[Lotus]

Me summarize?, no not likely, and these statements are from the PDF, there always be obvious conflicts between reporting research, so I've learned one needs to take them as a reference (not gospel) and since the volume as such is so incredibly absurd to summarize the content would be equally absurd. Or it just could be the mild dyslexia I had as a child, I dunno, making my eyes bleed shouldn't mean the same for you though (apologies), sometimes I assume what I post should be easily understood. When the lights came on something (E2,?? lol) triggered in me, although comprehension was an obstacle. (Denita@ dyslexia, who is imo brilliant).

so bear with me please.

Yes I did see the summary, and we also posted the same research paper, just a different link.
http://www.anaturalhealingcenter.com/doc...trogen.pdf


From wiki: According to Wikipedia - Estrogen "Though estriol is the most plentiful of the three estrogens it is also the weakest, whereas estradiol is the strongest with a potency of approximately 80 times that of estriol.[unverified]"

Although estriol is weaker, it is more plentiful, and 90% of estradiol is bound to SHBG. So do the math, Estriol is important for NBE. Approximately 10% of estradiol is free. Where as more estriol is free, and is 80 times less potent. Estriol already is about as effective as estradiol, for NBE because it is bioavailable.

10% of estradiol acting 80 times more than estriol. Whereas, let's assume 100% estriol is free, and is 1/80th as strong as estradiol. The free amounts of E2 to E3 become comparable, then.

---------------------------------------

From the PDF:

E3 in the liver is 8% as potent as E2 (Estradiol) and 14% as potent as E1 (Estrone).

E3 (Estriol) is a metabolic waste product of E2 (Estradiol) metabolism or produced by conversion from the progesterone concentration during pregnancy.

E2 (Estradiol) is instrumental in over 400 functions in the female body.

One of the metabolic products of elevated E3 (Estriol) is associated with an increased risk of developing breast and cervical cancer. At other times, E3 (Estriol) can be implicated as a source of interference in lab tests for E2 (Estradiol,) as it may lead to clinical testing error.

Some experts suspect that E1 (Estrone) may be responsible for the higher risk of breast and endometrial cancer, due to a high receptor binding rate and production in women who are obese. (These statements contradict earlier posts, my point exactly)


40 per cent of the SHGB protein circulates unbound in the blood stream in men (over 80 per cent in women), and albumin circulates unbound almost all of the time.

• Estradiol is the most potent estrogen produced in the body. It is synthesized from testosterone or estrone via aromatase or 17β-hydroxysteroid dehydrogenase, respectively.
  

• The total estradiol production rate in the human male has been estimated to be 35-45 μg (0.130-0.165 μmol) per day, of which approximately 20% is directly produced by the testes [13,14]. Roughly 60% of circulating estradiol is derived from direct testicular secretion or from conversion of testicular androgens. The remaining fraction is derived from peripheral conversion of adrenal androgens [15].
  

• The mean estradiol plasma concentration in men is only about 1/200 of the mean plasma testosterone concentration [16] and is comparable to estradiol levels found in women in the early follicular phase of the menstrual cycle.
  

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143915/

___________________________________________


E1 (Estrone) is not directly active in tissue, but can be readily converted by most women to E2 (Estradiol) for actual use, because it is considered to be an E2 (Estradiol) precursor. The conversion can go both ways, though meaning that E1 (Estrone) can also be considered a breakdown or even a storage form of estrogen. It is sometimes considered “safer” than E2 (Estradiol) by virtue of its weakness, but since large quantities and high doses are required to get the same effect as a smaller quantity of E2 (Estradiol), other experts consider it no more or less safe than E2 (Estradiol). Some experts suspect that E1 (Estrone) may be responsible for the higher risk of breast and endometrial cancer, due to a high receptor binding rate and production in women who are obese.


