#122

Lots on Acarbose in this thread: Acarbose Dose That Folks are Taking?

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#124

Thanks for the feedback.

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#125

A post was merged into an existing topic: 17 Alpha Estradiol: Use and Dosing Experiences

#126

I have moved all the discussion about people’s experiences dosing and using 17-alpha estradiol to a new thread here: 17 Alpha Estradiol: Use and Dosing Experiences

Please use this thread (17 alpha estradiol - Another Top Anti-aging Drug) only for new science / studies / research related to 17 alpha estradiol. Use all the other thread for discussion related to the practical issues of how to use it, dose it, and results from using it.

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#128

The solution 0.025% Ell-Cranell® alpha (17α-estradiol, Galderma Korea, Co., Seoul, Korea) is a stereoisomer of the female hormone 17β-estradiol and has been used for the past 30 years in Europe, as well as in South America. The drug inhibits the conversion of testosterone to the metabolite dihydrotestosterone (DHT) by suppressing 5α-reductase activity5. In addition, by inhibiting 17β-dehydrogenase, it impedes the conversion process of androstenedione to testosterone, resulting in a reduction in the syntheses of testosterone and DHT6. It also accelerates the conversion of testosterone to estradiol by stimulating aromatase, decreasing the level of testosterone and leading to a reduction in DHT7. In addition, the drug has been reported to stimulate the generation of hair follicular matrix cells8. Clearly the use of 0.025% Ell-Cranell® alphasolution on decreased hair loss in patients with androgenetic alopecia has been shown both effective and safe. Nonetheless, the drug is not imported into Korea, and studies on Korean patients have not been conducted. Therefore, we conducted this study to assess the safety and effectiveness of 0.025% Ell-Cranell® alphasolution in Korean patients with female pattern hair loss.

17-Alpha estradiol inhibits conversion of testosterone to DHT (dihydrotestosterone), reduces synthesis of testosterone and DHT. They also linked to the study above about increase in aromatase in hair follicles ex vivo.

17-B-estradiol (Estrogen) cream topically:

A more accurate blood test of estrogen, using LC MS which is more expensive:

Same test, higher end in estrogen reference range, and the complete opposite result, with the more accurate test.

ECLIA (standard):

image
image1237×80 27.7 KB

LC MS:

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image1242×159 74.7 KB

  • If measuring estradiol levels in patients on fulvestrant consider alternative methods, such as Liquid Chromatography-Mass Spectrometry (LC-MS).

It is also suggested for drugs like Fulvestrant to use the LC MS assay to measure estradiol levels.

This might be the same for 17-Alpha Estradiol.

In my country the difference is $34 USD vs. $60, it says also the more sensitive method is suggested to men.

I find it a bit complicated with different threads for 17-Alpha-E IMO, when the ‘use and experience’ thread started with scientific studies too.

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17 Alpha Estradiol: Use and Dosing Experiences
#129

Awesome, thanks for that. The difference in the tests is news to me, but makes sense.

For Marek the prices are $8 and $50.

Search: 10 results found for "estr" – MarekDiagnostics*

I tacked on some other tests when I did my first Sirolimus level test there, and sure enough my Estradiol read high, but so did my Free Testosterone, so it was on my list to look into.

My leading theory was that Biotin I had taken messed up those two tests:

which may still be the case, but maybe the Estradiol test was just garbage to begin with?

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#130

Recent work suggests that the effects of e2-alpha are simply through the normal estrogen receptors.

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#131

From a new study in rhesus macaques:

We found that our dosing regimens (0.30 and 0.20 mg/kg/day) were tolerable as evidenced by a lack of GI distress, changes in blood chemistry or complete blood counts, and unaffected vital signs. We also found that the higher dose did elicit mild benefits on metabolic parameters including body mass, adiposity, and glycosylated hemoglobin.

“Both of our 17α-estradiol trial doses elicited significant feminization to include testicular atrophy, increased circulating estrogens, and suppressed circulating androgens and gonadotropins.”

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#132

We suspect that the observed level of feminization results from a saturation of the endogenous conjugation enzymes, thereby promoting a greater concentration of unconjugated 17α-estradiol in serum, which has more biological activity. We also surmise that the elevated level of unconjugated 17α-estradiol was subjected to a greater degree of isomerization to 17β-estradiol, which is aligned with the sevenfold increase in serum 17β-estradiol in 17α-estradiol treated animals in our first trial. Future studies in monkeys, and certainly humans, would likely benefit from the development and implementation of 17α-estradiol transdermal patches, which are commonly prescribed in humans and would circumvent potential issues with bolus dosing effects.

