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Comment by wizzwizz4 | Hacker News Reader

I'm shocked that this wasn't widely known in the US. Reports from trans people, way back in the 1940s, show clear links between sex hormones and depression: a priori, one would assume such a relationship would exist here. The article appears to allege a cover-up:

> It is difficult to imagine what data could justify hiding in a drug safety review.

I've been sceptical of any direct relationship between "post-finasteride syndrome" and sexual function, but I've never doubted the direct effect on mental health of suppressing dihydrotestosterone in cis men. (Even if the pharmacological effects end shortly after cessation, which I suspect, a sudden and unexplained strong feeling of constant wrongness can be traumatic.) The part I find interesting is that most men seem to be just fine with taking finasteride, even orally.

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When I got it prescribed (in AU), my doctor told me he had many patients taking it with no side effects, and he also pointed out that the 1mg I was taking was much smaller than the 5mg some took for prostate enlargement. I also did some reading and never noted any links to depression. It just doesn't seem to always come up.

I think many men would also (naively) be happy to risk depression when confronted with impending hair loss. Ironically, maybe more happy chemicals are what's actually needed so we can feel like losing our hair is not the end of the world.

> Reports from trans people, way back in the 1940s, show clear links between sex hormones and depression: a priori, one would assume such a relationship.

We have a lot of data about trans women taking finasteride as part of HRT and depression, and the clear correlation runs in the exact opposite direction from what this article is talking about.

You might expect trans women to react differently to lower T levels than cis men for various reasons

Fin blocks the conversion of T to DHT, that rarely causes lower blood serum testosterone levels and can possibly even increase them depending on what else you've got going on hormonally.

Right, but it's not the serum levels that matter: it's the agonistic effect on various receptors. (Most) hormones don't have direct chemical effects on the body. According to Wikipedia:

> Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor (AR).

> Right, but it's not the serum levels that matter: it's the agonistic effect on various receptors. (Most) hormones don't have direct chemical effects on the body. According to Wikipedia:

>> Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor (AR).

Judging from this and your other comments in the thread, I'm assuming you're not an endocrinologist.

You're pulling quotes from tertiary sources that at first glance seem to support the argument you're making, but you're missing the broader context, which is that pharmacokinetics and our endocrine systems are way more complicated than you're giving them credit for. It's not as simple as "drug A makes X go down, and X does Y, so A decreases Y".

It would make a lot of people's jobs much easier if that were the case, but the clinical reality is actually much more complicated.

The endocrine system is indeed extremely complicated, but this is one of the simplest and best-understood parts of it. We know relatively little about the mechanism behind the psychological effects of sex hormones (for example, we have no idea why they seem to have different effects in different people, with some people being severely affected, and other people barely noticing), but we have a lot of data showing that there is an effect.

"Drug A makes X go down, and X does Y, so A decreases Y" is a good description of the operation of finasteride and dutasteride (if we disregard the unexplained differences between the effects of the two drugs (we'd naïvely expect one to be strictly "better" than the other, but this is not the case)) on everything except the brain. Everything else responds as you'd expect a priori from modelling hysteresis with pencil and paper. But there's a lot we don't understand about the brain.

indeed, finasteride raised my T levels slightly, from 18 ng/dL to 30 ng/dL. the same enzyme that converts T to DHT (5α reductase) can also to convert progesterone to DHT via the backdoor pathway, but i reckon that would have a very small effect for most cis men (where normal progesterone levels range from 0.0-0.5 ng/mL, compared to 2.0-24.0 ng/mL in cis women during the luteal phase, and much higher during pregnancy).

a sudden hormonal change can absolutely cause changes to mood and libido, but with finasteride these seem to be rare and generally mild. i would expect them to lessen or even disappear after some time of continued treatment. i wonder how often finasteride is discontinued before the body even has a chance to adjust to the new hormone levels. the claims that the side effects persist after discontinuation are particularly dubious, and they remind me of castration anxiety.

> You might expect trans women to react differently to lower T levels than cis men for various reasons

Sure but that's besides the point. I was responding to - and refuting - the claom:

> Reports from trans people, way back in the 1940s, show clear links between sex hormones and depression: a priori, one would assume such a relationship would exist here.

There's no reason to believe that the effects of hormones on depression in trans people are predictive of hormones taken by cis people in completely different doses for different reasons, but it's especially fallacious to assume that it's not only predictive, but predictive of the the exact opposite effect.

It's possible there's a separate mechanism responsible for gender dysphoria in trans men, and the remarkably similar symptoms in hypoandrogenic cis men, but Occam's razor.

Many trans men who go on testosterone report reductions in suicidality. If the theory is that gender dysphoria related to hormonal incongruence causes depression, then the data from trans women taking the medication supports the theory that cis men might really struggle with it.

> Many trans men who go on testosterone report reductions in suicidality. If the theory is that gender dysphoria related to hormonal incongruence causes depression, then the data from trans women taking the medication supports the theory that cis men might really struggle with it.

This is a really weird argument because it gets so many basic facts wrong. The most fundamental of which is the idea that taking finasteride means lower testosterone levels - it doesn't!

And I'm not even going into the issues with all the other confounding variables at play here, such as the motivations and dosing schedules for HRT being substantially different from other uses of finasteride.

I really don't know why you're bringing up data about HRT for transgender people that's nearly a century old in an article that's not about HRT, when we have plenty of data that's not only far more recent but far more germane to the topic at hand.

Taking finasteride means higher œstrogen levels, and reduced androgenic activity. There are subtle differences between the effect of testosterone and DHT (it's not just that DHT is a more potent androgen), but I wouldn't expect the effects of higher testosterone to counteract the effect of significantly-reduced DHT. Of course, the effects aren't too significant for most adult cis men, other than reduced hair loss.

I'm bringing up trans HRT in the 1930s (got the decade wrong, sorry!) because the Nobel Prize for the synthesis of testosterone was awarded in 1939. That discovery was made at the start of our understanding of what happens when you muck around with sex steroids: "what effect does this have on mental health?" has always been a question that people have considered, and I was frankly shocked by the article's claim that it hadn't been properly considered in the US.

Of course, others have pointed out that this article is more of a hit piece than a scientific work, so it appears my surprise was justified.

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