words, running a 5k every day would only increase my calories burned by 17%.

Working 8+ hours in a manual labour job on the other hand, will greatly increase the calories burned. If people who are stuck at home now don't change their usual eating habits, they will see some weight gains.

It is definitely good to exercise when attempting to lose weight, but I don't think the reason is not because it significantly changes the amount you breathe. If you exercise for 30 minutes you'll breathe about 4% more breaths that day.

You're not wrong, but consider other "stuck-at-home" factors that contribute to over-eating: depression, boredom, food/snack availability (just hop to the "fridge" and grab something).

And, correct me if I'm wrong, but you're still largely allowed to leave your house to get physical activity. With the gym closed I've taken up jogging every morning before the streets get busy to try and keep myself healthy.

And you control health primarily by activity.

The first things we closed were gyms and parks :-(

Wonder what the net loss is though, considering the vast amounts of money the process of getting a nation so obese has put into the economy. I don't mean to be calloused though, this is truly a horrible situation, and I do feel empathic towards people that are unable to take care of their body.

I tell people that if they would be considered brave for being without a shirt at the beach, then they are an at risk population

That's probably a little too inclusive. You can be healthy and still have a body nobody really cares to see shirtless.

I know a couple skinny chain smokers with alcohol problems. They go shirtless all the time -- southern VA, so that's how you do.

No way they are healthy, and if they catch the COVID they're going to suffer; if they don't then I bet they're gonna get cancer by 55. I'm related to them and not hoping for those outcomes, but they ain't gonna change and we've just accepted it.

Healthy or in shape? The terms are conflated too often for my liking. Same with food, low-calorie or low-fat / sugar foods are often labeled healthy, but IMO that lacks nuance.

They are factually low-calorie for example. Whether they're healthy is another matter entirely because that depends largely on your overall diet.

>a body nobody really cares to see shirtless

As a European, I find this (apparently American) sentiment to be abhorrent. Our bodies shouldn't be treated as sculptures for the public to adore.

Pretty sure this is a worldwide thing. Including Europeans.

It's certainly widespread, but it's not ubiquitous.

I live smack in the center of the US, and visited Hawaii in ~2000. I remember being pleasantly surprised how little people cared about that sort of thing, and was far more comfortable on the beach there than anywhere else I've been. I was with a group of locals, not tourists, so I assume it's a cultural thing.

> I tell people that if they would be considered brave for being without a shirt at the beach, then they are an at risk population.

Yet it affects males more than females. Hmmm. When you say "people" do you mean "male people"? Or when you say "beaches" do you mean "topless beaches"?

Maybe he sees the female population at risk?

tl;dr knowing specifically which part of good health steers public policy decisions

Like that "part of good health" really exists, right?

Better summary: "Who knows?"

The real summary of it is just:

"Is low testosterone a promoter of COVID-19 infection?

Is high testosterone a promoter of COVID-19 infection?

The elucidation of the role of testosterone in the battle towards COVID-19 infection turns out to be an urgent need.


But the answer can still be neither-nor in spite of the fact that "difference in the number of cases reported by gender increases progressively in favor of male subjects."

Attempt at a simple summary:

From what I see, low testosterone is a risk because there is a strong link between lower respiratory muscle activity and lower testosterone levels and high testosterone is a risk because high test -> more androgen receptor expressions -> more binding opportunities for TMPRSS2 and that gene seems to be an active factor in transcription of covid-19.

Its not a magic bullet but the TMPRSS2 angle is quite interesting since we could target drugs that temporarily minimize androgen receptor affectiveness to control the spread ( which might complicate other things in the meantime..)

Tangent, what's the state of drug discovery when it comes to simulating interactions of hormonal treatments with cells?

>> we could target drugs that temporarily minimize androgen receptor affectiveness to control the spread

Modifying key hormone functionality across the population, what could possibly go wrong? The impact on other diseases, not to mention behavior, is huge open question.

I mean the effects of spironolactone and cyproterone on people who are AMAB are well understood and any doctor in the country can titrate your dosage to get you at specific levels. It's not without effect, obviously, which is why trans women take it, but it's not unsafe or dangerous.

The distribution of testosterone in AMAB people ranges ranges from about 200 to 1000 ng/dl so there's a massive range for "normal" levels and trans women are proof that you can go much much lower for an indefinite period of time.

None of this is to say that this course of action is a good idea or would meaningfully help the spread of the rona but it's not as much an open question as you're making it seem.

Presumably this would only be done for those found to be at risk based on tested testosterone levels.

Fortunately the linked paper doesn't recommend it, only notes the stats and details and concludes that "The elucidation of the role of testosterone in the battle towards COVID-19 infection turns out to be an urgent need."

Seems pretty even-handed to me.

That's the difference between treating patients and reducing spread. Appling a preventative to a small population of at-risk individuals will help them individually but won't decrease spread with the population, won't decrease their exposure. That requires preventing the infection from spreading amongst all people, including those who are at no real risk.

This is one of those special situations where one contemplates a applying treatment to patients A B and C not to protect them from harm but to protect them from spreading something to patients D and E. The ethical difficulty is how one balances the potential increased in risks to ABC against the benifits to DE. What if hormone therapy to ABC reduces their lifespan? What it if causes long term behavioral or repoductive changes? How should that be balanced against D and E's chances of infection/death?

Remember that any widespread COVID therapy will likely be with us as long as the disease. Altering hormone levels across a population, potentially for many years or even decades, is a radical approach. And to think of altering testosterone amongst the reproductive-aged population, potentially modifying sexual development of exposed children too, to safeguard those beyond reproductive age from COVID? That's a very dangrous area.

