Everybody with ORAL 17-Alpha-Estradiol experience, please share your updated information below on your daily dose, effects (feeling in nipples?) - and especially if you have test results from hormone levels before and after - and information on sourcing + purity for ORAL use.
Please keep comments short, factual and scientific.
To set the background information, below I have pasted in Gemini latest models answer to my questions or see the original text on this link: https://gemini.google.com/share/f6754afe9d7b
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Can you summarise how people are using or experimenting with 17-alpha-estradiol (17a-E2) sometimes call other things and also include 16-alpha-Estradiol (16a-E2) if used. You can look at rapamycin.news or other places where people are reporting or discussing N=1 experimenting or off label use. Collect any information like dd, any calculations or discussions about dd, any reported effects or side effects, any costs and how they have sourced the molecules.
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Disclaimer: The following summary is for informational purposes only and does not constitute medical advice. 17-alpha-estradiol and 16-alpha-estradiol are potent biological molecules. Their use for life extension is off-label and experimental.
Here is a summary of how communities (such as those on rapamycin.news, LongeCity, and Reddit’s r/longevity) are discussing, sourcing, and experimenting with these compounds, focusing primarily on 17-alpha-estradiol.
1. 17-alpha-Estradiol (17$\alpha$-E2)
The Context: Interest in 17$\alpha$-E2 stems largely from the National Institute on Aging’s Interventions Testing Program (ITP). The ITP demonstrated that 17$\alpha$-E2 extended median lifespan in male mice significantly (roughly 19% increase in median lifespan) but had no benefit for female mice. It is considered a “non-feminizing” estrogen, meaning it binds much less avidly to classical estrogen receptors (ER$\alpha$, ER$\beta$) than the standard human estrogen (17$\beta$-estradiol), supposedly avoiding feminizing side effects while retaining metabolic benefits.
Sourcing and Forms
Users generally source this molecule in two ways:
- Pharmaceutical (Topical Alfatradiol):
- Products: Ell-Cranell and Pantostin.
- Origin: These are hair-loss treatments available over the counter in Germany and some other European countries. They contain 0.025% Alfatradiol (another name for 17$\alpha$-E2).
- Usage: This is the “safe” entry point for most biohackers because it is pharmaceutical grade (meaning high purity, low risk of 17$\beta$-estradiol contamination).
- Gray Market / Research Chemicals:
- Origin: Chemical synthesis labs in China.
- Reason: To acquire bulk powder for oral encapsulation or higher-dose experimentation.
- Risk: High concern regarding purity. Even a 0.1% contamination with 17$\beta$-estradiol could cause significant feminization (gynecomastia) in men.
Dosing (dd) and Calculations
There is significant debate on forums regarding the Human Equivalent Dose (HED).
- The Mouse Math: The ITP used 14.4 ppm in food.
- The HED Conversion: Users frequently calculate the HED to be roughly 40 mcg/kg to 50 mcg/kg. For an 80kg male, this implies a dose of roughly 3 mg to 4 mg per day.
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The Biohacker Reality: Most users are afraid to start that high due to fear of cross-reactivity or impurities.
- Low Dose: 50 mcg – 200 mcg daily (common for those using the hair tonic).
- Medium Dose: 1 mg – 2 mg daily.
- High Dose: 4 mg+ (rare, attempting to replicate ITP exactly).
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Administration Routes:
- Topical: Applying the hair tonic to the scalp (intended use) or inner wrists.
- Oral (Off-label): Many users measure out the liquid hair tonic (which is usually isopropyl alcohol, glycerol, and water) and drink it.
- Sublingual: Holding the liquid under the tongue to bypass first-pass metabolism.
Reported Effects
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Positive (Anecdotal):
- Improved skin quality (smoother texture).
- Reduction in visceral fat (consistent with mouse data).
- Hair preservation (expected, as it is a 5$\alpha$-reductase inhibitor).
- Improved glucose tolerance (some users track this with CGMs).
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Side Effects / Negatives:
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Nipple Sensitivity/Gynecomastia: This is the #1 reported fear and occasional side effect. Some users on
rapamycin.newsreported nipple soreness at doses over 2mg/day or when using questionable powder sources. This suggests either impurity (17$\beta$ contamination) or that at high enough doses, 17$\alpha$ still activates estrogen receptors. - Libido Changes: Mixed reports. Some report increased libido; others report a slight decrease, possibly due to interactions with testosterone metabolism.
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Nipple Sensitivity/Gynecomastia: This is the #1 reported fear and occasional side effect. Some users on
Costs
- Pharmaceutical (Pantostin/Ell-Cranell): Expensive for systemic use. A 100ml bottle (approx. €25-€35) contains 25mg of 17$\alpha$-E2. At a 1mg/day dose, a bottle lasts less than a month.
- Powder: Significantly cheaper (often $10–$50 per gram), but requires third-party testing (HPLC) which costs $200+, negating savings for small batches.
