ORIGINAL ARTICLE
Published: 06 August 2024Roshini Sathiaseelan, Jose V. V. Isola, Roberto Santín-Márquez, Daniel Adekunbi, Michal Fornalik, Adam B. Salmon & Michael B. Stout
17α-estradiol extends healthspan and lifespan in male mice without significant feminization or deleterious effects on reproductive function, making it a candidate for human translation. However, studies in animal models that more accurately replicate human physiology are necessary to establish 17α-estradiol dosing standards for clinical trials.
This study evaluated the tolerability of 17α-estradiol treatment in the common marmoset over a short treatment duration. We found that male marmosets tolerated two dosing regimens (0.37-0.47 or 0.62-0.72 mg/kg/day) as evidenced by the absence of gastrointestinal distress, changes in vital signs, or overall health conditions.
17α-estradiol treatment mildly decreased body mass, adiposity, and glycosylated hemoglobin, although these changes were not statistically significant in most instances. However, neither dose of 17α-estradiol elicited feminization in our study, thereby suggesting that optimized dosing regimens may provide health benefits without feminization in primates. Additional studies are needed to determine if longer duration treatments would also be nonfeminizing and elicit significant health benefits, which would aid in developing dosing regimens targeting healthy aging in humans.
Anyone remember how this dose compares on the arc of ITP studies to Human does scaling translation?
@Bettywhitetest , any chance you can get the full paper: A pilot study evaluating dosing tolerability of 17α-estradiol in male common marmosets (Callithrix jacchus) | GeroScience
The dosing and side effects are of great interest to me.
Interesting to compare this study to the Macaque study: 17-Alpha Estradiol - Another Top Anti-Aging Drug - #136 by RapAdmin
National Institute on Aging, ITP studies – 17α-Estradiol
The first attempt—cohort 5 —used a low dose (4.8 ppm) and it extended median survival in males, but not maximum lifespan. In the next ITP study using 17-Alpha Estradiol —cohort 7 —they gave a dose 3 times higher (14.4 parts per million) and it extended the measure of maximum longevity , as well as median longevity at all three sites for male mice, but not for females. In this study the males not only lived longer than regular old males, they lived longer than regular females.
People’s experiences dosing: 17 Alpha Estradiol: Use and Dosing Experiences
We can calculate / translate that dosing because we’ve done it on rapamycin. Here is a start, from rapamycin:
With rapamycin, I think daily dosing in mice is roughly equivalent to about once every 4 days or so in human terms given the speed that mice metabolize rapamycin is about 4 times faster.
| Sirolimus Dose |
Mouse mg/kg/day Dose |
Mouse: Blood/Sirolimus Level |
Human mg/kg/day Dose |
Dose for 60kg Human | Daily Dose adjusted for longer half-life (/4) |
|---|---|---|---|---|---|
| 4.7ppm | ∼2.24 | 3 to 4 ng/mL | 0.182 mg/kg | 10.92 mg | 2.73 mg |
| 14ppm | ~6.67 | 9-16 ng/mL | 0.542 mg/kg | 32.54 mg | 8.135 mg |
| 42ppm | ~20 | 23-80 ng/mL | 1.626 mg/kg | 97.56 mg | 24.39 mg |
| 126ppm | ~60 | 4.878 mg/kg | 292.68 mg | 73.17 mg | |
| 378ppm | ~180 | 45 to 1800 ng/mL | 14.634 mg/kg | 878.04 mg | 218 mg |
| Sirolimus Dose |
mg/kg/day Dose |
Blood/Sirolimus Level |
Male Median LS Increase | Female Median LS Increase | |
| 4.7ppm | ∼2.24 | 3 to 4 ng/mL | 3% | 16% | |
| 14ppm | ~6.67 | 9-16 ng/mL | 13% | 21% | |
| 42ppm | ~20 | 23-80 ng/mL | 23% | 26% |
Based on the FDA animal to human dosing conversion guide here.
Note: ½ life for sirolimus in mice is approx. 15 hours, vs. approx. 62 hours in humans. So, mice metabolize sirolimus approximately 4 times faster than humans.
Unfortunately no. This journal (GeroScience) placed your article behind a paywall and my institution doesn’t have access. GeroScience does have quite a few of its articles open access, but not this one.