blood levels

[R R H]

"Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT, 1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate."

https://www.ncbi.nlm.nih.gov/pubmed/22963114

[Naomi71]

In the United States where the server is located, it's very easy to get sued for providing information that causes harm to to others.

That's an imaginary legal problem. As long as you don't pretend to be a doctor, just speak for yourself and don't recommend your personal dosage to other people, any judge would consider it freedom of speech. To give you just one extreme example: there are girls idealizing anorexia nervosa, gathering on so called "pro ana/ thinspiration" fora. They constantly share information on how to starve themselves to death and there's not a judge in the world who can do a thing about that. You can't get sued for excercising your first amendmend rights. If people take messages like that out of context and start using that as a guideline for their self medication, that's personal responsibility.

We attempt to keep the site clean of dosage information so people who self medicate are unable to use us as a resource.

I  fully agree with that as a moral imperative, because I wish for all transpeople to be careful with their bodies, healthy and have a succesful transition process. I suppose we share the same goals. People self medicating should be discouraged from that every step of the way and one of the (less effective) ways to do that is to keep them away from dosage information. However, that information can be found everywhere, so it seems more effective to me to regulate that information in some way, rather than repressing it. Moderating people mentioning self medication and actively engaging  them seems the best thing to do.

Sites that post dosage information are either unaware of the risk they are taking or they have medical staff which provides them an additional layer of protection.

You seem to implicitly assume here that messages which could be misconstrued as information are information because of that. What you in fact suggest, is that David Chapman, the murderer of John Lennon, could sue JD Salinger, author of The Catcher in the Rye, because the book could be misinterpreted as containing a "trigger for assassination".

It all depends on context. If you pretend to be a medical doctor and start recommending dosages causing damage, that's a legal problem. If you just discuss your own dosage, that's freedom of speech.

Board staff is aware of members who self medicate and we do our best to get them in a proper treatment program as it's both safer and cheeper however countries like the UK have long delays for treatment so self medication is often used to get by until treatment is available.

Well, engaging with people self medicating seems an excellent thing to do

Your argument about the delays hits home. In Holland, we have the exact same problem with long waiting list, unnecessary diagnostics (we don't have informed consent) and our patient org, Transvisie, recently did a survey about the consequences of that. Turns out that 18% of the people who have to wait fifteen monnths or longer (the average delay before you get any hormones) starts self medicating, 15% loses their job, 18% of the relationships goes off the cliffs, 5% starts using drugs or alcohol and 60% experiences problems in public spaces (violence, looks, etc). So we're fighting for informed consent right now

My own diagnostic stage took me a year and it was the worst time of my life. I had already taken the decision to fully transition and to then just talk rather than getting your hormones amplifies the gender dysphoria. I didn't start self medicating though, did lose a job over it, lost my boyfriend, didn't start taking drugs or booze, but did experience violence presenting female and not passing in any way.

[KayXo]

So basically, if you want it all paid for, you stick to the rules. Those rules were formulated by the VU medical center and everyone on hormones gets the same dose and combination of t blockers and estradiol.

Despite individuals being different and not all the same. Their protocol, strangely, does not seem to take this into account.

Aust NZ J ObTtet Gvnaecol 1998. 38: 3: 45

"it is difficult to define a therapeutic drug concentration (...) because patients may vary in their oestradiol requirements. In addition, serum oestradiol levels may not necessarily reflect tissue oestradiol levels." The same can be said of doses.

Did you ever bring this issue up with the doctors and if so, what did they say? Is this due to their publishing studies where things must be standardized so findings may be valid? If so, are those women (participants) aware of this and agree to potentially sacrifice their own results (perhaps a regimen other than the standardized one would have produced better results) for a greater understanding of the effects of HRT in transsexual women? Do they need to sign a consent form?

"For venous thromboembolism, an explanation for the different effects by route of hormone administration is not as clear, although it has been suggested that the metabolites generated from the first-pass metabolism of estrogen may induce thrombogenic changes."[CMAJ. 2013 Apr 16; 185(7): 549–550.]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626805/

Orally, there is more estradiol entering the liver and thus triggering estrogen receptors in the portal vein, which leads to a greater change in the production of proteins and factors involved in coagulation.

Obstet Gynecol Clin North Am. 1987 Mar;14(1):269-98.

"The amount of estradiol leaving the liver following oral administration is substantially less than that which enters it through the portal vein. The systemic administration of estradiol avoids this initial hepatic metabolism. Furthermore, only 25 per cent of nonorally administered estrogen will go to the liver at each pass, and nonhepatic tissues would be exposed to a greater extent than after oral administration. Thus, peripheral administration of estradiol reduces the exaggerated hepatic responses in comparison to nonhepatic actions."

Minerva Endocrinol. 1989 Jan-Mar;14(1):41-4.

"Having no first pass effect on the liver, parenteral administrations have less influence than oral ones on the synthesis of certain proteins by the liver (increased SHBG, CBG, TBG, transferrin, ceruloplasmin, angiotensinogen, clotting factors VII, IX, X and X complex; decreased antithrombin III and anti Xa) and on lipid metabolism (increased biliary cholesterol, triglycerides and HDL, especially HDL2; reduced LDL)."

sublingual administration would also confer a lower risk of DVT. Very interesting.

