Susan's Place Transgender Resources

I know in the US, only Spironolactone is prescribed because Cyproterone isn't FDA approved, but from what I've read from non-Americans is that almost all of them are given Cyproterone Acetate as part of HRT.

Using Spironolactine in MtF HRT seems almost unheard outside of the US. The advantages I've found between the two seems to be that Cyproterone lacks the diuretic effect of Spiro, which really isn't that bad after after the first week or so (at least it's pretty much leveled off for me) and some studies on Cypro show it binds to and reduces androgen receptor activity slightly better than Spiro at similar doses. Seems like we need to take higher doses for the same effect.

Are we Americans getting stuck with the inferior option for HRT? For anyone that's used both, did you find one giving you more effective physical results?

It's a trade off of potential kidney damage (spiro) and liver damage (cipro) and the FDA decided that the increased liver risk isn't worth allowing cipro to be approved in the US. They act in different ways so there will likely be different perceived results. For me spiro was more effective in controlling symptoms.

I went on Spiro rather than CA. One side effect of CA is triggering quite sudden depression. I decided I would rather pee a bit more than be even more depressed :laugh:

As it happens I had no side effect from Spiro except for a beneficial lowering of BP.

Quote from: Cindy on September 24, 2014, 11:41:33 PM
I went on Spiro rather than CA. One side effect of CA is triggering quite sudden depression. I decided I would rather pee a bit more than be even more depressed :laugh:

I just went with CA.. And I got the depression.. To start with, I just stopped the CA for a while.. After which my gyno and I fiddled doses until we found a happy medium.

Yeah... I've been on both, and CA totally kicks your butt emotionally. I've never had such extreme highs and lows before, where Spiro alone is much more slow and steady. I got faster feminization on CA, but I don't know if the extreme highs and lows are worth it.

Quote from: Carrie Liz on September 25, 2014, 12:09:16 AM
Yeah... I've been on both, and CA totally kicks your butt emotionally. I've never had such extreme highs and lows before, where Spiro alone is much more slow and steady. I got faster feminization on CA, but I don't know if the extreme highs and lows are worth it.

More feminization is nice and kinda what I was interested in given how long the process is already. Emotional instability doesn't sound like fun though.

I don't really have a choice now but I'll be abroad for a year in a few months so I was considering my options. My current (us) doctor had no idea about CA at all.

I really wish this process would be more doctors educating us rather than the other way around. 

I took CPA pre-op, I live in Canada. Felt great on it, feminization was good but if I had to redo, I would have asked for bicalutamide instead. Fewer side-effects, safer overall and VERY strong anti-androgen, also approved in the US.

I came on here to comment about Spiro but need to mention about bicalutamide. It is unproven that Bicalutamide is 'safer overall.' In fact there are plenty of potentially fatal side effects, one of which I've managed to get (interstitial inflammation of the lungs) so I've been taken straight off it. On this thread there are links to the dangerous sometimes life-threatening side effects of bicalutamide which is untried and untested as a treatment for MtF's. I'm just warning forum members to exercise extreme caution: https://www.susans.org/forums/index.php?topic=210339.new;topicseen#new
Some people may be fine with it, but it doesn't help that your physician may not have heard of it, let alone as a transgender treatment.

As for Spiro, like a few other people I had an awful reaction to it. I was one of those whose blood pressure dropped through the floorboards and it very nearly killed me: when I woke up my heart was hardly beating and I couldn't stand up. It's a drug that the GiC in Britain won't administer for MtF's.

Before you think I'm an out-and-out pansy, I've had no issues with max finasteride, a drug I've got along with very well. That's a good example of what I'm getting at here: some people have a nightmare with fin. One person's medicine may be another's poison, so just please please don't take as gospel what someone tells you is fine and safe. It might be for them. It might kill you. Always get medical guidance and be tested.

Which I guess leaves CA (by the way I believe the abbreviation 'cipro' is normally reserved in the medical community for  ciprofloxacin).

Or ... orchiectomy. Which is basically what I am going ahead with now. I'm sick and tired of almost killing myself with drugs that don't suit my system.

xx

Please consider doses when mentioning side-effects with this drug. Men who take it due to prostate cancer take high doses, transsexual women usually take much less.

Quote from: Richenda on June 06, 2016, 12:20:02 AM

Which I guess leaves CA (by the way I believe the abbreviation 'cipro' is normally reserved in the medical community for  ciprofloxacin).

Funny thing is, those that can spell will shorten cyproterone acetate to cypro.

I've only ever used cyproterone acetate, I have had to make an adjustment to dose when the depressive side effects. I've also had 1-2 week periods where I didn't take it.. Even after 2 weeks without taking it, my T level didn't increase.

I'm on low CA / Cyproterone Acetate (;) ) now and seem to be fine with it. So that will be the first true anti androgen that has worked for me. It's only for 6 weeks prior to my orchie just to keep the T and E levels close to female, thus lessening the shock when the testicles are whipped out. Can't wait.

