[Stevenator_]

I'm still praying for you, Lotus <3

[Alexis P]

Happy to see you are doing better Lotus, i was worried about you not posting since more than a month.
The mention of MS or dementia quite scared me, if you feel better feel free to message me at any time.

[SweetO]

Lotus, never forget you have a fandom here LOL!  we love you so much   please update us whenever you can



PS: I made a little mistake not following your guidelines with DHEA. At first I only used it during follicular phase with Estrogen and olive oil. I had growing pains during the follicular phase but nothing else. It took me 1 month to realise you said DHEA along with PC   . So I use a bit with E during my follicular phase and then after ovulation, only 9 days with PC (to have my period). THE FEELING IS SO DIFFERENT, omg    !!! Also I feel like my boob meat is getting denser I don't know if that makes sense.

[Lotus]

Hi BN,

I've updated information covering cimetidine. 

Cimetidine is an H2 receptor inhibitor, meaning when histamine is inhibited in stomach acid (gastrin) estradiol (in plasma) will increase....and feminization is likely. When you inhibit let's say the enzyme "CYP3A4" you inhibit testosterone which then upregulates Estrogen. When CYP3A4's enzymes are induced (e.g. St.John's wort) its inhibiting E and likely promoting T.

Using H2 Blockers (H2-receptor antagonists) and to a lesser extent H1 receptors antagonists block stomach acid (aka. gastrin) increases plasma estradiol and prolactin. Drugs like cimetidine and ranitidine (others too) inhibit stomach acid, though ranitidine to a lesser extent nukes the cytochrome (CYP) P450 enzymes. Cimetidine is for a short time (I believe 2-4 weeks) to treat stomach acid. If you have normal stomach acid cimetidine and the like aren't necessary, as always consult a health professional. 

histamine (an allergic response, basically) is also produced in the CNS (central nervous system), but for this discussion we're limiting it to stomach acid. I've looked for alternatives and found a few that have a direct link to possibly increasing prolactin by way of reduced stomach acid:

Olives 
MSM 
Forskolin 

Coleus Forskohlii
Other Clinical Indications 
Research has shown forskolin stimulates thyroid hormone release and increases thyroid hormone production. 15,16 Forskolin has been shown to stimulate digestive secretions, including hydrochloric acid, pepsin, amylase, and pancreatic enzymes, 4,7 suggesting clinical benefits in digestive disorders and malabsorption. Animal research indicates forskolin exerts an antidepressant action via activation of cAMP. 33 In vitro research indicates forskolin has potent immune- stimulating properties. 34,35 
http://www.altmedrev.com/publications/11/1/47.pdf

Olives

In addition to their function as antioxidants, many of the phytonutrients found in olives have well-documented anti-inflammatory properties. Extracts from whole olives have been shown to function as antihistamines at a cellular level. By blocking special histamine receptors (called H1 receptors), unique components in whole olive extracts help to provide us with anti-inflammatory benefits. In addition to their antihistamine properties, whole olive extracts have also been shown to lower risk of unwanted inflammation by lowering levels of leukotriene B4 (LTB4), a very common pro-inflammatory messaging molecule. Oleuropein—one of the unique phytonutrients found in olives—has been shown to decrease the activity of inducible nitric oxide synthase (iNOS). iNOS is an enzyme whose overactivity has been associated with unwanted inflammation. Taken as a group, these research findings point to olives as a uniquely anti-inflammatory food.