Yes but some will inevitably be swallowed. The route of administration does not seem to be the only important factor, though.

Prz Menopauzalny. 2014 Oct;13(5):267-72.

"Oral estrogens increase the risk of venous thromboembolic complications to varying extents, probably depending on their type and dose used."

J Clin Endocrinol Metab. 2003 Dec;88(12):5723-9.

"The large differential effect of oral EE and oral E(2) indicates that the prothrombotic effect of EE is due to its molecular structure rather than to a first-pass liver effect (which they share)."

EE = ethinyl estradiol
E2 = estradiol

Andrologia. 2014 Sep;46(7):791-5.

"Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer"

BMJ. 2012 Oct 9; 345

"17-β-estradiol has been reported to be less thrombogenic than conjugated equine oestrogen.21 22"

The reason being that

Minerva Med. 2013 Apr;104(2):161-7.

"Estradiol itself has a lower impact on estrogen-hepatic proteins, and is more readily metabolized by the liver than ethinyl estradiol, the ethinyl group on which slows down that process. The structure increases the bioavailability of ethinyl estradiol compared with E2, but may also contribute to an increased likelihood of estrogen-related adverse events.40"

Equine (horse) estrogen in Premarin and ethinyl estradiol, being harder to break down by the liver, will pass through the portal vein, again and again, triggering receptors, again and again, hence greatly affecting coagulation whereas estradiol after first going through portal vein, will be strongly metabolized so that much less estradiol will survive and circulate through portal vein, again and again (enterohepatic circulation). Surprisingly, in my discussion with several doctors, few seem to be aware of this.

Oral bio estradiol, in very high doses, given to women with advanced breast cancer surprisingly led to a very low incidence of thromboembolic complications, despite their advanced age, as well.

Also this,

J Sex Med. 2016 Nov;13(11):1773-1777.

"From January 1, 2008 through March 31, 2016, 676 transgender women received oral estradiol-based CSHT for a total of 1,286 years of hormone treatment and a mean of 1.9 years of CSHT per patient. Only one individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10,000 person-years."

"93.8% of the transgender women receiving oral estradiol also were prescribed the antiandrogen spironolactone and 16.6% received the antiandrogen finasteride. Conjugated equine estrogens or oral progestins were prescribed to 6.2% and 4.0% of the total study population, respectively. In addition, three patients were prescribed intramuscular medroxyprogesterone acetate in combination with oral estradiol."

"the incidence of VTE observed in the present study is slightly lower than the 8 to 27 events per 10,000 person-years observed in the general population and lower than the 30 events per 10,000 person-years observed in postmenopausal women on unopposed estrogen therapy."

Unopposed estrogen therapy was conjugated equine estrogens so that it is not surprising that incidence was much less in this population which, for the most part, took oral bio-identical estrogen. Also, they were younger, BUT

"our population has a high prevalence of HIV and tobacco use and a large number of African-American individuals, which would be expected to increase the risk of thrombophilia."

There are also limitations of the study which could have lead to underreporting BUT the incidence still remains very low, especially considering a few were taking non bio-identical estrogen or medroxyprogesterone known to increase thromboembolism risks and considering four other factors (demographics) known to increase risks were present to a significant degree. The one incident occurred in someone severely obese (BMI of 37).

Also, this study

Exp Clin Endocrinol Diabetes. 2005 Dec;113(10):586-92.

"Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS."

"Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged."

The only DVT complication was seen in an individual with a pre-existing condition/genetic mutation, in a 62 yr old TS woman, oldest of the group. Out of 60 people. This complication could have occurred, regardless.

Estradiol levels ranged from 325-1183 pmol/L, at 12-24 months.

"Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT, 1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate."

https://www.ncbi.nlm.nih.gov/pubmed/22963114

The oral estrogen included bio-identical estradiol AND conjugated equine estrogens so despite their different effects on coagulation, they were grouped together as oral estrogen. Interestingly, relative risk of venous thromboembolism is LOWER with higher doses of bio-identical estradiol which suggests something else is at play here (i.e. confounding variables). Relative risk with conjugated equine estrogen is higher at higher doses.

[R R H]

Wow. That's so interesting Kay, or at least it is to me. There are a lot of variables showing up in those studies. It would be good to see surgeons finding consensus about this for MtF's prior to surgery, but that's another issue.

[Naomi71]

Despite individuals being different and not all the same. Their protocol, strangely, does not seem to take this into account.

Yes, but fortunately I respond well to that protocol.

Did you ever bring this issue up with the doctors and if so, what did they say? Is this due to their publishing studies where things must be standardized so findings may be valid? If so, are those women (participants) aware of this and agree to potentially sacrifice their own results (perhaps a regimen other than the standardized one would have produced better results) for a greater understanding of the effects of HRT in transsexual women? Do they need to sign a consent form?