No kidding on the Spiro blood pressure drop...I went in to get a test done at my endo's office that was a different appointment not related to HRT.  They took my BP prior to the test and it came out 130/80.  I had an hour and a half till my Endo appointment and at my normal time to take my Spiro.  Right after leaving the first doctor's office, I took my 100mg.

A little over an hour later I was given the prelims for my Endo appointment and my BP was 117/70.

I have to be careful for a few hours after taking it when I get up, so I usually take it after I am off work.

Spiro has been plenty effective in blocking out my T, which is now in normal female ranges and I am not sure what effect beyond that suppression that an AA provides.  What feminizing effect does one provide over the other?

Hi Kaity,

I'm not qualified to comment on your final question except that as I'm sure you know there's the debate between T blockers (CA, Spiro, bicalutamide, flutamide) and those which block T to DHT (dutasteride and finasteride). As DHT is 9x more powerful than T I would argue that DHT blockers are the most potent form of anti androgen. Then there's those which tackle the brain first: the GnRH inhibitors. An orchiectomy removes 95% of testosterone production.

You spiro bp drop tallies with mine except mine went through the floor. I woke up one morning with my heart scarcely beating: no exaggeration. It was horrendous.

Holy moly, Richenda!  I have never gone out like that and it sounds super scary!  Passing out is bad enough.

The thought I had was exactly that on the Spiro vs. Finastride.  I have several sisters local that use Finastride and they have had good results so far.  They have mentioned feeling really moody on it though, which is something that I have not had to deal with using Spiro.

Yeah it was really awful Kaity. So frightening. My pulse went below 30  :(

The one consistent anti androgen medicine I have taken right through is finasteride. I'll tread carefully here but I've been similar to my brother's prostate intake level if that makes sense. I've not noticed any bad side effects apart from some sinus-type headaches. This is where one person's medicine can be another girl's poison because I know lots of people have depression from finasteride (my brother does).

In terms of the effect I have almost no body hair now and significant breast enlargement, though that's presumably been helped by oestrogen.

My journey with other anti androgens has been a nightmare. In addition to the spiro issue, dutasteride spun me out badly and bicalutamide caused a dangerous reaction. I'm currently on low dose Androcur (CA) which seems okay so far.

Quote from: Richenda on June 17, 2016, 10:57:37 PMAs DHT is 9x more powerful than T

https://en.wikipedia.org/wiki/Dihydrotestosterone

"DHT has two to three times greater androgen receptor affinity than testosterone"

"The dissociation rate of testosterone from the receptor is five-fold faster than DHT.[5]"

QuoteDHT blockers are the most potent form of anti androgen

They are called androgen blockers and block all androgens to a certain degree. Some also reduce androgen production such as Spiro and cyproterone acetate.

QuoteAn orchiectomy removes 95% of testosterone production.

Prog Brain Res. 2010;182:321-41.

"after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin."

Despite this, we still have less than pre-menopausal women because their ovaries are another source from which androgen is produced.

I have to add something to this discussion.
If you give two options, I give you a third: No antiandrogens! There are countless patient reports and even a few minor studies that show that Testosterone can be supressed in 50-99% of the cases with estrogen and progesterone alone. The hypothalamus has a feedback mechanism that is activated either by testosterone or by estrogen+progesterone and will thus reduce the amount of requested hormones if there are sufficient hormones in the blood. So if your estrogen levels are high enough, testosterone will drop anyways. Those who got estradiol injections as I did in the late 1990ies almost never need antiandrogens as T was very low with that sort of estradiol in the blood. Of course, nowadays its not injections anymore but pills and transdermals and with pills taking adequate dosages is hard - with patches or gel however, an increased estradiol dosage that is high enough for the body to shut down its own hormone production is easily reached and not dangerous since transdermals do not increase liver issues and are not known to increase cancer risk or DVT risk significantly either.

That's very interesting Anjaq. It ties in anecdotally with conversations I've had out here in Thailand with MtF transsexuals. I've lost count the number of times I've been told that after a few years they no longer take Androcur (Cypreterone Acetate). This is invariably from girls who look totally female. I can well believe that estrogen can act as a powerful anti androgen. It's a shame that there aren't long term studies on this. I have a hunch that a short period of so-called anti-androgens followed by continuous estrogen might be sufficient for our needs.

Re my earlier post I also think in blood tests we possibly get fixated on T levels when it's DHT that is 9x more powerful. Drugs like Dutasteride, Finasteride and Bicalutamide effectively block the latter not the former. (Bic elevates endogenous estrogen due to inhibiting androgen feedback on GnRH secretion by the pituitary gland which actually elevates serum testosterone, but it stops having masculizing effects because the receptors are blocked: mind you I think it's a potentially dangerous drug.)