2. 16-alpha-Estradiol (16$\alpha$-E2)
The Context: There is very little experimentation with 16$\alpha$-E2 in the longevity community compared to 17$\alpha$-E2.
- Biology: 16$\alpha$-hydroxyestrone and 16$\alpha$-estradiol are metabolites of estrogen.
- Safety Concerns: In traditional endocrinology and oncology, the 16$\alpha$-hydroxylated pathway is often considered “pro-proliferative” and potentially genotoxic. High levels of 16$\alpha$-metabolites compared to 2-hydroxy metabolites are sometimes viewed as a risk factor for estrogen-sensitive cancers (breast/uterine).
- Biohacking Status: Because the ITP and other major longevity studies focused on the 17$\alpha$ isomer, and because of the potential carcinogenic reputation of the 16$\alpha$ pathway, most users actively avoid this molecule.
- Discussion: You will mostly find this discussed in threads analyzing urine hormone panels (like DUTCH tests) where users are trying to lower their 16$\alpha$ metabolites using supplements like DIM (Diindolylmethane) or CDG (Calcium D-Glucarate), rather than supplementing with it.
Summary of “N=1” Protocol Consensus
Based on recent threads (2024-2025 era discussions):
- Target Demographic: Almost exclusively males (due to ITP data).
- Preferred Source: Pantostin or Ell-Cranell (liquid).
- Preferred Route: Transdermal application to thinner skin (scrotal or inner arm) or oral consumption of the liquid.
- Starting Dose: 0.5 mg to 1 mg per day.
- Monitoring: Users watch closely for nipple tenderness. If it occurs, they stop immediately or switch to a tested source.
- Combination: Often stacked with Rapamycin and Acarbose (the “ITP Stack”).
Is there anyone that report about their sex hormone levels before and after 17a-E2 intervention and what are the results?
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While comprehensive clinical data in humans is still lacking, there is a growing body of N=1 reports (primarily from communities like rapamycin.news and Reddit) and recent animal studies that provide a look at hormone changes before and after 17$\alpha$-estradiol (17$\alpha$-E2) use.
The data reveals a “U-shaped” risk profile: low doses appear to be endocrine-neutral or even potentially “masculinizing” in terms of blood markers, while higher doses or impure sources lead to significant feminization.
1. The “Masculinizing” Paradox (Hypothalamic Effect)
Some of the most surprising recent data (both in rat models and early human N=1 reports) suggests that 17$\alpha$-E2 might actually increase testosterone in some contexts by acting on the brain.
- Mechanism: Recent research (e.g., eLife 2024) suggests 17$\alpha$-E2 may stimulate the Hypothalamic-Pituitary-Gonadal (HPG) axis by increasing GnRH (Gonadotropin-Releasing Hormone).
- Reported Result: In some rat studies and anecdotal biohacker reports, users saw a rise in Total Testosterone and a decrease in 17$\beta$-Estradiol (human estrogen).
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Biohacker Context: Some users on
rapamycin.newsreported that at low “tonic-scale” doses (approx. 250 mcg – 500 mcg/day), their blood work showed stable or slightly improved testosterone levels without an increase in systemic 17$\beta$-estradiol.
2. The “Feminization” Threshold (The Turning Point)
There is a clear “break point” where 17$\alpha$-E2 begins to behave like standard estrogen.
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Saturation Risk: In a 2023 study on Rhesus macaques (primates), researchers found that while low doses were tolerated, higher doses led to significant feminization:
- Suppressed Testosterone: Massive drops in circulating androgens.
- Elevated Estrogen: A seven-fold increase in 17$\beta$-estradiol.
- The Isomerization Theory: Researchers suspect that when the body is flooded with 17$\alpha$-E2, the enzymes that normally “clear” it become saturated, leading to the isomerizing (conversion) of 17$\alpha$ into the potent feminizing 17$\beta$-estradiol.
- N=1 Human Experience: Users experimenting with “bulk powder” (often at 2 mg–5 mg/day) frequently report nipple sensitivity and gyno symptoms. Those who get blood work during these symptomatic periods often find their Estradiol (E2) levels significantly elevated (e.g., moving from a baseline of 20 pg/mL to >50 pg/mL).
3. Summary of Reported Blood Work Changes
| Marker | Low-Dose N=1 (0.25–0.5mg/day) | High-Dose/Impure N=1 (2mg+/day) |
|---|---|---|
| Total Testosterone | Stable or Slight Increase | Significant Decrease |
| 17$\beta$-Estradiol (E2) | Stable | Significant Increase |
| DHT | Decrease (17$\alpha$ is a 5$\alpha$-reductase inhibitor) | Decrease |
| SHBG | Often Increases | Significant Increase |
| Glucose/A1c | Often improves (lower) | Mixed |
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4. Key Takeaways from the Community
- 5-Alpha Reductase Inhibition: Many users report a drop in DHT (Dihydrotestosterone). Since 17$\alpha$-E2 (Alfatradiol) is a known 5-alpha reductase inhibitor, this is expected and mirrors the effect of drugs like Finasteride, though it is often weaker at the doses used.
