Anti-androgenic therapy with finasteride in patients with chronic heart failure - a retrospective propensity score based analysis

#1

Abstract

Sex hormones influence the prevalence and the outcome of heart diseases. The conversion of testosterone to its more active metabolite dihydrotestosterone drives cardiac growth and dysfunction, while inhibition of this step by the anti-androgenic drug finasteride counteracts these pathological processes in preclinical models. In this retrospective, observational study, we aim to investigate whether finasteride, which is in clinical use mainly for prostate disease, might ameliorate cardiac hypertrophy and heart failure in patients. Retrospective chart review of 1041 medical cases with heart failure between 1995 and 2015 was conducted. Stratification was performed by concomitant prostate treatment status (tamsulosin versus finasteride). A propensity score analysis yielded a total of 328 matched medical cases without residual differences in the baseline patient characteristics. In this propensity score matched samples, anti-androgenic therapy with finasteride was associated with significantly reduced left ventricular hypertrophy (interventricular septal thickness 13.3 ± 2.4 mm control vs. 12.6 ± 2.1 mm finasteride group (p = 0.029); estimated average treatment effects on the treated: −0.7 mm, 95% CI mean difference −1.3 to −0.1). In this retrospective analysis anti-androgenic therapy with finasteride for prostate disease was associated with attenuated cardiac hypertrophy in patients with heart failure. Therefore, our data encourage further analysis of this approach in larger heart failure patient cohorts.

Full text:
https://www.nature.com/articles/s41598-019-46640-8

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#2

Thanks. Supportive of a deleterious involvement of increased androgen signalling in the cardiovascular system, which is increasingly well recognised. Additionally supports established evidence in animal models:

#3

The stupidity of most scientists is mind-boggling. Apparently DHT is “maladaptive”. This rogue chemical somehow survived 4 billion years of evolution despite its maladaptive effect…

“In the light of this evidence, our results provide additional support that the conversion of testosterone to dihydrotestosterone plays an essential role in mediating pathologic left ventricular hypertrophy and that, in turn, the inhibition of this conversion with finasteride might be a possible therapeutic option for the treatment of cardiac hypertrophy and heart failure16. This is especially appealing, since finasteride has been in broad clinical use for a number of years and is generally well tolerated, although rare side effects such as sexual dysfunction, depression and high Gleason grade prostate cancer were described39. In addition, comprehensive clinical data about finasteride already confirmed its cardiovascular safety40,41. Despite this strong evidence of a maladaptive role by androgens on myocardial remodeling42, some clinical trials on the other hand showed that testosterone supplementation in patients with chronic heart failure might enhance the patients’ functional capacity or skeletal muscle performance rather than affecting cardiac function or myocardial remodeling43,44,45,46,47,48,49. A previous study investigated the combined treatment with low-dose testosterone and finasteride in hypogonadal men50. In this study, testosterone treatment exerted beneficial effects on skeletal muscle mass, while finasteride co-administration prevented the deleterious impact on other tissues (like the prostate), indicating that not testosterone, but its conversion to the extremely potent dihydrotestosterone is maladaptive.

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#4

It is quite amazing at this point how so many of them are completely oblivious to the bigger picture of the “beneficial” or “maladaptive” effect being determined by tissue. What’s most amazing is the key principles of this do tie back to Charles Huggins work in the 1940s. That’s why what’s currently called “PFS” is going to one day be seen as such a big deal - it’s far more than a side effect of a drug and ties directly to cutting edge understanding. Just need to do a bit more work…ourselves, apparently…

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#5

Ok, sure. The point is that the effect of a substance should not be examined on separate systems but on the organism as a whole, as this is the unit on which evolution operates. Evolution has resulted in a fine balance between all chemical pathways in the organism that maximizes fitness.

P.S. I posted this before I read axolotl’s comment above, which says a very similar thing.

#6

Exactly. Most scientists apparently have absolutely no concept of evolutionary principles. This stupidity coupled with arrogance makes them look laughable, except that people die and will keep dying as a result.

#7

I agree with this. PFS will be a textbook case for many things including failing to understand the holistic nature of biology. This principle however has already been demonstrated in many if not most cases of chronic drug administration - from high dose vitamin supplementation to psychiatric drugs to statins. Medicine, however, because it is driven by profit, and people, because they are driven by wishful thinking, will not get it until AI starts making all decisions for us.