The other thing is that perhaps we also sometimes focus on those tests without looking at the other obvious body signs? After 18 months on finasteride and estrogen and only inter-mittent anti-androgens I have virtually no body hair and significant breasts. I lactate daily.

Anyway, I've pretty much decided I'm having an orchiectomy next month. That will take care of the T issue as it wipes out 95% of testosterone. In theory I might continue on a much reduced dose of finasteride but it's going to be important to watch for osteoporosis.

p.s. and androgen comes from the Greek andras for man so anything countering male hormones is an anti androgen including estrogen :)

Androgen is a wrong word because all the so called androgens are also existing in women. Did you know that a woman has usually more Testosterone than Estrogen in her body? And younger women have more than older men? Its really fascinating once you look into it. The distinction of Testosterone = Man and Estrogen = Woman is a fairytale, both hormones exist in both and are needed in both.

The people I spoke with used estrogen only from the beginning - no antiandrogens ever, not even for some months. Although for some this was the standard therapy so they had CPA for a while and then stopped. I cannot describe details here because of the rules (no dosages etc...), but it does work with slightly higher estradiol than recommended by many endocs - although many other endocs are totally fine with those dosages as they are far from crazy high. Just the maximum dosage of patches usually works fine with most.

the mechanism , as you mention GNRH , is this:
(https://www.susans.org/proxy.php?request=http%3A%2F%2Farbl.cvmbs.colostate.edu%2Fhbooks%2Fpathphys%2Fendocrine%2Fhypopit%2Flhfsh.gif&hash=65f653c457c1c4c97eb3a22d606cd8bf4b7c7803)

As you can see, the hypothalamus (GNRH) and pituary gland (LH and FSH) do regulate the bodys hormones. If there is not enough Tesosterone in the body, it will ramp up production until it registers enough testosterone again. This is regulating testosterone production and blood levels in males. However the glands do not care if it is testosterone or estrogen. For women it is more complex but essentially  also there more estrogen and progesterone in the blood means less LH and FSH and thus a downregulation of internal hormone production. Now the neat thing is - since the glands do not distinguish that much between testosterone and estrogen, they give the signal "I am full" when one of the two is high enough - and reduce LH and FSH and GNRH and thus the bodys own hormone production. This is why estrogen (maybe in combination with progesterone) alone almost always wil suppress T.
[this is a VERY simplified version of what is happening, so please do not be thrown off if you read about some details being different elsewhere, especially regaring the female hormone system which obviously is cyclical]

Now what many trans women seem to seek however is demaskulinization - no libido and erections anymore, reduced body hair etc. This often is reached only if you drop testosterone levels below that which is normal for females. So then, antiandrogens are loved because they can do that, but beware of the price - remember also women have a libido and life without it is not that great and that testosterone is also important for muscle growth (including growing new muscles in a more feminine shape) and many other body functions. When yout pubic hair starts to become very thin, its a warning sign, since only old and very young women have little pubic hair (unless you remove it of course ;) )

Richenda - your description was warning signs placed over it in my eyes. Please let a doctor do your blood tests soon - and be sure to measure prolactin! Lactating may be somewhat fun and a nice affirmation of being female, but it is also a sign of elevated prolactin levels usually and this is not healthy. Antiandrogens are known to increase the prolactin, especially Androcur which can cause Prolactinoma, a tumor of the pituary gland that produces prolactin.

Last but not least - be very careful with long term use of DHT blockers. There are massive reports about ill side effects of this. Google it. It can even cause some slight forms of dementia. Again, blocking out all and every "androgen" in the body is counterproductive as the female body also needs some of those hormones. Also be aware that progesterone is a soft DHT inhibitor. I and some others I know use Progesterone Gel on the temples and top of the head and it regeneratesd hair growth as it also reduces DHT production. (it is a 5 alpha reductase inhibitor).

Very wise words Anjaq about the tests. Thank you too for such a fabulous explanation of the mechanisms.

Let me just allay your fears a little about my lactation. I only have it when I'm breast pumping, which I do once a day for ten minutes to stimulate them. It has increased breast and areola size. The pumping always produces a small lactation.

My last test was 4 weeks ago and I will have another soon in Bangkok. My prolactin result was 14.7 ng/mL which is top end for a male but midrange for a non pregnant female (4.79 - 23.3)

I love what you have written which was so helpful. However, I do confess to being slightly anxious over the idea of high dosage anything, including estrogen. Part of the reason I'm having an orchiectomy in six weeks is so that I can cut out entirely all anti-androgens (I believe this is correct: I will literally be taking none of them) and just keep a lose dose of estradiol valerate. Removal of testicles makes one the same as a GRS post-op MtF. As you rightly point out, there are side effects and consequences for most all of the meds we take and that concerns me.

I have been on both, on and off for about 5 years. I think both are horrible and just bad for the body. The good thing about cypro is it's mild progesterone effect, which helps a little bit in developing breasts. But it's side effects are worse than spiro, possibly for the same reason. Spiro made me nauseous, gave me night cramps, and I became bloated.

