[Lotus]

Thanks Lotus for the posts. I now see that you were answering our posts, but I at least wasn't seeing this. . Mind you, I'm still trying to wrapt my mind around the various implications. From what you or your links say, extremely low SHBG levels are possible in conjunction with extremely low T levels, and if the results of my recent hormone level tests were reported correctly to me, my T was <0.7 and my SHBG <1.0. I suspect that in each case these readings represented 'lower than the lowest our lab can detect' which may be why no free T was calculated. They are presumably values on the Canadian or European scale, but even if multiplied up to the US scale are still abnormally low for people of either sex, in effect off the bottom of the scale. My NP does not wish to prescribe me T because of my heart condition. Despite the low levels, I suspect that PM is keeping me feeling good. PM is such a complex substance, and considered in Thailand to be beneficial for men as well as women, that it occurs to me to wonder whether it might contain androgenic as well as estrogenic components. Nothing in endocrinology ever seems to be straightforward.

All the very best from

Thanks Annie,

So what to make of all this, some interesting facts about (SHBG) and what different responses there are:

ie -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.


Low SHBG. SHBG is a protein that bind to testosterone and estradiol and creates a "reserve" or pool of these critical hormones. Some men, for reasons not totally understood yet, have very low SHBG levels. This condition is usually tied to a suite of symptoms including insulin resistance and liver dysfunction that I outline in my link on Low SHBG. Practically speaking, a low SHBG guy will clear out his testosterone and estradiol so quickly, i.e. urinate them out of his system, that his plasma levels are too low. This can give him mediocre HRT results and many other problems. If you are low SHBG, please join us on the Peak Testosterone Forum and ask some questions there as this is a whole subject on its own.

Hi Annabel,

Just done some research and yes some phytoestrogens do bind to SHBG but not all. Phytoestrogens also increase SHBG because they act like estrogens.

Source:
Dietary Isoflavones Affect Sex Hormone-Binding Globulin Levels in Postmenopausal Women
Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG)

Denita

[Lotus]

This is the difference between Aromatase and Aromatase Inhibitors or also known as (AI's).




   

[Lotus]

Aromatase

• There's an enzyme in the bodies of both men and women called aromatase. Its primary action is to produce female sex hormones, or estrogens. It produces them from male sex hormones (androgens) such as testosterone and their precursors.
  

• Aromatase also converts androstenedione (a sex hormone precursor) to the female hormone estrone, another estrogen, although weaker than estradiol.
  

• If you increase the activity of aromatase, you can increase levels of female sex hormones (estradiol, estrone).
  

• If you decrease the activity of aromatase, you can decrease levels of female sex hormones, while increasing relative levels of male sex hormones, e.g. testosterone.
  

• Men's bodies normally contain some level of estrogens, in addition to testosterone and their kind. Likewise, women's bodies contain some level of male androgens including testosterone.
  

• The ratio of male-to-female hormones contributes to our masculinity or femininity. Aromatase is one chemical that can tweak that ratio. It operates the same in both men and women, although an array of compounds can affect its activity.
  

________________________________________________________________

Testosterone-has two metabolites that pose potential problems for aging males and also for bodybuilders and athletes. One is estradiol (testosterone is converted to estradiol by the enzyme aromatase) and the other is dihydrotestosterone (DHT) (testosterone is converted to DHT by the enzyme 5-alpha reductase). As men age, there is a dramatic decrease in testosterone production, but without a corresponding decrease in the production of estradiol and DHT. Even though testosterone levels have plummeted, the aromatization of testosterone to estradiol is maintained, or even accelerated, and more testosterone is also being aromatized in fatty tissues. This creates excess levels of estradiol and, as a consequence, a blood level ratio of testosterone to estradiol that continues to decline, tipping the scale in balance of an estradiol-dominant environment.

