#1

B/c male sex hormones just SUCK and i HATE having them

Sinclair posted a tweet showing that male uncastrated sheep epigenetically age more quickly.

All the trans ppl I know prefer bica to spiro (spiro can cause spiro bodies)… A lot of them also know how to source cheap bica.

https://hrt.cafe/bicalutamide/

Also does estradiol itself suppress testosterone?

athways by which 17aE2 alters mTORC1 function are uncertain, though it is noteworthy that many of the effects of 17aE2 on male mice are absent when this agent is given to males that had been castrated at 3 months of age (Garratt et al., 2017), implying that testosterone or some related hormone is required for effective 17aE2 action.

#2

There’s also the study where Korean eunuchs had an incredibly high number of centenarians.

The thought of longevity through this method crossed my mind for only a moment though.

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#3

Not even for a moment…sex is probably the reason (or at least one of the reasons) many people want increased healthy longevity :wink:

But yes, probably effective for longevity:

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#4

Yeah but some people can’t get any sex, or it is completely unimportant for them (for me, male sex hormones/organs have caused nothing but pure pure misery). Thankfully it is not the most important thing bc I don’t look like a man, but god I just want to be castrated (and I have ALWAYS wanted to be castrated). The red tape is just too much for me.

Also some just want to be in control of their sex drive (one asked me for bica b/c he didn’t want to have a high sex drive all the time)

#5

Go for Dutasteride then.

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#6

Why Dutasteride over bica?

#7

Keeps your prostate healthy, helps you keep your hair on your head, and lowers sex drive…

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#8

But the ITP suggests that males respond better to many interventions…

@AlexKChen you have historically ducked this question but what are you doing for resistance and cardio vascular exercise? Is your BMI below the healthy range? Imo, having a sustainable and effective training program should supersede any diet or drug.

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#9

@AlexKChen a new paper you may find interesting.

While not something i would ever consider, there seems to be a case to be made for men to get “fixed”, while younger and then reverse the process when and if you want to have kids? Though i don’t know if just cutting the tubes would make any difference… I wonder if there are surgical options that can be reversed but also lower aging (short of removal of gonads)

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#10

Thanks for the reference - I’ll look into it

Jessica Hoffman has done important research in this (see Spaying and neutering dogs can help them live longer - News | UAB )

Austad and Hoffman say spayed and neutered pets live longer, healthier, happier lives because they have fewer behavioral issues and they are less susceptible to infections, degenerative diseases, and traumatic/violent causes of death. Spaying also protects female dogs, spayed before their first estrogen cycle, from mammary cancer.

Oh definitely, they would definitely eliminate the suffering and problem of IRL /incels. I probably lost 3-4 entire years to “girl issues” alone - “girl issues” includes being in relationships one shouldn’t have ever been in which then makes the time wastage a MUCH MORE relatable problem

(my drive is now so low that I’m thankfully almost guaranteed to be over them). I am strongly in favor of increased eunuchdom.

More on eunuchs - https://www.reddit.com/r/AskHistorians/comments/5ocwv1/in_chinese_literature_it_often_seems_that_eunuchs/

The Blog Comment That Achieved an Internet Miracle - The Atlantic is super-important too. Not everyone is privileged enough to be able to attract a female mate. I know people who are bitter at not having one. The entire process is incredibly socially wasteful, and it’s just better for the world for there to be castrated (and un-bitter/un-ravenous!) people who focuses entirely on science/the Internet.

There are very very very few cause areas I am willing to donate to (given my limited funds) - promoting voluntary human castration is one of these few areas.

[if only getting castrated in Thailand was easier…]

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#11

Women live longer and we are not sure of all of the reasons why. Osterine and Lgd-4033 are a couple of molecules that could be useful for men. They bind to the androgen receptor and help to grow muscle, bone, and connective tissue. They also cause the pituitary to lower luteinizing hormone, testosterone, and sex hormone binding globulin. Bodybuilders use/abuse these chemicals to grow muscle, but they also turn off the testes. Castrated men often suffer from osteoporosis, but lgd-4033 prevents osteoporosis. I would be concerned about heart disease with long term use of these research chemicals. Some testosterone aromatizes into estrogen in a healthy male and this seems to protect the heart. Eunuchs do not have more heart disease than average as far as I know. Does the adrenal cortex regulate estrogen in a castrated male? There are no long term studies of lgd-4033 for the purpose of chemical castration in humans or animals, but it seems like a good candidate. We do know that lgd-4033 halts benign prostate hyperplasia, and may prevent or treat prostate cancer… As with so many molecules we need good studies.

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#12

Here is some information on castrated dogs. They have a lot more hip problems: Golden retriever study suggests neutering affects dog health.

Chemical castration seems preferable to removal of the testes since it is often reversible to some extent.