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#133

These are pretty high dosing levels… for a 70kg person, thats 14mg to 20mg a day. I wonder how they determined that dosing level. I’ll shoot an email to the paper author.

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#134

Using standard allometric scaling, the dose would be divided by 3.1 to determine the human equivalent.

0.2 ÷ 3.1 × (your weight in kg).

For a 175 lb man:

0.2 ÷ 3.1 × 79.3787 = 5.12 mg

So using the most typical scaling formula, their lower dose in the macaques would be about 5 mg in a 175 lb man.

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#135

Some other recent studies on 17 alpha-estradiol:

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#136

Here is the full Macaque estradiol paper:

Assessing tolerability and physiological responses to 17α-estradiol administration in male rhesus macaques

Stout et al. 2023 (17a Macaques).pdf (915.8 KB)

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17-alpha-Estradiol Study in Marmosets
#137

I’ve been in contact with the authors of this paper, and I’m thinking it might be valuable to talk with them and get some questions about this paper answered. If you’ve had a chance to review the paper and have some questions - please post them here.

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#138

17α-estradiol Alleviates High-Fat Diet-Induced Inflammatory and Metabolic Dysfunction in Skeletal Muscle of Male and Female Mice

Skeletal muscle has a central role in maintaining metabolic homeostasis. 17α-estradiol (17α-E2), a naturally-occurring non-feminizing diastereomer of 17β-estradiol that demonstrates efficacy for improving metabolic outcomes in male, but not female, mice. Despite several lines of evidence showing that 17α-E2 treatment improves metabolic parameters in middle-aged obese and old male mice through effects in brain, liver, and white adipose tissue little is known about how 17α-E2 alters skeletal muscle metabolism, and what role this may play in mitigating metabolic declines. Therefore, this study aimed to determine if 17α-E2 treatment improves metabolic outcomes in skeletal muscle from obese male and female mice following chronic high fat diet (HFD) administration. We hypothesized that male, but not female, mice, would benefit from 17α-E2 treatment during HFD. To test this hypothesis, we used a multi-omics approach to determine changes in lipotoxic lipid intermediates, metabolites, and proteins related to metabolic homeostasis. In male mice, we show that 17α-E2 alleviates HFD-induced metabolic detriments of skeletal muscle by reducing the accumulation of diacylglycerol (DAGs) and ceramides, inflammatory cytokine levels, and reduced the abundance of most of the proteins related to lipolysis and beta-oxidation. In contrast to males, 17α-E2 treatment in female mice had little effect on the DAGs and ceramides content, muscle inflammatory cytokine levels, or changes to the relative abundance of proteins involved in beta-oxidation. These data support to the growing evidence that 17α-E2 treatment could be beneficial for overall metabolic health in male mammals.

bioRxiv. posted 1 June 2023, 10.1101/2023.05.30.542870

http://biorxiv.org/content/early/2023/06/01/2023.05.30.542870

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#139

Still hoping that 17-Alpha Estradiol is semi-permeable of the scalp. Have been using Pantostin for a month now. Difficult to find any evidence from Google searches about the permeability of this hormone. However, given that other hormones are often delivered through skin patches have assumed it would work. Wish I could find out, if it isn’t working would like to know so I could start taking it orally (Dissolve chemical and mix with oil). Do you know where I can find information about the skin permeability of 17-Alpha?

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#140

17α-estradiol Alleviates High-Fat Diet-Induced Inflammatory and Metabolic Dysfunction in Skeletal Muscle of Male and Female Mice

Skeletal muscle has a central role in maintaining metabolic homeostasis. 17α-estradiol (17α-E2), a naturally-occurring non-feminizing diastereomer of 17β-estradiol that demonstrates efficacy for improving metabolic outcomes in male, but not female, mice. Despite several lines of evidence showing that 17α-E2 treatment improves metabolic parameters in middle-aged obese and old male mice through effects in brain, liver, and white adipose tissue little is known about how 17α-E2 alters skeletal muscle metabolism, and what role this may play in mitigating metabolic declines. Therefore, this study aimed to determine if 17α-E2 treatment improves metabolic outcomes in skeletal muscle from obese male and female mice following chronic high fat diet (HFD) administration. We hypothesized that male, but not female, mice, would benefit from 17α-E2 treatment during HFD. To test this hypothesis, we used a multi-omics approach to determine changes in lipotoxic lipid intermediates, metabolites, and proteins related to metabolic homeostasis. In male mice, we show that 17α-E2 alleviates HFD-induced metabolic detriments of skeletal muscle by reducing the accumulation of diacylglycerol (DAGs) and ceramides, inflammatory cytokine levels, and reduced the abundance of most of the proteins related to lipolysis and beta-oxidation. In contrast to males, 17α-E2 treatment in female mice had little effect on the DAGs and ceramides content, muscle inflammatory cytokine levels, or changes to the relative abundance of proteins involved in beta-oxidation. These data support to the growing evidence that 17α-E2 treatment could be beneficial for overall metabolic health in male mammals.

