[it_ll_be_fine]

Lotus, I've been away for quiet awhile and to find out that you have CML is just devastating. 

Considering you are in the accelerated phase, and considering it went undiagnosed for so long, has your doctor broached the topic of a bone marrow transplant?

It has shown to be successful in other patients and it I think has a better success rate than TKI's alone. 

I'd have to believe that the short term expense for your insurance, considering it could send you into remission, would be a no brainer. 

Thinking of you!

[Lotus]

Lotus, I've been away for quiet awhile and to find out that you have CML is just devastating. 

Considering you are in the accelerated phase, and considering it went undiagnosed for so long, has your doctor broached the topic of a bone marrow transplant?

It has shown to be successful in other patients and it I think has a better success rate than TKI's alone. 

I'd have to believe that the short term expense for your insurance, considering it could send you into remission, would be a no brainer. 

Thinking of you!

Hi, it_ll_be_fine, thanks for your question, advice and concern.  (Welcome back). 

I don't think we're at that point of doing a BMT (bone marrow transplant) just yet... I could be wrong, lol. I'll be going through some new rounds of testing in April, such as a BCR-ABL scan and looking close at my blast cells. My one and only BCR-ABL came back at 82% (meaning of the blood cells tested 88% were cancerous). Currently, I'm on a TKI (tyrosine kinase inhibitor) for my CML (chronic myeloid leukemia) that's lowered my WBC (white blood cell) levels to what's considered at the top end of normal reference range. So, the medication is doing its job… but, I still get to enjoy all the crappy parts of having CML side effects I'm a fighter though, and that's what I'm doing (@ fighting). 

Thank you for your thoughts on BMT, if I get there I'll let everyone know.   

[Lotus]

Edit (4/2/24) Hi BN, updating the plan to reflect new additions. 

Continuing the research, there's a strategy in using vitamin D3 and calcium (and actual relatable science) together in the Lotus NBE program, along with MSM that's been thought out very carefully that I'll share asap. But this first, vitamin D3 actually increases IGF-1, so as we worry about not getting enough IGF-1 for breast growth you've been getting if you've followed my plan…or taking 5,000iu to 7,000iu of vitamin D3 per day. Which is perfectly safe limits to take within these amounts, period. 

Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency
Pietro Ameri et al. Eur J Endocrinol. 2013
Abstract

Objectives: Previous studies suggested that vitamin D modulates circulating IGF1. We investigated this effect in adults and its clinical relevance in the management of GH deficiency (GHD).

Design and methods: IGF1 levels were prospectively measured before and after 12 weeks of treatment with oral vitamin D3 (5000 or 7000 IU/week) vs no intervention in 39 subjects 61.9±7.9 years old. The frequency of IGF1 values ≥50th age- and sex-specific percentile in relation to vitamin D status, as determined by the concentration of 25-hydroxyvitamin D (25(OH)D), was retrospectively assessed in 69 GHD patients (57.4±16.6 years) on stable hormone replacement and with 25(OH)D and IGF1 concurrently measured.

Results: Treatment with 5000 and 7000 IU vitamin D3/week significantly raised 25(OH)D by 12.7±8.4 and 13.1±6.5 ng/ml respectively (both P<0.001 vs baseline). In the 7000 IU group, IGF1 levels also significantly increased by 31.3±36.7 ng/ml (P=0.01). Neither 25(OH)D nor IGF1 significantly varied in controls. IGF1 was ≥50th percentile more frequently in GHD patients with 25(OH)D levels ≥15 than <15 ng/ml(65.9 vs 40.0%, P<0.05). Logistic regression with adjustment for recombinant human GH (rhGH) dose, vitamin D supplements, gender, use of thyroid hormones, corticosteroids or estrogen/testosterone, and season revealed a significant positive association between ≥15 ng/ml 25(OH)D and IGF 1 ≥50th percentile (OR 4.4, 95% CI 1.0-18.8, P<0.05). A significant negative correlation between 25(OH)D concentrations and rhGH dose was found after correcting for age and IGF1 (β -0.042, P<0.01), but not after further adjusting for sex, thyroid, adrenal or gonadal replacement, and season (β -0.037, P=0.06).

