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Hrt (Pharmacokinetics)

#1

* bobie asked if I wouldn't mind talking about ways to improve Hrt, soooo, I've got a few cliff notes I've collected over the past few years I could share. I'll be honest though, I'm not seeing (IMO) why taking herbal supplements with pharma meds represents sins against nature, (unless you don't follow the recommended guidelines or interactions), and that information (for the most part) is on a product website, and comes with the medication, (interactions).

For instance: you take vitamins and minerals normally while on HrT right?, I'm suggesting supplements that benefit both breast growth and redistribution of fat.

Fact: some essential fatty acids block DHT, help protect against breast cancer, reduce free radicals and inflammatory response.

Now what I've seen two things happen from Estradoil and DHT, they both have something to do with FAT stores. Estrogen creates visceral fat and big butts lol, DHT burns fat but is also present in visceral fat. Testosterone helps to burn visceral fat too.

Prolactin- stores fat in the breast, IMO (prolactin) creates IGT (insufficient growth tissue) in higher concentrations, also increases areaola growth-aka puffy nipples. SSRI, lowers dopamine which creates more prolactin and progects puffy nipples, but you also need progesterone which mediates the growth of alveoli (milk making glands, more on that later). Stimulate those nipples people, that helps increase prolactin.

But, what makes a program better?, (imo, knowledge),...for NBE & HRT it's some new and old things: It's hard to hear someone say "here, take these and we'll see you in a few years (estimates from medical experts on how long hrt takes). But...in 6-12 months people get impatient, hell......sooner than that right?.

Peptide Hormones
IGF-1 (insulin like growth factors)
Small and large molecules (kinda ties into peptides)
PGE 1 & 2
Carrier proteins
Timing of medications (that's a big one)
Inflammation (another big one)
Cortisol
Hydration (biggie)
Fast E metabolism
DIM = anti-DHT (newer one)
Having ample protection against breast cancer causing agents, along with reducing the risk factors or mediators of DVT, ocular changes, increased bleeding risks with certain medications, (interactions).


Well shoot......Rolleyes......it's more than I care to list, (you get the point).

Btw, my opinion is my own, I'm not an expert, this info doesn't represent medical advice, just what I've come to understand. Statistically speaking a large percentage (I've seen it somewhere, I'll find it) states that before TG's seek medical care for transition they find (use) DIY methods. So, do your homework, speak to someone (professionally). On the other hand, NBE is self medicating too, so let's spare the hypocritical viewpoints please.

This thread is about using techniques to improve hrt, talk about drug therapy, therapeutic levels, etc.
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#2

It shouldn't come as a surprise that hormone levels in older genetic males are comparable to menopausal hormones levels, and for that matter, I list the studies regarding obesity:

Androgen generation in adipose tissue in women with simple obesity – a site-specific role for 17b-hydroxysteroid dehydrogenase type 5
http://joe.endocrinology-journals.org/co...1.full.pdf

Granted, aromatase is increased in belly fat in obese men, (especially in older overweight males). However, in older obese females, DHT is present in visceral fat, (something to consider). In other words, get rid of the belly, it could hamper breast growth.

In this next study it explains about progesterone being present in fat tissue. IMO, (and from experience) progesterone cream applied directly to breasts increases breast fat.

From the abstract:
"The results in this study suggest that progesterone may be one regulator in the local conversion of estrogen precursors into potent estradiol in normal breast tissue."

Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle
http://joe.endocrinology-journals.org/co...3.full.pdf
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#3

Any thoughts about taking photo-estrogens while on HRT?

I ask because FG seems to be help with my asthma so I would like to keep it going, but not sabotage my development.
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#4

(30-05-2015, 02:43 AM)CalmlyAndrogynous Wrote:  Any thoughts about taking photo-estrogens while on HRT?

I ask because FG seems to be help with my asthma so I would like to keep it going, but not sabotage my development.