No, never brought it up. Why would I? I'm there for my own transition process and don't feel that's the time and place to make some kind of political point, get into all kinds of conflicts with doctors I need on my side. It's working for me. I did sign a consent form for them to take extra blood  for research purposes. Their protocol is  WPATH6 (outdated) with a few alterations that are the result of negotiations with insurance companies and a few governmental institutions, so I believe the existing protocol is a matter of bureaucracy rather than research. VUmc takes care of the full transition process under one roof and arranges for the diagnosis, hormones and all operations. It has advantages and disadvantages.

[Naomi71]

I don't think I have the intellectual curiosity to want to know all the research about hormones, what study contradicts the other, etc. Just some basic stuff about my own medication and dosage, measurement units, how my other medicines correlate with my hormones and bloodlevels so I don't do anything stupid, but I trust my doctor to make the right decisions and keep up with that research.

HRT is only a part of the whole transition process and I'm much more concerned with the emotional and physical changes I'm going through than the actual science behind it. That was different before I started taking hormones, but it seems that whole analytical side of me is gone. Although I know it's well intended, it even upsets me to have to go through such a litany of sciency stuff. Maybe I'd engage in all that research when my HRT wasn't working, but fortunately it is.

Sorry.

Even my reason for wanting a higher dose of estrogen was all but scientific. All my friends got a higher dose and I felt left out. Kind of childish. It was my psychologist who recommended it to the genderteam treating me, because not having the standard dose stressed me out. There probably is some science and biochemistry behind my feeling of well being now I'm on a higher dose, but I'm not truly concerned about that.

[KayXo]

Understood. Your well-being is of utmost importance. 

[LizK]

.... There probably is some science and biochemistry behind my feeling of well being now I'm on a higher dose, but I'm not truly concerned about that.

The why doesn't matter, maybe its the higher dose maybe its not...you are happier and not in any danger. Great outcome for you.....fantastic

Liz

[Naomi71]

Understood. Your well-being is of utmost importance. 

The problem with someone random making scientific claims on the interwebs is that it's an extremely unreliable source of information. Quoting all these studies looks very authoritative, but do you have a professional background in that kind of research? How can I tell you're not merely cherrypicking, misinterpreting, or quoting out of context? To find that out, I will have to factcheck all your sources which is a lot of work (too much to bother with)  and to add insult to injury, you seem to have a tendency to quote a lot of sources without making evident what exactly you mean to say by them.

For example: in one of your messages to me on another forum (that i left), you recommended spiro rather than cypro to me, because that would allegedly lower my blood pressure. Beneath that statement you came up with a lot of important sounding quotes, none of them even mentioning spiro. You all of a sudden turn out to be skilled in the field of cardiology as well, even going as far as claiming that certain combinations of hormones could replace the heart meds that I'm taking. Well, i already experimented with that and it nearly killed me. So let's not.

It's just tiring and I really prefer to rely on an actual endocrinologist and cardiologist for this kind of advice. I have both, so I'm good Also, for efficiency's sake, I prefer to just hear their conclusions in their own words instead of  a random bunch of quotes from papers they base those conclusions on.

So that stresses me out to engage with. It's not good for my well being.

[KayXo]

I don't recommend, I express my opinions on the matter based on the research I come across, trying to remain objective at all times and not cherry picking because my goal is to get at facts, as much as possible. I have principles I abide by and I try to remain as unbiased as possible for own well-being and that of others. I assure you I'm a honest person that is not interested in winning arguments or pride, I dislike these things. I try to consider all perspectives and I spend tens of thousands of hours researching the matter, reading all possible perspectives on the matter. If I am wrong about something, I will admit it and will change my mind. I try to keep up as much as possible with the latest research without dismissing older research as well. I am not a doctor and I don't pretend to be one. I just quote studies. But, you should indeed question whatever I (or anyone) present and doing all that work of fact checking is indeed tiresome and if it compromises your well-being, then I empathize with your position.

I disagree on one point though. Even professionals, doctors are fallible and make mistakes so that double checking, talking to other professionals, reading research material can be useful and in a few instances, life-saving, as I've realized in the past. I no longer blindly follow recommendations after all the wrongdoings I have come across. That is just me, to each their own. But, I also don't let myself get too paranoid and not trust anything anyone says. There is only so much research I can conduct, I have other priorities in my life too. So, there is a point when you have to say to yourself, enough is enough and I'll just cross my fingers and hope these experts are right. Faith!

I don't really see where I may be misinterpreting or quoting out of context but perhaps if you pointed out exactly where I did this, I may realize my own wrongdoing and if so, I apologize in advance. I try to make things as clear as possible but if you have difficulty understanding, I apologize again and would do everything in my power to makes things more understandable.

My goal is to inform so that you may relate this information to your own doctors and incite constructive discussions which may benefit not only you, but the doctor and their own patients. I am open to criticism and always willing to learn. Everyone of us can provide useful feedback and has something important to say and add to the discussion. Every voice is important.

Spiro doesn't allegedly lower blood pressure. This is a fact, as many in this forum can attest to. Several studies also confirm this. Whereas cyproterone acetate, as far as I know, doesn't and actually can lead to water retention, I think, due to its glucocorticoid effects. As always, double check with your doctors and available resources but you say you don't have the time or willingness so what am I to do?

