17 Alpha Estradiol: Use and Dosing Experiences

This study used 3 min sublingual in 50% ethanol and got good results;

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Thereā€™s a lot to this to generalize and provide data for, but understanding the fundamentals of rheumatology, unspecific autoimmune attacks increase with age, thatā€™s why immunity should not be boosted in aging populations rather than modulated which we do not have therapies for.

Estrogen is known to be a primary cause of autoimmune disorders in males and females. ER alpha rather than beta is the greatest risk factor. Although receptor density is different, the risks are the same for both male and female, but greater in women.

The topic is not only lupus, fundamentally autoimmune conditions or unspecific age-related attacks. Based on this evidence on a large population scale, 17 alpha estradiol and healthspan indication, it does not meet the criteria. Even if someone doesnā€™t have a diagnosed autoimmune condition it will still increase the risk of age-related autoimmune attacks.

It is an interesting compound nonetheless and we can learn from it, Iā€™m not confident its actionable for large populations especially when some of the risks are not easily measurable.

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Are you aware of any data that suggests that women taking Estradiol as HRT have increased risk of auto-immune disease (compared to women not taking Estradiol)? It seems that men taking the 17-Alpha estradiol version may be a comparable situation.

Iā€™m just trying to get some better quantification data on the risks. If anyone can find numbers on the absolute risk, it would be intereting.

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Some resources for people who want to learn more about this possible risk:

Here: https://www.scientificamerican.com/article/why-nearly-80-percent-of-autoimmune-sufferers-are-female/

Here: https://www.medpagetoday.com/meetingcoverage/oar/74787

Here: Sex Hormones in Acquired Immunity and Autoimmune Disease - PMC

Increased risk [of Lupus] has been associated with higher lifetime levels of estrogen exposure. In a cohort of 238,308 adult women evaluated prospectively over 27 years, the 262 women diagnosed with SLE over the course of the study were analyzed for relative risk factors. Increased risk was associated with early menarche (aged less than 10 years; relative risk: 2.1; 95% CI: 1.4ā€“3.2) and oral contraceptive use (relative risk: 1.5; 95% CI: 1.1ā€“2.1).[69] Menstrual irregularity increased risk of SLE diagnosis in a Japanese caseā€“control study.[70] Menstrual cycles of abnormal length (either long and short) increased risk as well.[71] Estradiol treatment of mouse lupus-prone strains produces disease onset, increases autoantibody production, and increases risk of mortality.[23]

Above Quote, from Here: https://www.medscape.com/viewarticle/775536_6

Here: https://www.tandfonline.com/doi/full/10.1586/eci.10.60

Here (PDF) Sex-based Differences in Auto-immune Diseases

Quote from the above PDF:

Generally, estrogens, in particular 17- Ī² *estradiol (E2) and prolactin, act as enhancers at least of humoral immunity, and testosterone and progesterone as natural immunosuppressants [3]. Sex hormones have different effects depending not only on the concentration but also on the type of target cell and the receptor subtype expressed on a given cell type.

At periovulatory to pregnancy levels [8], E2 has mainly anti-inflammatory effects, by inhibiting production and signaling of pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1* Ī² and IL-6, and natural killer (NK) cell activation, and by inducing expression of anti-inflammatory cytokines favoring a T helper 2 (Th2) phenotype [9], such as IL-4, IL-10 and transforming growth factor (TGF)-* Ī²*, and by activating regulatory T cells (Treg) [10]. At lower concentrations, E2 stimulates TNF, interferon (IFN)-* Ī³*, IL-1* Ī² *and NK cells, while it enhances antibody production by B cells both at high and low concentrations [9]. Prolactin increases antibody production, regulates the development of CD4+ T cells and triggers pro-inflammatory cytokine production [11].

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Searching around for data on the absolute risk / incidence / prevalence of Lupus in men I came across this information below. The rate / risk of Lupus in men is about 10% (or 1/10th) that of women.