Conclusions: Vitamin D increases circulating IGF1 in adults. As a result, a better vitamin D status may ease the achievement of normal IGF1 values in GHD.

Vitamin D regulates IGF1 concentrations in the liver, the main source of circulating IGF1

Pueraria mirifica @ 500-1500pm (daily) estrogenic, acts more like E1 (estrone) that initiates breast buds).
Progesterone cream- 1/4 teaspoon per breast (3-4 times per week, and only use after you've developed breast buds). If using prescription progesterone pills the dosage ranges between 100mg to 300mg. If I'm using progesterone as a topical application I'd only recommend 1 progesterone taken either orally or rectally. 
MSM 1-3g per day. antioxidant, taking msm facilitates a pro-breast growth pathway called STAT5, it's a protein synthesizer, Meaning it helps raise growth hormone.
Vitamin D3 & Calcium, helps with breast growing. If you take Calcium you need V-D3 to become more biologically active. Source vitamin D3 with organic olive oil. 
Melatonin (dosage varies per person), taking this is going after REM and Deep sleep stages (@ body healing), and other things. 
Reishi extract- 2X per day (anti-androgen) follow manufacturers dosing guidelines though, the higher the polysaccharides the stronger anti-androgen. Like this one below, it's organic and 35% polysaccharides. 
Green Tea Extract - 2x per day @ 45% to 90% EGCG 100mg to 200mg capsules each taken 2x per day, ideally taken with Reishi. I prefer decaffeinated GTE (I drink coffee so I don't need the extra caffeine). I attached a picture as an example, though this product is expensive. I look for minimal additives when sourcing suppliments, like no silica, silicone dioxide (which basically is the same as silica) maltodrexin, which stimulates insulin.

Technically, MSM stimulates the stat5 pathway which facilitates phosphorylation and the nuclear translocation and DNA binding...in other words it helps with breast growth. MSM also stimulates prolactin and enhances GH (growth hormone)lol. 

Additionally, there's no reason to take a break (e.g. 5/2 or 6/1) because DHT doesn't take a day off. Nor is there ANY reason to follow the cis-female menstrual cycle because cis-males don't have ovaries. Following the menstrual cycle is essentially running something like PM or estradiol for the 14 days followed by running PC (progesterone cream) for the remaining cycle stopping PC before the females next period (menstruation), it's pointless and not in the best interest of growing breasts on this forum. I used to promote doing the 5/2 cycle years ago to give receptors a chance to reset, I no longer support that theory. 

[attachment=21661]

I'll be adding my topical program and other supplements asap. 

[Lotus]

Reposting this post from 2021, I hope it explains a few things for folks.

Hi BN,

My apologies for the late response. A couple weeks ago I thought I contracted Covid19, I had quite few of the symptoms. Test results came back negative (thankfully), however my symptoms still persisted. Symptoms of the flu, brain fog, sleeping for long periods and fatigue lingered for 2 weeks. I thought what if the covid test was a false negative. I mean what else could it be right?...nonetheless it's been dreadful. 

Anyways lol, fighting zero motivation is a real buzz kill for me, though I'm starting to get back on track. 

Lol, little did I know the above statement was when my Leukemia (CML) showed up, sigh... It went undiagnosed till June of 2023.

Oh, one last thing, something I wanted to illustrate but haven't gotten to it yet, it's easy to explain and it goes like this:

Picture an androgen molecule traveling through our circulation (blood supply, or other routes) trying to locate an androgen receptor, when it does it'll cross over the cell membrane into what's known as the cytoplasm...now if the androgen molecule doesn't see a 5 alpha reductase inhibitor it'll naturally want to synthesize to DHT before it makes its way into the nucleus, and once inside the mitochondria the deed is done, DHT won. 