I am not a cardiologist either and am neither skilled or had training in that field. But, I report what studies find and then you decide what you want to do with that. Ignore it, or consider it, talk it over with people that ARE skilled and experienced and see what they say.

I am sorry for stressing you out. That was/is not my intention. I hope you will forgive me and truly, you must know that the well-being of each and everyone of you is what matters to me. I care not about my credibility or reputation. My goal is increased awareness, just and respectful treatment of transsexual women and any minority group in this world. I will admit to being stubborn at times and overly persistent. I am far from flawless but every day, I strive to become a better person but I won't ever be perfect. Imperfection is just fine with me. 

Take care and all the best to you, Naomi.

Sincerely,
Kay

[Naomi71]

I don't recommend, I express my opinions on the matter based on the research I come across, trying to remain objective at all times and not cherry picking because my goal is to get at facts, as much as possible. I have principles I abide by and I try to remain as unbiased as possible for own well-being and that of others. I assure you I'm a honest person that is not interested in winning arguments or pride, I dislike these things. I try to consider all perspectives and I spend tens of thousands of hours researching the matter, reading all possible perspectives on the matter. If I am wrong about something, I will admit it and will change my mind. I try to keep up as much as possible with the latest research without dismissing older research as well. I am not a doctor and I don't preten to be one. I just quote studies. But, you should indeed question whatever I (or anyone) present and doing all that work of fact checking is indeed tiresome and if it compromises your well-being, then I empathize with your position.

In an earlier message, I already defended that freedom to express any opinion, as well as my freedom to criticize your way of exercising that right. You can claim to spend tens of thousands of hours researching these matters, but I would have to take your word for that. And even if you did, your knowledge was never tested by other professionals, you never treated patients, never diagnosed anyone, nor does reading a lot of research prove you understood what you just read, let alone your capacity for synthesizing that knowledge in a working hypothesis. You never did any exams testing your knowledge. Reading up on research is an armchair thing. A hobby. I hope you understand the limitations of that.

Contrastingly, my own endocrinologist did her job for almost 25 years at VU university, which actually has the oldest gender clinic worldwide. She treated thousands of transpeople, her knowledge was tested by peers and she and her team don't just read up on research to which she has better access than you do being a part of academia, they also publish their own research. It has a reason that the latest WPATh convention was hosted in Amsterdam.

I'm not willing to research all that medical stuff, I'm a literary scientist. So I spent tens of thousands of hours studying fairy tales (I specialized in the sleeping beauty), oral traditions, James Joyce and the mechanics of interpretation. I speak seven languages, but only had one year of chemistry and biology in highschool. Given my own limitations and general lack of interest in medical issues, I need to trust someone. Would it be wise to trust you, or my endocrinologist?

I don't want to factcheck your claims, these kinds of publications bore me to no end and I hardly uiderstand the language used in it. I intend to keep it that way.

I disagree on one point though. Even professionals, doctors are fallible and make mistakes so that double checking, talking to other professionals, reading research material can be useful and in a few instances, life-saving, as I've realized in the past.

Of course doctors aren't infallible, but it's reasonable to assume that you're more fallible, not even being qualified as a doctor. Also, when you make a mistake, you cannot be held accountable for that, there are no checks and balances on your dissemination of knowledge. When my endocrinologist makes a mistake, disciplinary hearings will be held and she may even be thrown out of her profession.

When I bring my broken car to a mechanic, there's always a slim chance she made a terrible mistake, causing me to crash and die on the road. But the chance of that happening would be higher when I'd let an unqualified friend fix my car.

I don't really see where I may be misinterpreting or quoting out of context but perhaps if you pointed out exactly where I did this, I may realize my own wrongdoing and if so, I apologize in advance. I try to make things as clear as possible but if you have difficulty understanding, I apologize again and would do everything in my power to makes things more understandable.

Nope, I leave your claims unchallenged and am entirely unwilling to factcheck. I don't want to be forced to read up on research that bores me and instead choose to trust the professional treating me. How could I presume to falsify medical knowledge if I don't even know the difference between units of measurement?

My goal is to inform so that you may relate this information to your own doctors and incite constructive discussions which may benefit not only you, but the doctor and their own patients. I am open to criticism and always willing to learn. Everyone of us can provide useful feedback and has something important to say and add to the discussion. Every voice is important.

Look, I have 45 minute meetings with my endo and we have more pressing matters to discuss than the unqualified opinions of some anonymous person on a forum. You seem to assume that she has no knowledge of the things you came up with, which is presumptuous with an aftertaste of narcissism. You may be willing to learn, but who says she's willing to teach? And no, not every voice is important. Relevance depends on qualifications.

Spiro doesn't allegedly lower blood pressure. This is a fact, as many in this forum can attest to. Several studies also confirm this. Whereas cyproterone acetate, as far as I know, doesn't and actually can lead to water retention, I think, due to its glucocorticoid effects. As always, double check with your doctors and available resources but you say you don't have the time or willingness so what am I to do?