The article doesn't say that low testosterone is a risk, it says that low testosterone might be a risk.

You also ignored the entire half of the article which says that high testosterone also might be a risk.

Looking forward to the cyproterone shortages after people start trying to suppress testosterone to avoid catching covid.

Speaking only for myself, I found this article to be particularly difficult to comprehend. If there are any physicians or molecular biologists who could more plainly summarize the authors' conclusions, I would greatly appreciate it.

From what I can gather: SARS-CoV-2 uses ACE2 in the alveolar epithelium as an entry receptor. ACE2 may also be involved in regulating cytokine activity and in viral replication. "Pro-inflammatory cytokines have a central role in the progression of COVID-19 infection." Anti-cytokine therapy may help reduce pulmonary inflammation in C19 patients. ACE2 is also present in the leydig (testosterone producing) cells of male rats. Long-term smokers express higher levels of ACE2 in their lungs. COPD patients are more likely to have low testosterone levels. And low testosterone has been linked to increased Pro-inflammatory cytokine activity. ——> Maybe testosterone reduces inflammation and, by extension, mortality, in COVID-19 patients? (I still do not really understand how the production of ACE2 in the leydig cells is related to this.)

Or, on the high-testostetone side: Androgen receptors activate the transcription of TMPRSS2, a transmembrane serine protease found primarily in prostate epithelium. "TMPRSS2 activity is regarded as essential for viral spread and pathogenesis in the infected hosts." ——> Elevated testosterone in some young men may increase TMPRSS2 activation, and be a common cause in the relatively small number of severe cases in that age group.

The question is: should men after a certain age supplement with testosterone injections?

If it's a key hormone, why Covid19 seems to attack especially men?

Those men likely suffer from low T. One of the associated diseases that go along with Covid-19 deaths is diabetes - most men with diabetes have terrible Testosterone profiles. In addition those men, as we know from the stats are unhealthy as they come generally.


Notice the middle charts concerning age and disease.

But women have lower T.

I'm not a doctor, but my understanding is that women have a different hormonal profile than men and thus having a lower absolute amount of testosterone is not necessarily a problem; the problem is when the balance is not right between testosterone, estrogen, and others.

The point is that it suggests that low testosterone alone is not the cause of the effect they're seeing here.

Like anything with health, it is the system not the parts that matter.

> Q: What are the implications of women’s genetic superiority for the current coronavirus pandemic?

> A simplified way of thinking about that is this: A specific gene on the X chromosome, TLR-7, is often used to recognize single-stranded RNA viruses like the novel coronavirus. Having two versions gives them an advantage in recognizing the virus.

> Additionally, we think that COVID-19 uses its spike protein to enter cells in the body. They do that by unlocking the ACE2 protein on the surface of the cell. And, as it turns out, the ACE2 gene is on the X chromosome. Which means all of men’s cells are using that same [version of the] ACE2 gene. So if they unfortunately encounter a strain of COVID-19 that has a spike protein that can perfectly unlock their ACE2 and enter their cells, men are in big trouble quickly.

> On the other hand, in females’ cells, 50 percent are going to be using likely a slightly different version of the ACE2 than other cells. It’s much more difficult for a strain of corona to have a spike protein that could equally infect both populations of cells.


This comment is simply not on topic.

The article doesn't claim that testosterone is correlated with Covid19 in any way, it merely says that it might be, and solicits further research. So your question isn't a response to anything in the article.

The HN guidelines explicitly say to not accuse people of not reading the article, but it's hard to have any reasonable discussion if people don't.

The word "key" does not reveal if it's positive or negative, just that it's important. On the other hand - nor does the article. Variance could be explained not only by testosteronje levels, but also by behavior and environemnt. You know - men and women differ.

Because men in 2020 have statistically lower testosterone than men decades before them.

You make a good point, Covid barely bothered men before late 2019.

But that doesn't actually address the question. Why not women, who have less testosterone? Just because men have less than a generation ago, they still probably have more than women.

This CoViD outbreak is the worst on record, you’re right.

Source on that? Or just a quip about a lack of perceived "toughness"?

Edit: Wow looks like it's true, TIL!

If you cut and paste the comment you are replying to into ddg/google you literally get hundreds of references. It’s a very well known phenomenon linked especially to increased obesity.

That article starts off with interesting science (T dropping 50% in a century, T possibly boosted for a generation by cigarettes, etc) and then takes a weird turn at Tyler Cowen and meanders into speculative woods.

Do you have a source for 'cigarettes boost T'? Is it the nicotine or some other chemical in cigarettes?

Not the best immediate source, but it identifies a study which you can look up if this isn't satisfactory:


Thank you!

Just thinking aloud here, but maybe not because testosterone is bad in this case, but because estrogen is protective. I've heard, but I don't have a source, that women fair better than men in many health aspects right up to menopause and then it reverses. If anyone knows of a citation for or against that I'd love a link.

I can see this information playing into some troubling right-wing tropes about masculinity. Basically, if you are an Alpha (High T) you won't get sick, but if you are a weak Beta (Low T) you will. Therefore, if you get sick from Covid and you are a man, you are weak and somehow deserve it.

I hope this does not play out like this and everyone is rational and compassionate, but I doubt it.

Alpha vs Beta (as far as that concept is useful) is a question of behavior, attitude, and being able to love yourself; not T levels. Your comment betrays that you have a very shallow understanding of these topics. I encourage you to do some reading on this from first sources to get an understanding of the topic.

I am not saying that I believe or agree with any of this just that I can see this valid research being twisted to fit a very toxic narrative that already exists.

In the spirit of good faith, I think the comment was explaining the (incorrect) tropes, not supporting these ideas as fact.


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