Progesterone

[KayXo]

I do have a tendency to listen to unbiased expert opinion.

Experts are human beings too. They can make mistakes and are never totally unbiased (emotions, beliefs can get in the way, much too often actually). Even experts disagree amongst each other so who do you listen to then? Always best to look at both sides of the coin to come up with the most unbiased conclusion possible in the end. I just needed to say this and realize you don't want to argue about this.   

Honestly, I'm even on the fence about progesterone! I've read and heard the pros and cons. I'm trying it out, again, just to see for myself. Time will tell, in my case.

[Apples Mk.II]

Today I proposed again adding progesterone to the mix:

"No way... We only tried it on a few patients, and the neoplasm risk is too high. So no"

Still, I get a bit of it from Androcur.

[kira21 ♡♡♡]

progesterone was a complete biological waste of time for transgender women, there is no biological proof for efficacy, no credible scientific evidence of an effect.

I take it that he didn't mean that it had no effect on *anything* what so ever, rather on 'feminisation' or rather breast development? Did he confirm this?

I am interested in other aspects beyond breast growth (which is important too but still). They include cognitive functions, protections against  health complications, mood and a bunch of other things.

Here are some snippets of things on my reading list (these are not my words from here)

Far too many Trans Women have a chronically low level of thyroid function (hypothyroidism). ..and that's enough to give you "dysphoria" by itself....So this latest research alerts us to looking at just how the various components of our HRT might be affecting our Thyroid Condition. And PROGESTERONE is one key.

http://www.ncbi.nlm.nih.gov/pubmed/23252963




Based on these data, which are now included in the guidelines, the use of transdermal estradiol and micronized progesterone could reduce or possibly even negate the excess risk of VTE, stroke, cholecystitis, and possibly even breast cancer associated with oral HRT use."

http://www.ncbi.nlm.nih.gov/pubmed/22432810



Brain function and health ( some may be interested in this: Restores erections)
http://www.healthwatchersnews.com/2010/09/progesterone-and-the-nervous-system/


Progesterone concentrations were significantly positively associated with verbal memory and global cognition in the early group women.
They conclude that "Positive associations for progesterone and sex hormone binding globulin merit additional study."

http://www.ncbi.nlm.nih.gov/pubmed/23800538



There are other studies that tie progesterone to cognitive functioning and repair.

[kira21 ♡♡♡]

Today I proposed again adding progesterone to the mix:

"No way... We only tried it on a few patients, and the neoplasm risk is too high. So no"

Still, I get a bit of it from Androcur.

It might be worth discussing the difference between progestins with your endo.

•Natural, 'body-identical' progesterone, devoid of any androgenic as well as glucocorticoid activities but being slightly hypotensive due to its antimineralocorticoid activity, appears to be the optimal progestogen in terms of cardiovascular effects, blood pressure, VTE, probably stroke and even breast cancer (contrary to synthetic progestogens and particularly MPA, which appear to be mitogenic on breast cells, in synergism withestrogen).

http://www.ncbi.nlm.nih.gov/pubmed/23848491


Basically *natural* progesterone seems to have a positive effect on breast cancer where as they synthetics have a negative effect.

I am not making that assertion, just pointing out some of the literature I am reading.

[KayXo]

I started taking a low dose of Prometrium every evening almost 3 weeks ago.

I did feel a bit better the day after I started, & was better able than before to cope with thoughts of suicide that day after that.  The big surprise for me was on the day after my 5th capsule:  It felt as if the depression that had stifled me for over 30 years had completely left.  It has been a little over two weeks now, & it still hasn't returned.

I'm so happy for you and really hope it continues to be so. This is in sharp contrast to medroxyprogesterone acetate which was often prescribed to us in the past which seemed to increase suicidal tendencies in a few and other stuff too like aggression, anxiety, etc.