[Lotus]

Sorry double posted, oops

[Candace]

My observation is, I don't see how anybody is immune to xenoestrogens these days given the are a part of everything we do, eat, breath etc. I bring my shopping home and 90% of it is packaged in plastic and the meats are packaged by the cheap SMELLY glad wrap that makes you sinus's want to shrivel up an die
All my supplements liquid or otherwise, all supplied in plastic bla bla you get my drift. Milk, juice, everything IN PLASTIC.

So if you want to focus on trying to eliminate Xenoestrogens by way of Dim or cruciferous veggies etc are there any other supporting nutrients you might need to take to support the body assuming you did in fact start some "die off" effect of eliminating the Xenos? I heard potentially if you don't have certain nutrients while trying to eliminate the bad estros the effects can be disasterous. IF you have covered this I apologize in advance as I haven't scrutinized the post, just the xenos caught my eye..

Second yes you need to have a good functional 'elimination process going on DOWNSTAIRS' (to put it nicely) so increase fibre by way of pysillium husks or the likes. What I want to know is can you're body get used the increased fibre like Metamucil, pysillium if you take it daily and render it ineffective or is it suitable for daily continuous use???

One strategy is to look for containers made of either glass or plastics with recycle codes 2, 4, or 5 and to never heat even those "safer" plastics. Cash register receipts have BPA so don't touch them more than necessary. Eat canned food only if you know for certain that the can lining is BPA-free.

Phase II detoxification conjugates toxins with methyl groups, acetyl groups, glutathione, sulfate, glycine, or glucuronic acid. Methylation needs folic acid (from either lemon peel extract or 5-methylfolate: the synthetic folic acid isn't completely converted in the first pass so you get unmetabolized folic acid that can mess with natural killer cells), B12, and choline. The choline RDA is tough to get: I need to supplement 7.2 g of the triple-strength lecithin. (Choline bitartrate is too poorly absorbed to bother with. I would use alpha-GPC if it was cheaper. CDP-choline is probably a bad idea because it converts to uridine which could cause a nucleic acid imbalance. Orotate converting to uridine and causing such an imbalance is thought to be the mechanism by which it increases cancer risk.) My dietary software, CRONometer, doesn't list choline so I had to add it up from this USDA database to calculate the deficiency.

Glutathione can be increased with whey protein (although whey is probably pro-aging because it's an mTOR stimulant) or something that activates Nrf2/ARE like resveratrol. The maximum benefit is at a concentration of 1 micromolar, which is close to my best guess (2 micromolar) of what you get from Revgenetics Nitro250. (Resveratrol is a supplement which needs sophisticated formulation to get absorbed. Most mainstream brands use unformulated 50% extracts, and a lot of the other 50% is emodin which is an MAO inhibitor and which also causes diarrhea at doses needed to activate Nrf2/ARE.)

I'm not sure if we need to boost sulfate. Hopefully MSM covers this base. Glycine can be obtained from gelatin, collagen, or pure glycine powder, which is sweet as sugar. Also note that glycine is able to detox methionine and extend maximum lifespan in rats. I look at it as glycine from connective tissue balancing out methionine from muscle tissue and therefore simulating eating the whole animal like our evolutionary ancestors did.

Calcium d-glucarate enhances glucuronidation by preventing the glucuronic acid from being pulled off of the toxin.

I think fiber is OK for daily use. You can copy the moldies and Lymies who take cholestyramine half an hour before eating so that it's in position to grab toxins in the bile as it gets secreted. If it doesn't soak up the toxins, they can be reabsorbed through enterohepatic recirculation. Activated carbon is another thing people use. I just use generic Miralax. I'm not very concerned about chronic toxins in my individual body, and Miralax cuts colorectal cancer risk in half. It's not a mechanical effect, it's a chemical effect that downregulates a growth factor.

[Dynseli]

http://www.breastnexus.com/showthread.php?tid=21747 'Serum Estriol and Estetrol'
http://www.altmedrev.com/publications/3/2/101.pdf 'Estriol: Safety and Efficacy'

"Estriol has a much lower affinity for binding to SHBG; therefore, a greater percent is available for biological activity." [than estradiol]

"While estriol appears to be safer than estrone and estradiol and, in some situations, provides some protection against carcinogenesis, it appears its use in breast cancer patients with active disease or with patients at high risk for breast cancer should be approached with caution."