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#13

I just ordered 2 months ( 28 tablets per strip) of estradiol valerate 2mg for testing. However, i may not take it daily, probably interchange it with DHEA every one or two days.

Estrogen exerts negative feedback at the hypothalamic-pituitary level, leading to decreased endogenous testosterone production from the gonads, along with feminizing effects by action at estrogen receptors

https://academic.oup.com/jes/article/5/9/bvab068/6231851

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#14

Is your goal just to raise estrogen levels? It seems like taking estradiol—which has an estrogen binding affinity of 100%—would be much more potent and potentially riskier compared to estriol, which has only a 10% affinity.

There is some discussion about the relative safety of estriol if you haven’t already seen it: The latest Interventions Testing Program (ITP) study Results (May, 2024) - #59 by LVareilles (though the ITP study used the 16-hydroxy version of estriol and not pure estriol as mentioned here: Next estrogen that extended male mice lifespan 16 alpha-hydroxyestradiol - does anyone knows anything about this? - #8 by Neo).

I personally am considering trying out estriol cream now which does apparently raise blood levels of estrogen from what I have read on the subject.

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#15

i read both threads but found all of them difficult to purchase online, therefore i added estradiol into my order list of sirolimus. May lower the dosage frequency to avoid negative impact.

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#16

I suspect that all the regular Indian suppliers can get you Estriol… (83 rupees to the US$), so very cheap.

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#17

i didn’t find this one, maybe my next order, btw, thanks :pray: for pointout it’s available.

#18

David Sinclair allegedly uses finasteride and this might be one reason he looks young.

Finasteride seems to be the one, but can’t ablating testosterone do it in?

I think the source might be related to x.com

I got a blood test of testosterone of 193 just two days ago. I wonder what happened, the only changes were (1) taking statins, (2) taking estriol.

from a email newsletter:

#1: Microdosing finasteride to age more gracefully (?)

David Sinclair looks very young for his age. The guy is 54 but looks like 40. Many people (and even he himself) “claim” that this is due to his intake of resveratrol and NAD-concoctions. Bullshit. The guy has been taken finasteride for decades, which is probably the primary reason behind him aging so gracefully.

A friend of mine who noticed incipient alopecia with 25, has been on finasteride (0.25mg) for about 15 years. He is now 42 but looks about a decade younger than he is.

Ashton Kutsher also aged incredibly well in his 30s – presumably/partly due to him taking dutasteride for hair loss. After coming off, he seems to have aged quite a bit.

Similarly, people with long-standing hypogonadism often look much younger than they are. Conversely, people on TRT seem to age incredibly fast – and fat redistribution may not be the whole story.

DHT not only drives hair scalp hair loss, but it leads to accelerated skin aging due to a number of mechanisms which ultimately come down widespread changes in gene expression. These effects include maturation of hair follicles, pore size and sebum production, and elastin breakdown.

Next to body composition, the skin and its appendages (e.g., hair) are the primary things we can see of another person and therefore are our predominant guide to judge someone’s age.

As a simplification, estrogens (particularly estradiol) keep the skin firm, elastic, and youthful, whereas androgens (particularly dihydrotestosterone) do the opposite.

Back in November/December, I was on TRT. During this time, I noticed small hairs growing in my biceps area. I am quite a non-hairy person and the excess virilization worried me. I jumped on a microdose of finasteride (0.05mg per day – so 1/20th of the recommended dose for hair loss) and the hair growth caused by TRT mostly reversed over a 3-4 month period. This was fascinating to see. I tested my blood levels of DHT and at this dose, they were at around 400 (range: 300-800).

In terms of side effects, for the first two weeks my erections were weak and my nipples puffy. This worried me but I am glad I stuck with it. Thereafter, no (noticeable) side effects for me. Libido and erections are as good as ever.

Initially, I also felt and behaved subtly “less manly” but I am not sure how much of that was in my head. Anyway, changing neurosteroids and DHT levels surely has at the very least a subtle effect on my neurocognitive and emotional functioning but hard to say how large that effect is. So, I think that it was not exclusively in my head.

All the fear-mongering around post-finasteride syndrome did indeed scare me. However, I figured that in case of worrying side effects I could just taper off (cold-turkey withdrawal is associated with PFS). Furthermore, a dosage of 0.05mg per day is unlikely to cause permanent issues (I may be wrong in this regard).

Given the effects of DHT on the visual aspects of aging, from now on, I plan on using a microdose of finasteride to age more gracefully.

The small reduction in dopamine levels due to AR being highly expressed in the ventral tegmental area can be managed with ultra-low doses of rasagiline.

This is an experiment I am currently running and just as with other experiments, the outcome is uncertain. As of now, I have been on a microdose of finasteride for 4 months and things look good. However, it could very well be that I´ll stop using the finasteride at some point.