E3 (Estriol) is the weakest of the three major estrogens. In fact, it is 1,000 times weaker in its effect on tissue than other estrogens. E3 (Estriol) is a metabolic waste product of E2 (Estradiol) metabolism or produced by conversion from the progesterone concentration during pregnancy. E3 (Estriol) usually is the culprit for morning sickness during pregnancy. However, it can still have some effects on a limited number of estrogen receptors. It is formed in the liver and is 8% as potent as E2 (Estradiol) and 14% as potent as E1 (Estrone). Once E3 (Estriol) is bound to an estrogen receptor, it blocks the stronger E2 (Estradiol) from acting there. Therefore, it is considered to have both estrogenic and anti-estrogenic actions. There is also some evidence that because it is so weak and blocks the stronger forms, E3 (Estriol) can be considered to have effects comparable to E2 (Estradiol) in regard to occupying as many receptors as a “need share level” of E2 (Estradiol). Yet the risk rises to the same level with E3 (Estriol), when compared to the other estrogens. One of the metabolic products of elevated E3 (Estriol) is associated with an increased risk of developing breast and cervical cancer. At other times, E3 (Estriol) can be implicated as a source of interference in lab tests for E2 (Estradiol,) as it may lead to clinical testing error.

___________________________________


Binding Characteristics

SHBG, also known as testosterone-estrogen binding globulin (TeBG), sex steroid binding globulin (SSBG), or sex steroid binding protein (SBP), specifically binds 17β-hydroxysteroids in a 1:1 ratio. The glycosylated heterodimer (80 to 100 kDa) binds 5α-dihydrotestosterone (DHT) most tightly, followed by testosterone and estradiol.

SHBG in Healthy Subjects

SHBG is synthesized by liver cells and has a 7- day half-life in circulation. In both sexes the SHBG concentration sharply increases just after birth and gradually declines until puberty. Male and female children have similar SHBG concentrations (ranging from 80 to 175 nmol/L) until the onset of puberty, when SHBG levels decrease more rapidly in males than in females.2 Table 2 shows average SHBG levels for healthy adults. In pregnant women, the SHBG level increases from conception until about week 30, reaching concentrations 6 to 10 times higher than in nonpregnant females.

The circulating androgen concentration affects SHBG synthesis. Elevated testosterone causes SHBG synthesis to decrease, while high estrogen stimulates SHBG production. The regulation of SHBG synthesis, combined with SHBG’s high affinity for testosterone compared to estrogen, results in SHBG effectively amplifying the estrogen level.

[Dynseli]

Most sources say that Estrone (E1) is a high risk for cancer. It is also a hormone in high amount after menopause.

Which point were you saying it was contradicting? That paper is from a company, and probably not on pubmed. While many points in that paper may be correct, it is their choice of wording, calling it a waste product, instead of a metabolite, and it assuming that estriol is not good because it doesn't convert back into estradiol. Estriol is not a waste product, but one if its metabolites is a waste product. Pubmed Reviews have more information from different sources put together by importance, and interpret results.

[Lotus]

Most sources say that Estrone (E1) is a high risk for cancer. It is also a hormone in high amount after menopause.

Which point were you saying it was contradicting? That paper is from a company, and probably not on pubmed. While many points in that paper may be correct, it is their choice of wording, calling it a waste product, instead of a metabolite, and it assuming that estriol is not good because it doesn't convert back into estradiol. Estriol is not a waste product, but one if its metabolites is a waste product. Pubmed Reviews have more information from different sources put together by importance, and interpret results.

My conflict is that E1, E3 is reported to increase cancer risks, which in all actuality it's all estrogens tbh.

So establishing what's actuatully revelant is our (my?) burden imo, you know the type (Social Justice Warrior) only just rephrase it to be "NBE Truth Warrior"

Dispelling The BS at least attempting too.

[Lotus]

From the linked research that was posted I find this study interesting in the fact that Estriol concentrations were increased during menstrual cycles. And this statement in particular:

With estriol circulating at nearly 10 times the concentration of estrone and estradiol, it appears at least a possibility that there must be unknown significant biological activity for this “weaker” hormone.

