I'm looking for answers so I'll get straight to it, rather than bore you to tears with backstory - blah, blah, blah...

I've been on Spiro for 6-months and now my endo has put me on low-dose estrogen patches. The endo said they put me (and presumably others) on low-dose estrogen for the next 5-months, because an initial low-dose helps with breast development, rather than hitting a high-dose early. My endo is knowledgeable and seems to know their stuff, but they didn't really provide a coherent explanation for this approach.

So, is my endo's low-dose estrogen approach sound, or is it nonsense?

I can't say I've heard of it before. The usual reason to do it like that is in case something goes wrong. Adding one drug at a time makes it easier to work out whats causing it, and low dose means that if it does go wrong it won't be as bad as it could be.

6 months seems excessive.

Obviously I'm no doctor, but I have enough bad experiences with doctors that I'm not overly trusting of them. I'd suggest you keep an eye on what blood levels they think are correct as well once your on the full dose.

Quote from: AnonyMs on January 27, 2016, 06:10:23 AM
I can't say I've heard of it before. The usual reason to do it like that is in case something goes wrong. Adding one drug at a time makes it easier to work out whats causing it, and low dose means that if it does go wrong it won't be as bad as it could be.

That would be a comforting theory, except that my endo knows that I've had a year of high-dose estrogen in the past, a few years ago. I was fine. Thrived on it in fact. But that was in Sydney Australia, and now I'm in lovely yet conservative, moderate Perth. Meh.

Mind you, I wasn't on any antiandrogens the last time I used estrogen patches, as opposed to this time, where I'm on high-dose Spiro which is lowering my T levels, albeit very gradually.

Quote6 months seems excessive.

Yes, depressingly so. Then again, a poster from another trans forum made this comment:

"[M]y doctor said it's always best to start on the lowest dose possible and increase it gradually. This not only enables the body to get used to and adapt to the new Estrogens, but would lead to a more natural physical transformation."

So I'm thinking the low-dose approach is designed to be a kind of pseudo-puberty, where the body's reservoir of hormones builds gradually, thereby providing me with a more natural physical development. Seems a bit of stretch, though - would it really make a difference? Schools of thought, I guess.

I'm highly interested to see what answers appear on this. I was started on a similar approach as well. The slowly building for a more natural pseudo puberty is a comforting thought. However I question if that's the doc's intentions. Time will tell. Actually i'll ask at the next app.

OK Ladies,

This is my experience.

My endocrinologist was very open about antiandrogens and estradiol. He gave me several options and let me choose.

I went with estradiol under the tongue, finasteride and spironolactone at the high end of normal doses.

After almost 1 year, I now wear a 42D. I am very happy. Please note that genetic heritage also plays a very important role here.

It would appear to me that if estrogens in puberty and pregnancy in natal women are related to larger breasts that the same thing should happen to us new girls. I think that low doses are very cautious and should only be used for smokers who are many times more likely to throw a blood clot than non-smokers. My endocrinologist noted that I have NEVER smoked and put me on the higher doses right away, but well within the normal range. He also measures blood levels to confirm that I am on the right track.

Note to Moderators: If my discussion violates the rules, please delete my comment. I tried hard to answer without mentioning my specific doses.

Quote from: Serverlan on January 27, 2016, 06:44:00 AM
"[M]y doctor said it's always best to start on the lowest dose possible and increase it gradually. This not only enables the body to get used to and adapt to the new Estrogens, but would lead to a more natural physical transformation."

So I'm thinking the low-dose approach is designed to be a kind of pseudo-puberty, where the body's reservoir of hormones builds gradually, thereby providing me with a more natural physical development. Seems a bit of stretch, though - would it really make a difference? Schools of thought, I guess.

I bet he made that up and there's no real evidence for it. There's very little decent research in trans medicine.

1) I personally think it's harmful to give an anti-androgen alone even for a few weeks. Make us feel lousy for the most part, can have repercussions physically (but more so long-term, years) and every day counts.

2) I think it's wise to start low as you are at your most sensitive in the beginning. But, not too low either. If you start too high too quickly, you are missing the opportunity of having been able to respond to lower doses, which can also mean less $$$ spent. Once you start high, if you go back to lower (should your doctor think levels are too high), then you will surely get less optimal results and suffer from it. Best to start low, IMO.

Lastly, levels don't say much expect to say that at a random point in time, you had this much of estradiol. It won't reveal anything else that is useful to you. Levels aren't a gauge of health risks either, as evidenced by studies. You already know from how your body is responding and how you feel if HRT is working for you so really, levels don't add anything interesting.

Hrm... Very mixed opinions and experiences, which I thank everyone for.
I don't seem to have any other option than trusting my endo, though I have already considered changing endos (with the backing of my highly supportive GP).
On the plus side, I already feel a lot better on even low-dose estrogen after months of Spiro alone.

I had heard about this approach several times before from girls treated by endocrynologists specialized in transgender care at Spanish Social Security. By the way, the reason explained by them was that their bodies didn't have enough "active estrogen receptors" at that time so higher E doses would be useless. Then, after 3 months approximately, they begun to raise their dosages to normal ranges.

