Susan's Place Transgender Resources

It seems it has been forever since I have posted and I wanted to pose a question to the board. I have searched and found some articles on the question, but I wanted to put some serious thought into this only because I fear the current "standard" is incorrect.

The current consensus for cross hormone therapy is to target the "average" pre-menopausal hormone levels for females - the recommended levels based on the Endocrine Society is <200 and the Royal College of Psych is <140.

First question: where did this come recommendation come from? Was this just considered a good idea? or is this some who started therapy and said, "this sounds good." I tend to feel it is the later because there is no research I can find that says this is appropriate. Here are my arguments.

1) Everyone is different - we try to compartmentalize everyone into nice little boxes. this is blatantly wrong in so many ways. Every single person out there metabolizes medications completely different than someone else. Some people can tolerate certain medications - where as others it may cause serious side effects. Simple example - Lisinopril or ACE inhibitors for high blood pressure - one of the side effects is cough. it doesn't effect everyone, but for those that it does it means you shouldn't take the medication. Same should hold for cross-gender hormone therapy.

2) Doses matter - similar to the above - dosing makes a difference - obviously metabolism varies from person to person. I am a perfect example of this. My dosage is actually quite low, but my "lab values" on very low doses stays high throughout the injection period.

3) Lab values do not correlate with effect - people respond to different circulating levels of hormones. Again this should be fairly obvious. Some people need higher levels to have a feminizing response - others not so much. For some it's not the level, but the fact that it is there. We are just now figuring this out with Vitamin D levels - some people don't need so much, but other need replacement vitamin D. Go figure - One of the tenants of medicine is treat the patient, not the lab value.

4) Blood-Brain Barrier - just more physiology going on here - body/blood levels do not necessarily correlate with what actually enters the brain.

I am sure there is more to this than what I am writing - this was just my thoughts starting out.

So, again - why the 200? - checking this graph: https://upload.wikimedia.org/wikipedia/commons/c/c8/Hormones_estradiol%2C_progesterone%2C_LH_and_FSH_during_menstrual_cycle.svg

Ranges from 50-400 pg/ml or 100-1600pmol/L - that seems like pretty wide variability to me. Actually, the thing I notice with the graph is it does not go above 400pg/mL suggesting even wider ranges than what I have posted.

Thoughts?

Eliza

Levels greater than 200 pg/ml occur in a spike of only 3 out of 30 days.  They are much lower most of the rest of the time.  So targeting a level of 200 pg/ml, or less, still gives one a much higher average level than CIS females.  It does not appear unreasonable to me.


It is better to be hated for what you are than to be loved for what you are not.
André Gide, Autumn Leaves

You bring up valid points. The doctor I see doesn't place much value at all on lab results, preferring to go on how it feels (to the patient). At first I didn't really like this approach, and got on a waiting list for a proper endocrinologist. One appointment later and I'm going back to the first lady.

In moving upward through the dose range, I eventually hit a dose where things felt right. The dosages leading up to it didn't really feel wrong, but at a certain level it felt like things started to click and sink in properly or something. Not sure how to explain it - it felt less like my body was in limbo or yo-yo'ing back and forth between a dosage increase and when I would get used to it, and was settling into proper function and rhythm. I feel that is my minimum proper dosage level, though I haven't tried going above it to see if it manages to feel even more right.

All that said, they have found elevated prolactin levels which has forced me to cut my dose in half and go get some tests to see if my pituitary gland is growing bad things. So maybe monitoring E levels and basing dosage on them is the way to go after all? I don't know.

Quote from: IdontEven on November 18, 2016, 07:05:26 PM
You bring up valid points. The doctor I see doesn't place much value at all on lab results, preferring to go on how it feels (to the patient). At first I didn't really like this approach, and got on a waiting list for a proper endocrinologist. One appointment later and I'm going back to the first lady.