It's best to remove the testes than to use an anti-androgen, as it will block all androgens. Not only T, but other useful androgens that the body needs. After all these years I come to believe that anti-androgens are somewhat overrated for their effects. Estrogen has to be the main thing that triggers the greatest changes, blocking T helps but doesn't seem to be as effective as removing the testes completely.

I had a discussion about long term HRT.  I understand that I will be on HRT in some form or fashion for the rest of my life, so I wanted to get a better understanding of what I could expect.

I will be on transitional dosages of E and an AA for 2 years.  After that, if I elect to not have surgery we will likely drop the AA.  I asked about dropping it and she said that likely E alone will keep any T suppressed and that continued use of an AA will likely not be necessary.  These are likely's, keep in mind.  We won't actually know until the time arrives, but based on similar results...she thinks I will be a common case.

It is my understanding that the AA does nothing really for the development and that E (and P, if used) are the primary facilitators of our outward traits.  I have seen men with prostate issues who use AA's and they do develop feminine traits over time, but nothing like what I have experienced in under a year.

I have increases 2 cup sizes and have some pretty nice hips building and when my endo and I discussed things, she explained that E alone did this and that the T suppression really only helped my E receptors to "wake up" quicker.

No matter, a steady supply of E alone will lower T levels over time.

Quote from: Richenda on June 18, 2016, 08:02:26 PMI can well believe that estrogen can act as a powerful anti androgen. It's a shame that there aren't long term studies on this.

Long term studies are not needed to confirm what is basic science, that high enough estrogen and/or progesterone levels in the blood will shut down signal to gonads through negative feedback inhibition and cease production of T. Injections are available today and many transwomen take them, including myself.

QuoteRe my earlier post I also think in blood tests we possibly get fixated on T levels when it's DHT that is 9x more powerful. Drugs like Dutasteride, Finasteride and Bicalutamide effectively block the latter not the former.

Bicalutamide blocks ALL androgens and that means both testosterone and DHT, while finasteride and dutasteride inhibit enzyme(s) responsible for T to DHT conversion, therefore reducing DHT concentrations ONLY.

QuoteI lactate daily.

This can possibly indicate a prolactinoma, a benign pituitary tumor. Breast stimulation can also lead to galactorrhea. To determine if this is indeed a prolactinoma, doctors usually check prolactin levels and do an MRI. In transsexual women, prolactinomas were reported in those taking cyproterone acetate and/or non bio-identical estrogen/progestogen.

QuoteAnyway, I've pretty much decided I'm having an orchiectomy next month. That will take care of the T issue as it wipes out 95% of testosterone. In theory I might continue on a much reduced dose of finasteride but it's going to be important to watch for osteoporosis.

Osteoporosis is prevented by a small amount of estrogen. To maintain female characteristics, health (physical and psychological), energy and youth (slow down ageing), some E is needed post-op.

Quote from: anjaq on June 19, 2016, 04:25:34 AM
Did you know that a woman has usually more Testosterone than Estrogen in her body?

Regardless, the end result is feminization of the body. And it also depends on where she is in her cycle or if she is pregnant. 1 ng/dl (usual units for T, in the US) = 10 pg/ml (usual units for E, in the US). So, if a woman has 600 pg/ml estradiol (mid-cycle), it's equal to 60 ng/dl and T may well be under that...during pregnancy, estradiol can go up to 75,000, hence 7,500 ng/dl, well above testosterone levels.

QuoteAnd younger women have more than older men?

http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/83686

Lowest total testosterone in adult men is 240 ng/dl, highest 75 ng/dl in women.
Lowest free testosterone in adult men is 2.29 ng/dl (at 95/100+ years) vs. 1.08-1.09 ng/dl in young women (15-18 yrs, 20-25 yrs)
Same pattern for bio-testosterone.

According to this source, young women do NOT have more testosterone than older men, be it TOTAL, FREE or BIO-AVAILABLE.

http://www.healthtestingcenters.com/testosterone-free-total.aspx

Men 270-1070 ng/dL (9-38 nmol/L)
Women 15-70 ng/dL (0.52-2.4 nmol/L)

Men 50-210 pg/mL (174-729 pmol/L)
Women 1.0-8.5 pg/mL (3.5-29.5 pmol/L)

So again, according to this source, the lowest in men is still much above female range.

QuoteIts really fascinating once you look into it. The distinction of Testosterone = Man and Estrogen = Woman is a fairytale, both hormones exist in both and are needed in both.

But, to different degrees so men masculinize and women feminize.

QuoteHowever the glands do not care if it is testosterone or estrogen.

Or progesterone and hence, most progestins...why cyproterone acetate and medroxyprogesterone acetate reduce T, LH and FSH.