That may or may not be true, but my point was, that you didn't prove that with the quotes you came up with, which didn't even mention spiro. But you went further than that and even claimed that my hormonal treatment could replace my heart meds. Now that's a dangerous claim to make. It may well be an effect of spiro that it lessens one's blood pressure to some extent, but only if the cause of that high blood pressure is an elevated level of aldosterone. Did you read this research paper about it?

Even the Wikipedia page on spiro states:

"...a Cochrane review found adverse effects at high doses and little effect on blood pressure at low doses in the majority of people with high blood pressure."

So I'll just stick with my present medication if you dont mind, which causes a 125/70 heart rate. If it ain't broken, don't fix it.

I am not a cardiologist either and am neither skilled or had training in that field. But, I report what studies find and then you decide what you want to do with that. Ignore it, or consider it, talk it over with people that ARE skilled and experienced and see what they say.

Yes, you made that abundantyly clear with your ill adviced remarks on spiro that you in fact are not a cardiologist. If I'd follow your advice, I'd be back to a 182 heart rate in no time. Your advice could kill me. You were obviously unaware of the study I just presented to you and instead presented studies as "proof" that didn't evern mention spironolactone. You were just disseminating hot air.

I am sorry for stressing you out. That was/is not my intention. I hope you will forgive me and truly, you must know that the well-being of each and everyone of you is what matters to me. I care not about my credibility or reputation. My goal is increased awareness, just and respectful treatment of transsexual women and any minority group in this world. I will admit to being stubborn at times and overly persistent. I am far from flawless but every day, I strive to become a better person but I won't ever be perfect. Imperfection is just fine with me.

Yes I forgive you and just hope that you will show a little more modesty in presenting your emphatically unqualified opinions.

Love, hugs and no hard feelings,

Naomi

[Lucie]

I agree that reading and studying informations given by Kay and other people about HRT, on Susan's or other discussion panels, takes me a significant amount of time and can be sometimes rather stressful and tiring.
However I have to admit that all these informations have been and still are much much helpful to me for discussing my treatment with doctors and making it as successful and free of adverse effects as possible.

[Naomi71]

The problem is, that it isn't necessarily information, but might well be misinformation. Like in the spiro example I debunked. Research already proved that high doses of spiro generally have adverse affects on blood pressure and low doses do nothing, but Kay presented spiro as an effective blood pressure medicine, even going as far as claiming the spiro could replace my heart meds. If I had heeded that opinion, it could have killed me.

It's also about the way Kay frames her opinions (I know a little bit more about epistemology than medicine). They're presented as objective, propositional knowledge (knowledge being justified true belief) instead of opinion, I don't see a shred of doubt or a disclaimer in a statement followed by a set of impressive research quotes. It's presented as fact instead of opinion, which is misleading.

[Lucie]

Kay presented spiro as an effective blood pressure medicine, even going as far as claiming the spiro could replace my heart meds. If I had heeded that opinion, it could have killed me.

I do not self-medicate and I'd never consider as prescriptions advices given about HRT here or elsewhere. I take them only as elements (among others) to be discussed with my doctors.

[KayXo]

Research already proved that high doses of spiro generally have adverse affects on blood pressure and low doses do nothing, but Kay presented spiro as an effective blood pressure medicine

Spironolactone COULD perhaps be an effective blood pressure medicine (as well as having anti-androgenic actions) and an option given your situation (to be ultimately determined by doctor) at typical doses prescribed to transsexual women. Doctors will usually start low (but not too low) to see how patient reacts.

I take them only as elements (among others) to be discussed with my doctors.

Exactly that. I present information others may or may not be aware so that it may be critically examined with health experts. There is a chance it could be helpful or not. Experts don't always know everything, as I've several times realized and may benefit from their own patient's research and feedback. Mine did and she thanked me. My doctor welcomes and even encourages me to share any pertinent studies I come across with her. Working together with one's doctor is, I believe, the optimal and most effective approach instead of the traditional, he/she says and I follow.

I once went to see a doctor who held a prestigious position in endocrinology, who treated many transsexual patients before and who knew nothing about cyproterone acetate's effects on prolactin going as far as denying it when studies (and plenty of anecdotal evidence) clearly show otherwise. Another very reputable endocrinologist claimed HRT in transsexual women would increase the risk of breast cancer when it was found and concluded in studies that this was not the case so I corrected him and he finally agreed.

My point here is not to put down doctors and I don't blame them for not knowing everything (they are busy, they can only do so much) but to simply say that on occasion, being armed with extra knowledge in the matter puts you at an advantage, where you can share information with your doctor that he/she may not be aware of. Help them become better informed, is what I'm saying and protect yourself of potential mistreatment or increase your odds of getting the best treatment possible. My endocrinologist even admitted that what he valued most was his patient's feedback and that is how he learned the most, not what he was taught at school (i.e. Cambridge University). HRT treatment of transsexual individuals is certainly not something you learn about in medical school but on the field, through your patients and by reading as much on the research pertinent to the matter, as possible, the latter being somewhat of a problem for doctors that just don't have the time, sometimes, to keep up and read all that stuff.

[Naomi71]

Ah yes. All those wretched ignorant doctors who know next to nothing about their own profession. Lay people should help them!