For myself, I'm on my second capsule and noticed that I'm already much more relaxed than usual. And I definitely welcome this as I tend to be quite an anxious person although I appear calm and composed on the outside. Feel really great! BUT, I also expected these effects since orally, high levels of allopregnanolone are produced and have a strong anxiolytic effect, similar to benzodiapenes like Valium, Ativan, Xanax. So, let's see how long these effects persist but progesterone also appears to have a similar albeit weaker calming effect.

Crossing fingers for both of us.

[KayXo]

Today I proposed again adding progesterone to the mix:

"No way... We only tried it on a few patients, and the neoplasm risk is too high. So no"

Still, I get a bit of it from Androcur.

Neoplasm risks? First I hear of this associated with bio-identical progesterone. If this is true, we should expect this to be a risk for pregnant women whose progesterone levels skyrocket, up to 400 ng/ml. At best, we can expect our levels to reach maybe 50-60, considering how much we usually take.

I suspect that your doctor may be confusing progesterone for other progestins, namely the much dreaded medroxyprogesterone acetate. Do they realize the difference between both, in terms of effects, molecular structure, etc? I've provided several references to that effect that you could show them.

And by the way, you are taking a progestin (Androcur) which is far worst in terms of potential side-effects than bio-identical progesterone so I don't quite understand the reasoning behind prescribing this progestin with a reputation to cause depression in some (confirmed by Gooren although he states it's transient and other endocrinologists in the UK treating transsexual women), increase prolactin significantly, increase clotting risk, effects also confirmed by Gooren's studies and yet refusing to prescribe progesterone which has none of these effects and can actually improve depression in some!

[KayXo]

Indeed Akira, if one searches through the literature, there is extensive evidence for progesterone's beneficial effects on the body and for contribution to breast growth.

Here just a few more.
http://www.ncbi.nlm.nih.gov/pubmed/7640409

"These data indicate that the proliferative stimulus of the mammary lobule is more intense during the luteal phase of the normal cycle and may probably be due to a synergistic action between progesterone and estradiol."

http://www.ncbi.nlm.nih.gov/pubmed/8879685
"The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01)."

CLIMACTERIC 2005;8(Suppl 1):3–63
Pharmacology of estrogens and progestogens: influence of different routes of administration

"In the breast of primates, progestogens may reduce the expression of the ERa and PR, but the estrogen-induced proliferation of the mammary epithelium is not inhibited, but enhanced by progestogens203."

"In contrast to the endometrium, progesterone and most synthetic progestins enhance the proliferative
effect of estrogens on breast epithelium."

"the mitosis rate in breast cancers was observed to be higher in the luteal phase than in the follicular phase325 »

Which, by the way, does not imply that progesterone contributes to breast cancer since it just states that there is more cell division in breasts with cancerous cells. Whether the cell division involves cancerous cells or not is another story. That's why I also tend to believe that it is best to keep levels constant as fluctuations in a woman's menstrual cycle end up resulting in constant cell death and division, increasing risk, possibly (not a fact), of breast cancer.

To date, there have been no studies, to my knowledge (but, of course, I'm very limited in my knowledge) that have shown a link between bio-identical progesterone and increased breast cancer incidence. But, if there are such studies, please bring them to our attention. We want facts. Or maybe in the future, we will find something...but to date, no association as opposed to androgenic progestins like medroxyprogesterone acetate.

AUTHOR Shyamala G
Division of Life Sciences, Lawrence Berkeley
National Laboratory, University of California,
SOURCE J Mammary Gland Biol Neoplasia 1999

ABSTRACT:
Progesterone was identified as a mammogenic hormone several years ago
but until now its role has been obscure. Recently the role of
progesterone signaling in mammary development is becoming more clear.

The most significant observations to emerge from these studies are

(1) progesterone receptors are essential for lobuloalveolar [but
not ductal] morphogenesis.

TITLE: Interaction estradiol-progesterone au niveau des cellules
mammaires humaines normales et pathologiques.
[Estradiol-progesterone interaction in normal and pathological human
breast cells]

AUTHORS: Mauvais-Jarvis P; Kuttenn F; Gompel A; Malet C; Fournier S
SOURCE: Ann Endocrinol (Paris) 1986;47(3):179-87

ABSTRACT
adequate cell differentiation can be obtained with the successive
and synergistic action of estradiol (E2) and progesterone (P),
essentially because the progesterone receptor (PR) synthesis
implicates the previous action of E2
via its E2 receptor (ER). In normal breast, E2 stimulates the growth
of the ductal system whereas the development of acini depends on P
secretion.