Depends on the amount taken, taking a small dose would seem (imo) not to interfere with Estradiol as a larger dose (which smaller doses of phtyos are more effective than large doses), helps provide "some" prostrate and breast cancers protection. People with nut and chick-pea should stay clear of FG. Some studies exist, but it has to deal with diosgenin and fenugreek seeds. Clearly, the evidence I've read leads me to believe it's an adaptogen. Most phytoestrogens have an affinity for ER-b (estrogen receptor beta), which is more a breast cancer protective, ER-a (estrogen receptor alpha) is the proliferative estrogen receptor, the one that promotes growth, and FG seeds are positive for ER-a. But, one study showed there was a bump in DHT after workouts (using FG), I can't find it anymore, not sure why?, I list it here because it's the only reference regarding how FG increases DHT, (or as they say it's lacking). The study involved fitness resistance:

Over the course of the study, total and bioavailable (“free”) testosterone increased 6.57% and 12.26%, respectively, in the subjects taking fenugreek. Estradiol and DHT levels also increased (26.6% and 6.10%, respectively), though not significantly. No changes in hormone levels were found in the placebo group



(14-04-2015, 03:01 AM)Lotus Wrote:  T. foenum-graecum (aka-Fenugreek)

Here's another related study concerning FG, MCF-7 is positive for ER-a, which FG clearly shows positive cell sensitivity and stimulates growth. And while I believe some phtyoestrogens down-regulate cell lines and receptors resulting in an anti-estrogenic and influence androgens, FG hasnt shown that specificity except in one study, which I noted.

Estrogen-like activities and cytotoxicity effects of Thai herbal medicines as natural ingredients in anti-ageing

With respect to herbal medicines traditionally used as a galactogogue to increase inadequate breast milk supply, only T. foenum-graecum promoted the growth of MCF-7 cells in a dose-dependent manner.

http://www.nanotec.or.th/en/wp-content/u.../64525.pdf


MCF-7 cells are useful for in vitro breast cancer studies because the cell line has retained several ideal characteristics particular to the mammary epithelium. These include the ability for MCF-7 cells to process estrogen, in the form of estradiol, via estrogen receptors in the cell cytoplasm. This makes the MCF-7 cell line an estrogen receptor (ER) positive control cell line.
http://www.mcf7.com

(14-04-2015, 04:04 AM)Lotus Wrote:  Does this mean Fenugreek makes it to the top of NBE herbs list?, maybe, if the product was verified for potency and quality I'd be inclined to say it's in the top two or three. Our beloved PM actually down regulates breast growth in higher concentrations, which has been previously reported and backed by scientific evidence here at BN. Which means, breast growth falls short (eventually), and simply becuase it's an anti-estrogenic and has slight androgenic properties. The binding affinity leans more towards ER-b than ER-a, plus, it acts more like E1 estrone.

It's plausible to alternate or cycle PM, for instance, every other day, or 3-4 days on and 3 off. During the alternated days supplement with other herbs, e.g. vitex, red clover, fenugreek. Finding legitamte NBE herbs becomes the next obstacle to overcome. It's an unregulated industry, so......it would be nice if an herbal manufacturing company stepped up to the plate and had their products verified by an independent source (lab) with no interest, in the meantime, I won't hold my breath. Rolleyes


Is Fenugreek a Phytoestrogen?.
http://www.breastnexus.com/showthread.php?tid=19654

[Image: attachment.php?aid=8344]
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#5

Here's some information from a blogger about Finasteride (btw, excellent work by the blogger, link is posted below). One important distinction about Finasteride is in the highlighted text, perhaps mediating GABA-A modulation is something worth looking into.

allopregnanolone (ALLO) and Tetrahidroteoxicorticosterone (THDOC)
(allosteric modulators) of GABA-A receptors,

The way finasteride causes post finasteride syndrome in certain individuals is unknown. Finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT), but also causes changes in testosterone levels, LH and FSH. 1 Finasteride also blocks the biosynthesis of various neuro steroids such as allopregnanolone (ALLO) and Tetrahidroteoxicorticosterone (THDOC), which are isoforms of the enzyme 5 alpha reductase. ALLO and THDOC are positive modulators (allosteric modulators) of GABA-A receptors, which have the same mechanism of action of anxiolytic drugs such as benzodiazepines. 2, 3 Finasteride has been shown to inhibit the biosynthesis of these neuro steroids, which can be one of the causes for the emotional and sexual symptoms reported. 4 However, some symptoms, such as muscle wasting, loss of body hair and the continuation of symptoms long after the medication has been discontinued, have not been explained yet. Because some patients with SPF have normal or high levels of testosterone - but at the same time a complete clinical state of hypogonadism - it has been hypothesized that these individuals have developed a form of resistance to androgen hormones. 5