The second data set presents the estrogen levels of five women on different days of their menstrual cycles (Table 2). Because this was a preliminary study and the date of the estriol peak was unknown, the five subjects were tested at different times of the cycle. Subject 1 had blood drawn on the 7th, 10th, 14th, 17th and 24th days of the cycle. The estrogen quotient was lowest (EQ 7.1) on day 7 and increased to a high of 14.5 on day 24. Subject 2 was tested on the 7th, 12th and 21st days of the cycle. The estriol concentration followed a slight upward slope, but due to a peak in the estrone and estradiol concentrations, the EQ reached a minimum of 9.2 on the 12th day of the cycle. Subject 3 also exhibited an increase in estriol level as the cycle progressed; how- ever, the EQ was nearly the same on the 4th and 10th day (8.4 and 7.4 respectively), but due to a drop in estradiol and estrone on the 19th day, the EQ rose sharply to 17.7. Subject 4 had the earliest data point — the 2nd day of the cycle. The estrone and estradiol were both very low which was to be expected (1 pg/mL and 7 pg/mL respectively), but interestingly the es- triol remained fairly high at 303 pg/mL, yield- ing a very high EQ of 37.9. Subject 5 had samples drawn on the 8th, 10th and 26th day of the cycle. The EQ regressed from 14.0 on day 8 down to 7.9 on day 10 and soared to 29.1 on day 26 (the latest day of the cycle in our study).


Conclusion

The fractionated estrogen concentration data from the population of 26 women shows that the estriol in every case was at least three times as great as the concentration of estradiol and estrone combined. In fact, the average EQ for the population was 8.9. With estriol circulating at nearly 10 times the concentration of estrone and estradiol, it appears at least a possibility that there must be unknown significant biological activity for this “weaker” hormone. (One might draw a parallel with the history of DHEA research).

The conclusion that may be obtained from the five-women research project inves- tigating fractionated estrogen concentrations at different times of the menstrual cycle is that estriol is in higher concentration than both estrone and estradiol every day of the cycle that this study tested. It was observed that very early in the cycle (day 2) and very late in the cycle (day 26) the two subjects had very high Estrogen Quotients. As we know, estrone and estradiol are very low both late and early in the cycle, but it is very interesting to see that estriol does not seem to display the same proportionate drop in concentration.

The findings of this study necessitate additional research including more patients, more data points over the span of the cycle, and urine fractionated estrogen studies.

For more information on therapeutic applications of estriol see: Estriol: Safety and Efficacy. Altern Med

http://www.anaturalhealingcenter.com/doc...trogen.pdf

Apologies for drifting of topic.

[Dynseli]

As you said earlier, E3 breaks down into many chemicals, one of which is carcinogenic, it's true. E1 according to scientist consensus is carcinogenic, most sources say it. The paper also assumes that E1 is safer than E2, because it is weak, its not necessarily a contradiction, but it is a big assumption. E3, however is safe compared to estradiol. The 3 hormones may have their problems and may possibly aggravate cancer, but E3 is just way safer than E2.

The paper may have a conflict of interest because it's by pharmaceutical company. It may not be wrong, but it's its choice of words and the assumptions it makes. Also, I think it said estriol is discouraged from being prescribed in the US, while saying its more accepted in Europe. An estriol prescription isn't necessary

This is WebMD's UK website on it http://drugs.webmd.boots.com/drugs/drug-...triol.aspx . Note BootsWebMD is also commercial (and European).

[Lotus]

Thanks lovely,

You've been very helpful

[Lotus]

I'm going to re-post this post from earlier: the link isn't good anymore, too bad though, it was a great article:

DHT is public enemy number one for boob growth, roughly 98% of Total T is not active, and out of that 2% is what's considered Free T (bio-active). Once Free T is converted to DHT it can't convert back to Free T.

We also know that too much E turns off those receptors and feedback is locked, so what to do?.

