[Lotus]

I wasn't convinced about a point of no return. Turns out, science explains that certain motor neurons exposed to estrogens and growth hormones does promote dysmorphia. Another study (mouse) showed that PM had this same effect in the liver and brain......

I do believe certian proteins (e.g. STAT5) can have an effect too, in our brain and liver. Additionally, I'm certain will find another protein linked enzyme (from the CYP family of enzymes) that will explain another brain/liver/hypothalamus cross link.

Male-to-female transsexuals have female neuron numbers in a limbic nucleus.
Kruijver FP1, Zhou JN, Pool CW, Hofman MA, Gooren LJ, Swaab DF.
Author information
Abstract
Transsexuals experience themselves as being of the opposite sex, despite having the biological characteristics of one sex. A crucial question resulting from a previous brain study in male-to-female transsexuals was whether the reported difference according to gender identity in the central part of the bed nucleus of the stria terminalis (BSTc) was based on a neuronal difference in the BSTc itself or just a reflection of a difference in vasoactive intestinal polypeptide innervation from the amygdala, which was used as a marker. Therefore, we determined in 42 subjects the number of somatostatin-expressing neurons in the BSTc in relation to sex, sexual orientation, gender identity, and past or present hormonal status. Regardless of sexual orientation, men had almost twice as many somatostatin neurons as women (P < 0.006). The number of neurons in the BSTc of male-to-female transsexuals was similar to that of the females (P = 0.83). In contrast, the neuron number of a female-to-male transsexual was found to be in the male range. Hormone treatment or sex hormone level variations in adulthood did not seem to have influenced BSTc neuron numbers. The present findings of somatostatin neuronal sex differences in the BSTc and its sex reversal in the transsexual brain clearly support the paradigm that in transsexuals sexual differentiation of the brain and genitals may go into opposite directions and point to a neurobiological basis of gender identity disorder.

In other words, men have twice as many hormone secreting neurons as women. This suggests that you (males) traveling down the NBE or pre hrt pathway may already, without realizing it, are predominantly in the female neuron range. (Just an opinion).

Haha, lol.....you've been warned.

This process takes place in two places, in the liver and the brain.


In estradiol, it induces expression of CYP2B9 , deoxymiroestrol -also induces the expression of CYP2B9. In the liver CYB2B9 (an enzyme (or protein) in the family of cytochrome P450 enzymes) is expressed. PM expresses this enzyme CYP2B9, which induces the expression of Growth Hormones. This expression signal is picked up by the hypothalamus, which then secretes growth hormones (e.g. glucocorticoid hormones) which escalates the dysphoria (aka GID).




Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver
http://www.sciencedirect.com/science/art...3X0500555X



Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice: Endocrinology: Vol 156, No 3
http://press.endocrine.org/doi/pdf/10.1210/en.2014-1429


Frontiers | Sexual Differentiation of the Rodent Brain: Dogma and Beyond | Neurogenomics
http://journal.frontiersin.org/article/1...00026/full


female-specific murine Cyp2b9 gene expression by growth or glucocorticoid hormones.
Sakuma T1, Kitajima K, Nishiyama M, Mashino M, Hashita T, Nemoto N.
Author information

Abstract
CYP2B9 is a constitutively and female-specifically expressed P450 isoform in mouse livers. Hypophysectomy-induced CYP2B9 mRNA expression in males to a level similar to that in females, while the operation did not affect females. Twice-daily injection of growth hormone (GH), which mimics the male pattern of GH secretion, significantly repressed hypophysectomy-induced mRNA expression in males. The same treatment completely suppressed expression in intact females. Treatments with synthetic glucocorticoid dexamethasone (DEX) suppressed expression of CYP2B9 mRNA in intact females, but not in GH-treated and un-treated hypophysectomized females. In primary cultured mouse hepatocytes, CYP2B9 mRNA expression was concentration-dependently suppressed by natural glucocorticoids such as hydrocortisone and corticosterone as well as by DEX. Glucocorticoid-mediated suppression was partially inhibited by RU486, a potent antiglucocorticoid. In contrast, RU486 by itself suppressed expression of CYP2B9 mRNA. These observations suggest that the sexually dimorphic expression of CYP2B9 is partly due to suppression by the masculine plasma GH profile and by glucocorticoid hormones.