QuoteFor women it is more complex but essentially  also there more estrogen and progesterone in the blood means less LH and FSH and thus a downregulation of internal hormone production.

In women, there is actually a positive feedback mechanism whereby estrogen, during the follicular phase, actually increases LH and FSH production (up to a critical point) leading to even more estrogen and ovulation induction.

QuoteNow what many trans women seem to seek however is demaskulinization - no libido and erections anymore

I never aimed for no libido and thankfully, have plenty of it on E and P despite low T values (around 8 ng/dl, free T undetectable), under normal female range. Perhaps not as intense but this also depends. :)

Quoteremember also women have a libido and life without it is not that great and that testosterone is also important for muscle growth (including growing new muscles in a more feminine shape) and many other body functions. When yout pubic hair starts to become very thin, its a warning sign, since only old and very young women have little pubic hair (unless you remove it of course ;) )

Again, despite my very low T, I have thick, dark, dense pubic hair and not much muscle mass has been lost. I can still see my abs.

QuoteAntiandrogens are known to increase the prolactin, especially Androcur which can cause Prolactinoma, a tumor of the pituary gland that produces prolactin.

The only anti-androgen associated (no causal effect established, to be fair) with prolactinoma is cyproterone acetate. Other anti-androgens do not raise prolactin levels.

QuoteLast but not least - be very careful with long term use of DHT blockers. There are massive reports about ill side effects of this. Google it. It can even cause some slight forms of dementia. Again, blocking out all and every "androgen" in the body is counterproductive as the female body also needs some of those hormones.

Were these effects observed in individuals with no hormone replacement in the form of estrogen to prevent dementia? Some inviduals, born XY, completely androgen insensitive, do fine without ANY androgen so I question the importance of it for normal functioning if E is high enough to compensate for it.

QuoteAlso be aware that progesterone is a soft DHT inhibitor.

The only study to have shown this was an in-vitro study where concentrations of progesterone were supraphysiological, way above what we can reach. I also question this claim for this reason.

QuoteI and some others I know use Progesterone Gel on the temples and top of the head and it regeneratesd hair growth as it also reduces DHT production. (it is a 5 alpha reductase inhibitor).

Were serum or scalp DHT levels reduced after the use of the gel? Could these results have occurred anyways, if gel hadn't been used? We need hard proof to make claims such as these.

Quote from: Richenda on June 19, 2016, 06:44:19 AM
However, I do confess to being slightly anxious over the idea of high dosage anything, including estrogen.

1) Cardiovascular and clotting risks

. Ciswomen are reported to be much less affected than men by cardiovascular complications despite pregnancy levels of estradiol and levels of up to 650 pg/ml every menstrual cycle. Their risks increase (and approach that of males) at around menopause when estrogen levels DROP. Studies have strongly suggested a protective role for estrogen. I can provide these studies.

. Studies in men with prostate cancer (ages 49-91) have shown that estradiol levels up to approx. 700 pg/ml were safe. There were no cardiovascular complications or incidences of thrombosis. In fact, researchers stated high levels could be PROTECTIVE. Additionally, it was observed that estrogen improved lipid profiles, without cardiovascular deterioration and that it may improve cardiovascular disease and mortality, long-term. These men were treated with high dose injectable or transdermal (patches) estradiol. I can provide you those studies. 

. Pregnant women have levels that go as high as 75,000 pg/ml and yet the risk of having a DVT or pulmonary embolism is less than 0.02 % with thromboembolism being 5 times as more likely post-partum (when levels drop) and pulmonary embolism being extremely rare during pregnancy and more common post-partum (when levels drop). I can provide you the evidence as well.

. Four studies show circulating levels of estradiol not to be a useful criterion of risk of thrombosis, as despite high levels, no increased risk was found AND rather the route of administration/type of estrogen is more indicative of the risk. Here, two of them.

Am J Obstet Gynecol. 1993 Dec;169(6):1549-53.
Fibrinolytic parameters in women undergoing ovulation induction.

"As serum estradiol levels increased throughout each phase (maximum mean estradiol 739.8 pg/ml)"

"Down-regulation of the fibrinolytic system was observed as estradiol levels increased. However, thrombin formation did not change, thus suggesting that elevated circulating estradiol alone does not predispose to a thromboembolic event."

Br J Obstet Gynaecol. 1990 Oct;97(10):917-21.

"There is some anxiety about the possible harmful sequelae of supraphysiological estradiol levels but no data are currently available to show any deleterious effects of these levels on coagulation factors, blood pressure, glucose tolerance or the occurrences of endometrial or breast cancer (Hammond et al. 1974; Thom et id. 1978; Studd B Thom 1981; Armstrong 1988)."


. Arch Sex Behav. 1998 Oct;27(5):475-92. In this study, transsexual women were given high dose intramuscular E and some were prescribed medium-high doses of oral E. In spite of this, there was not one incidence of thrombosis.