Spironolactone COULD perhaps be an effective blood pressure medicine (as well as having anti-androgenic actions) and an option given your situation (to be ultimately determined by doctor) at typical doses prescribed to transsexual women. Doctors will usually start low (but not too low) to see how patient reacts.

No Kay, please. It could not. Did you even read the research I linked to in my reply to you? I already tried to explain to you, that spiro only works as a high blood pressure inhibitor if that pressure is caused by a thyroid disorder, resulting in elevated levels of aldosterone in your body. Spiro is an aldosterone inhibitor and definitely doesn't work as a high blood pressure inhibitor in general like you continue to falsely suggest, notwithstanding evidence to the contrary, that you for some reason choose to ignore. Thing is, my aldosterone levels are just fine, the high blood pressure has other causes. In my case, it's a hereditary thing.

I also showed you, that even with people who have that thyroid disorder, it's not working in low doses and has adverse effects in high doses. So no. in my case it could not have that effect under any circumstance.

More importantly, you're trying to solve a nonexistent problem. With the heart medication I'm presently taking, my blood pressure levels are just fine and I get half the standard dose of cypro, that already made my testosterone unmeasurable (below 0.5).

So no, I will not bother my cardiologist and endocrinologist with this. It's nonsens.

p.s. You still failed to come up with research proving all the wonderful workings of spiro as a general high blood pressure inhibitor. You don't have to come up with lengthy quotes, but why don't you provide me with a few links to all that great research you're referring to?

[KayXo]

Obstet Gynecol. 2015 Mar;125(3):605-10.

"In transgender women, estrogen therapy, with or without antiandrogen therapy, was associated with lower BP."

"Transgender women were treated with estrogens. Fourteen (88%) were given sublingual micronized 17-beta estradiol (...). One subject was given (...) estradiol via transdermal patch, and one subject received estradiol valerate (...) intramuscular every 2 weeks. All but one transgender woman (who wished to retain erectile function) were administered spironolactone"

"Transgender women (persons assigned male at birth, but who identify as females and who use estrogens with or without an anti-androgen to develop female secondary sex characteristics) had normal median baseline and 6 month body mass index (24.8 kg/m2 (IQR=4.3) and 23 kg/m2 (IQR=4.5) respectively). Both systolic and diastolic median blood pressures in this group dropped significantly from baseline to 6 months (130.5 mmHg (IQR 11.5) to 120.5 mmHg (IQR 15.5) p=.006; 78 mmHg (IQR 21) to 67 mmHg (IQR 12), p=.001 respectively)."

"All transgender women had estradiol levels at least in the physiologic female – range at 6 months, with 3/16 (19%) having supraphysiologic levels > 1000pg/dl (including the one transgender woman using intramuscular estradiol valerate). At 6 months, free testosterone was in the female physiologic range in 14/15 (93%), however only 10/15 (66%) had total testosterone levels in the female physiologic range (Table 4)."

Arch Sex Behav. 1989 Feb;18(1):49-57.

"The clinical and hormonal response to 12-month therapy with the antiandrogen, spironolactone, in conjunction with near-physiologic doses of female gonadal steroids in 50 transsexual males, is presented."

"The antihypertensive medication, spironolactone, is an effective therapy for androgen excess in women (Cummings et al., 1982; Shapiro and Evron, 1980; Messina et al., 1983). Although it was created as a mineralocorticoid antigonist, it is a true antiandrogen since it interferes with dihydrotestosterone action in the pilosebaceous unit. Spironolactone has multiple other actions including lowering testosterone (T) production by reduction of cytochrome P450, decreasing sex hormone binding thereby increasing free T clearance, and lowering gonadotrophins (Givens, 1985)."

"This study reports three changes to conventional therapy for transsexual men: (i) near-physiologocal doses of cyclic oral conjugated estrogen, (ii) cyclic or continuous medroxyprogesterone, and (iii) spironolactone."

"Systolic blood pressure dropped (128 +/- 14 to 121 +/- 14 mm Hg, p less than 0.05). The clinical response, including decreased male pattern hair, breast development, feminization, and lack of erections was excellent in most subjects."


Interesting study I came across...

J Sex Med. 2016 Nov;13(11):1765-1772.

"Eighty-two patients were included in the spironolactone group and 31 patients were included in the CPA group. Baseline HDL and prolactin levels were not significantly different between the two groups. At 12 months, HDL increased by 0.10 mmol/L (SD = 0.24) in the spironolactone group but decreased by 0.07 mmol/L (SD = 0.21) in the CPA group (P = .002). The difference remained significant after adjusting for baseline HDL, use of lipid-lowering drugs, and age. The change in prolactin was +3.10 μg/L (SD = 5.70) in the spironolactone group and +11.8 μg/L (SD = 8.63) in the CPA group (P < 0.001). This difference also remained significant after adjusting for baseline prolactin level."

"These data suggest that spironolactone use in transgender women increases HDL levels and that CPA has the opposite effect. CPA also is associated with a larger increase in prolactin. These factors should be considered when choosing between these two antiandrogen agents."