In moving upward through the dose range, I eventually hit a dose where things felt right. The dosages leading up to it didn't really feel wrong, but at a certain level it felt like things started to click and sink in properly or something. Not sure how to explain it - it felt less like my body was in limbo or yo-yo'ing back and forth between a dosage increase and when I would get used to it, and was settling into proper function and rhythm. I feel that is my minimum proper dosage level, though I haven't tried going above it to see if it manages to feel even more right.

All that said, they have found elevated prolactin levels which has forced me to cut my dose in half and go get some tests to see if my pituitary gland is growing bad things. So maybe monitoring E levels and basing dosage on them is the way to go after all? I don't know.

What have your levels been and where arevthey at now? I was at 300 my last test and my endo kind of freaked and cut my dosage by a third. I'd be fine with all of it but it feels like the process is slowing downxor maybe even going backwards. Its really got my brain zingin' and sometimes I feel like I'm spinning my wheels.

Quote from: eliza2014 on November 18, 2016, 06:29:27 PM
It seems it has been forever since I have posted and I wanted to pose a question to the board. I have searched and found some articles on the question, but I wanted to put some serious thought into this only because I fear the current "standard" is incorrect.

The current consensus for cross hormone therapy is to target the "average" pre-menopausal hormone levels for females - the recommended levels based on the Endocrine Society is <200 and the Royal College of Psych is <140.

First question: where did this come recommendation come from? Was this just considered a good idea? or is this some who started therapy and said, "this sounds good." I tend to feel it is the later because there is no research I can find that says this is appropriate. Here are my arguments.

1) Everyone is different - we try to compartmentalize everyone into nice little boxes. this is blatantly wrong in so many ways. Every single person out there metabolizes medications completely different than someone else. Some people can tolerate certain medications - where as others it may cause serious side effects. Simple example - Lisinopril or ACE inhibitors for high blood pressure - one of the side effects is cough. it doesn't effect everyone, but for those that it does it means you shouldn't take the medication. Same should hold for cross-gender hormone therapy.

2) Doses matter - similar to the above - dosing makes a difference - obviously metabolism varies from person to person. I am a perfect example of this. My dosage is actually quite low, but my "lab values" on very low doses stays high throughout the injection period.

3) Lab values do not correlate with effect - people respond to different circulating levels of hormones. Again this should be fairly obvious. Some people need higher levels to have a feminizing response - others not so much. For some it's not the level, but the fact that it is there. We are just now figuring this out with Vitamin D levels - some people don't need so much, but other need replacement vitamin D. Go figure - One of the tenants of medicine is treat the patient, not the lab value.

4) Blood-Brain Barrier - just more physiology going on here - body/blood levels do not necessarily correlate with what actually enters the brain.

I am sure there is more to this than what I am writing - this was just my thoughts starting out.

So, again - why the 200? - checking this graph: https://upload.wikimedia.org/wikipedia/commons/c/c8/Hormones_estradiol%2C_progesterone%2C_LH_and_FSH_during_menstrual_cycle.svg

Ranges from 50-400 pg/ml or 100-1600pmol/L - that seems like pretty wide variability to me. Actually, the thing I notice with the graph is it does not go above 400pg/mL suggesting even wider ranges than what I have posted.

Thoughts?

Eliza

I've said this several times before. Consider the following:

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

"it is difficult to define a therapeutic drug concentration when considering implant therapy because patients may vary in their oestradiol requirements (...). In addition, serum oestradiol levels may not necessarily reflect tissue oestradiol levels."

CLIMACTERIC 2005;8(Suppl 1):3–63

"Even though there is a significant correlation between
the serum concentrations of estradiol and their
clinical effects, e.g. on hot flushes or bone mass,
the serum level of an individual woman does not
predict the therapeutic effect. As shown in Figure 1,
the number of hot flushes differs largely in
patients who showed identical estradiol levels
during transdermal hormone therapy1. This casts
considerable doubts on the usefulness of regular
measurements of hormone levels for the prediction
or control of a therapeutic success."