Bimodal action of miroestrol and deoxymiroestrol, phytoestrogens from Pueraria candollei var. mirifica, on hepatic CYP2B9 and CYP1A2 expressions and antilipid peroxidation in mice —
http://www.ncbi.nlm.nih.gov/pubmed/22260863


A sexually dimorphic nucleus in the human brain | Science
http://science.sciencemag.org/content/22...2.abstract


Discriminating Activation of CYP2B9 Expression in Male C57BL/6 Mouse Liver by β-Estradiol
https://www.researchgate.net/publication...-Estradiol


Biological Evaluation of Deoxymiroestrol, a Potent Phytoestrogen from Pueraria candollei var. mirifica
Udomsuk L1, Putalun W1, Juengwatanatrakul T2, Jarukamjorn K1*
Introduction: Deoxymiroestrol is a phytoestrogen isolated from tuberous roots of Pueraria candollei var. mirifica (Leguminosae). Since deoxymiroestrol showed strong estrogenic-like activitiy, it is worth to investigate its biological activity on enzymes related drug metabolism, cytochrome P450s (P450), and sex hormone synthesis pathway, as well as its anti-lipid peroxidation in both in vitro in primary mouse hepatocytes and in vivo in mouse liver. Methods: P450 activities were evaluated in both primary mouse hepatocytes and mouse liver. Expression of CYP1A1, CYP1A2, CYP1B1, CYP2B9, AhR, and ARNT mRNAs were quantified by real- time RT-PCR while their activities were assessed by benzyloxyresorufin and methoxyresorufin O-dealkylation, respectively. Enzymes involved in sex-hormone synthesis pathway in male testes were semi-quantified by RT-PCR. Lipid peroxidation was measured in mouse brain. Results: In primary hepatocytes, expression of AhR, ARNT, and CYP1A1 mRNAs was suppressed whereas that of CYP1B1 was induced by deoxymiroestrol, in which the gene expressions were time- and concentration-dependent patterns compared to those of estradiol. In vivo in mice, deoxymiroestrol enlarged female uterus-weight and -volume as comparable to estradiol. As estradiol did, deoxymiroestrol induced expression of CYP2B9 mRNA whereas those of CYP1A2 were suppressed. Assessment of testicular enzymes involved in sex hormone synthesis pathway showed suppression of 3β-HSD, 17β-HSD1, and CYP17 expressions with those of CYP19 mRNA was slightly decreased by deoxymiroestrol. In addition, the expression of 17β-HSD2 was increased resulting in decreasing estradiol synthesis as that noted by estradiol. In addition, deoxymiroestrol possessed anti-lipid peroxidative activity in mouse brain. Conclusion: These observations suggested deoxymiroestrol as a potential alternative medicine for estradiol according to its distinctive abilities on regulation of related hepatic P450 enzymes and sex hormone-synthesis responsive enzymes, with its beneficent anti-oxidative potential.
Keywords: CYP1A1, CYP1A2, CYP2B9, AhR, ARNT, CYP17, 3β-HSD, 17β-HSD1, 17β-HSD2, deoxymiroestrol, estradiol, primary mouse hepatocytes, anti-lipid peroxidation

----------------------------
as noted earlier:

The CYP17 MspA1 Polymorphism and the Gender Dysphoria.

Abstract
INTRODUCTION:
The A2 allele of the CYP17 MspA1 polymorphism has been linked to higher levels of serum testosterone, progesterone, and estradiol.
AIM:

To determine whether the CYP17 MspA1 polymorphism is associated with transsexualism.

METHODS:
We analyzed 151 male-to-female (MtF), 142 female-to-male (FtM), 167 control male, and 168 control female individuals. Fragments that included the mutation were amplified by PCR and digested with MspA1. Our data were compared with the allele/genotype frequencies provided by the 1000 Genomes Data Base, and contrasted with a MEDLINE search of the CYP17 MspA1 polymorphism in the literature.

MAIN OUTCOME MEASURES:
We investigated the association between transsexualism and the CYP17 MspA1 polymorphism.