So I'm attaching an earlier post about changing the androgen ratio inside our bodies, and why is this important?, well I'll tell ya...until you change the path of androgens inside the androgen receptor (as noted above) you won't see much breast growth. 

So what's the magic ratio?, in normal males the ratio is roughly 85% T to 15% E. If you're a numbers person (like me) you'll see how it makes sense using an anti androgen that inhibits DHT by 90%, imho this number reverses that male T ratio to one of which is favorable for breast growth. 

That's all for now I guess. Thank you to all for your prayers and concern, I deeply regret not responding in a timely manner. Seriously though, I had zero drive to do anything but sleep, maybe it was just the flu, I dunno, I'm just happy to be on the mend. ❤

Greetings,

I posted this study in 2015 to show the importance of having progesterone in your program. The takeaway here is that without progesterone while taking estradiol and anti-androgen breasts don't mature. Meaning the alveoli, breast ducts and breast buds don't develop to tanner stage 5 potential.

In another study an assay of human male hormone receptors in breast tissue found the following (and this in regards to each being equal to 100%, not the total of the three being @ 100%, follow?).

Breasts
Estrogen receptors @ 94%
Progesterone receptors @ 93%
Androgen receptors @ 57%

So, in human male testes we have the following productions:

Testes
Testosterone @ 85%
Estradiol @ 15%

Anti-androgens inhibit T/DHT between 30-90%. When T is lowered to 50ng/dL and below its considered chemical castration... but, you still can have function. Though results may vary, using T cream or viagra may help. 

So this is how my thinking goes:

Use progesterone cream to reduce T/DHT in breast tissue.

And in the testes reduce that testosterone of 85% to 5 to 10% using an effective anti-androgen that inhibits @ 80%.

Simple, right?. I believe one could tweak these numbers to how they wish to proceed. Meaning some don't want breast development while others do. We just massage these numbers to create a small imbalance favoring feminization but no breast development, I would do that by just using progesterone cream on the breast...no PM (or estradiol) and an anti-androgen titrated to 45-50% or flip the script geared towards breast growth, and titrate even more for the full feminization.

[SweetO]

Lotus! How are you? So cool to see you around!!

[SweetO]

"until you change the path of androgens inside the androgen receptor (as noted above) you won't see much breast growth. "

Wow. This makes A LOT of sense. 

If progesterone helps with DHT reduction, and let's say, you only have PC...would it make sense to use an anti-androgen along with P? Unfortunately in Europe progesterone gel and estrogen are heavily controlled, no chances of getting it unless for pregnancy/vitro for cis-females    still figuring out what I can do. The only thing is Progesterone Cream and as you have stated before, it is because it has lower absorption rate hahaha.


In short, progesterone is needed to magic happen, right? E and an anti-androgen alone wouldn't work out.  Maybe this is why I feel during follicular phase but not real growth   

PS: I am improving my vitamin D levels finally, L    Went from 13 to 42 in six months! Hopefully I'll improve faster now we are getting sunshine everyday in Barcelona

[Lotus]

Hi Sweets, 

Congrats on raising your Vit-levels. I've been researching Progesterone for years, the one thing I discovered was how taking progesterone lowers allopregnanolone which causes depression. I told myself I wasn't going to make this post into a TLR, well… It didn't work because there's so many side notes to explain. Tomorrow I'll add the Allopregnanolone supplement I've been taking. 

Finasteride inhibits allopregnanolone, which through its pathway causes depression by lowering allopregnanolone. Allopregnanolone is a modulator of GABA-A. 

Progesterone is a neurosteroid, meaning it crosses the blood/brain barrier and originates via cholesterol. The CNS (central nervous system)... progesterone is produced (synthesized) in the CNS and can cause many disorders (e.g. depression from pms, agitation, anxiety, etc) if allopregnanolone gets reduced by 5α-reductase. This happens in both sexes, but progesterone is produced elsewhere (like adrenals, ovaries, testes etc) Allopregnanolone doesn't appear to affect the breasts, I'm still trying to fact-check that though. 