Maturitas, 12 (1990) 171-197

"When the serum concentrations of natural or synthetic sex steroids are measured
at short time-intervals after administration and repeatedly during long-term
treatment, it becomes obvious that there are large intra-individual and interindividual
variations. This holds true for both the contraceptive steroids and the natural
oestrogens and does not apply solely to the oral route. Long-term studies
indicate that an important influence is exerted by predisposing factors, particularly
the metabolic capacity of the liver, on the pharmacokinetics of sex steroids.
Large variations in oestradiol and oestrone levels can be observed in an individual
woman from day to day or from hour to hour, even during transdermal therapy
with oestradiol"

So that measuring levels is inaccurate too, for this reason.

Ideal range for transsexual patients was arbitrarily set, no research supports this.

Quote from: Deborah on November 18, 2016, 07:01:36 PM
Levels greater than 200 pg/ml occur in a spike of only 3 out of 30 days.  They are much lower most of the rest of the time.  So targeting a level of 200 pg/ml, or less, still gives one a much higher average level than CIS females.  It does not appear unreasonable to me.

Depends on the graph you're looking at. Based on http://lakecharlesobgyn.com/Images/hormones-1.jpg

Starting on day 7, levels begin to surpass 200 pg/ml until day 14, then around day 17, they rise again to 200 pg/ml + until day 26. 7-13 = 7 days AND 17-26 = 10 days. So out of a total of 28 days, 17 days are marked by levels of 200 pg/ml or more.

Also, women experience pregnancy, where for 9.5 months, levels range anywhere from 1,000-75,000 pg/ml. Some women have several pregnancies so that their average levels during reproductive years would be higher. Traditionally, women spent much more time being pregnant and less time cycling every month so that naturally, it would seem women should have, on average, relatively high levels of estradiol through their reproductive years, higher than today. See later...

Then, we need to ask ourselves why mimic ciswomen? We aim for development (and maintenance) of female secondary sexual characteristics (i.e. breasts). When girls entered puberty and developed breasts, for instance, their growth hormone levels were significantly higher, sensitivity probably different (i.e. greater) due to age, they didn't have male characteristics as we do so that aiming for more or less similar levels is not, in my opinion, justified (different population with different needs), especially considering the fact that studies have shown higher levels to pose relatively low health risks when bio-identical estradiol is taken, especially non-orally.

I didn't have breast growth at at 230 pg/ml but only at around 500-700 pg/ml. Had I remained at less than 200 pg/ml, it would have been unfortunate for me. I also feel and look better at higher levels. In the end, it depends on the person and this should be determined by the doctor based on their findings in their patients. 

I found this statement from a study particularly interesting:

Horm Metab Res. 1994 Sep;26(9):428-31.

"pseudopregnancy may be useful and effective in osteopenia and lacking secondary sexual development due to gonadal dysgenesis like in Ullrich-Turner syndrome (after completion of growth), where substitution doses of ovarian hormones may be not sufficient enough to guarantee satisfactory response."

So, that depending on circumstances, higher levels may be needed with very little side-effects, it appears.

"We have experience with therapeutic pseudopregnancy in about 200 patients with mammahypoplasia (Lauritzen 1992). Its rate of objective and subjective tolerance is excellent."

"Investigations of lipids, liver enzymes and haemostasiology to be published later will show the absence of unwanted metabolic effects of this regimen."

"In conclusion, our data show, that the treatment (...) by means of high parenteral estrogen-progestogen depot injections is effective. Virtually no side effects occurred. The therapy is well accepted by the patients."

Quote from: IdontEven on November 18, 2016, 07:05:26 PMAll that said, they have found elevated prolactin levels which has forced me to cut my dose in half and go get some tests to see if my pituitary gland is growing bad things. So maybe monitoring E levels and basing dosage on them is the way to go after all? I don't know.

Symptoms of a prolactinoma (benign pituitary tumor) usually include headaches, vision problems and galactorrhea. Levels also will usually remain high and might even continue increasing. If they drop in accordance with estrogen levels, that appears to be a good sign.