RESULTS:
A2 frequency was higher in the FtM (0.45) than the female control (0.38) and male control (0.39) groups, or the MtF group (0.36). This FtM > MtF pattern reached statistical significance (P = 0.041), although allele frequencies were not gender specific in the general population (P = 0.887). This observation concurred with the 1000 Genomes Data Base and the MEDLINE search.

CONCLUSION:
Our data confirm a sex-dependent allele distribution of the CYP17 MspA1 polymorphism in the transsexual population, FtM > MtF, suggestive of a hypothetical A2 involvement in transsexualism since the allele frequencies in the general population seem to be clearly related to geographic origin and ethnic background, but not sex.
© 2015 International Society for Sexual Medicine.

KEGG ORTHOLOGY: K00512
http://www.kegg.jp/dbget-bin/www_bget?K0...9.9+R02211

[Dianna1395]

I have to agree with FlameSabers.
Best method is to control your testosterone.

I'd suggest you poke around. Vitex, chaste berry (same thing); spearmint tea; reishi mushroom. Probably others I forgot.

You'll want to see a doctor to get baseline hormones, too. Full hormone panel, meaning free testosterone, SHBG, Testosterone and DiHydroTestosterone, and (the other T type whose name I forget), plus prolactin, estrone, estradiol, and.. E3, whose name I ALSO forget. X) (EDIT: ESTRIOL!)

Questions to consider: What is the reason for this? (E.G., frigid wife demands you control your impulses is not impossible, so confirm to yourself why you're doing this.)
If you feel you want sensitivity in your nipples, maybe massage and remapping your erotic zones would work?
But you need to explore the why first, because there are problems with reducing hormones the wrong way, or too much, and for too long. Osteoporosis. Liver problems. Mental Issues like dementia. Impotence and sterility, loss of strength, changes in thinking.

So be careful and start slow. Make sure it's the right decision. And feel the wife out, as she needs to have a say in this - it affects her as well. And be prepared to get breasts whether you want them or not. You might want to factor that in - are you feminine, can you pass? Are you ok with having breasts as a man?

Sometimes we get bad reactions....

-Dianna

[going no where]

thanks for all of the replies. I really appreciate everyone taking the time. You seem like a great bunch. This gives me alot to think about. I think the key is just going slow and seeing how my body reacts. It might do nothing. If it does do something then I think I might be inclined to stop and re-evaluate things.
I have looked into just reducing my T with other herbs that wont cause any feminising effects though that just seems boring I guess. I'm not sure why.
I guess if I'm being honest with my self the feminising effects or the potential of it are tantalizing and sexy. Though that obviously comes with greater risk. Is the juice worth the squeeze though? I've read so many talk about how much they like it, though their intents may be different then mine. I'm sure that plays a role. I will have to look deeper into this and evaluate what my desires really are. Though thats difficult not knowing how the benefits could feel like. I might like them, I might hate them.

[shaneny]

I would say take one a day for two weeks and see if you like how it feels taking it, how your body is reacting, not just from a change stand point, but how you feel, mentally and physically.

I enjoy my breaks, but it also makes me want it more.

[going no where]

I enjoy my breaks, but it also makes me want it more.

See this is one of the things that concerns me. Ive read this from numerous people on the forums. Thanks for being honest. At least I know some people like how it makes them feel and want that feeling. How many times have you taken a break? Do you find it harder to take that break?

@lotus, thanks for all of that info but im not a science guy so it was a little hard to understand. But if i'm understanding it correctly your saying some of us have the chemistry in our brains pushing us towards the feminine side already and that introducing hormones can encourage it even more?
If that is the case then yes I should be extremely careful ha ha.
I've had feminine desires off and on for about 5 years now. They come and go. I usually get really into it for a while and then purge everything. Then the desires will creep back into my life. Alot of you seem concerned about my wife and her stake in this. I agree she obviously has some say. We have had some very difficult heart to hearts in the past over some issues and they went fine. I'm sure talking with her on this one wouldnt be anymore difficult. Our last discussion was about pegging. She was pretty against it. Mostly because she sees it as dirty. She said we might be able to try it sometime but that hasnt happened. Anal play for me is much much more enjoyable then penile for me hence no worries on loss in that area. And me and the wife rarely have PIV sex. Overall our marriage is great.
I'm not sure if I mentioned this before but this was kinda her idea in a sense. She said I pester her too much for sex(which in reality is about once a month). So one night she was reading online and came across an article by a women who said her husband had too high of a libido and how she had him take chasteberry to lower it. It was a win win for them. So I researched the idea and ended up looking into PM.