Pathways:
Estradiol or Estrone + 16a-OHase --> Estriol

16α-Hydroxyandrostenedione + 17-OH-SDH or aromatase --> Estriol

The combination of enzimes 16a-OHase, 17-OH-SDH, aromatase, and 3b-OH-SDH are important for the production of estriol.

Abbreviations:
3β-OH-SDH = 3b-Hydroxysteroid dehydrogenase
17-OH-SDH = 17-Hydroxysteroid dehydrogenase
16α-OHase = 16a-Hydroxylase
Estrone (E1)
Estradiol (E2)
Estriol or Oestriol (E3)
Oestetrol, Estetrol, or 15-alpha-hydroxyoestriol (E4)

[Dynseli]

Pubmed reviews:
http://erc.endocrinology-journals.org/co...2/315.long 'Aromatase and gynecomastia'
http://www.princehenrys.org/files/media/...Polska.pdf 'Aromatase research and its clinical significance'

[Lotus]

Pubmed reviews:
http://erc.endocrinology-journals.org/co...2/315.long 'Aromatase and gynecomastia'
http://www.princehenrys.org/files/media/...Polska.pdf 'Aromatase research and its clinical significance'

Great find, from the second link you listed I found this related study which is extremely interesting. (Note the family in the study). A healthy approach to express CYP19A1 gene exists, finding it can unlock a huge potential, I have my own theory though lol.

Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome
http://www.hindawi.com/journals/ije/2012/584807/


Implication for the Hypothalamus-Pituitary-Gonadal Axis Function

It is notable that a similar degree of FSH-dominant hypogonadotropic hypogonadism is observed in the three types, although E1 and E2 values and E2/T ratios are much higher in the inversion type than in the duplication and deletion types (Table 1). In particular, FSH was severely suppressed even after GnRH priming in the duplication type [4]. This implies that a relatively mild excess of circulatory estrogens can exert a strong negative feedback effect on FSH secretion primarily at the pituitary. This would be consistent with the results of animal studies that show strong inhibitory effect of E2 on transcription of FSH beta-subunit gene in the pituitary cells and almost negligible effect on synthesis of LH beta-subunit and secretion of LH [18, 19]. In this regard, while T responses to hCG stimulation are normal in the duplication and the deletion types and somewhat low in the inversion type, this would be consistent with fairly preserved LH secretion in the three types and markedly increased estrogen values in the inversion type. In addition, whereas fertility and spermatogenesis are normally preserved in the three types, this would be explained by the FSH-dominant hypogonadotropic hypogonadism, because FSH plays only a minor role in male fertility (spermatogenesis) [20].

________________________________

Binder et al. studied a family with seven men in three generations affected with gynecomastia that was in- herited in an autosomal dominant pattern [67]. Their testosterone levels were decreased while oestrone and oestradiol were in the high normal range. A strong association of the TTTA repeat polymorphism in the
CYP19A1 gene was observed. In a similar family, the same molecular marker associated with the phenotype was reported by Stratakis et al. [64]. Increased aromatase activity in fibroblasts and strong immunostaining for aromatase in breast tissue samples from family members with gynecomastia were shown. A new promoter was revealed in the non-coding region of the CYP19A1 gene. Its activation could possibly lead to the increased aromatase gene expression.
Other alterations in the promoter region of CYP19A1 were described by Shozu et al. [65]. In three men with severe gynecomastia of prepubertal onset and hypo- gonadotrophic hypogonadism resulting from severe oestrogen excess, two novel gain-of function mutations led to the overexpression of aromatase in many tissues. Heterozygous inversions in the 15q21.2–3 region caused the constitutively active cryptic promoters that normally serve to transcribe two ubiquitously expressed genes — FLJ or TMOD3 — to lie adjacent to the aromatase coding region. Similar regional rearrangements resulting in the formation of cryptic promoters for aromatase gene and its overexpression were described recently by Demura et al. [68].