TITLE: Effects de la progesterone et des progestatifs sur la glande
mammaire.
[Effects of progesterone and progestational hormones on the mammary
gland]
AUTHORS: Gorins A; Denis C
SOURCE: Arch Anat Cytol Pathol 1995;43(1-2):28-35

ABSTRACT:
The growth of the mammary gland during the active genital period
depends on a delicate balance between the action of the two major
female sex steroid hormones, estradiol and progesterone. The
regulation of growth and maturation of the gland primarily depends on the combined action of estradiol and progesterone.


TITLE Endocrine therapy of transsexualism and potential
complications of long-term treatment.
AUTHOR Futterweit, Walter
SOURCE Archives of Sexual Behavior. Date: 04-05/1998
ABSTRACT:

"the addition of a progestin is indicated initially or several months following onset of estrogen therapy which may have an additional effect on breast enhancement."

This statement, made by an expert who treats, as part of team in Germany (I believe), transsexual women and has done so for several years. 

And there are so many more like this...

[Jill F]

Well, I'm on day 7 of my 4th P cycle and mah bewbs are definitely sore and jigglier than ever.   I'm also crazy horny, but mentally so and not physically.

[KayXo]

you also know my suspect: both cis M and W have some P, but after SRS it perhaps sets off completely, so I think it's still better with than without it.

Men have VERY low levels of P (progesterone) whereas womens' levels fluctuate from low (similar to men) to high during the second part of their cycle (luteal phase). It is true that following orchiectomy or SRS, our levels decline even more as some of it is produced by testicles but I don't think it's significant.

Anyways, time will tell...for me and for you, eventually.

I was actually thinking of our conversation before adding the P and it got me thinking of the role of P in our well-being and overall development. It may be one of the reasons I decided to finally add it.

[KayXo]

Well, I'm on day 7 of my 4th P cycle and mah bewbs are definitely sore and jigglier than ever.   I'm also crazy horny, but mentally so and not physically.

Both these effects seem to come up quite often with transsexual women, even on other progestins.

[KayXo]

Interesting to note as well is progesterone's metabolites, their effects on the body and how they can either be suppressed or increased by certain agents.

Progesterone converts to 5-alpha dihydroprogesterone by means of 5 alpha reductase enzymes, found in various tissues in the body like the liver and the brain. 5-alpha dihydroprogesterone then converts to allopregnanolone and they both interchangeably convert to each other. Allopregnanolone interacts with the GABA receptor and as such, exerts significant anxiolytic effects, reducing anxiety and helping with depression in the process. It is also an anti-convulsant, thus an overall calming neurotransmitter.

But, if finasteride or dutasteride is taken, 5 alpha reductase activity is significantly reduced, thereby reducing allopregnanolone concentrations in the process and ultimately reducing the anxiolytic effects. Also, since 5 alpha reductase activity is very much concentrated in the liver, oral intake vs other routes of progesterone will tend to increase allopregnanolone more and have stronger anxiolytic effects. Finally, it is believed that grapefruit is a potent inhibitor of CYP3A4 present in the digestive tract and liver. CYP3A4 metabolizes progesterone to other inactive, (weaker?), forms. If one takes grapefruit with oral progesterone especially, the resulting effect is increased levels of progesterone (which may vary from one person to another) and hence increased levels of allopregnanolone, thus stronger anxiolytic effects as I'm finding out.

And finally, progesterone appears to affect other enzymes that metabolize many other drugs like CYP2A9 and so may interact with other medications one may be taking but your doctor and pharmacist will know this and will advise you.