I know several transsexual women who changed their blood pressure medication to Spironolactone after starting transition and had positive outcomes. Not only did it lower blood pressure but it inhibited androgen significantly. This needs to be discussed with a physician, of course as each case is different so while, it may be doable and beneficial for some, it may not for others. There is no harm in simply bringing it up with doctors and see what they say.

[Naomi71]

You've only managed to come up with research that really doesn't prove your point about spiro, although you present the information deceptively to make it look like it does if one takes a superficious look at it. A little intellectual integrity would be nice.  All of the papers you quote from show combinations with other substances that lower blood pressure too and your first paper even explicitly states, that the lower blood pressure was also accomplished without antiandrogen therapy (that is, spiro).

In an earlier reply I mentioned cherrypicking, misinterpreting and taking out of context. You did all of that.

Obstet Gynecol. 2015 Mar;125(3):605-10.

"In transgender women, estrogen therapy, with or without antiandrogen therapy, was associated with lower BP."

"Transgender women were treated with estrogens. Fourteen (88%) were given sublingual micronized 17-beta estradiol (...). One subject was given (...) estradiol via transdermal patch, and one subject received estradiol valerate (...) intramuscular every 2 weeks. All but one transgender woman (who wished to retain erectile function) were administered spironolactone"

That doesn't prove its because of the spiro these women have lower blood pressure. In fact it was proven that estradiol protects against hypertension, so this is a misrepresentation. Are you now taking research results out of context to create the false suggestion it was all because of the spiro? To wit (from "estrogen and hypertension")

" Both animal experimental and human clinical investigations suggest that estrogen engages several mechanisms that protect against hypertension, such as activation of the vasodilator pathway mediated by nitric oxide and prostacyclin and inhibition of the vasoconstrictor pathway mediated by the sympathetic nervous system and angiotensin."

Additionally, the lower blood pressure was also accomplished without the spiro, like you quoted yourself.

The clinical and hormonal response to 12-month therapy with the antiandrogen, spironolactone, in conjunction with near-physiologic doses of female gonadal steroids in 50 transsexual males, is presented."

"Systolic blood pressure dropped (128 +/- 14 to 121 +/- 14 mm Hg, p less than 0.05). The clinical response, including decreased male pattern hair, breast development, feminization, and lack of erections was excellent in most subjects."

Doesn't prove anything either about spiro, because gonadol steroids already have beneficial cardiovascular effects. To wit (from "Effects of Gonadal Steroids and Their Antagonists on DNA
Synthesis in Human Vascular Cells"):

"Gonadal steroid–dependent inhibition of VSMC proliferation and stimulation of endothelial
replication may contribute to vascular protection and remodeling responses to vascular injury."

The "interesting study" you came across doesn't even look at blood pressure.

So no, you didn't prove anything, but just took some research out of context that doesn't  prove a causal relationship between spiro and lower blood pressure.

[Naomi71]

I know several transsexual women who changed their blood pressure medication to Spironolactone after starting transition and had positive outcomes.

Anecdotal "evidence" doesn't prove a thing either.

[KayXo]

All of the papers you quote from show combinations with other substances that lower blood pressure too and your first paper even explicitly states, that the lower blood pressure was also accomplished without antiandrogen therapy (that is, spiro).

Indeed, you are right. I was pressed for time so didn't manage to mention the other studies but they are nonetheless interesting although not showing unequivocally that spironolactone alone reduces blood pressure.

The "interesting study" you came across doesn't even look at blood pressure.

Indeed, you are right again. It does not pertain to the matter at hand but came across it so thought it was interesting to mention it since these anti-androgens are typically prescribed to us, pre-op.

So no, you didn't prove anything, but just took some research out of context that doesn't  prove a causal relationship between spiro and lower blood pressure.

Hypertension. 2007;49:839-845

"We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment."

"During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: ±18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of ≈3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension."

The dose used was lower than what is typically prescribed to transsexual women. Adverse effects, as expected. Among those, some we don't mind at all like gynecomastia.

Addition of spironolactone very effective in resistant hypertension
31-8-2015 • ESC - London 2015

The principal results of the Prevention And Treatment of Hypertension With Algorithm based therapY (PATHWAY) - Optimal treatment of drug resistant hypertension - PATHWAY 2
Presented at the ESC Congress 2015 by: Bryan Williams (London, UK)

"PATHWAY 2 examined whether additional diuretic therapy with spironolactone would be the most effective at reducing BP compared to treatment with two other antihypertensives that have different mechanisms of action: doxazosin which acts to reduce arterial resistance, and bisoprolol which acts to reduce cardiac output.
The study included patients with resistant hypertension who were already treated with maximally tolerated doses of a combination of three drugs"

"In 314 patients, spironolactone had superior HSBP control compared to placebo (a reduction of 8.70 mmHg, P<.001); doxazosin (a reduction of 4.03 mmHg, P<0.001), and bisoprolol (a reduction of 4.48 mmHg, P<0.001); as well as the mean of doxazosin and bisoprolol (a reduction of 4.26 mmHg, P<0.001)."

"Overall, almost three quarters of patients with uncontrolled blood pressure saw a major improvement in their blood pressure on spironolactone, with almost 60% meeting a stringent measure of blood pressure control (P<0.001)."