Anyway, my doctor at Social Security started me straight high from the beginning.

I have never heard it as a reason for starting low dose HRT. I suppose it is possible, but it's a first hearing that explanation for it. Hugs
Mariah

Ha! Just read some old threads from this and other sites (don't think I can post them here) that refer to a study claiming the existence of something called "breast bud fusion", which may be caused by Spiro and/or the early introduction of high-dose estrogen. Judging by the responses, the study seems to be a bit dodgy. Who knows, so many opinions!

If a doctor gives an explanation for something, like the lack of receptors or what not, I would then ask...could you please provide the evidence you base your statement on? Any studies on that? You will soon find out the veracity of their statements.

Sadly, some doctors like to use our ignorance about the matter against us. KNOWLEDGE IS POWER. Read as much as you can, remain critical at all times.

Hm... Maybe I should get a second opinion from another endo. What worries me above all else, aside from a dubious breast development rationale, is that I've already been on Spiro for 6mths and will stay on it for at least another 5mths, with the only relief being that I've just started taking E, albeit a low dose. I am concerned. 

This is the study that refers to "breast bud fusion" due to estrogen administered at too high a dose too early.

QuotePredictive Markers for Mammoplasty and a Comparison of Side Effect Profiles in Transwomen Taking Various Hormonal Regimens
L. J. Seal, S. Franklin, C. Richards, A. Shishkareva, C. Sinclaire, and J. Barrett

Intro
Breast development in transwomen is an important issue, affecting general psychological functioning. Current hormonal therapies are imperfect, with 60% of patients requesting mammoplasty.

Objective:
The objective of the study was to identify which hormone regimen is associated with the greatest subsequent request for augmentation mammoplasty.

Results
There were significantly more self-medicating individuals than controls in the mammoplasty group (11.5 vs. 6%, P < 0.05). The type of estrogen use did not affect the outcome. Compared with other antiandrogens, spironolactone use was significantly higher in those requesting mammoplasty (4.8 vs. 1.8%, P = 0.002).

However, later in the guts of the study the author notes the following.

QuoteWith regard to the use of antiandrogens, overall there was no statistically significant difference in the use of antiandrogens between those requiring breast augmentation and controls. Comparing the types of antiandrogens used, however, showed that previous spironolactone use was higher in those requesting breast augmentation as compared with other, more specific antiandrogen types (4.8 vs. 1.8%, P = 0.025). [italics mine]

The author also later states Spiro's alleged "breast bud fusion" effect could be the result of Spiro creating too much E, therefore leading again to poor breast development outcomes due to high dose E. But in this postulation he refers to self-medicators who are less likely to be monitoring levels. As such, even if Spiro has a possible negative effect when unmonitored, the link to Spiro leading to more cases of breast augmentation is only a concern if a user's levels are not being checked, leading to a too high dose and poor breast development (even if this latter claim itself is true).

Quoteit also has a significant estrogenic action at the doses used in transwomen. One can postulate that this could lead to an excessive estrogenic action and consequent poorer breast outcome by the same mechanism as that seen when patients self-medicate with estrogens.

Quote from: Wednesday on January 27, 2016, 10:13:51 PM
I had heard about this approach several times before from girls treated by endocrynologists specialized in transgender care at Spanish Social Security. By the way, the reason explained by them was that their bodies didn't have enough "active estrogen receptors" at that time so higher E doses would be useless. Then, after 3 months approximately, they begun to raise their dosages to normal ranges.

Anyway, my doctor at Social Security started me straight high from the beginning.

Same here, I was put on a high dose from the beginning and on top of that also started P at the same time.

"There were significantly more self-medicating individuals than controls in the mammoplasty group (11.5 vs. 6%, P < 0.05). The type of estrogen use did not affect the outcome. Compared with other antiandrogens, spironolactone use was significantly higher in those requesting mammoplasty (4.8 vs. 1.8%, P = 0.002)."

It could just be that Spiro is a less effective anti-androgen vs. others, androgen being a strong inhibitor of breast development or that self-medicators have a personality temperament that makes them more likely to seek breast augmentation and to self-medicate or that self-medicators happened to use Spiro more often. These are all associations and I'm afraid no cause and effect can be concluded from this.

The difference between anti-androgens was not even significant.
"With regard to the use of antiandrogens, overall there was no statistically significant difference in the use of antiandrogens between those requiring breast augmentation and controls."


On spironolactone and estrogen

Expert Opin Drug Saf. 2012 Sep;11(5):779-95.

"displaces estrogen from sex hormone-binding globulin (SHBG) and increases the peripheral conversion of testosterone to estrogen leading to elevated estradiol [12].Estradiol levels decrease and testosterone increase significantly 3 – 6 months after stopping spironolactone [12]."

Ann Intern Med. 1977 Oct;87(4):398-403.

"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."

Hypertension is usually treated with lower doses of Spironolactone relative to what is prescribed to transwomen.

"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."

I wouldn't call the increase in estradiol levels phenomenal, LOL. An increase by 17 pg/ml is very small when one considers range in females during menstrual cycle to be 20-650 pg/ml.