The thing I am mostly scared about is a potential flare-up of pubertal gynecomastia – which I am monitoring closely (with some raloxifene on hand). On a genetic level, estrogen and androgen receptors have somewhat opposing effects in some tissues. The reduction in DHT tilts the balance between androgens and estrogens towards estrogen signaling, thus causing gynecomastia in some people.

Just as with everything else in life, there are tradeoffs. In this case, I am reducing some of my “manliness” (though probably subtly) in favor of better skin aging, not developing excessive amounts of body hair, preventing hair loss (which I currently have no signs of), and a large reduction in my risk for prostate cancer (my dad had a total prostatectomy last year).

I will write an article about my thoughts on 5-alpha reductase inhibitors soon.

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Opinion about Finasteride and DHT
#19

Would you mind sharing how long have you been taking estriol? The brand and dosage?

#20

Once again, the existence of PFS is not backed by any strong science.

The US Food and Drug Administration (FDA) had advised that the PFS petition “does not provide reasonable evidence” of a link to suicide, but in August 2022 added suicidal ideation (SI) and behaviour to the adverse reactions listed for finasteride. According to the FDA statement, the PFS petition “does not provide reasonable evidence” of a causal link between finasteride and persistent SD, depression, or suicide. However, on the basis of reports from patients using the 1-mg dose for AGA, the FDA is “requiring the addition of SI and behaviour” to the listed AEs.

US Food and Drug Administration Warning Regarding Finasteride and Suicidal Ideation: What Should Urologists Know? - ScienceDirect

Nor does finasteride significantly impact the kind of DHT that is commonly found in the human brain.

According to Harris et al. ([28](javascript:;)), finasteride is a potent inhibitor of human 5α-reductase type 2 (with an IC50 value of approximately 5 nmol/L) and a poor inhibitor of the type 1 isoform (with an IC50 value of approximately 500 nmol/L). Therefore, our dose-response analyses with finasteride and MK386 as inhibitors and 0.1 μmol/L androstenedione as substrate suggest the predominant, if not exclusive, activity of the 5α-reductase type 1 isozyme in the mature human brain.

Characterization of the 5α-Reductase-3α-Hydroxysteroid Dehydrogenase Complex in the Human Brain1 | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic (oup.com)

I can’t say anything about the effects of finasteride on feeling “manly” because I don’t feel any different that before finasteride. I can still get angry, my lifts are ever-increasing and even the quality of my erections remained unchanged.

With that being said, there’s no direct evidence showing that either finasteride or dutasteride are longevity drugs. There is some animal research and a bunch of observational trials showing a correlation between balding and heart disease, indicating that (high levels of) DHT may be a risk factor.

Finasteride delays atherosclerosis progression in mice and is associated with a reduction in plasma cholesterol in men - Journal of Lipid Research (jlr.org)

The experiments done with 17-alpha estradiol, another 5ari, do show a significant lifespan extension in uncastrated male mile but 5ar inhibition is only one possible explanation for their longevity.

Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice - Garratt - 2018 - Aging Cell - Wiley Online Library

In humans, finasteride use significantly reduced prostate cancer incidence over a 7 year period with no change in acm and a potential slight increase in high-grade prostate cancer incidence that may or may not be related to better detection.

In the updated analysis, men taking finasteride had a 30 percent decrease in the relative risk of developing prostate cancer compared with men who took a placebo: 10.5 percent of men in the finasteride group were diagnosed with prostate cancer versus 14.9 percent of men in the placebo group. This reduction in risk was explained solely by the prevention of low-grade cancers—those with a Gleason score of 6 or less—which present little health risk but, nonetheless, are often treated with radical surgery or radiation. The risk of such cancers was 43 percent lower in the finasteride group than the placebo group.
The men who took finasteride were more likely to be diagnosed with high-grade cancer compared with the men who took a placebo: 3.5 percent of all men in the finasteride group versus 3.0 percent of all men in the placebo group, a relative increase of about 17 percent.
The survival rates at 15 years were very similar between the two groups: 78.0 percent in the finasteride group versus 78.2 percent in the placebo group. When the researchers looked specifically at men who had been diagnosed with prostate cancer, the survival rates for individuals diagnosed with prostate cancer were also very similar between the two groups.

Subsequent analyses of the PCPT data suggested that the observed increase in high-grade prostate cancers in men taking finasteride was due, at least in part, to improved detection. For example, finasteride shrinks the volume of the prostate, potentially making high-grade cancers easier to detect on biopsy. However, concerns that finasteride might cause a true increase in the risk of high-grade prostate cancer—and death—have remained, so the PCPT investigators analyzed long-term follow-up data for trial participants to look for mortality differences between finasteride-treated men and placebo-treated men.

Finasteride for Prostate Cancer Prevention - NCI

Overall, finasteride is probably good for your prostate health and potentially heart health but I don’t attribute Dr. Sinclair’s supposed “youngness” to it. If he were bald he would look older of course.

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