Well you have to think in terms of reactivating those receptors, you know!!, clear them out to start the process over,

Question- what's the half life of E (not miroestriol)...does anybody get where this is going?.

I have often wondered the same thing! I think its crucial to metabolize these active hormones efficiently or they will build up in the liver much sooner than they normally do, causing the receptors to shut down/ feedback loop effect. For ex, as much as DIM is apart of men's formulas and women's to rid E excess, I think the most important part of what we need from it is actually being able to use these hormones as they flush out of the system. The liver is so important in nbe and metabolizing hormones. The abundance of free running hormones in the blood can be from poor liver function.

I think that is why the Cycling of "hormones" format is so important. It creates the re sensitivity factor consistently. I'm starting to think this is why plateaus happen after a while, loaded receptors and acute poor functioning of the liver.

This totally explained why my first attempt in nbe went detrimental. I had blood tests confirm free high estrogen and testosterone ( from high DHEA) and progesterone (though lowest of them all). And of course, I got some serious androgen conversion. I had no nbe success at all and the worst bumpy skin after months of taking all sorts of herbs (mainly estrogenic).So one can have high levels of E hormones and have no breast developmental effects at all, yet have mild masculating effects . I sadly developed some nice little stray hairs on my areola that were never there before
They were gone thankfully after cleansing months in.

Im convinced, that DHT is the little devil that breaks nbe success. I would personally like to raise my T levels as I am naturally low, but I am so sensitive to DHT conversion from my wonky adrenals.

Hi Tibetan,

Thank you-Brilliant!!,

I wish we focused on what you just posted more often, there's so many things out there that's robbing breast growth these days. Xeno-hormones comes to mind, but this statement struck me, matter of fact the whole article did.

The good estrogen causes no damage and drives immediately to the colon or to the bladder where it leaves the body. The bad estrogen backfires, gets stuck in reverse, and speeds back to the breast where it wreaks havoc. If this bad estrogen finds a parking spot on a breast cell, it will rapidly speed up cell division. If you have a lot of bad estrogen in your body, your risk of breast cancer goes up significantly.

Ok the rest of this is a read, but I think it's very important and won't (shouldn't) harm the brain, so press on my pretties.

http://www.womenswellnessconsulting.com/...index.html

Okay, with this understanding of all the different kinds of estrogen, lets look at how estrogen is processed within the body. Understanding how estrogen is produced, used, broken down and eliminated by your body – the estrogen pathway - is important. It will help you to understand the protocol better and make choices that support your optimum level of wellness.

I am going to quote Christine Horner, M.D. directly, from her book, Waking the Warrior Goddess, (which I highly recommend.) She has an analogy that is very simple and easy to understand.

"To understand the estrogen pathway better, lets use the analogy of a car ride. Your trip begins in the ovaries where estrogen is made and then is released into the blood. The blood vessels are like highways and estrogen flows through these blood vessel highways to get to its target destinations. When estrogen travels in the blood, it either travels alone or is attached to a substance called a "protein binder" (HSBG, Human Sex Binding Globulin), -the difference between driving alone and carpooling. When you carpool in certain cities, you can use a special high-speed lane, usually on the far left. In this lane, you can't exit from the highway. If you're driving alone, you can't use these high-speed lanes. You must travel in lanes that have access to exit lanes. Like the person driving alone, only the estrogen that travels alone – without a protein binder, SHBG – can exit from the blood-vessel highway. In this case, we are concerned about the off-ramp for only one destination: the breast tissue.

When estrogen reaches the breast, it looks for a place to "park". Parking spaces represent the "estrogen receptors", which estrogen binds to on the breast cell membranes. There are estrogen receptors all over your body, but the highest concentrations are found in the uterus and breast. Because of the relatively large number of estrogen receptors in these tissues, they respond more to estrogen than the other tissues in the body do.

When estrogen binds to an estrogen receptor, it "turns it on". A turned-on receptor causes cells to start dividing. Estrogen receptors don't turn on like a simple on/off switch. Instead, they turn on like a rheostat, a light switch with a dimmer.