"None of our patients developed deep vein thrombosis or embolism during cross-gender hormone therapy performed in our clinic."

2) Breast cancer risk

. In transsexual women, breast cancer incidence is very low, close to that of men not on HRT and significantly lower relative to ciswomen (as per Dr. Gooren and his team, leading specialists of HRT treatment in transwomen). Only 17 cases reported since 1968 despite decades of very aggressive, high doses of oral estrogens and non-oral estrogens (intramuscular). Only one proven case reported in Holland among Gooren's patients in decades of treatment despite high doses of E for several years. Studies to support this.

. In men with prostate cancer treated with high dose estrogen over the years, since the 1960's, breast cancer is extremely rare. Supporting evidence.

. High dose estrogen has actually been used to treat ciswomen afflicted with breast cancer, in one instance, with increased effectiveness relative to tamoxifen, one of the drugs of choice in its treatment. 

. The incidence of breast cancer from one country to another were not found to be correlated with levels of estrogens. In fact, the only significant finding was a higher level of estradiol in a subpopulation (adolescents) of the country (during the luteal phase) with the least incidence of breast cancer.

. The more childbirths a woman (hence, the more pregnancies when levels of E are sky high), the lower the risk of breast cancer. On the other hand, celibate nuns are historically known to have a higher incidence of breast cancer risk, going as far back as the 1700's.

. Breast cancer risk is highest in women over the age of 40 and especially 50, when estrogen levels drop.

. Studies in mice and observations that carcinoma incidence is increased post-pregnancy suggest high levels of estradiol are protective. 

3) Uterine cancer risk

. YOU HAVE NO UTERUS

4) Prolactinoma

. Ciswomen have very high levels of prolactin, up to 600 ng/ml (ug/L), during pregnancy and continue to have high levels during breastfeeding which can sometimes last a few years. Despite this, the fact that estradiol levels can also peak quite high during a menstrual cycle (up to 650 pg/ml) and women's history of taking birth control pills or HRT involving estrogens that strongly affect pituitary gland, the prevalence of prolactinoma has been estimated to be 0.1% in women.  Doctors/health authorities do not ask mothers to stop breastfeeding their children or not become pregnant again due to risk of prolactinoma.

. Causation has not been established between the use of estrogen or pregnancy and prolactinoma in women.  Association between OC/HRT use and prolactinoma may have more to do with the increased likelihood that women with prolactinoma use treatment to regulate menstrual cycle disrupted by prolactinoma.

. There is a negligible impact of either birth control pills, HRT or pregnancy (when E levels are very high) on small pituitary adenoma in women. Pregnancy has even shown to have a favorable effect on microadenomas with spontaneous remission ranging from 17-35% (Presse Med, 17 (1998), pp. 2117–2119) vs. 13-15% in those who have not undergone pregnancy. From J Clin Endocrinol Metab. 2007 Aug; 92( 8 ):2861-5.
"Changes in tumor vasculature resulting in pituitary necrosis, microinfarction, or hemorrhage have been suggested as potential mechanisms to explain how pregnancy might lead to normalization of prolactin (21)."

. Arch Sex Behav. 1998 Oct;27(5):475-92. In this study, transsexual women were given high dose intramuscular E and some were on medium-high dose oral E. In spite of this, there was not one incidence of prolactinoma.
"we detected no prolactinoma as described by other authors (Asscheman et al., 1988, 1989; Kovacs et al., 1994; Gooren et al., 1980)."

. In my extensive search through incidences of prolactinoma in transsexual women, the only incidences reported were found to be in those women who took high doses of non bio-identical forms of estrogen orally (ethinyl estradiol, equine estrogens) most often with high doses of cyproterone acetate, OR a combination of estradiol enanthate and dihydroxyprogesterone acetophenide, all known to abnormally elevate prolactin levels (in the last case due to progestogen component). Incidences in women taking bio-identical estradiol without the above mentioned agents taken simultaneously have NEVER been reported to date. Incidences in male to female transsexuals are also RARE, only 8 cases reported in the literature as of 2015 despite sometimes very high doses of estrogen taken during several decades. Studies to support.

I'm POST-OP and on a high dose of intramuscular E. Supervised by three doctors who approve, one of whom is an author of a book on female hormones, another a trans-specialist endocrinologist from the University of Cambridge. My blood tests results show no change in clotting factors, or liver enzymes, or lipids, insulin, glucose, c-reactive protein. Nothing is out of range given my high levels of E2, which are in the range of 1,000-4,000 pg/ml. I've also been on high doses of oral bio-identical estradiol for several years. I started HRT in 2004.

I read from many other transwomen pre and post-op who have taken high doses of bio-identical E parenterally with high levels of E and their blood test results always came back normal. Most were above 40 yrs old.