Interestingly,

Clinical Pharmacology & Therapeutics
Volume 24, Issue 4, pages 465–473, October 1978

"To evaluate the long-term effects of spironolactone, 30 normal males were randomly divided into three groups(...)"

"The study was double blind and lasted 10 months."

(doses were typical of what is prescribed for transwomen)

"The concentrations of testosterone, estradiol, estriol, luteinizing hormone, follicle stimulating hormone, progesterone, and prolactin were also determined before treatment and at two-month intervals during treatment."

"Spironolactone induced no significant changes in the metabolic clearance of androstenedione or testosterone. Plasma concentrations of the various hormones did not change as a result of either spironolactone or the development of gynecomastia. Inhibition of testosterone synthesis or alteration in its metabolic clearance by spironolactone does not appear to be the cause of spironolactone-induced gynecomastia in man."

And,

J Clin Endocrinol Metab. 1977 Aug;45(2):255-60.

"One group of nine men took *mg daily for 4 weeks, none for 4 weeks, then *mg daily for 4 weeks."

"The serum concentrations of FSH, LH, testosterone and estradiol, however, did not change during either period, nor did the FSH and LH responses to synthetic gonadotropin-releasing hormone."

"Another group of 9 men took * mg of spironolactone daily for up to 24 weeks. During this time, 6 developed gynecomastia and 2 noted a decrease in libido." (dose was higher than typical for most transwomen)

"No change occurred in the mean serum concentrations of FSH, LH, testosterone or estradiol."

"We conclude that spironolactone-induced gynecomastia and occasional semen abnormalities do not appear to be due to changes in the serum concentrations of testosterone or estradiol. We hypothesize that these changes may be related to binding of canrenone to tissue androgen receptors."

From these studies alone, it appears that higher doses of spironolactone (typically comparable to what transwomen take) did not increase estradiol. Smaller doses (probably) in the other study resulted in a very small increase in estradiol levels.

Spironolactone appears to have a significant blocking effect of androgens at the receptor.

So, when authors state that
"it also has a significant estrogenic action at the doses used in transwomen." I strongly question this and the researchers' objectivity. The increase, if any, in E2, is too small to even make such a strong statement.

The authors of this study seem to have a bias, a negative opinion of high estrogen levels (due to ignorance) and seem to have an agenda, that of trying to discourage transwomen of self-medicating (or supplementing) by asserting that, if you do, too high estrogen levels can actually backfire and prevent optimal breast development by causing breasts to fuse too early which is a hypothesis invented by them, not based on any study. Could it be they are trying to regain control over their patients for research purposes or for personal purposes?

Too many other factors have been ignored in the discussion.

So when it is said...

"One can postulate that this could lead to an excessive estrogenic action and consequent poorer breast outcome by the same mechanism as that seen when patients self-medicate with estrogens."

Studies do not indicate that the addition of spironolactone leads to significantly higher levels of estradiol, if any. Self-medicators may seek breast augmentation, NOT because they took too much estrogen (and poorer breast growth outcome) but because the trait or motivation (wanting bigger breasts, their demands being higher) that led them to seek breast augmentation is the same trait/motivation that led them to self-medicate. This is why associations are weak in research because there are CONFOUNDING VARIABLES!

One wonders as well...how come pregnant women have increased breast growth when estrogen levels are VERY high?

Seeking mammoplasty is also not necessarily an indication of poorer breast growth outcome but perhaps more of individual expectations/ambitions and personality. Hence, it is an unreliable criteria for determining breast growth. Rather one should take measurements of breasts, determine degree of proportionality to body to determine whether breast growth outcome is poor or not. Also, time on HRT is an important factor.

In any case, jumping to conclusions is extremely difficult. One should be cautious.

But...here is this study I just came across

J Urol (Paris). 1981;87(9):635-8.

"The authors examined the influence of spironolactone on the concentration of testosterone, 5 alpha - dihydrotestosterone (DHT), progesterone, oestradiol (E2), LH, and FSH in 47 patients with prostatic hypertrophy, aged from 60 to 80 years."

"There was a considerable fall in the concentration of testosterone and of DHT and, at the same time, an increase in the concentration of progesterone, E2 and LH. "

I wonder if the increase in E was significant, probably not.

Quote from: Tech_Nymph on January 27, 2016, 06:55:58 AM
I'm highly interested to see what answers appear on this. I was started on a similar approach as well. The slowly building for a more natural pseudo puberty is a comforting thought. However I question if that's the doc's intentions. Time will tell. Actually i'll ask at the next app.

Hi Tech_Nymph! Did you manage to get any answers re this topic?

My endo Rx'd me spiro and E at a low (but not lowest) dose and had me come back in 3 months for bloodwork. He would then increase it and have me return in another 3 months...the idea was to get to max dose of E within a year, but I kinda cheated the system by rescheduling a few weeks earlier than 3 months (doc figured this out, and was ok with it because I was not having any bad numbers in the blood nor any bad symptoms)...end result was max dose in 8 months, and I was a B within a year and a half...now at 4 years I'm going to be getting a C cup soon.

YMMV