The rate at which cells divide in response to estrogen is affected by many factors. First, the rate depends on the strength of the estrogen. There are strong estrogens (ESTRADIOL, ESTRONE, XENOHORMONES) and weak estrogens (ESTRIOL, PHYTOESTROGENS). Strong estrogens speed up cell division and therefore, increase the risk of cancer. Weak estrogens slow down cell division, therefore reducing the risk for cancer.

Parking at an estrogen receptor causes a lot of wear and tear on the estrogen. After awhile, it needs to go in for service. So, the estrogen leaves the estrogen receptor and heads for the liver (service station). The liver is the great detoxifier of the body. It breaks down toxins and other natural substances to prepare them for elimination.

Estrogen is broken down in the liver, and is influenced by the presence of certain chemicals. It is either broken down into a "good" kind of estrogen (Technically known as 2-hydroxyestrone) or a "bad" kind of estrogen (16-alpha hydroxyestrone). For instance substances in cruciferous vegetables and flax create more of the good kind, while environmental toxins (xenohormones) create more of the bad kind. The difference between good and bad estrogen is that good estrogen causes the cells to divide very slowly, whereas bad estrogen causes them to divide rapidly. Bad estrogen can also cause mutations or mistakes in how the cells grow that increase your risk of cancer even more.

The good estrogen causes no damage and drives immediately to the colon or to the bladder where it leaves the body. The bad estrogen backfires, gets stuck in reverse, and speeds back to the breast where it wreaks havoc. If this bad estrogen finds a parking spot on a breast cell, it will rapidly speed up cell division. If you have a lot of bad estrogen in your body, your risk of breast cancer goes up significantly.

In the colon, estrogen is either eliminated or absorbed back into the blood. If it is absorbed back into the blood, it adds to the total amount of estrogen in your body, and therefore, adds to your risk. There is a simple solution: eat more fiber. Fiber binds to the estrogen in your colon and eliminates it."

I would like to add a little bit here to Dr. Horner's reference to the "protein binder" sex hormone-binding globulin- SHBG. Understanding this protein can make a big difference in your understanding of the "big picture" of hormone health and balance. It is a critical player with a big impact on all our hormones.

As Dr. Horner mentioned, estrogen (and other hormones) that are bound to SHBG are in the "carpool lane" and cannot make random exits from the bloodstream. Only "free" (unbound) estrogen can roam through various tissues of the body searching for estrogen receptor sites to lock on to. In terms of our risk for breast cancer, it is only the free estrogen that concerns us. However, there is more to the story.

The inner intelligence of the body doesn't want hormones running wild or falling below a certain level. It wants normalcy, hormonal law and order. To achieve this, your body utilizes these sex hormone-binding globulins, which are produced by the liver.

These proteins chaperone individual hormone molecules though the blood. Should the hormones reach too high a level, the protein binds and inactivates them – sort of like a handcuffing effect. The protein not only transports but also regulates and assists in the access process at target cell sites.

If the estrogen level goes too high, an alarm goes off in the liver, the body's master chemical factory. It pumps out extra SHBG. In reaction to a high tide of estrogen, your liver can produce up to three times the normal amount of SHBG.

The problem is that this special protein doesn't just bind up some of the excess estrogen. It binds up – and inactivates – some of the other important hormones, such as thyroid hormone, growth hormone and testosterone (which is more important for women than you might think!)

You may have heard of a condition referred to as "Estrogen Dominance". This is where the body is flooded with higher than necessary levels of estrogens, which might be produced by your own body, or come from a toxic source, xenoestrogens. Usually it is a combination of both.

In addition to the deleterious effects we have already discussed in regards to excess estrogen in the body, there is now a complicating factor. High levels of estrogen in the body trigger the release of sex hormone-binding globulin, as the body tries to maintain balance by inactivating some of the excess estrogen. But, at the same time the estrogen is being inactivated, the release of high amounts of SHBG causes other important hormones to become bound and inactive as well.