The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0ā€“6.1) and 72.8 (95% CI 70.8ā€“74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by captureā€“recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males.

The incidence for males is under 1 per 100,000 people, and prevalence about 12 per 100,000 people. See table and source paper below. Overall this seems like a very low risk for the average male. Though, of course, if you have a genetic predisposition to Lupus as revealed by genome mapping, then the risk is likely higher.

Source Table: Table - PMC

Source Paper:

More broadly, one might also consider risk factors for all autoimmune diseases:

Risk factors include:

  • Some medications. Talk to your healthcare provider about the side effects of medications for blood pressure, statins and antibiotics.
  • Having relatives with autoimmune diseases. Some diseases are genetic ā€” they run in families.
  • Smoking.
  • Already having one autoimmune disease. Youā€™re at a higher risk of developing another.
  • Exposure to toxins.
  • Being female ā€” 78% of people who have an autoimmune disease are women.
  • Obesity.
  • Infections.

Source, Cleveland Clinic: Autoimmune Diseases: Causes, Symptoms, What Is It & Treatment

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That baseline rate of lupus seem very small, including absolute risk. I deleted my posts about this.

It would be nice to find a genetic test that can more likely be trusted, using polygenic risk score.

Something like this, where there is a percentile of polygenic score and prevalence of X disease. Where you can upload data in 23andme format, get percentile of polygenic score:


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Was this the sensitive estrogen test?

($60 vs. $33)

Sensitive test can take longer, the place I checked it is analyzed once a month. Review here says it took 30 days.

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Why not simply use the Pantostin on the scalp as this formulation is intended for? The scalp should offer similar absorption to the forearm.

Thanks for the link. Iā€™m ordering some as well; letā€™s see how it goes.

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With the added transcutol, you are right that it would probably get absorbed equally well on the scalp. But I have no bald spots, so I am worried the scalp would be more messy and waste some of the product that gets stuck on my hair.

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I received the Pantostin from Germany 10 days after ordering. Cost $53 for 300ml of 0.25mg/ml topical application scalp solution. So about $0.7/mg, although not sure how much of it gets absorbed into your bloodstream.

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Any plans to do a blood test before starting to get a baseline on some of your hormones? perhaps something like this: Male Basic Hormone Panel | Blood Test - Life Extension

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Thatā€™s a good idea. Iā€™ve never used LEF; do they simply use Quest/Labcorp for sample collection?

Yes - you pay LEF, they give you a blood labs requisition receipt that you take toā€¦ I think its Labcorp. Yes - it is. Details here: Lab Testing Services ā€“ Unlock Better Health - Life Extension

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There are lots of other companies doing the same thing - I think for slightly lower cost. Search in the forums on ā€œLab testsā€ and youā€™ll find them.

It doesnā€™t provide the sensitive estradiol test. Why do you prefer taking that test?

That was just the first one I found that seemed to cover the key hormonesā€¦ Iā€™m honestly not sure what is the best one. I will have to check my hormone levels and see what might make sense - I did a ā€œMale Panel Blood Testā€ a few months ago: Male Panel | Blood Test - Life Extension

Are you thinking this is the best one? Estradiol, Sensitive | Blood Test - Life Extension

Any experience with these types of tests?

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Yes. I donā€™t have experience with those types of tests. I posted more detail why the sensitive test is better here: 17-Alpha Estradiol - Another Top Anti-Aging Drug - #128 by AnUser

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The sensitive Estradiol test is not needed since you pay extra to measure levels that are low for males, and this is intended to verify that cancer treatment is effectively suppressing all hormones (for example). In this case we are trying to check if the Estradiol levels are elevated, in the range that is normally only seen in women, so the normal test should be fine.

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Why do you believe we are only trying to check if estradiol levels are elevated in men to normal levels of women?

I know nothing about male hormonesā€¦ or female hormones for that matter, but would the more sensitive test perhaps be helpful in identifying a trend towards higher estradiol levels be helpful even it its not yet in the range of women?

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