As always, double check, do your own research, talk to doctors. I could be wrong, I'm not a doctor or specialist and could have missed something along the way. ;)

Take care and all the best. :)

Quote from: kaitylynn on June 19, 2016, 08:38:40 AM
It is my understanding that the AA does nothing really for the development and that E (and P, if used) are the primary facilitators of our outward traits.  I have seen men with prostate issues who use AA's and they do develop feminine traits over time, but nothing like what I have experienced in under a year.

The reason being they don't take E as well. But, in those taking bicalutamide especially and also in the case of cyproterone acetate, some breast growth is observed (up to 70-80%, according to wikipedia, other sources state up to 50%) as well as some degree of feminization.

E alone can have a significant impact on development but only if T is reduced sufficiently (in the vast majority of people) and sometimes, because pellets or injectables aren't available (or doctor refuses), an anti-androgen is necessary as orally, too high doses of E can sometimes be problematic, usually for the older population but this is subject to debate as well since I know some older transwomen who do well on high doses of oral bio E.

QuoteI have increases 2 cup sizes and have some pretty nice hips building and when my endo and I discussed things, she explained that E alone did this and that the T suppression really only helped my E receptors to "wake up" quicker.

Androgen is an inhibitor of feminization and its absence will trigger full feminization as is the case, for instance in individuals completely insensitive to androgen, despite their very low level of E, who develop breasts (often larger than ciswomen) and hips and are very feminine.

QuoteNo matter, a steady supply of E alone will lower T levels over time.

Depends on how much E and to what degree T is lowered.

Quote from: KayXo on June 21, 2016, 01:57:47 PM

This can possibly indicate a prolactinoma, a benign pituitary tumor. Breast stimulation can also lead to galactorrhea. To determine if this is indeed a prolactinoma, doctors usually check prolactin levels and do an MRI. In transsexual women, prolactinomas were reported in those taking cyproterone acetate and/or non bio-identical estrogen/progestogen.

My prolactin level is fine and I breast pump so you're talking nonsense. Again, you're not a medic and I am now regularly seeing someone who is so back off the internet diagnoses. I'm also weary of your impressive-sounding but highly selective and usually extremely old studies to back up your one-sided views. You should be much more balanced in my opinion and stop coming across to people on here like a medic. You're not one and I have personally found some of your undoubtedly well-meaning advice to be dangerous.

Quote from: Richenda on June 21, 2016, 06:27:52 PM
My prolactin level is fine and I breast pump so you're talking nonsense.

Yes, I read this in your later post, I replied immediately to the post before so was unaware you were stimulating your breasts but did write:

"Breast stimulation can also lead to galactorrhea." as an alternative explanation to why you might be lactating.

QuoteAgain, you're not a medic and I am now regularly seeing someone who is so back off the internet diagnoses. I'm also weary of your impressive-sounding but highly selective and usually extremely old studies to back up your one-sided views. You should be much more balanced in my opinion and stop coming across to people on here like a medic. You're not one and I have personally found some of your undoubtedly well-meaning advice to be dangerous.

I'm sorry you feel this way but I have, time and time again, stated that I am NOT a doctor, that people should discuss these matters with health professionals and my only intention is to share information with others, usually in the form of studies, so that they may be better informed. :)

I quote old and new studies, sometimes as recent as 2015 (in the case of bicalutamide, provided a study from 2014), it depends. I try to remain objective and so, do not believe I am selective. I'm open to contradicting information and this is the only way, I believe, to get at accurate information. Again, I appreciate your feedback and providing those links on bicalutamide. :)

Quote from: Richenda on June 19, 2016, 06:44:19 AM
My last test was 4 weeks ago and I will have another soon in Bangkok. My prolactin result was 14.7 ng/mL which is top end for a male but midrange for a non pregnant female (4.79 - 23.3)

I love what you have written which was so helpful. However, I do confess to being slightly anxious over the idea of high dosage anything, including estrogen.

The prolactin is ok then, very good.

"High" dosages of estrogen can be a problem, yes. One has to take into account some thing sthere.

a) in most women the estrogen can go pretty high for some days in a month and it is probably not harming them - most importantly though, during pregnancy, estrogen levels are massively high and those women are very healthy. It should be balanced with progesterone though, otherwise one can have "estrogen dominance".

b) one has to distinguish between "estrogens" and estradiol, estrone and estriol. those three are all estrogens. Usually doctors only measure estradiol and the pills and gels all have estradiol in them. However what is problematic is not a high estradiol level but a high overall estrogen level. Few doctors measure "total estrogen". The reason this is problematic is: If you take estradiol pills, your estradiol will be only 1/10th of the total estrogen level, the remainder mostly being estrone (which is much less feminizing and has much more unwanted effects). If you take transdermals, the ratio will be about 1:1 or 1:2 and with injections it is more like with women not getting hormone treatment at a ratio of 1:1 or 2:1 (twice as much estradiol as estrone. You see - depending on that raio, your overall estrogen level may be actually lower, while your measured estradiol level appears higher, but its all about the ratio and the "unseen" total estrogen level.