Olives
http://www.whfoods.com/genpage.php?tname=foodspice&dbid=46

Histaminergic regulation of prolactin secretion.
Knigge UP1.
Author information

Department of Surgical Gastroenterology, Hvidovre Hospital.
Abstract
Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following systemic infusion of the amine. In Addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1-receptors, while following systemic administration this effect is mediated via H2-receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional PRL stimulatory action not related to blockade of H2-receptors. This non-specific action is not exerted by the chemically different H2-receptor antagonist ranitidine. Since HA has no effect directly at the pituitary level, the actions of the amine may occur at different sites within the hypothalamus by an effect on hypothalamic transmitters regulating PRL secretion. Dopaminergic as well as serotonergic neurons are involved in the mediation of the action of HA, since the dopamine (DA) concentration in the pituitary portal vessels is decreased by central or systemic infusion of HA, and since blockade of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta-endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation of the PRL response to HA. In men the effects of HA on PRL secretion are similar to the effects in male rats. Systemic infusion of HA stimulates PRL secretion via H1-receptors and inhibits PRL secretion via H2-receptors. The PRL-stimulatory effect of HA is caused by an inhibition of the dopaminergic system, while the PRL-inhibitory effect of HA may involve other transmitters than DA. In contrast to its stimulatory effect in men, HA had no effect on basal PRL secretion in women, but enhanced the PRL response to TRH. In rats or in humans the PRL stimulatory effect of HA is not caused by the cardiovascular actions of the amine.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of histamine and H1 and H2 receptors on prolactin and luteinizing hormone release in humans: sex differences and the role of stress.
Pontiroli AE, De Castro e Silva E, Mazzoleni F, Alberetto M, Baio G, Pellicciotta G, De Pasqua A, Stella L, Girardi AM, Pozza G.
Abstract
The present experiments were performed to investigate the possible role of histamine and its receptors, H1 and H2, in the control of PRL and LH release in normal adult humans of both sexes. Histamine infusion (200 microgram, iv, in 15 min) induced PRL and LH release in men; in women, histamine inhibited LH release without affecting PRL release. Two H1 antagonists, dexchlorpheniramine (10 mg, iv) and promethazine (50 mg, im), reduced PRL release in both sexes, stimulated LH release in men, and inhibited LH release in women. Cimetidine, an H2 antagonist (400 mg, iv), elicited PRL release in both sexes, more consistently in females than in males, and was without effect on LH release in either sex. These data suggest that in humans, the effect of histamine on PRL release is linked to H1 and H2 receptors, which respectively stimulate and inhibit PRL release independently of sex. The effect of histamine on LH release appears to depend on sex and to be mediated only by H1 receptors. To rule out the possibility that the effects of histamine are merely due to a nonspecific stress reaction, we have evaluated PRL and LH release in otherwise normal men and women undergoing surgery for gallstones. Surgery was accompanied by PRL release in both sexes, more evident in women, and by LH release only in men. These results indicate that the effect of histamine on PRL and LH release in humans is linked to sex and H1 and H2 receptors and is not due to stress; further studies are required to clarify the possible mechanism and site of action of histamine in modifying PRL and LH release in humans.

