Spironolactone vs Cyproterone acetate

[2cherry]

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.

[kaitylynn]

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.

[KayXo]

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.

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.

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.

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.

I 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.

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.

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.

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.

And 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.

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.

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

However 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.

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.

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.

Now 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.

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 )

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.

Antiandrogens 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.

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.

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.

Also 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.

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).

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.

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.

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.

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.

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.

No 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.

[Richenda]

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.

[KayXo]

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.

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.

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.

[anjaq]

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.



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

[anjaq]

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.

[KayXo]

It 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.

the 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.

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.

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!

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.

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.

Like 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.

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.

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

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.