I thought it was important to note all this especially the part about finasteride/dutasteride as many of us take it and it might influence how progesterone affects us if we take it orally. Now, you know!

p.s.: allopregnanolone is the reason why you feel sleepy, sedated, dizzy, drunk, may have 'interesting' dreams when you take progesterone orally. BUT, the body does get used to it after awhile so the response is much less exaggerated.
p.s.s: taking it with food also increases bioavailability and will also increase its sedative, anxiolytic effects as a result. So, just beware!
   

[Shantel]

In spite of what all the educated experts have to say about whether or not it is of any use to trans women, it is a fact that progesterone levels are elevated at a certain point in the female cycle and is believed to enhance the development of the lobules and ducts of the female breast. A great number of transexual women swear by it, I use a topical progesterone on occasions and feel that it's given me a boost. So obviously it has a purpose beyond it's function during pregnancy and use with estrogen in menopausal women as a hedge against endometrial cancer. Some gender care providers don't think it's valid for use by MtF's because the effects can't be seen and quantified and I suspect that somewhere in the backs of their brains they are stuck thinking only in the terms "men becoming women" which limits their ability to think outside of the man box in terms of progesterone's application as part of MtF HRT, It's subtle but I know it's there.

[KayXo]

So, my libido is definitely up...had a sexual dream last night and almost had an orgasm! I see better, almost like my vision was a little clouded before...and I'm very relaxed, no tension at all in my body and that is rare for me!  Breasts also look rounder, areolas larger and fuller. Breasts hurt less than usual, much less.

[Mirian]

Shantel, we pretty share the same viewpoint.

I think that, since beginning of times, knowing that cis women have both E and P as
their main sexual hormones, any attempt to feminize a cis male body thru its whole
transition and subsequent life should have included both hormones. I mean, as a naive,
intuitive approach before of anything else. Because at the end, wouldn't giving just E
without P sound a bit like giving just P without E ? This still at conceptual level and yet
without scientific case studies.
Now we all agree, more or less, that such case studies involving TG people and
BIODIENTICAL hormones are still perhaps absent in the literature. There's just some
research from the past mostly made with those dreadful and perhaps lethal mixes of synthetic
estrogens and progestINS. And we can't base on those of course (the problems is that
most endocrinologists around still refer to those instead !) And what is even worst, they
often don't care if a patient reports she/he feels bad or suffers symptoms doctors can't
explain, they simply tell you that's impossible, period. There's often no will by their
side to accept that every patient is her/his own story, and thus HR therapies MUST be
carefully adapted and tweaked on a case by case basis - that expecially LISTENING to the
patients !
So at the end I judge that those doctors saying just "no, progesterone (maybe actually
still thinking to progestINS, too) has no purpose for you" are actually founding themselves
on NO scientific bases.

[Mirian]

So, my libido is definitely up...had a sexual dream last night and almost had an orgasm! I see better, almost like my vision was a little clouded before...and I'm very relaxed, no tension at all in my body and that is rare for me!  Breasts also look rounder, areolas larger and fuller. Breasts hurt less than usual, much less.

First thing I would suggest you suddently: in the case you might experience some you might define negative
effects (not now, perhaps by some more weeks ?), don't think to suddently suspend it, rather try to adjust
the dose. I suspect it's a matter of tweaking with the E/P ratio, something which possibly varies widely
between person and person. I read somewhere that too much P may be as bad as too little P.

Second: you talked of vision. Very interesting !!! I never talked of that before but now... I actually noticed
ALSO vision issues when I suspended Yasmin and switched to bioidentical E only ! (For those people who
don't know or remember my story: https://www.susans.org/forums/index.php/topic,155516.0.html, also
I then started a similar topic on tgboards) Notice that I halways had 11/10 since I was born and I never
had any vision problems. Now I started experiencing focusing issues, increased minimal focusing distance
(presbyopia), fatigue reading books or text on the monitor, even worsening of my eye's capability to
focus at infinite (I'm now maybe just 10 or 9 tenths)... in general, it's as my eyes lost some flexibility or
simply became drier. And curiously enough, when I started some little Androcur again (upon my endo's
suggestion, which is a weak progestin) my vision improved ALMOST as before. And you are now reporting
a similar thing happened to you after having added P. Very interesting indeed !