__

(More on GABA AND THE GABA-A RECEPTOR later) in the meantime I'll link this website which is using alternative methods (great site btw).
Anxiety attack symptoms
http://www.progesteronetherapy.com/anxie...z3bpcZFE2P
________________________________________

Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride With Persistent Sex
http://www.psychiatrist.com/JCP/article/...n0911.aspx

New research, published in the Journal of Clinical Psychiatry, finds that men who developed persistent sexual side effects while on finasteride (Propecia), a drug commonly used for male pattern hair loss, have a high prevalence of depressive symptoms and suicidal thoughts.

Conclusions: Clinicians and potential users of finasteride should be aware of the potential risk of depressive symptoms and suicidal thoughts. The preliminary findings of this study warrant further research with controlled studies.


Studies

"Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride With Persistent Sexual Side Effects. "
Michael S. Irwig, MD. Journal of Clinical Psychiatry, 2012 DOI: 10.4088/JCP.12m07887
http://www.sciencedaily.com/releases/201...101330.htm

"A new look at the 5alpha reductase inhibitor Finasteride" (2006):
CNS Drug Rev. 2006 Spring;12(1):53-76.

http://www.propeciahelp.com/forum/viewtopic.php?f=8&t=202


"5alpha-reductase inhibitors and erectile dysfunction: Connection" (2008 study):
Erdemir F, Harbin A, Hellstrom WJ.

http :/ / www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=19090946


Finasteride induced depression:
In the study, a controlled group of 128 men, with a daily dose of 1mg per day, had clear and significant increase in depression, verified by BDI and HADS in patients taking finasteride.

Rahimi-Ardabili B, R Pourandarjani, Habibollahi P Mualeki A (2006).
"Finasteride induced depression: a prospective study"

http://www.ncbi.nlm.nih.gov/pubmed/17026771

Finasteride robustly increases anxiety and depression in animals:
Römer B , Gass P (December 2010). "Finasteride-induced depression: new insights into possible pathomechanisms." Journal of Cosmetic Dermatology

http://www.ncbi.nlm.nih.gov/pubmed/21122055

Depression associated to the use of Finasteride
In this study, using 1mg dosage, Finasteride induced moderate to severe depression in 19 of the 23 participants, or 83%, including notably, all female subjects. University of Milan: http://www.ncbi.nlm.nih.gov/pubmed/12433...t=Abstract

"Adverse Side Effects of 5α-Reductase Inhibitors Therapy: Persistent Diminished Libido and Erectile Dysfunction and Depression in a Subset of Patients"
Published on December 2010 on The Journal of Sexual Medicine

http://onlinelibrary.wiley.com/doi/10.11...x/abstract
Authors:
Abdulmaged M. Traish PhD
Dr. Andre T. Guay MD
Dr. D Michael Zitzmann, PhD
Dr. John Hassani MA.
Michael L. Hansen MD


"Finasteride and Neuroactive Steroids."
The study concluded that there was a drastic reduction of neuro active steroids after a period of four months, with controlled groups that used doses of Finasteride 1mg and 5 mg. Observe the decrease in allopregnanolone (-303.1%).


"Finasteride and Neuroactive Steroids."
Published in Prague Medical Report m 2009 (Vol. 110)


Study indicates finasteride inhibits the conversion of hormones into neurosteroids in the brain. These neurosteroids have antidepressant, antianxiety and anticonvulsive effects.