I've been taking Allopregnanolone to ease the side-effects of taking progesterone rather than taking GABA (which is poorly metabolized in humans).

 

GABA decreases with age (Al-Sarraf, 2002). Perhaps more importantly, GABA’s half-life is about 17 min in mice (Kakee et al., 2001). If the half-life has a similar short duration in humans, direct administration of GABA is unsuitable as pharmacological treatment of epilepsy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594160/

pregnenolone, progesterone, and their reduced metabolites are the most important steroids that can be formed de novo from cholesterol within the brain.
https://www.sciencedirect.com/science/ar...via%3Dihub

The Allopregnanolone to Progesterone Ratio Across the Menstrual Cycle and in Menopause
This preliminary study is the first to characterize the allopregnanolone to progesterone ratio, as a proxy for metabolism of progesterone to allopregnanolone, across the menstrual cycle and in non-depressed post-menopausal women using serum GC/MS measurements for both allopregnanolone and progesterone. As we hypothesized and now show, the ratio of allopregnanolone to progesterone decreases across the menstrual cycle; our data show that this decrease is 8-fold from the follicular to the luteal phase despite the increase in both progesterone and allopregnanolone across the cycle. Pineles et al. recently demonstrated by GC/MS that the ratio of ALLO (which includes allopregnanolone and its stereoisomer pregnanolone) to 5α-DHP – the immediate allopregnanolone precursor – increases from the follicular to the luteal phase (Pineles et al., 2018), which may be due to increased gene expression of 3α-HSD by estradiol (Mitev et al., 2003; Pineles et al., 2018). Despite these findings suggesting increased activity of 3α-HSD during the luteal phase, we show that levels of allopregnanolone do not increase proportionally to progesterone levels. We hypothesize that 5α-reductase may be saturated in the luteal phase from high progesterone levels, as it has been shown that 5α-reduction is the rate-limiting step in conversion of progesterone to allopregnanolone (Cai et al., 2018; Do Rego et al., 2009). Alternatively, it is possible that more progesterone is metabolized to pregnanolone through increased activity of 5α-reductase or 3α-HSD. Preclinical studies suggest that modulation of GABAA transmission by allopregnanolone plays a role in the pathogenesis of mood disorders. There are as yet few clinical data supporting a link between allopregnanolone and mood disorders, although, of note, a recently published placebo-controlled trial of an oral positive allosteric modulator of GABAA receptors (SAGE-217) demonstrated efficacy in major depressive disorder when administered for 14 days (Gunduz-Bruce et al., 2019). Our finding that the allopregnanolone/progesterone ratio decreases in the luteal phase suggests that relative allopregnanolone deficiency may be implicated in premenstrual syndrome or luteal phase mood disorders, although the cause of PMDD is likely multifactorial with hormonal, genetic, and psychiatric contributors. More studies investigating the role of allopregnanolone in the pathogenesis of mood disorders are needed.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935417/

Endocrinology of the Male Reproductive System and Spermatogenesis Https://www.ncbi.nlm.nih.gov/books/NBK279031/

I've put together some research on the effects of PM, sorry, it's complicated.

As estradiol did, induced expression of CYP2B9 mRNA whereas those of CYP1A2 were suppressed.

CY2B9 mRNA induced testosterone in women

CYP1A2 -aromatase (suppresses) 

HSD-17B2 suppressed (E2 and T pathway)

17β-HSD1 suppressed (E2 pathway)

3β-HSD suppressed (which catalyzes all steroids)

CYP17 (Human 17,20-lyase) activity is stimulated 10-fold by CYPB5 

CYP19 mRNA (aromatase) slightly decreased by 

____________________________

Posted research: 

The backdoor pathway proceeds from 17 OH-Prog to 17 OH-Prog, 17 OH-DHP, 17 OH-Allo, androsterone, androstanediol, and then to DHT, all in the testes.