Prolactin levels go way up during pregnancy (and breastfeeding), up to 600 ng/ml because of (during pregnancy) very high levels of estrogen (estradiol up to 75,000 pg/ml) and progesterone (up to 300 ng/ml). Women traditionally spent most their lives being in either state during their reproductive years and survived to have many children. Do we tell women to avoid pregnancy/breastfeeding because of this?

http://gladwell.com/john-rock-s-error/

"The Dogon grow millet, sorghum, and onions, raise livestock, and live in adobe houses on the Bandiagara escarpment. They use no contraception. Many of them have held on to their ancestral customs and religious beliefs. Dogon farmers, in many respects, live much as people of that region have lived since antiquity. Strassmann wanted to construct a precise reproductive profile of the women in the tribe, in order to understand what female biology might have been like in the millennia that preceded the modern age. In a way, Strassmann was trying to answer the same question about female biology that John Rock and the Catholic Church had struggled with in the early sixties: what is natural? Only, her sense of "natural" was not theological but evolutionary. In the era during which natural selection established the basic patterns of human biology–the natural history of our species–how often did women have children? How often did they menstruate? When did they reach puberty and menopause? What impact did breast-feeding have on ovulation?"

"Among the Dogon, she found, a woman, on average, has her first period at the age of sixteen and gives birth eight or nine times. From menarche, the onset of menstruation, to the age of twenty, she averages seven periods a year. Over the next decade and a half, from the age of twenty to the age of thirty-four, she spends so much time either pregnant or breast-feeding (which, among the Dogon, suppresses ovulation for an average of twenty months) that she averages only slightly more than one period per year. Then, from the age of thirty-five until menopause, at around fifty, as her fertility rapidly declines, she averages four menses a year. All told, Dogon women menstruate about a hundred times in their lives. (Those who survive early childhood typically live into their seventh or eighth decade.) By contrast, the average for contemporary Western women is somewhere between three hundred and fifty and four hundred times."

"But over all she believes that the basic pattern of late menarche, many pregnancies, and long menstrual-free stretches caused by intensive breast-feeding was virtually universal up until the "demographic transition" of a hundred years ago from high to low fertility. In other words, what we think of as normal–frequent menses–is in evolutionary terms abnormal. "It's a pity that gynecologists think that women have to menstruate every month,"Strassmann went on. "They just don't understand the real biology of menstruation.""

Prolactin
edited by Nelson D. Horseman

« neither pregnancy (77) nor prolonged usage of hormonal contraceptives have been demonstrated to induce "de novo" appearance of prolactinomas (78)."

Ann Endocrinol (Paris). 2007 Jun;68(2-3):106-12.

"In women with microadenomas, pregnancy generally has little impact on their adenoma, delivery is normal and breast-feeding is allowed."

J Clin Endocrinol Metab. 2007 Aug;92( 8 ):2861-5.

"Despite the tumor expansion and pituitary growth that occurs during gestation, observational studies have shown that pregnancy has a favorable effect on the natural history of preexisting prolactinomas. Prolactin levels are lower after delivery than before conception and complete remission of hyperprolactinemia has been reported in 17–37% of women after pregnancy (19, 20). 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)."

Despite high doses of estrogen in the past amongst transsexual women, since the 1960's, there only have been 8 cases of prolactinomas reported, 5 of which were associated with the use of cyproterone acetate which tends to abnormally stimulate prolactin synthesis, 2 of which were associated with the use of another non bio-identical progestogen known to favor prolactinoma in rats and where the use of non bio-identical estrogens was quite prevalent. There has been to date no prolactinoma reported, associated with the use of exclusively bio-identical E and P.

Andrologia. 2015 Aug;47(6):680-4.

"Prolactinomas in oestrogen-treated MtoF persons are
rare. In the Amsterdam Gender Clinic between 1975 and
2006, 2306 MtoF transsexual subjects were treated. The
mean age at initiation of treatment was 29.3   12.7 years,
with a range of 16–83 years. Mean follow-up in these
subjects was 21.4 years, providing a total of 51 173
person-years of exposure and follow-up. Follow-up of
20 years or more was available of 303 individuals,
including follow-up of 30 years or greater in 151. In this
population, only one case of a prolactinoma was encountered."

