Finasteride delays atherosclerosis progression in mice and is associated with a reduction in plasma cholesterol in men

Just for more of a background.I am clinical immunologist who is often consulted for drug hypersensitivity but unfortunately I often have to distinguish between immune reactions and adverse reactions

I often use the risk of NSAID’s, a very familiar and frequently used to help patients understand the risk of a certain reaction. Most people are not satisfied with terms like “very low risk” however if I phrase it in terms of relative risk of casual use of ibuprofen - it makes a lot more sense.

The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) system has estimated that more than 100,000 hospitalizations and more than 16,000 deaths in the United States each year are due to NSAID-related complications. Yes, majority is likely (?) caused by chronic use of NSAID’s, however there are many cases of deaths from anaphylaxis, asthma exacerbations, renal failure, bleeding, MI and stroke resulting from even short term use in susceptible population.

AFAIK there no direct death or hospitalizations due to chronic finasteride use. When it comes it’s sexual dysfunction risks I would refer to this paper.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481923/#:~:text=Moderate-quality%20evidence%20was%20found,that%20of%20placebo%20(RR%2C%200.88](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481923/#:~:text=Moderate-quality%20evidence%20was%20found,that%20of%20placebo%20(RR%2C%200.88)

In view of the conflicting and continuing data and importance of the subject, the International Society of Hair Restoration Surgery (ISHRS) established a Task Force on Finasteride Adverse Event Controversies to evaluate published data and make recommendations. The taskforce posted their initial update on the subject as follows:

“To date, there is no evidence-based data substantiating the link between finasteride and persistent sexual side effects in the numerous double blinded, placebo controlled studies using finasteride 1 mg for hairloss. Reports of persistent sexual side effects have come from a variety of sources with some internet sites attracting individuals claiming to have sexual and psychological issues related to finasteride. While continued difficulty having erections after discontinuing finasteride has been reported in post-marketing surveillance the incidence of this problem remains unknown."

Benefit of finasteride in terms of longevity is obviously hair preservation. Many members of this forum not only want increase their healthspan but also look young. Having hair helps that a lot - I don’t think I need to search for study to prove that. There are some data that show that 1 in 5 bald men contemplate suicide as result of their alopecia.

Another benefit of finasteride: “We previously reported the results of the Prostate Cancer Prevention Trial, in which 18,882 men were randomly assigned to receive finasteride or placebo for 7 years. The study’s primary end point — the prevalence of prostate cancer during the 7 years of the trial — was met: the relative risk of prostate cancer with finasteride was 24.8% lower than the risk with placebo”

[https://www.nejm.org/doi/full/10.1056/nejmc1809961#:~:text=The%20study’s%20primary%20end%20point,than%20the%20risk%20with%20placebo.][(https://www.nejm.org/doi/full/10.1056/nejmc1809961#:~:text=The%20study’s%20primary%20end%20point,than%20the%20risk%20with%20placebo.)]((https://www.nejm.org/doi/full/10.1056/nejmc1809961#:~:text=The%20study’s%20primary%20end%20point,than%20the%20risk%20with%20placebo.))

So putting both in perspective:
NSAID’s have a clear risk of mortality and morbidity even with short term use and (other than using aspirin in MI setting) no strong evidence based benefit for most disorders AFAIK - feel free to correct me. Other pain modalities can be used. RISK >BENEFIT in most cases.

FINASTERIDE has a low risk of reversible side effect of sexual dysfunction and definite benefit of hair preservation and reduction of prostatic cancer. BENEFIT>RISK in most cases.

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Dr. Bart,
First thing, I’m not interested in going back and forward on dueling articles. That isn’t why I’m on this board. I’d however point out the data on prostate cancer is a mixed one, risk of low grade is decreased, but high grade appears increased. Low grade rarely does anything exciting, and is massively overtreated (obviously depends upon age and years of expected life remaining as to what I do as a clinician).
Secondly, the NSAID argument is not relevant here, as every time I Rx anything I look at risks, benefits, and alternatives. In my setting there is solid evidence for the uses I prescribe these for in regard to benefits, and the risks are well known. There are many patients who I do not use these medications on due to their individual characteristics (age, renal function, anticoagulation, prior vascular disease or upper GI bleed history).
Thirdly, I see nothing compelling that changes my opinion on this particular drug. If folks want to take it, certainly they can. If there is sexual dysfunction, consider whether this medication is contributory, and be aware this is a well documented side effect, and may not be reversible. I can cite multiple reasonable peer reviewed articles on this - and the group can certainly search this themselves.
Overall, my point was simply to make sure the group is aware that experienced clinicians have seen sexual dysfunction with this agent, there is published literature on this topic, and I appreciate some groups dispute this finding.

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Many articles exist regarding reversible side effects. But is there any actual rct showing the existence of the supposed PFS conditon other than the ones sponsored by the PFS Foundation which recruit their own forum members and don’t even have a control group?

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Don’t they show the opposite conclusion, that it doesn’t exist?

It’s pretty damning evidence to me.