[Dianna1395]

Hi, wmpwiwlw,
Sounds like Chasteberry / Vitex is a good place to start. you might also want to consider pharma, dutasteride or finasteride, if you have any family history of male pattern baldness. (I like the idea of herbs better, but the cost is prohibitive sometimes, and for what you're talking about, it now sounds like Pharma might be cheaper in the long run. You'll need to check, see if insurance would cover, etc.)

PM will work to revitalize you in a feminine sense, and you'll want to be sure of what you want in the long term. You might end up turning into a girl, essentially; will your wife be happy or upset with that? Or, maybe you'll want to become a Poly arrangement of some sort?

Though I would politely point out, once a month isn't exactly that often. If she just doesn't like sex, maybe... there's breach of contract. Don't want to explain the whole thing, but there's a contract in marriage, and sex is part of the deal. Something else to keep in mind, there might be a better arrangement to consider, too. Depends on what you want, and what the costs are, same as PM or Pharma. Can't advise you on that part...

-Dianna

[paul]

It's not for everyone, but for perky and sensitive nipples you may want to consider nipple piercings. They do work, but again, not for everyone.

Paul

[going no where]

Hi Diana,
I talked with the wife about taking PM and told her what it does and the possible side affects. I may have not been completely truthful with her but I did say feminine traits maybe possible along with some breast growth which in reality is possilbe just lower T with other herbs. Obviously she didnt think breasts on a man was a good idea but she said lowering my libido may be a good try. I also explained changes are slow and that stopping would most likely halt any progress. So she seemed ok with giving it a go. Would she be ok with me turning into a women? No I dont think so and thats not my goal. AS for sex, we've talked about this many times over the years. there is really no easy answer. She only wants sex when she feels like it. She has a demanding job and we have 3 kids. Its alot of work for everyone and can be exhausting especially during football season, two of my kids play. Things havent gotten bad enough yet to look to other relationship styles.

Hi paul, I have thought about nipple peircings but heard they are really painful. I have given myself a prince albert peircing and love it but it didnt give me any more sensitivity. I dont even wear the jewelry anymore though I still have the hole. I dont regret it though.

[going no where]

I took the sage test today. Not sure how accurate these are but here is the results. any thoughts?

S.A.G.E. Test Results
Your Raw Score is: 350, which indicates that overall you are Androgynous

Your appearance is Masculine

Your brain processes are mostly that of a Androgynous person.

You appear to socialize in a feminine manner.

You believe you have mild conflicts about your gender identity.

You indicated your were born Male.

ANALYSIS:
Male to Female possible Transsexual
NOTES:

Your answers indicate you have altered your physical appearance to look like the opposite sex.
Your answers indicate you may be AUTOGYNEPHILIC. Your answers indicate you may fit the following type(s):
Physiologic: arousal from the idea of having opposite sex physiology. This does not necessarily mean you WANT the physiology of the opposite sex, you just find the IDEA of it exciting.

[Dianna1395]

Hi, wmpwiwlw,
General consensus seems to be, tests like SAGE and COGIATI are mostly nonsense.
OTOH, they seem to align pretty closely with the people I've chatted with over the years. Confirmation bias, maybe?

There was a "guess your gender" test on Spark eons ago, it didn't ask anything that would specifically match a man's or woman's stereotype. It asked about favorites, which word was more disgusting, which death seemed worse, lots of other outlandish things, but then made a determination based on your answers. Statistically, it seemed to be right about 80% of the time, because given "answer A" and "Answer B", men chose one, women the other, statistically.
Wish I could find it, since I've had to "man up" so much for so long, it would be interesting to see if it's changed for me.

BTW, I learned to game the SAGE and COGIATI, and the quiz at the Albany Gender Clinic site, too...