Prolactin-lowering releasing drugs. Mechanisms of action and therapeutic applications.
Müller EE, Locatelli V, Cella S, Peñalva A, Novelli A, Cocchi D.
Abstract
Drugs whose systemic and/or central administration induce suppression or stimulation of prolactin secretion are reviewed. The most commonly used prolactin-lowering drugs include: (a) direct-acting dopamine receptor agonists (e.g. dopamine, apomorphine and the ergot derivatives); (b) indirect-acting dopamine agonists (e.g. amphetamine, nomifensine, methylphenidate, amineptine); © drugs which impair serotonergic neurotransmission (e.g. the neurotoxin 5,7-dihydroxytryptamine and the serotonin receptor antagonists methysergide and metergoline); (d) gamma-aminobutyric acid [GABA]-mimetic drugs (e.g. GABA, muscimol, ethanolamine-O-sulphate, sodium valproate); (e) histamine H2-receptor agonists; and (f) cholinergic (muscarinic and nicotinic) receptor agonists. Major prolactin-stimulating agents comprise: (a) dopamine receptor antagonists (e.g. classic and atypical antipsychotic drugs); (b) drugs differently capable of impairing central nervous system dopamine function (e.g. blockers of dopamine neurotransmission such as alpha-methyl-p-tyrosine and 3-iodo-L-tyrosine, false precursors such as alpha-methyldopa, and inhibitors of L-aromatic amino acid decarboxylase such as carbidopa and benserazide); © drugs enhancing serotonergic neurotransmission (e.g. the serotoninergic precursors tryptophan and 5-hydroxytryptophan, direct-acting serotonin agonists such as quipazine and MK 212, and indirect-acting serotonin agonists such as fenfluramine); (d) blockers of serotonin reuptake (e.g. fluoxetine, fluvoxamine and clovoxamine); (e) H1-receptor agonists; and (f) H2-receptor antagonists (e.g. cimetidine). Some of the above classes of drugs (e.g. the indirect-acting dopamine agonists, dopamine receptor antagonists, GABA-mimetic drugs, dopamine receptor blocking drugs, and H2-antagonists) may be useful for selecting among hyperprolactinemic patients those with a prolactin-secreting tumor in an early stage of the disease. Direct-acting dopamine receptor agonists, notably the ergot derivatives; are potent anti-galactopoietic agents, can revert impaired gonadal function to normal in both female and male patients with hyperprolactinemia, and may have antiproliferative effects on pituitary prolactin-secreting tumors. All prolactin-stimulating agents, but especially the dopamine receptor antagonists, are liable to induce alterations in gonadal function in subjects of either sex. In addition to their usage for diagnostic or therapeutic purposes, the above drugs appear to be invaluable tools for enabling a better understanding of the neurotransmitter control of prolactin secretion.
http://www.ncbi.nlm.nih.gov/pubmed/6133737


Ann Intern Med. 1977 Oct;87(4):398-403.
Pathophysiology of spironolactone-induced gynecomastia.
Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH.
Abstract
Peripheral blood levels of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone and the metabolic clearance rates of testosterone and estradiol, as well as the peripheral conversion of testosterone into estradiol, were measured in 16 patients with hypertension. Six of these patients were treated with spironolactone and developed gynecomastia. The other 10 patients served as control subjects. The blood testosterone level in the spironolactone-treated group (2.7 +/- 0.5 ng/ml) was significantly less (P less than 0.02) than in the control group (4.4 +/- 0.4 ng/ml). On the other hand, blood estradiol levels in the spironolactone group (30 +/- 4 pg/ml) were significantly greater (P less than 0.01) than in the control group (13 +/- 2 pg/ml). These changes were primarily due to significant increases in the metabolic clearance rate of testosterone (P less than 0.02) and in the rate of peripheral conversion of testosterone into estradiol (P less than 0.001) in the spironolactone-treated group. Thus, spironolactone does alter the peripheral metabolism of testosterone resulting in changes in the ratio of testosterone to estradiol, which could contribute to the production of gynecomastia.
PMID: 907238

Safety issues relating to long-term treatment with histamine H2-receptor antagonists.

Sabesin SM1.
Author information
Abstract
H2-receptor antagonist therapy is associated with a low incidence of adverse reactions. Adverse events reported in clinical trials of ranitidine in daily doses of up to 1200 mg include headache, tiredness and mild gastrointestinal disturbances, but the incidence is similar to or less than that for placebo. High doses of cimetidine (> 5 g/day) can cause reversible impotence or gynaecomastia. While ranitidine exhibits no clinically significant drug-drug interactions, cimetidine interacts with many drugs metabolized by cytochrome P450. In contrast to ranitidine and cimetidine, where safety data are available for up to 10 years of continuous therapy, experience with famotidine and nizatidine is limited. The safety of long-term H2-receptor antagonist therapy needs to be considered in relation to the potential consequences of prolonged acid suppression, including the risk of proliferation of gastric flora and the risk of developing enterochromaffin-like cell hyperplasia, which could in turn, theoretically, lead to gastric malignancy. Such problems have not been observed in patients during long-term therapy at low or full doses of H2-receptor antagonists. Standard doses of currently available H2-receptor antagonists permit acid secretion in response to food and other stimuli, and this daily acid tide prevents persistent bacterial colonization.

