Hi Alexis, 

Pheraps now you will have more time to chill, recover and focus on your researches!
By the way, i wanted to thank you for the research you shared here, it is pretty interesting to see how trans people end up with the same mammary glands as cis-girls if they take progestative antiandrogens!

 
You're welcome, I'll definetly have more time next week for sure, I'm having back surgery (to make repairs) early next week. So if I make posts that are gibberish you'll know it's the pain meds talking.  

There's a difference between USP progesterone and wild yam progesterone. USP progesterone is bioidentical (as in made by humans) as opposed to wild yam made in a lab. WY isn't progestative, apologies. Though in the absence of using estradiol it helps with aveolargenesis (ductal growth).
___________________________________________

Here's some research I put together based on science literature. Progesterone suppresses activation and crosstalk between PR (progesterone receptor) and prolactin/Stat5 signaling to inhibit milk protein gene expression. These changes are reflected in reduced activation of JAK2 and PAK1, resulting in downregulation of pSTAT5.

However, MSM stimulates the activation of the Jak2/STAT5 signaling pathway to help secrete milk protein. MSM also stimulates  GH (growth hormone) induced activation of Jak2/STAT5b and prolactin production.

Why is this important?, progesterone downregulates the Jak2/STAT5 pathway that inhibits milk proteins and affect terminal end buds (TEB's which are the branch like structures that fill out breasts) growth and alveologenesis. Taking MSM helps to restore what progesterone destroys during its protein metabolism. We also learned progesterone is catabolic to protein expression in breast tissue. Now we can address this catabolism (breakdown of proteins) by adding amino acids to the mix...possibly tyrosine and proline to strengthen the protein loss. Or possibly consuming more protein in our diet. 
______________________________________________
Regulation of the JAK2-STAT5 Pathway by Signaling Molecules in the Mammary Gland
https://pubmed.ncbi.nlm.nih.gov/33282878/
Scribble promotes alveologenesis in the pregnant mammary gland for milk productionScribble promotes alveologenesis in the pregnant mammary gland for milk production
https://pubmed.ncbi.nlm.nih.gov/32213656/
Prolactin regulates ZNT2 expression through the JAK2/STAT5 signaling pathway in mammary cells
https://pubmed.ncbi.nlm.nih.gov/19494234/
Jak2 Is an Essential Tyrosine Kinase Involved in Pregnancy-Mediated Development of Mammary Secretory Epithelium
https://academic.oup.com/mend/article/16/3/563/2741654?login=false

Hi Alexis, 

You're welcome, I'll definetly have more time next week for sure, I'm having back surgery (to make repairs) early next week. So if I make posts that are gibberish you'll know it's the pain meds talking.  

There's a difference between USP progesterone and wild yam progesterone. USP progesterone is bioidentical (as in made by humans) as opposed to wild yam made in a lab. WY isn't progestative, apologies. Though in the absence of using estradiol it helps with aveolargenesis (ductal growth).
___________________________________________

Here's some research I put together based on science literature. Progesterone suppresses activation and crosstalk between PR (progesterone receptor) and prolactin/Stat5 signaling to inhibit milk protein gene expression. These changes are reflected in reduced activation of JAK2 and PAK1, resulting in downregulation of pSTAT5.

However, MSM stimulates the activation of the Jak2/STAT5 signaling pathway to help secrete milk protein. MSM also stimulates  GH (growth hormone) induced activation of Jak2/STAT5b and prolactin production.

Why is this important?, progesterone downregulates the Jak2/STAT5 pathway that inhibits milk proteins and affect terminal end buds (TEB's which are the branch like structures that fill out breasts) growth and alveologenesis. Taking MSM helps to restore what progesterone destroys during its protein metabolism. We also learned progesterone is catabolic to protein expression in breast tissue. Now we can address this catabolism (breakdown of proteins) by adding amino acids to the mix...possibly tyrosine and proline to strengthen the protein loss. Or possibly consuming more protein in our diet. 
______________________________________________
Regulation of the JAK2-STAT5 Pathway by Signaling Molecules in the Mammary Gland
https://pubmed.ncbi.nlm.nih.gov/33282878/
Scribble promotes alveologenesis in the pregnant mammary gland for milk productionScribble promotes alveologenesis in the pregnant mammary gland for milk production
https://pubmed.ncbi.nlm.nih.gov/32213656/
Prolactin regulates ZNT2 expression through the JAK2/STAT5 signaling pathway in mammary cells
https://pubmed.ncbi.nlm.nih.gov/19494234/
Jak2 Is an Essential Tyrosine Kinase Involved in Pregnancy-Mediated Development of Mammary Secretory Epithelium
https://academic.oup.com/mend/article/16/3/563/2741654?login=false