- The “Pure” Powder Problem: The most common reason for “bad” blood work (high 17$\beta$-E2) in the community is suspected impurity. Because 17$\alpha$ and 17$\beta$ are enantiomers, they are very difficult to separate during synthesis. Even a 1% contamination of 17$\beta$ in a “pure” 17$\alpha$ powder can ruin a male’s hormone profile.
- Testing Protocol: Sophisticated N=1 experimenters use LC-MS/MS (Liquid Chromatography-Mass Spectrometry) for their follow-up blood work, as standard “immunoassays” for estradiol can sometimes struggle to distinguish between the α and β isomers, leading to false high-estrogen readings.
Would you like me to find specific dosing protocols or “safe” sourcing strategies that users on these forums have developed to avoid these hormone spikes?
Sources
Yes please
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Based on discussions from rapamycin.news, Reddit, and recent primate research, biohackers have developed specific strategies to navigate the risks of feminization while attempting to replicate the lifespan benefits seen in mice.
Below is a breakdown of the protocols, “safe” sourcing strategies, and testing methods reported by experimenters.
1. “Safe” Sourcing Strategies
Community consensus strongly favors pharmaceutical-grade sources over “raw” chemical powders due to the extreme potency of the β-isomer (standard estrogen).
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The European Pharma Route: Most users source Alfatradiol (the INN for 17$\alpha$-E2) as a topical hair solution. Brand names include:
- Ell-Cranell (0.025%)
- Pantostin (0.025%)
- Cost: Approximately $30–$40 per 100ml. One bottle contains 25 mg of the active molecule.
- The Powder Warning: Biohackers frequently warn against buying bulk powder from “grey market” chemical labs. A common finding is that even 99% pure powder can contain 1% 17$\beta$-E2, which at a 2mg dose would provide 20 mcg of 17$\beta$—enough to significantly elevate estrogen in men and cause breast tissue growth.
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Third-Party Testing: Users on
rapamycin.newssometimes pool money for HPLC testing of bulk batches. If you consider powder, the “safe” strategy is to only buy from batches with community-verified lab reports.
2. Dosing Protocols (The “Biohacker DD”)
Calculations are usually based on the NIA ITP mouse dose (14.4 ppm), which converts to a human equivalent dose (HED) of roughly 4 mg/day for an average male. However, most humans start much lower.
Protocol A: The “Micro-Dose” (Scalp/Topical)
- Dose: 0.25 mg to 0.5 mg daily.
- Method: Applying 1–2ml of Ell-Cranell to the scalp or thin skin (forearms).
- Goal: Primarily hair preservation and a “safe” entry into systemic exposure.
Protocol B: The “Moderate Oral” (ITP-Inspired)
- Dose: 1.0 mg to 2.0 mg daily.
- Method: Users measure out 4ml to 8ml of the 0.025% hair tonic and consume it orally (often mixed with water or juice).
- Note: Because these tonics are mostly isopropyl alcohol, some users let the alcohol evaporate or look for compounding pharmacies (mostly in the US/private) that can create a cleaner oral solution.
Protocol C: The “Macaque Protocol” (Warning)
- Dose: 4 mg+ daily.
- Context: Recent studies in Rhesus macaques showed that doses reaching this HED level caused significant feminization (lower testosterone). Consequently, the community has largely “retreated” from the 4mg dose, with most experimenters staying under 2mg/day.
3. Monitoring and Mitigation
To prevent side effects, experimenters use the following “Safeguard Protocol”:
- Baseline Bloods: Essential markers include Total Testosterone, Free Testosterone, DHT, and Estradiol (Sensitive LC-MS/MS assay).
- The “Nipple Test”: This is the primary subjective bio-marker. If any itching, sensitivity, or puffiness occurs behind the nipple, users immediately discontinue or halve the dose.
- Frequency: Some users dose EOD (Every Other Day) rather than daily, theorizing that 17$\alpha$-E2 has a long half-life in humans, though this is not yet clinically proven.
- The “Sensitive” Assay: Standard estrogen tests at regular labs can be inaccurate when 17$\alpha$ is present. Users specifically request LC-MS/MS (Liquid Chromatography-Mass Spectrometry) tests to ensure the lab is correctly identifying 17$\beta$-E2 and not getting a “false high” from the 17$\alpha$ supplement.
4. Summary Table of Costs & Values
| Source | Concentration | Mg per Bottle | Monthly Cost (at 1mg/day) | Risk Level |
|---|---|---|---|---|
| Ell-Cranell | 0.025% | 25 mg | ~$35 | Low (Pharma Grade) |
| Pantostin | 0.025% | 25 mg | ~$35 | Low (Pharma Grade) |
| Raw Powder | 98–99% | 1,000 mg | ~$2–$5 | High (Isomer Contamination) |
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