(https://www.susans.org/proxy.php?request=http%3A%2F%2Fi.imgur.com%2Fm70bclq.png&hash=44b709f232964a66d11a57814759c076155a6590)

And last but not least, when I talked about "higher" estrogen levels, I did not mean to take 2 or 3 times the normal dosage. That would be problematic. For most, using the maximum dosage recommended by the manufacturer of those products is enough. Like the strongest dosage of patches available regularly. Injections seem to be ideal as they mimick the estradiol/estrone ratio of natural female hormone systems most closely and I heard of no case yet where this did not supress testosterone significantly when using the dosage recommended by the producer.

But yes - Orchie is another way out , then of course the question is mute which antiandrogen to take ;)

Oh and because I just saw there was some argument about this:
I am a Doctor, but not THAT kind of doctor (loosely quoted from BBC's "Dr Who", but totally applies to me in this case ;) ) - to be precise, I did a PhD in a biochemical field, but not in medical science.

Quote from: anjaq on June 23, 2016, 03:02:48 AMIt should be balanced with progesterone though, otherwise one can have "estrogen dominance".

As I've found out through my own research, browsing through tons of websites and scientific studies/articles, the idea of estrogen dominance is pretty much a myth based on no solid scientific data and which stems from the fact that women with a uterus who only take estrogen increase their risk of having uterine cancer, which clearly is not relevant to us.

Many women will testify that taking estrogen alone suffices and that the addition of progesterone isn't helpful or even makes things worse. What I've come to realize is that every individual is different and for some, progesterone is a welcome addition, for others, not so much, regardless of how high or low estrogen levels are.

Quotethe remainder mostly being estrone (which is much less feminizing and has much more unwanted effects).

What are the unwanted effects of estrone? Are these substantiated by studies in vivo in humans? Estrone can convert back to estradiol.

QuoteIf you take transdermals, the ratio will be about 1:1 or 1:2 and with injections it is more like with women not getting hormone treatment at a ratio of 1:1 or 2:1 (twice as much estradiol as estrone. You see - depending on that raio, your overall estrogen level may be actually lower, while your measured estradiol level appears higher, but its all about the ratio and the "unseen" total estrogen level.

Whether the ratio makes a difference in terms of optimal feminization or overall health risks is subject to debate and has not been sufficiently explored by science such that we really don't know. We cannot just assume that because a ratio similar to ciswomen is achieved that it is healthier because it is what nature intended. This theory needs to be tested so one must remain objective. I suspect estrone perhaps blocks estradiol from binding to receptors and that too much estrone is detrimental to estradiol's effects but who knows?! This was never shown in any study.

I personally have had more positive effects on injections while others may do better on oral. Interestingly though, I have less breast growth overall on injections than on orals so go figure!

QuoteAnd last but not least, when I talked about "higher" estrogen levels, I did not mean to take 2 or 3 times the normal dosage. That would be problematic. For most, using the maximum dosage recommended by the manufacturer of those products is enough.

The normal or maximum dose set by the manufacturer is usually for post-menopausal women or women who've had hysterectomy or are amenorrheic or even women and men with some type of cancer so that none of these recommendations pertain to us. The maximum set for ciswomen who are post-menopausal seems to be rarely, if ever, enough for transwomen as their goals is not relief of post-menopausal symptoms but feminization which often appears to require higher doses.

There is much variance amongst doctors worldwide in how much is prescribed to their transgendered patients so that really, the only normal for us is what is set by the Endocrine Society in the Standards of Care which is regularly updated every few years, I believe and the recommendations aren't a strict guideline either.

My doctors, for instance, have no problem with me taking high dosages of E and P as they have read the research I have provided them with, checked my blood tests results and concluded that high levels aren't the issue as much as the type of estrogen one takes and how it is taken. Some other doctors also share this viewpoint, supported by scientific data but many don't because of the issues with older forms of estrogen in past decades in either transwomen or ciswomen.

QuoteLike the strongest dosage of patches available regularly.

This is a good illustration of how what is recommended by the manufacturer is often not the same as what doctors prescribe to their transgendered patients who usually end up taking more, at least until full development is reached and even then.

QuoteInjections seem to be ideal as they mimick the estradiol/estrone ratio of natural female hormone systems most closely and I heard of no case yet where this did not supress testosterone significantly when using the dosage recommended by the producer.

The dosages recommended by the manufacturer are not the same as those usually prescribed for transgendered women.

Quote from: anjaq on June 23, 2016, 03:07:28 AM
Oh and because I just saw there was some argument about this:
I am a Doctor, but not THAT kind of doctor (loosely quoted from BBC's "Dr Who", but totally applies to me in this case ;) ) - to be precise, I did a PhD in a biochemical field, but not in medical science.

I am also NOT a doctor so please do your own research and consult your doctors.  :)