Hello Lotus, thank you again for your precious research for all of us!
I wish you the best outcome from the surgery, especially for the recovery. I only once had surgery and it was devastating, i really hope the doctors will handle everything with care. <3
All clear about USP Progesterone and the Wild Yam one, thank you for the explanation. Unfortunately am still a little confused about the bottle am currently using, they use a tricky wording which makes it a little unclear, seems like USP bioidentical but they then put a paranthesis with wild yam in it. I directly share the picture of the ingredients on this post, i appreciate a lot to know what you think about this labelling.

This new update you wrote and shared here is surprisingly eye-opening. I did try MSM in the past for just a few days, i didn't like the taste and for a lack of privacy i got it thrown away. I thought i wasn't missing anything special because those only 3 days i tried it, but if the job of MSM is to cooperate with Progesterone Cream, then it means i really should give it another try! Since i already take Progesterone Cream with my program, it could only benefit from this!

About tyrosine and proline i'll think about it, seems like there are some capsules supplements on Amazon, which i could take at some point. Do you think they could be some reliable sources? and are they a priority addition into the program?

As always, thank you so much for the help and insight you give to us all, Lotus always giving hope and help <3

Attached Files

---

Hello All,

Long time fellow traveler, recently returned after ~18 month layoff due to health issues. I have a new screen name from Lisa Jenn because I gave up trying to recover log in info ?

First, Lotus it is so great to see not only your progress and decisions in moving forward, but also the absolutely astounding depth of your research and interpretation for us non-science nerds! I hope you have a speedy recovery from both your back surgery and your encounter with Omicron. I have spent a great deal of the last 5 days reading and trying to absorb both your Anti-androgen thread and this magnum opus. It is so interesting and helpful to see the evolution in both. THANK YOU!

I wanted to add a publication I didn’t see in either thread on hops:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570471/

It has some interesting info.

I have started a program based on Lotus’ two above ref’d threads, and will continue until my stocks are depleted, but I am extremely interested in the use of the latest, using primarily the low dose estradiol and progesterone creams. Anyone that has a longer term experience using them, please share by post or PM. I’m especially interested in the higher dose estradiol cream.

Thanks to all of you who actively contribute! Your knowledge and experiences are helpful to all in the Nexum community.

Cheers,

Lisa

Lisa,

Your link above does not work. I have been using 8pn Hops for close to 2 years. It has worked very well for me.

-Kay

Lisa,

Your link above does not work. I have been using 8pn Hops for close to 2 years. It has worked very well for me.

-Kay

I tried 8PN and got some strange side effects. I react to very small doses. The link does work, you have to cut off the last character or maybe the last 2 characters. The article is very good. Thanks for finding it.

Lisa,

Your link above does not work. I have been using 8pn Hops for close to 2 years. It has worked very well for me.

-Kay

Hi Kay, try this!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570471/

Title of article: Flavonoids as Phytoestrogenic Components of Hops and Beer

I’m thinking of taking a low dose 8pn (10mg) along with a low dose PM (100mg)

Cheers!

Lisa

Thank you Lisa for the link! 8pn has many health benefits, especially it is anti-cancer. I take Swanson Estro 8pn. I take one in the morning and one at night. When I started out, I just took one in the morning for the first month.

Thanks Kay, that’s what I’ve ordered! I’m digesting this thread and the AntiAndrogen Thread Lotus wrote, and the progression over time for each is really interesting. The main thing I’m seeing is a theme of ‘less is more’ (supplements, not boobs! ?).

I relate that to distance running. Years ago the coaching philosophy was ‘more is better,’ which resulted in speed plateaus, burnout and injuries. Now the common philosophy is a slow progression, hard easy days, and rest periods. Runners still can do 100 mile weeks, just not at race pace every day! In both training and NBE changes are being made to the body that take time!