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:

The pathways of androgen biosynthesis. The classic pathway and the alternative “backdoor pathway” are shown. The classic pathway proceeds from 17OH-Preg to DHEA, to androstenedione or androstenediol to testosterone in the testis, and thence to DHT in genital skin. The backdoor pathway proceeds from 17OH-Preg to 17OH-Prog, 17OH-DHP, 17OH-Allo, androsterone, androstanediol, and thence to DHT, all in the testis. The enzymes and cofactors shown in the classic pathway are: P450scc (cholesterol side-chain cleavage enzyme), StAR (steroidogenic acute regulatory protein), P450c17 (17α-hydroxylase/17,20-lyase), 3β-HSD (3β-hydroxysteroid dehydrogenase, type 2), cytochrome b5, 17β-HSD3 (17β-hydroxysteroid dehydrogenase, type 3), and 5αR2 (5α-reductase, type 2). The alternative pathway is characterized by the presence of three additional enzymes: 5αR1 (5α-reductase, type 1), reductive 3α-HSD (AKR1C2/4), and oxidative 3α-HSD (17β-HSD6, also known as RoDH and/or AKR1C4). Steroid names include: 17OH-Preg, 17-hydroxypregnenolone; 17OH-Prog, 17-hydroxyprogesterone; 17OH-DHP, 17-hydroxydihydroprogesterone (5α-pregnan-17α-ol-3,20-dione); 17OH-Allo, 17-hydroxy-allopregnanolone (5α-pregnan-3α,17α-diol-20-one); androstenediol, androsta-5-ene-3β,17β-diol; and androstanediol, 5α-androstane-3α,17β-diol.


Cytochrome P450 17A1 (zona reticularis) of the adrenal cortex suppressed steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.


Cytochrome P450 17A1, or steroid 17-alpha-monooxygenase, or 17α-hydroxylase/17,20 lyase/17,20 desmolase is an enzyme that in humans is encoded by the CYP17A1 gene. It is found in the zona reticularis of the adrenal cortex. This gene encodes a member of the cytochrome P450 Superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.

More specifically, CYP17A1 acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity), or acts upon 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side-chain off the steroid nucleus (the lyase activity).

[IanW55]

Hi Lotus, Can you please time out to look at these for me, I got these off Amazon, are they any good or should i put them in the bin.
Thanks
xx

[Lotus]

Hi Ian, the RR you listed should work… unless you have an allergic reaction to the microcrystalline cellulose & rice extract, which the latter is a form of maltodextrin. I listed some information on maltodextrin, which I don't use, but that's me. Like I said, it should work (& be safe).   

Maltodextrin is a white powder made from corn, rice, potato starch, or wheat.

Maltodextrins are closely related to corn syrup solids — the one difference is their sugar content.

Both undergo hydrolysis, a chemical process involving the addition of water to further assist breakdown. However, after hydrolysis, corn syrup solids are at least 20% sugar, while maltodextrin is less than 20% sugar.

Maltodextrins are closely related to corn syrup solids — the one difference is their sugar content.

Both undergo hydrolysis, a chemical process involving the addition of water to further assist breakdown. However, after hydrolysis, corn syrup solids are at least 20% sugar, while maltodextrin is less than 20% sugar.
https://www.healthline.com/health/food-n...bad-for-me

Maltodextrin can cause a spike in your blood sugar.

[Manue]

I've been taking Allopregnanolone to ease the side-effects of taking progesterone rather than taking GABA (which is poorly metabolized in humans).

Hello Lotus,

I read with interest your approach to managing progesterone side-effects with Allopregnanolone instead of GABA, considering the latter's poor metabolism in humans. Have you considered the potential benefits of adjusting your diet, specifically increasing protein and saturated fats to elevate LDL levels while keeping triglycerides (TGs) low? This dietary strategy might offer the mental clarity and productivity boost you're seeking, akin to the effects of Allopregnanolone but through nutritional means. From my experience, maintaining strict adherence to this regimen has notably enhanced my mental performance. It might be worth exploring as an alternative approach to managing your side-effects.