Among them Allopregnanolone and Tetrahydrodeoxycorticosterone.
"A new vision on Finasteride"
Department of veterans, Portland, USA.

http://www.ncbi.nlm.nih.gov / pubmed/16834758? Dopt = Abstract

Male infertility associated with the use of finasteride.
Study of the human reproduction unit, Albert Einstein Hospital, Sao Paulo -

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0041-87812004000400009&tlng=es&lng=en&nrm=iso

Links of various studies relating finasteride use to infertility, sperm motility problems and fail in spermatogenesis:
http://www.propeciahelp.com/forum/viewtopic.php?f=8&t=245

Study with photographic evidence that the shrinkage of the prostate induced by finasteride is caused through cell death (apoptosis).
Dalhousie University, Halifax, Canada:

http://jcem.endojournals.org/content/81/2/814.abstract

Study proves that finasteride alters levels of testosterone, DHT, hormone luteinizing, follicle stimulating hormone.
Uroclínica from the Health Ministry, Ankara, Turkey:

http://www.ncbi.nlm.nih.gov/pubmed/95895...t=Abstract


Finasteride alters cholesterol levels after 6 months of treatment.
University of Parma,

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10996351&dopt=Citation

Chemical castration effect related to the use of finasteride.
Chart of the American Environmental Agency EPA

http://www.epa.gov/comptox/bosc_review/2...Barton.pdf

Links to various studies about finasteride, both 1mg and 5mg:
http://www.propeciahelp.com/forum/viewforum.php?
f=8&sid=511e2201fa63bd8c5ee8ad81f4ca7e4b

http://finasteridesyndrome.blogspot.com/p/studies.html
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#6

Thanks for doing this lotus, i have probably gone way over the top with this but heres a bit of an overview, im 32 years old, have been on hrt for just over a year now including my month on pm, I am on the overweight side at approx 210lbs at 5ft 11” tall, largely I think due to the insane appetite I have had since starting hrt and lack of regular exercise over the winter, the decapeptyl injection has now taken care of the appetite and im now being a lot more careful with what I eat, both in type of food and quantity, breast development, not great really as to me a lot of it seems to be fat, dont know if im expecting too much? Whilst I measure 37.5” underbust and 40” bust the glandular tissue that I can feel is still pretty small at maybe 4cm across, a job to say how thick it is but it feels fairly flat still

This is what I take including supplements and a bit on diet

6mg estradiol hemihydrate (split 9am, 2pm and 9pm)
GnRH agonist, Decapeptyl SR 11.25mg injection every 12 weeks
2.5mg finasteride (split 9am and 9pm)

1 holland and barrett vegan multivitamin and mineral, each contains

Vitamin A 800μg RE (2,664 I.U.) 100%
Vitamin D 5μg (200 I.U.) 100%
Vitamin E 20mg ¬-TE (29.8 I.U.) 167%
Vitamin C 90mg 113%
Thiamin (Vitamin B1) 2.5mg 227%
Riboflavin (Vitamin B2) 2.8mg 200%
Niacin 18mg NE 113%
Pantothenic Acid 6mg 100%
Vitamin B6 6mg 429%
Vitamin B12 2.5μg 100%
Folic Acid 300μg 150%
Calcium 200mg 25%
Iron 14mg 100%
Zinc 15mg 150%


1 holland and barrett calcium and magnesium, each contains
calcium 500mg
magnesium 250mg

1 holland and barrett biotin, each contains
Biotin 300mcg

1 opti 3 omega 3, each contains

Eicosapentaenoic acid 250mg
Docosahexaenoic acid 500mg
total omega 3 780mg
vitamin d3 5mcg

Diet

Breakfast
1 Extra large free range boiled egg
2 pieces of warburtons seaded bread toasted with butter and marmite
1/2 pint of tropicana smooth orange juice
1 strong mug of caffateria coffee with 2 sugars and milk



Lunch
Main cooked meal of the day, varies but am trying to eat healthier, have smaller portions and have more vegetables

Dinner
200grams of watermellon, or if im particularly hungry then also 2 pieces of warburtons seaded bread sandwich, filling often peanut butter & honey or cheddar cheese & pickle or cheddar cheese & marmite

Supper
Small palm full (approx 20) of whole almonds and sometimes a bit of cadbury's milk chocolate

Drink & Alcohol
During the day i drink tap water, the only coffee i now have is at breakfast, i try not to drink alcohol during the week, if i drink alcohol it tends to be a bottle of white wine over a weekend but im now trying not to drink every weekend
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#7