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

When ovarian estrogen synthesis ceases at the menopause, estrogens continue to be synthesized in different tissue compartments from circulating androgens. The key pathway is aromatization of androstenedione into estrone, probably accounting for as much as 90% of the total estrogens synthesized in a postmenopausal woman (Fig. 1). Aromatase, also called estrogen synthetase, is a cytochrome P450-dependent enzyme symbolized as CYP19A1 and catalyzes three consecutive hydroxylation reactions converting C19 androgens to aromatic C18 estrogens. The aromatase enzyme may also use testosterone as a substrate to convert testosterone into estradiol (Fig. 1); however, since the circulating testosterone levels are lower than those of androstenedione, and aromatase has lower activity on testosterone than androstenedione, the contribution of this pathway to estrogen synthesis is only modest. Upon receiving electrons from NADPH-cytochrome P450 reductase, aromatase converts androstenedione and testosterone to estrone and estradiol, respectively (Fig. 1).


CHAPTER 10. The Breast
http://www.sciencedirect.com/science/art...9074000103

CHAPTER 3. Prolactin in Human Reproduction
http://www.sciencedirect.com/science/art...9074000036

Pharmacogenetics of anti-estrogen treatment of breast cancer
http://www.sciencedirect.com/science/art...1782#f0005

584807.fig.001
Figure 1: Simplified schematic representation indicating the genomic structure of CYP19A1. CYP19A1 is located on 15q21.2 adjacent to DMXL2 and GLDN and consists of at least 11 noncoding exons 1 and nine coding exons 2–10 [9, 10]. Each exon 1 is accompanied by a tissue-specific promoter and is spliced alternatively onto a common splice acceptor site at exon 2 [9–13].
http://www.hindawi.com/journals/ije/2012/584807/

[Dynseli]

Chapter 10, the Breast, is very good. It has a lot of information that I was looking for, plus a little bit more, in one place. I'll add it to biology.

I don't think genetics should be messed with. What is proved, however, is the importance of aromatases. Anti-reductases, and plant based analogs are also imporant. 16a-OHase through liver conversion might also be important for forming estriol from other estrogens, which is safer and more bioavailable than estradiol.

https://www.ncbi.nlm.nih.gov/mesh/?term=...ydroxylase Steroid 16-alpha-Hydroxylase (16a-OHase) This enzyme is shown in the above link 'Estriol: Safety and Efficacy' under Figure 1.Biosynthesis of estrogens. It shows the pathway from Dehydroepiandrosterone (DHEA), to Androstenedione, to testosterone, to estradiol, to estriol. The chart shows aromatases making conversions to estradiol, estrone, and estriol.

I wonder if blessed thistle which has a role in helping the liver, and is also a lactogogue has an effect in any way on an estrogen pathway.

On the other hand, estriol may not be normal for the body to synthesize in large amounts, so it may possibly be irrelevant. Estriol is synthesized by a small amount by the liver, and also by a large amount by a placenta.

[Dynseli]

Aromatase is way more useful than I thought. It kills two birds with one stone: reducing androgens which directly inhibit breast size, and it makes estrogens. One example is the effectiveness of aromatase to cause major gynecomastia. Aromatase-inhibitors do the opposite. LH, androgen, or dhea may not even be necessary. Many times, LH increases on its own based on feedback or everyday foods. I hypothesize that topical aromatases may be highly effective. I wonder if topical tea tree and lavender are aromatases.

5-alpha-reductase-inhibitors are useful for preventing testosterone conversion into the more inhibiting DHT. Aromatase reduces the amount of testosterone available to turn into DHT.

Liver health is very important, first of all for overall health, and secondly it uses the enzyme 16a-OHase to break down estradiol into the more bioavailable estriol. Does Milk thistle support this function?

Aromatase mostly takes care of estrogens. There are also progestogens and prolactin.