From everything I’ve read and experienced, a ‘less is more’ philosophy, along with regular breaks,  is key to healthy, long term NBE. We’ll see!

Cheers,

Lisa

Hello Lotus, thank you again for your precious research for all of us!
I wish you the best outcome from the surgery, especially for the recovery. I only once had surgery and it was devastating, i really hope the doctors will handle everything with care. <3

Hi Alexis, surgery was successful. Recovery (dealing with pain) is another thing lol, but that's expected when having major surgery.

[font=Arial]All clear about USP Progesterone and the Wild Yam one, thank you for the explanation. Unfortunately am still a little confused about the bottle am currently using, they use a tricky wording which makes it a little unclear, seems like USP bioidentical but they then put a paranthesis with wild yam in it. 

Forgive me Alexis but I don't see WY listed in the ingredients. 

[font=Arial]Since i already take Progesterone Cream with my program, it could only benefit from this!

Some Progesterone creams have MSM in the ingredients, the amount isn't listed as being a proprietary blend. To achieve the benefits of MSM the dosage needs to be 3grams (or = to 3,000mg). 

[font=Arial]About tyrosine and proline I'll think about it, it seems like there are some capsules supplements on Amazon, which i could take at some point. Do you think they could be some reliable sources? and are they a priority addition into the program?

Some protein or collagen powders have the amino acids needed for breast growth. But...some of these products are ridiculously overpriced and come with unwanted ingredients. 

[font=Arial]As always, thank you so much for the help and insight you give to us all, Lotus always giving hope and help <3

Aw thank Alexis, as always you're so sweet.

First, Lotus it is so great to see not only your progress and decisions in moving forward, but also the absolutely astounding depth of your research and interpretation for us non-science nerds! I hope you have a speedy recovery from both your back surgery and your encounter with Omicron. I have spent a great deal of the last 5 days reading and trying to absorb both your Anti-androgen thread and this magnum opus. It is so interesting and helpful to see the evolution in both. THANK YOU!

Wow, hi Lisa...so good to hear from you again. Thank you for the kind words. I hope you achieve the results you're looking for this time around. I find the creams useful as skin penetration (or absorption) avoids the first pass metabolism. Estradiol is a small molecule @272.4 and progesterone at 314.5 is well below the Dalton rule of 500.0 (info provided below). Thank you for the attached links.  Fwiw, the following is what I've posted on Hops, hope it helps.

PM and hops, hmm...sounds interesting. I can't see much conflict, but it could work. Reportedly, cell receptors number in the 100,000+ per cell, of that???, how much ERa to ERb would depend on the preferential binding of a supplement/med. though I would keep PM during the day while taking HOPS at night giving a boost towards growth hormone. 

 8-pin ( known as " Prenylnaringenin " ) is a flavonoid...a phytoestrogen in HOPS. In relation to PM, deoxymiroestrol (in PM) has been identified as stronger than HOPS in a few studies, (probably stronger at ER-a over ER-b), I believe we have posted a study or two about it though, still needs verifying. 

As mentioned, HOPs is 70x stronger in ER-b (beta) binding than estradiol....

Hi Marcy, 

From the studies I've seen, HOPS is 70 times more potent for ER-b (estrogen receptor beta) over estradiol and 20,000 times less potent at ER-a (estrogen receptor alpha) over estradiol. If I didn't mention already, HOPS upregulates progesterone receptor mRNA (signaling). Besides stimulating IGF-1 HOPs enhances thermogenesis in BAT (brown adipose tissue, aka " fat " ), which means counteracting increases body fat......I know right, I'm thinking beer means beer belly imo, didn't make sense, but here's the study. 
http://www.ncbi.nlm.nih.gov/m/pubmed/26098641/

FWIW I don't think HOPS will comprise HRT, for me I'd take it at night time for the IGF-1 stimulation and promotion of PR (progesterone receptor).  