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I don’t think we have exactly what you are asking for. So we don’t know the answer to this question to the level we would get from an RCT. This however in no way means that this isn’t a common and significant issue.
The faculty who lecture with the American Academy of Anti-Aging and Regenerative Medicine in the area of endocrine, who have broad based experience in men’s health - most of whom run high volume practices treating men for testosterone deficiency and erectile dysfunction, feel this is a common cause of problems in that area of sexual dysfunction.
Yes, they have a lot of other patients with sexual dysfunction, but they feel that those who have had finasteride leading up to this are often very difficult to treat and improve.
As I don’t have huge clinical experience in that space yet - but now have my first patient where this is likely an issue - I’ll gather my opinion and experience on this.
The fact a high quality study looking at exactly this issue hasn’t been done, doesn’t prove that it doesn’t exist. The whole point I’d say of being on the Rapamycin board is the underlying philosophy of looking at risks/benefits/alternatives, and sorting out what to do in an area where we don’t have RCA’s.
Furthermore as a physician, I have to sort out what I offer my patients and what I’m not willing to. I’ve never written an Rx for this medication, and I’m not at a point where I think I would. I’m however open minded and will look at evidence as presented … but certainly in the anti-aging/longevity space, I don’t see a role of this particular medication right now, based on what I’ve read. There are much better candidates to be focused on.

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It is difficult to establish causality between finasteride and persistent sexual side effects. On one side, a small number of people do get ED while on finasteride which is very likely related to increased aromatization. On the other side, finasteride may benefit the cardiovascular system which is key to maintaining erectile function. Even the existing mice data is not conclusive regarding finasteride’s influence on penile function and that is with mega doses and finasteride acting as a dual 5ar1/2 inhibitor in mice as opposed to a selective 5ar2 in humans.

most of whom run high volume practices treating men for testosterone deficiency and erectile dysfunction, feel this is a common cause of problems in that area of sexual dysfunction.

Testosterone deficiency is not the same as lack of DHT. Finasteride and dutasteride increase testosterone by 10-20% on average too.

Yes, they have a lot of other patients with sexual dysfunction, but they feel that those who have had finasteride leading up to this are often very difficult to treat and improve.

Are there any credible case reports regarding this? We do have some regarding finasteride and fertility where it took 3-6 montths for fertility to recover to normal levels.

but certainly in the anti-aging/longevity space, I don’t see a role of this particular medication right now, based on what I’ve read.

It has its role in treating BPH and hairloss. The former is an age-related condition while the latter matters for visual aging.

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I sure some of this forum would like to know.

Is an acronym for?

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It’s the opposite of the placebo effect. So when someone believes something negative will happen to them from medication, they will be more likely to experience said negative effect even if the pill they are given is just a placebo.

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Is it the absence of even a placebo?

Placebo: “I feel so full of energy after taking NMN”
Nocebo: “I got mouth sores from sugar pills in the Pearl Trial while believing it was rapamycin”

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New video from The Mann. In this video he is discussing population-based studies.

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Abstract

Objective To estimate the risk of erectile dysfunction in men who used 5-α reductase inhibitors to treat benign prostatic hyperplasia or alopecia.

Design Cohort studies with nested case-control analyses.

Setting UK Clinical Practice Research Datalink.

Population Two populations of men free of risk factors for erectile dysfunction and other sexual dysfunction or its treatment: men aged 40 or more with benign prostatic hyperplasia who received a prescription for a 5-α reductase inhibitor (finasteride or dutasteride) or α blocker, or both, and men aged 18-59 with alopecia.

Exposures In the benign prostatic hyperplasia study, exposures were classified as 5-α reductase inhibitors only, 5-α reductase inhibitors+α blockers, or α blockers only. In the alopecia study, exposures were finasteride 1 mg or no treatment.

Main outcome measures Cases were men with a diagnosis of erectile dysfunction or treatment (procedure or prescription for a phosphodiesterase type 5 inhibitor) during follow-up. We calculated incidence rates and adjusted incidence rate ratios with 95% confidence intervals. We also conducted nested case-control analyses to control for major confounders, and calculated adjusted odds ratios with 95% confidence intervals.

Results In the population with benign prostatic hyperplasia (n=71 849), the risk of erectile dysfunction was not increased with use of 5-α reductase inhibitors only (incidence rate ratio 0.92, 95% confidence interval 0.85 to 0.99; odds ratio 0.94, 95% confidence interval 0.85 to 1.03) or 5-α reductase inhibitors+α blocker (1.09, 0.99 to 1.21, 0.92; 0.80 to 1.06) compared with α blockers only, and remained null regardless of number of prescriptions or timing of use. The risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia, regardless of exposure. For the alopecia population (n=12 346), the risk of erectile dysfunction was not increased for users of finasteride 1 mg compared with unexposed men with alopecia (1.03, 0.73 to 1.44; 0.95, 0.64 to 1.41).

Conclusion 5-α reductase inhibitors do not seem to significantly increase the risk of incident erectile dysfunction, regardless of indication for use. Risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia.

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Dr. Bart,
I worked as a statistician and programmer and have an M.D. (from University of California), 4 board certifications, including the Anti-Aging and Regenerative Medicine. I’m not self proclaimed, I’m objectively certified and a specialist in this area, and additionally in emergency medicine, family medicine and in Australia as a rural generalist, emergency physician, and GP.
I don’t insult you, and I’m certainly not framing your difference of opinion as a disservice to the group. I don’t understand the objection and need to stomp out anyone who has different experience and knowledge, such as this, which is an issue that many clinicians and patients have experienced. We can debate causation, and I doubt we will have an RCT clearly showing one way or the other.
As someone who has a license to prescribe, I’m not anticipating prescribing this medication for BPH or for hair growth as I have other options that I prefer. I’m indeed open minded to see further evidence on longevity, and if it is convincing I’ll change my mind.
Taking things down a level is certainly appropriate.

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Someone just needs to data mine all the big finasteride RCT’s and we will have the best approximation of an answer.

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