Supplemental estrogens? (eg 17-alpha-estradiol but also the others)

[Alex K Chen]

They may be protective on high oxidative stress seen in autism (but really, they are neuroprotective *in general*) and it would do so much to reduce the gender lifespan gap

17-beta-estradiol is easier to get as a prescription and you can occasionally take them and stop upon the first sign of breast-growth (I have done this several times)

Greg Timblin (https://thesaijolab.org/lab-members) also studies estrogens, though he studies the ROS-hormesis-inducing ones and maybe not the kind we're looking for the most.

Edited April 10, 2023 by InquilineKea

[mccoy]

Inquiline, if you talk about autism, that's an exceedingly complex subject. For example, some antipsychotics  taken by autistic individuals like risperidone increase the prolactin blood levels, inhibiting testosterone. Now what would be the effect adding another testosterone inhibitor?

It is true that estrogen may be beneficial by testosterone inhibition, it is known that hi levels of T has often an over-activating effect on the brain of autistic adolescente (well, it has such an effect on non-autistic individuals as well).

[Alex K Chen]

https://longevity.technology/news/unlocking-longevity-potential-glycanages-approach-to-longevity-healthspan-and-menopause/

[Gordo]

On 4/9/2023 at 12:05 AM, InquilineKea said:

you can occasionally take them and stop upon the first sign of breast-growth (I have done this several times)

What do you have against breasts?  I think you should see how long you can take it for and share your longevity data for the greater good!

[IgorF]

Dont we all already get more than we want like this book describes?

https://www.amazon.com/Estrogeneration-Estrogenics-Making-Sick-Infertile/dp/1946546011

I don't think it is so big problem as the book introduces but for a few percents of people it probably makes a real harm.

W/o a strong reason I would not like to mess with hormonal networks, unless a chance for having something bad will be less than 20% and  there is a strong evidence for something really beneficial

Br,

Igor

[Alex K Chen]

https://www.sciencedirect.com/science/article/pii/S0013935123008599

[Alex K Chen]

Quote

 

• It turns out that if you give 17⍺-estradiol to male mice, it pushes their lifespan way beyond females
  • It’s not merely mimicking the good stuff, if there is good stuff that 17ꞵ-estradiol does in females; if so, it wouldn’t go much further than females are
  •  It goes significantly beyond normal females or drug-treated females, because the drug doesn’t affect female longevity at all 

What 17⍺-estradiol binds to, in which cells, in which tissues, what it’s turning on biochemically is at this point quite obscure 

• There are at least two labs working on this:
• 1 – Mike Stouts in Oklahoma
• 2 – Mariana Sadagurski at Wayne State, who is Rich’s former student
• They’ve published some really nice papers getting at the issue of what a 17⍺-estradiol actually doing, physiologically, what does it bind to? 
• Mariana, her last three papers and her just awarded grant are focused on what 17⍺-estradiol does in the brain
  • What it does to estrogen-sensitive and estrogen-insensitive parts of the brain
• Rich wishes there were more labs diving into that question: 
  • What is the target? 
  • What is the receptor? 
  • What is the physiological effect? 

Is 17⍺-estradiol as potent in males as rapamycin?  

• Rich would have to double-check
• He thinks it’s about a 19% increase [data pooled from the 3 ITP sites showed a mean lifespan increase of 12%]
• The original dose of rapamycin is there or slightly below that
• We now have a better result with rapamycin
• Further, when rapamycin is combined with acarbose, we can kick the male lifespan up to a 29% increase 
  • It’s the largest percent increase we’ve ever gotten, and also it’s the first time we’ve gotten an increase by combining two drugs together

“We now have a better result with rapamycin. When we combine it with acarbose, we can kick the male lifespan up to 29% increase… That’s our winner.”‒ Rich Miller 

Have you combined 17⍺-estradiol with rapamycin yet? 

• We’re testing it now, and several other groups are testing it also, because it’s a good idea
• Rich knows of at least on startup company that’s trying it as well
• Peter finds the 17⍺-estradiol fascinating ‒ there’s something about the lack of clarity around  the mechanism of action, and there’s the sex difference that can’t be attributed to any mimicking of 17ꞵ-estradiol
  • Given that males leapfrog the females and the females accrue no benefit

Insight into what Rich though was going on with 17⍺-estradiol, and how badly they were wrong 

• Mike Garratt collaborated with a guy named Mo Jain to look at steroids in the tissues of mice treated with 17⍺-estradiol (among other things), and he noticed something really interesting
  • He found two steroids that were members of the estriol family (not estradiol) that were elevated at least 20-fold in males that got the drug 
    • [reported as estriol‐3‐sulfate and 16‐oxoestradiol 3‐sulfate, metabolized from 17⍺-estradiol]
    • And they were not elevated in females at all
  • It was a male-specific production of estriol when 17⍺-estradiol was given, and we knew it was sex specific because if he castrated the males before the drug, you didn’t see the estriol production
• The conversion from estradiol to estriol depended upon testosterone or some other testicular hormone
• So Rich thought estriol was going to be the one that is going to work in both males and females
• The dataset is 90% complete, and we’ll probably start writing it up in a month or two when we have 90% of the mice dead, but we had 50% of the mice dead
• We’ve presented at meetings, and the data says that that guess was partially right and partially wrong
• The hydroxy version of estriol is great for males 
  • It’s actually at least as good as 17⍺-estradiol
  • We won’t know until we have the last few deaths, but it’s terrific
  • That was a good guess: you don’t need 17⍺-estradiol because the estriol works terrific
• However, we thought it would work in females, and it is the first drug we’ve found that diminishes lifespan in females
  • So the idea that it would work to benefit females was wrong
  • It is for mysterious reasons harmful in females

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101/

Edited December 30, 2023 by InquilineKea