So, Lotus, what does that mean? In regards to Finasteride you just posted above.
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#8

Hi bobie,

Nice post. Well, I look at it this way, you won't grow breasts on VS (Victoria Secret) fat, you know, like a skinny runaway model with 1% body fat. Heck no, we live in the real world......... where it's jelly donut fat, lmao. Rolleyes celebrity cover shots take the liberty to "air brush" the hell out of them, it's unrealistic, w/impossible expectations for the average person to live up too. Dodgy

I'm glad you gave some background, thanks. Maybe we focus on how E2 is metabolized, I like the GnRH therapy, in fact, I've found that FSH stimulates the synthesis of E2, so.....in the feedback loop from LH maybe there's a point to add something to FSH, (stimulating the pulsatile signal), exciting stuff. RolleyesBig Grin

Control of Endocrine Activity
http://www.vivo.colostate.edu/hbooks/pat...ntrol.html

Talk to you later. Wink
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#9

(03-06-2015, 08:37 PM)iaboy Wrote:  So, Lotus, what does that mean? In regards to Finasteride you just posted above.

Hi ia,

It's new information I found a few days ago, I would take it to mean we should read up on it, weigh out the information (if so desired). In other words, it's information we didn't have before to make an informed decision.
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#10

Two postmenopausal studies on E2, which in comparison they relate to most genetic males here at BN, (hormone levels).

Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17 beta-estradiol.

Price TM1, Blauer KL, Hansen M, Stanczyk F, Lobo R, Bates GW.
Author information
Abstract
OBJECTIVE
To investigate the pharmacokinetic profiles of different doses of micronized 17 beta-estradiol administered by oral or sublingual routes.
METHODS:
Single doses of micronized 17 beta-estradiol were administered orally (1 mg, 0.5 mg) or sublingually (1 mg, 0.5 mg, 0.25 mg) to six postmenopausal women in a randomized clinical trial. We calculated pharmacokinetic parameters for estradiol (E2) and estrone (E1) of maximum serum concentration, time to maximum serum concentration, terminal half-life, area under the concentration curve, and oral clearance. Serum levels of E1 sulfate also were compared at 4, 12, and 24 hours after dosing.
RESULTS:
Sublingual administration resulted in rapid absorption with significantly higher E2 levels than did comparable oral dosing. Estrone levels did not vary with route of administration but correlated with the dosage administered. Estrone sulfate levels correlated with the dosage administered and also tended to be higher with sublingual administration. Sublingual administration resulted in a significantly lower E1 to E2 ratio during the 24 hours than did oral administration.
CONCLUSION:
Sublingual administration of micronized 17 beta-estradiol results in a rapid, burst-like absorption into the systemic circulation, yielding high E2 levels that fall rapidly
over the first 6 hours.

____________________________________

17beta-estradiol.

Burnier AM, Martin PL, Yen SS, Brooks P.
Abstract
The sublingual absorption rates, the sustained effects, te biologic activity, and the metabolism of micronized 17beta-estradiol (E2) were measured in 10 postmenopausal women. E2 (0.5 mg) was administered in a single sublingual dose to five of the patients. An alternate-day schedule with the same dosage was used for the other five patients. In the single-dose study, a twenty-six fold increase in serum E2 and a ninefold increase in serum estrone (E1) concentrations were observed 1 hour after the sublingual deposition of E2 (0.5 mg). Serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly decreased within 6 hours. The rise in E2 was early and peaked in the first 2 hours. The rise in E1 was slower and progressive, reaching its maximum thirteenfold increase at 4 hours, and remained two and one half times the baseline of 29 pg/ml at 24 hours, whereas E2 returned to the baseline level of 24 pg/ml. When micronized E2 was given in a dosage of 0.5 mg sublingually every other night, increased circulating levels of estrogens continued to be elevated at a minimum two and one-half fold baseline level for the week of study.

Mean levels (CMax) after 1 hour in this study were 773.6 pg/ml. Estrace 1 mg, cut in half (0.5 mg).
http://www.ncbi.nlm.nih.gov/pubmed/6786097
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