What instead I'm a bit concerned of (or simply it should be better understood) if what you reported about
increased libido and your breast hurting less. Increased sexual drive, libido, sexual dreams and so on
would in theory be rather an androgenic effect - something which may be welcome or course, depending on
people, but still I see it as androgenic effect. Am I wrong ?

Also (from my experience but not just mine) when breasts hurt is a symptom they're growing, or that
at least they stay alive. Am I wrong here ? I always experienced that at least. When I stopped Yasmin and
switched to plain E, I lost at least 50% of my breasts and they stopped hurting. Now that I'm on some
Androcur they grew back and they hurt again. Now I don't mean it's soo nice having painful breasts, but
well, it would actually be a great thing if they could still grow or stay alive without hurting at all

[KayXo]

First thing I would suggest you suddently: in the case you might experience some you might define negative effects (not now, perhaps by some more weeks ?), don't think to suddently suspend it, rather try to adjust the dose. I suspect it's a matter of tweaking with the E/P ratio, something which possibly varies widely between person and person. I read somewhere that too much P may be as bad as too little P.

I agree 100%. I thought of that as well, just today and will be doing that. 

What instead I'm a bit concerned of (or simply it should be better understood) if what you reported about increased libido and your breast hurting less. Increased sexual drive, libido, sexual dreams and so on would in theory be rather an androgenic effect - something which may be welcome or course, depending on people, but still I see it as androgenic effect. Am I wrong ?Also (from my experience but not just mine) when breasts hurt is a symptom they're growing, or that at least they stay alive. Am I wrong here ?

I thought of the same exact thing! Perhaps both are induced by increased relaxation on progesterone. Libido will surely increase if one is more relaxed, one will be more receptive. AND, if one is relaxed, vessels that carry blood to breasts will also be more relaxed, dilated, thus the reduction in pain. Pubertal cisgirls, as compared to us, have much less pain in their breasts even though they grow considerably...so perhaps it's because of the P that they get cyclically every month. Or, yes, it could be increased androgenic effects from P being slightly anti-estrogenic and thereby reducing estrogen's anti-androgenic effects. Too soon to tell. But, I've never heard of significant androgenization being associated with bio-identical progesterone, perhaps the growth of few extra hairs here and there, but no more. I think the ratio of P to E may also count for something so that too much P may depress E too much, causing increased androgenization, amongst many other undesirable effects like PMS.

[Mirian]

I neither ever read or heard of androgenic effects related to P. Also I would point out once more what that
so pretty girl we have here named Jennygirl always told us: she never took any AA, just E+P. Jenny can you
confirm ? Maybe it's just about some genetic luck though.

Btw, I know some cases of women who really got ugly during pregnancy: swollen, fat hair, some excess
hair here and there, also sometimes acne. Also a friend of mine reported me severe hair loss during
pregnancy.  While most of women don't. But we can't know whether it's just about their P or some other
pathology (ovaric cistis ?) or even simply increased congenital T production.
Or, even, adrenal androgens induced by stress (and that would mean they rather produce not P enough,
since it would have a calming effect)

[KayXo]

It's crazy how much you talk like me (or I talk like you, lol!), it's like I'm reading myself! Anyways, our brains work the same, you and me. 

[kira21 ♡♡♡]

I have heard that there is good evidence for just e and p usage,  to control t. P will reduce t by itself it seems,  as will e. I was reading some advice for handling trans patients from and endocrinologist society that promoted the use of people to control the if aa's were not enough by themselves or were not possible. Sorry for the phone type,  I am on my phone. 

[calico]

His opinion was that once uterine transplantation was mainstream in young transgender women (which is happening) then it would be essential for those who wished to carry a fetus as the biological role of progesterone is in the reproductive systems of females but essentially biologically useless for women not in a reproductive phase of life.

Woah.......   Not to be going off topic to much but...  I am totally interested in knowing more about this.