2023.05.30.542870v2.full.pdf (2.9 MB)

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#141

In this study, they say that pomegranate seed oil contains 17-alpha-estradiol. Interesting.

But since I don’t know of any pomegranate juice or extract that is standardized for 17-alpha-estradiol it is not meaningful to chase 17-A-E that way. But the knowledge makes pomegranates even more exciting.

“The pomegranate seed oil (PSO), containing 17-α-estradiol, is one of the newly found phytosterols with synergistic health effects on estrogen related physiological conditions. Herein, PSO was assessed for its potential improving effects on bone characteristics in a rat model of menopausal syndrome.”

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#142

Interesting. There is some science showing pomegranate extract (polyphenols and punicalagins), increases testosterone levels. A friend of mine takes a pomegranate supplement and it doubled his free testosterone levels.

Didn’t one of the studies on 17ae2 report that the mice were more muscular?

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#143

Role of Estrogen Receptor α in Aging and Chronic Disease

We also discuss how 17α-estradiol administration elicits health benefits in an ERα-dependent manner, which provides proof-of-concept that ERα may be a druggable target for attenuating aging and age-related disease burden.

HEALTH BENEFITS OF AGONIZING ERα WITH 17α-ESTRADIOL

Although estrogen replacement therapies improve a variety of comorbid conditions and likely elicit benefits on aging processes [136-139], chronic administration has been linked with greater cancer and cardiovascular risks in some female populations [140,141]. Additionally, elevated serum 17β-E2 in males is associated with stroke risk [142], prostate cancer development [143], and feminization [144]. Therefore, the challenge remains of determining how best to exploit the beneficial effects of systemic estrogen therapies while circumventing adverse biological consequences. We and others have begun to address this biological challenge through the use of 17α-estradiol (17α-E2). 17α-E2 is a naturally-occurring diastereomer of 17β-E2 [145,146] that is present in both mammalian sexes [147-149], although circulating levels are quite low. 17α-E2 is also a minor constituent of estrogen replacement therapies [150] but only possesses about 3%–4% of the binding affinity to ERα that 17β-E2 does [151]. 17α-E2 has predominantly been studied as a neuroprotective hormone with mild to moderate efficacy in both male and female models of ischemia, Alzheimer’s, and Parkinson’s diseases [147,150,152-155]. It was not until recently that the effects of 17α-E2 on systemic aging, longevity, and conditions that promote aging (e.g., obesity) were evaluated. The National Institute on Aging Interventions Testing Program has shown that 17α-E2 extends lifespan in male mice when treatment is initiated in mid-life [156,157] and late-life [158]. The magnitude of lifespan extension with 17α-E2 treatment in male mice is similar to that of calorie restriction [159] and rapamycin administration [160], which indicates 17α-E2 elicits potent effects that could conceivably be translated to men.

Our previous work has established that 17α-E2 administration reduces calorie intake and adiposity in conjunction with dramatic improvements in metabolic parameters (e.g., glucose tolerance, insulin sensitivity, ectopic lipid deposition) in obese and/or aged male mice [161-165]. We surmise these benefits underly the lifespan-extending effects of 17α-E2. Others have also reported that 17α-E2 treatment elicits benefits on glucose tolerance, mTORC2 signaling, hepatic urea cycling, markers of neuroinflammation, and sarcopenia [166-170]. Importantly, male-specific benefits occur without overt feminization of sex hormone profiles [161] or reproductive function [171]. Female mice are generally unresponsive to 17α-E2 treatment [166-170,172,173], unless subjected to chronic high-fat feeding over several months (unpublished observation) or following OVX [174]. Until recently the receptor(s) that mediate the actions of 17α-E2 were believed to be uncharacterized [146,148,154,175], although our recent report clearly demonstrated that the majority of health benefits attributed to 17α-E2 treatment are ERα-dependent [163]. This report also established that the hypothalamus and liver are the primary organ systems where 17α-E2 signals to regulate metabolic homeostasis in male rodents. Additional studies are needed to determine if 17α-E2 acts predominantly through ERα in a cell-type-specific manner in the hypothalamus and/or liver to modulate not only systemic metabolic homeostasis, but also aging and longevity. Although not definitive, the data generated thus far indicates that ERα agonism by 17α-E2 in hypothalamic neurons and/or hepatocytes may hold therapeutic potential for attenuating mechanisms that promote aging and chronic disease burden in men.

full paper

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