Hop and red clover extracts, as well as 8-PN upregulated progesterone receptor (PR) mRNA in the Ishikawa cell line. In the MCF-7 cell line, PR mRNA was significantly upregulated by the extracts, biochanin A, genistein, 8-PN, and IX. The two extracts had EC50 values of 1.1 and 1.9 μg/mL, respectively, in the alkaline phosphatase induction assay. Based on these data, hops and red clover could be attractive for development as herbal dietary supplements to alleviate menopause-associated symptoms.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1815392/pdf/nihms14948.pdf

-HOPS (8-PIN) stimulates IGF-1...growth hormone stimulates IGF-1 (insulin growth factor). This action stimulates new growth.  Exercise & sleep, whey (denatured), cayenne pepper stimulates IGF-1 and circulation (inhibits androgens in the prostate). Vitamin D stimulates IGF-1

Mammary gland development requires both systemic hormones and local growth factor-mediated tissue interactions. Classical hormone ablation/replacement experiments, and more-recent genetic analyses in mice, have shown that post-pubertal gland development requires systemic hormones from ovary [estrogen (E) and progesterone (P)], pituitary [growth hormone (GH) and prolactin (PRL)] and adrenal gland (glucocorticoids) (Topper and Freeman, 1980). Loss of ovarian or pituitary function leads to failure of hormone-dependent ductal elongation after puberty, with E and GH participating primarily in ductal elongation and P and PRL participating primarily in alveolar development. Glucocorticoids enhance (but are not essential for) ductal elongation and are required for alveolar function in lactation.
http://dev.biologists.org/content/136/9/1423.full

_______________________________

The high doses of E(2) and 8-PN caused secretion in the mammary gland, whereas proliferation and progesterone receptor expression were stimulated by both E(2) doses and the high 8-PN dose. E(2) and 8-PN share many effects in the three studied organs, but some differences in the mechanism of action appear to exist.
https://www.researchgate.net/publication/6947557_Morphologic_changes_induced_by_oral_long-term_treatment_with_8-prenylnaringenin_in_the_uterus_vagina_and_mammary_gland_of_castrated_rats


Nanotechnology-based Drug Delivery Systems as Potential for Skin Application: A Review
https://pubmed.ncbi.nlm.nih.gov/32867631/

The 500 Dalton rule for the skin penetration of chemical compounds and drugs
Authors
* Jan D. Bos, Marcus M. H. M. Meinardi
* First published: June 2000Full publication history
* DOI: 10.1034/j.1600-0625.2000.009003165.xView/save citation
* Cited by: 370 articles

Jan D. Bos, Department of Dermatology A0-235, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
Tel.: +31 20 566 2587. Fax: +31 20 696 0076
e-mail: j.d.bos@amc.uva.nl
Abstract
Abstract: Human skin has unique properties of which functioning as a physicochemical barrier is one of the most apparent. The human integument is able to resist the penetration of many molecules. However, especially smaller molecules can surpass transcutaneously. They are able to go by the corneal layer, which is thought to form the main deterrent. We argue that the molecular weight (MW) of a compound must be under 500 Dalton to allow skin absorption. Larger molecules cannot pass the corneal layer. Arguments for this “500 Dalton rule” are; 1) virtually all common contact allergens are under 500 Dalton, larger molecules are not known as contact sensitizers. They cannot penetrate and thus cannot act as allergens in man; 2) the most commonly used pharmacological agents applied in topical dermatotherapy are all under 500 Dalton; 3) all known topical drugs used in transdermal drug-delivery systems are under 500 Dalton. In addition, clinical experience with topical agents such as cyclosporine, tacrolimus and ascomycins gives further arguments for the reality of the 500 Dalton rule. For pharmaceutical development purposes, it seems logical to restrict the development of new innovative compounds to a MW of under 500 Dalton, when topical dermatological therapy or percutaneous systemic therapy or vaccination is the objective.
http://onlinelibrary.wiley.com/doi/10.1034/j.1600-0625.2000.009003165.x/abstract

Molecular Weights: (g/mol)

Aloe Vera- 270.24

Palmitic- 270.46

Stearic - 298.52

Oleic - 282.46

Linoleic - 298.48

Almond oil - 106.12

Estradiol - 272.4

Soybean oil -292.2

http://biodiesel.org/docs/ffs-performace_usage/chemical-weight-formula.pdf?sfvrsn=4