Comparative pharmacodynamics and pharmacokinetics of cimetidine and ranitidine.
Richards DA.
Abstract
Ranitidine and cimetidine are competitive antagonists of histamine at H2-receptor sites in the gastric mucosa. Both drugs reduce output of basal and stimulated gastric acid and pepsin secretion in normal healthy subjects and duodenal ulcer patients. Pharmacodynamic and pharmacokinetic differences exist between the drugs, some of which are of clinical significance. Ranitidine is a 6-8 times more potent inhibitor of gastric secretions and also causes a greater reduction in intragastric acidity of nocturnal secretions after usual therapeutic doses. Absorption from the gastrointestinal tract of both drugs is good, with peak plasma concentration occurring approximately 90 minutes after oral administration. Systemic bioavailability is approximately 70% with cimetidine and 50% with ranitidine. Both drugs demonstrate biexponential elimination curves from the plasma after intravenous administration and a bimodal curve after oral administration which is probably the result of enterohepatic recirculation. The elimination half-lives of cimetidine and ranitidine are 1.7-2.1 hours and 2.1-3.1 hours, respectively, with apparent volumes of distribution approximating 50L and 75L, respectively. Both drugs are eliminated, largely unchanged, via the kidneys. Major differences between these agents are found in cimetidine's biological activity at sites other than the gastric H2-receptors. These include: antiandrogenic effects with the appearance of feminizing characteristics in men, especially with large doses, like those used to treat Zollinger-Ellison syndrome; interference with the hepatic P-450 mixed-function oxidase enzyme system, which results in drug interactions with warfarin, phenytoin, theophylline and other drugs; and central nervous system effects characterized by confusion, particularly in elderly patients and those with renal failure. Such side effects have not been directly related to ranitidine treatment and substitution of ranitidine for cimetidine has reportedly provided effective alternative treatment in patients intolerant to cimetidine.

Cimetidine blocks testosterone synthesis
https://www.researchgate.net/publication..._synthesis

The Effects of Cimetidine on the Oxidative Metabolism of Estradiol
https://www.researchgate.net/publication..._Estradiol

More info to follow:

>More info to follow bringing all this into focus.

AWOO!

Ok so bringing this into focus. A few years ago I posted some information (shared below) regarding cimetidine and how it inhibits stomach gastrin and thereby increases estradiol. Cimetidine and H2 inhibitors aren't the only game in town that inhibits gastrin. Forskolin and aloe vera and some other agents inhibit gastrin. Explaining what somatostatin does is explained in the link below. Trust me when I say somatostatin is about as bad for breast growth as DHT. In closing, inhibiting somatostatin seems to up our game for promoting breast growth. One final note about forskolin, it improves thyroid function, so much so in my case it reversed my hashimoto's of 15 years.

Somatostatin
http://www.vivo.colostate.edu/hbooks/pat...tatin.html

Using H2 Blockers (H2-receptor antagonists) and to a lesser extent H1 receptors antagonists block stomach acid (aka. gastrin) increases plasma estradiol and prolactin. Drugs like cimetidine and ranitidine (others too) inhibit stomach acid, though ranitidine to a lesser extent nukes the cytochrome (CYP) P450 enzymes. Cimetidine is for a short time (I believe 2-4 weeks) to treat stomach acid. If you have normal stomach acid cimetidine and the like aren't necessary, as always consult a health professional.

https://www.breastnexum.com/showthread.php?tid=17436&pid=196127&highlight=cimetidine#pid196127
Post # 3990..

This study demonstrates that the administration of cimetidine to men decreases the 2-hydroxylation of estradiol and results in an increase in the serum estradiol concentration.

The Effects of Cimetidine on the Oxidative Metabolism of Estradiol
https://www.researchgate.net/publication..._Estradiol

[Stevenator_]

Lotus! It's so good to see you again! Thank you for posting clarity on the things that you do. There is so much valuable information contained within this thread!

Thank you again and I hope you're feeling much more better!