In this way estrogen dominance not only raises our risk for breast cancer, but can cause a cascade effect on other important hormones as well.

The effect on you is not immediate. It takes about six weeks before you usually start to experience the fallout from the lowered hormonal activity. Quantities of your important anti-aging hormones have now been taken out of commission. In essence, the available amount of these hormones falls to levels you might have when you are years older. The body becomes less "alive". Perhaps the skin becomes less radiant, the vagina drier. Lowered thyroid, for instance, can cause weight gain, fatigue, coldness and dry skin. These are all signs of a thyroid deficiency. Elevated SHBG can cause such multiple effects.

[Dynseli]

So the breakdown will eventually happen from estradiol into estriol. What we want is a healthy breakdown of estriol into the safe metabolite.

So according to your post, is the theory that certain phytohormones increase the good metabolite? The rest of your theory, with what I'll add to it, is that toxic environmental estrogens turn human estriol into more toxic metabolites. On pubmed, there are a lot of examples of synthetic environmental toxic byproducts getting into the body and causing unhealthy/unsafe/tumorous/cancerous/odd growth. I agree that fiber is important to flush the body of toxins. Fiber (that is indigestible by humans and cancer tissue) is also digested by bacteria, that produce anti-carcinogens. Fibers are a source of beneficial phytochemicals (probably due to beneficial bacteria). I theorize that milk thistle is also important here.

I hope you took note how I tried to get around the problem of SHBG tying up estradiol, and theorized if estradiol gets broken down into estriol, by increasing progesterone and prolactin.

Also, phytohormones being broken down isn't much of a problem. A few of their metabolites also produce the same effects as the original phytohormones. Even if it is weaker, it still adds to and has a beneficial effect.

[Lotus]

Here's an update on some novel approaches towards aromatase.

cAMP-dependent signaling pathways (cyclic adenosine monophosphat).
COX2 inhibitors (PGE2), problematic
protein kinase A (PKA)
Free fatty acids



aromatase expression is switched to promoters I.3 and II which are transactivated by protein kinase A (PKA) and cAMP-dependent signaling pathways.

These are promoters genes for aromatase.



   

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142499/

[Lotus]

Shh!, Vitamin D is a potent aromatase promoter.


Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation.


Abstract
OBJECTIVE:
Current evidence suggests that extragonadal estrogens play an important role in bone metabolism. Estrogen biosynthesis is catalyzed by P450aromatase, encoded by the CYP19 gene. The aims of this paper were to study CYP19 gene expression in human osteoblasts under several hormone and cytokine treatments and to define promoter regions involved in this regulation.

METHODS:
CYP19 transcript levels were measured from primary human osteoblasts and MG-63 cells by real-time PCR in basal conditions, and in response to seven different hormones and cytokines. Four promoters of CYP19 gene were cloned upstream of the luciferase gene and transfected into MG-63 cells. The effect of vitamin D and dexamethasone in these promoter activities was evaluated.

RESULTS:
Vitamin D and dexamethasone were potent stimulators of CYP19 transcription, while testosterone and 17beta-estradiol stimulated moderately. Promoter pII proved the most potent in driving transient luciferase expression. Promoter I.4 displayed moderate activity, while promoters I.3 and I.6 were weak. A region upstream of exon I.3, including exon I.6, was identified as containing repressor elements of promoter pII. Promoter I.3 activity was modulated by repressors located within exon I.3, while an enhancer of promoter I.4 was detected within exon I.4. In the absence of fetal calf serum, dexamethasone stimulation was observed on promoters I.3 and I.4, while vitamin D stimulation acted only on promoter I.3.

CONCLUSIONS:
Four regulatory regions of promoters pII, I.3 and I.4 are relevant to CYP19 expression in human osteoblasts. Vitamin D and dexamethasone modulate transcription through these regions.