"Spironolactone was the best drug at lowering blood pressure in 60%, whereas bisoprolol and doxazosin where the best drug in only 17% and 18% respectively."

"Spironolactone was well tolerated with no significant excess adverse effects with the caveat that serum potassium levels and renal function should be monitored on treatment and treatment duration was too short to assess incident gynecomastia (~6% in longer-term studies)"

"Spironolactone unequivocally showed to be the most effective treatment for resistant hypertension."

"According to prof. Williams, the findings "challenge the concept that that resistant hypertension cannot be treated adequately with drug therapies, and suggest that treatments which have a natriuretic action, in that they promote sodium excretion, are likely to be the most effective"

Methodist Debakey Cardiovasc J. 2015 Oct-Dec;11(4):235-9.

"Spironolactone and eplerenone both affect reductions in blood pressure either as mono- or add-on therapy; moreover, they each afford survival benefits in diverse circumstances of heart failure and the probability of renal protection in proteinuric chronic kidney disease."

"Hyperkalemia should always be considered a possibility in patients receiving either of these medications; therefore, anticipatory steps should be taken to minimize the likelihood of its occurrence if long-term therapy of these agents is being considered."

Nephrology (Carlton). 2015 Aug;20( 8 ):567-71.

"At 6 months, systolic BP decreased by 24 ± 9.2 mmHg (from 163.6 ± 8.6 to 139.6 ± 8.1 mmHg) in the spironolactone group, compared with 13.8 ± 2.8 mmHg (from 162 ± 7.9 to 148 ± 6.4 mmHg) in the furosemide group (P < 0.01). Diastolic BP fell 11 ± 8.1 mmHg in the spironolactone group compared with 5.2 ± 2.2 mmHg in the furosemide group (P < 0.01)."

"Spironolactone is more effective than furosemide for control of BP in RHT patients, with a positive added effect on albuminuria. Spironolactone is safe in patients with mild kidney impairment, although serum potassium should be closely monitored, especially in diabetics."

Medicine (Baltimore). 2014 Dec;93(27)

"This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension. Patients with office systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial."

"One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned to receive (...) spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization."

"At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of -9.8, -13.0, -10.5, and -9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office. The respective DBP differences were -3.2, -6.4, -3.5, and -3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003). Adverse events in both groups were comparable. The office SBP goal <14 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001). Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control."

Med J Aust. 1980 Feb 9;1(3):124-5.

"Once-a-day therapy with spironolactone has been compared with a twice-a-day regimen in an open crossover trial in patients with essential hypertension. When compared with placebo, both treatments significantly lowered blood pressure. Twice-a-day therapy provided slightly better blood pressure control than the once-a-day dosing schedule. There were only minor differences in biochemical findings between the two regimens. Three of the 17 patients developed reversible gynaecomastia."

J Hypertens. 2013 Oct;31(10):2094-102.

"Low dose spironolactone exerts significant BP and urinary albumin creatinine ratio lowering effects in high-risk patients with resistant hypertension and type 2 diabetes mellitus"

Am J Cardiol. 1990 Jun 19;65(23):36K-38K.

"In a double-blind, randomized, multicenter study of 194 patients with moderate hypertension, spironolactone and nifedipine were found to reduce blood pressure (BP) to about the same extent and in the same percentage of patients after 45 days of treatment (47 and 50%, respectively)."

Am J Cardiol. 1987 Oct 1;60(10):820-5.

"Despite limitations inherent in the interpretation of data banks, it is concluded that spironolactone administered in daily practice reduced BP without inducing adverse metabolic adverse effects"

Eur J Clin Pharmacol. 1982;21(4):263-7.

"Since there is only scanty, indirect information about the mechanism of the hypotensive effect of spironolactone, 9 patients with essential hypertension were studied according to a randomised double-blind, cross-over protocol."

"After spironolactone there was a significant decrease in the systolic and diastolic blood pressures in the supine, sitting and standing positions; the sitting systolic and diastolic blood pressure decreased by (mean +/- SE) 27 +/- 4mm Hg (p less than 0.001) and 11 +/- 4mm Hg (p less than 0.02), respectively."

"The present data confirm the hypotensive properties of spironolactone and show that this effect is associated with dilatation of muscle and skin arteries in many but not in all the patients."

Hypertension. 1980 Sep-Oct;2(5):672-9.

"In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of (...) spironolactone were investigated in 45 outpatients with primary hypertension"

"All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients."

"Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature."

J Endocrinol Invest (2015) 38:269–282

"Spironolactone is the anti-androgen most
widely used in the United States. It has similar properties to
those of cyproterone acetate, as it directly inhibits testosterone
secretion and blocks the binding of testosterone to its
receptors. When it is used, blood pressure and electrolytes
need monitoring to avoid hypotension and/or hyperkalemia."

J Sex Reprod Med Vol 1 No 1 Summer 2001
Towards optimal hormonal treatment of male to female
gender identity disorder

"Spironolactone's hypotensive effect
is an advantage in many cases, but in a small minority of
patients, particularly in the leaner and very physically
active individual, the hypotensive effects necessitate a
change in therapy"