<3

[Jessi]

Thank you very much, Lotus, for the updated information on cimetidine- something I'm interested in since I have GERD; I've just been taking a low OTC dose in the evenings along with my omeprazole in the mornings, as I've found literature that says a PPI/H2 blocker combo taken like that does a really good job with keeping the acid under control.  The studies were of various other '-dines' but cimetidine is my choice for obvious reasons.  Not sure I understand most of what you posted, but I sure do appreciate it.  Seems as if I don't care about function down under (wouldn't be the end of the world) or take other meds that could interact (I don't) and don't get confused from being old, then I'm good with the stuff.

Read back along this thread- first off those photos were fabulous!  But more importantly you have my prayers, I hope they can do something to slow/stop the white matter business, and hoping for the leukemia to get wiped out.  My dad had some less common form of leukemia, and they managed to cure (not remission, cure, gone undetectable come back in couple years) it with some sort of gene therapy that was administered rather like chemo is administered via IV, with side effects darn near as nasty, but it knocked the stuff out.  The stuff is beatable.  Many good thoughts your way, and thank you for everything you do here!  Don't think anyone can be put out if you don't feel up to the forums at times, but it's clear you're fretted over and missed when you are absent.  Get well!

[HelloDiDi]

As there was recent talk about the topical protocol and how there's ton of misinformation being posted and people being still clueless no matter how many times the actually good information has been put out there, I just posted to my thread about how I'm doing it right now and I even separated the core ideas which have been put out by Lotus in this thread and explained many times over. I want to pull attention here, this thread is massive gargantuan job to dig through, but there's so much good information, just go and read and be patient and you'll find it all. Interpreting the science jargon can be quite exhausting. I have had to search for terms and words to understand a lot of it, but that effort hasn't been wasted, quite the opposite, I've learned so much things that I never dreamed to learn...

I have become more knowledgeable on hormone functions than many endocrinologists ever will. And that's thanks to Lotus with her resourcefulness and effort to put all this information out here and link to studies and explain everything. She's been one of the biggest enablers of my transition by sharing information. There's no way I could be at this situation doing almost everything DIY style on my own without BN forum and all the fantastic stuff information here. Its helped me to find the right people and dive into the endocrinology rabbit hole in the best possible way.

I want to voice my appreciation for Lotus for countless hours posting all this stuff, its priceless. 

[Eloise]

Lotus, amazing stuff!! One of the studies you quoted said: “antiandrogenic effects with the appearance of feminizing characteristics in men, especially with large doses.” So, naturally, what constitutes a ‘large dose’??  

Glad to see you posting.  Hope you are feeling better.    

[Lotus]

I'm still praying for you, Lotus <3

Thank you Stevenator, prayers... well wishes, spells and incantations that helps cure me is welcomed. 

[Lotus]

Happy to see you are doing better Lotus, I was worried about you not posting for more than a month.
The mention of MS or dementia quite scared me, if you feel better feel free to message me at any time.

Hi Alexis, well… my CML (chronic myeloid leukemia) went from 32% in april to 94%. The test is called the BCR-ABL1, it checks (usually) 500 blood cells and gives a percentage of cancer cells. In my latest test (in August) 94% of my cells tested were cancer cells. That's up from 32% in April of this year and 84% when I was first diagnosed. When I first tested positive for leukemia my blood cells were 84%, and I was a mess. Now, lol… I'm worse. 

On a side note (funny story) I asked my oncologist for pain meds for the leukemia pain… which most cml patients describe having bone pain. Mind you I've been told many times in the past and I quote “pain meds are only for cancer patients”… lol, right. My oncologist proceeds to inform me she only prescribes pain when you're dead, I mean near dead. But not less than 5 minutes earlier the oncologist said I'll be dead in 2yrs if I don't respond to the treatment plan. Haha, well… It's been one year now and I'm worse off than I started off at. Oh well, that's gatekeepers for yah. 

So, if you don't hear from me for a period of time means I'm dealing with unrelenting pain and migraines. Apologies in advance.