"In Trangender Clinic of Hospital das Clınicas, at the
Medical School of University of Sao Paulo, 166 MtoF
transsexuals have been followed since 1996. Unsupervised
use of oestrogens was estimated in 88.2% of the total
cases. The mean age at initiation of oestrogen use was
21.4   7.2 years, with a duration of oestrogen administration
ranging from 9 to 48 years. In this population,
abuse of injectable hormones was noted sometimes in
combination with oral oestrogens. Even though the majority of subjects
followed at our clinic have used extremely high doses of oestrogen during
several years, the frequency of prolactinomas in our
group was very low. This was also the case in the Amsterdam
gender clinic in subjects who had used very high doses of
oestrogens."

Also,

JAMA. 1983 Apr 22-29;249(16):2204-7.

"Relative to the risk for women who had never used an OC, the risk of prolactinoma for women who had used OCs for birth control was 1.3 (95% confidence interval, 0.7 to 2.6). This risk was 7.7 for women who used OCs for menstrual regulation (95% confidence interval, 3.7 to 17.0). Previous findings of an association between OC use and prolactinoma may have resulted from OC treatment of menstrual irregularity in women with an undiagnosed prolactinoma."

OC = oral contraceptive

So that prolactinoma was the driving factor behind using OC in the first place. This is why one must be cautious with associations, a cause and effect is tricky.

I take a high dose of estrogen parenterally (non-orally) and a high oral dose of progesterone with levels of E2 between 1,000-4,000 pg/ml and prolactin levels anywhere from 80-130 ng/ml. My doctors aren't concerned as this is normal, prolactin increases as estrogen levels increase. When my estrogen levels decrease, so do my prolactin levels. A perfectly linear relationship.

To resume, exogenous estrogen (or high estradiol levels) have not been shown to cause prolactinoma, this incidence is very rare in transsexual women and never been associated with the (exclusive) use of bio-identical estrogen/progesterone AND women with a preexisting condition such as microadenomas are allowed to go through with pregnancy (despite high levels) because there appears to be a negligible impact from it.

You can share this with your doctor. I'm not one so always do everything with your doctor only. This serves as information only. Please be safe. :)

KayXo,
Thank you for the input - that was exactly what I suspected. I have seen your post before, but I was hoping there was something more definitive as to why there was a push to hit <200. Maybe a name to point to. Now that I know this was arbitrarily set, I can make arguments as to why I am responding differently. To me it is funny how medicine has been trying to create "evidence based" reasons for prescribing medications, and yet, here is a perfect example of someone just choosing a number, which I can't stand. Who was the person or person's who chose the number - what were their credentials? what evidence do they have that it works or is appropriate? What if 200 is too little? or too much? Sigh, there is so much left to be done for the community and medicine that it feels it will never catch up. A big problem with this is people will stubbornly cling to a number saying it is right, when in reality it may not even be close.

Eliza

 

To be fair, I investigated further:

J Clin Endocrinol Metab. 2009 Sep;94(9):3132-54

"Serum estradiol should be maintained at the mean daily level for premenopausal women (<200 pg/ml)"

As I explained, this does not take into account pregnancy (or lactation, or even earlier periods before menses when girls begin developing female characteristics) so that if considered, mean daily levels over the course of the premenopausal period should be quite different. Then, we must ask ourselves: is what we observe in women today natural and the normal course of a woman's hormonal pattern? Probably not. So that at a time when things were more natural, women bore many more children and the mean daily level for premenopausal women would be quite different.

If their goal is to truly mimic ciswomen's pattern, then why not start from the beginning at thelarche, when girls begin to develop breasts and other female traits as this is our goal too. But, as I explained, trying to aim for such levels when growth hormone levels and sensitivity differ so drastically from ours would be wrong and make no sense.

So that really, in the end, we just don't know what is right for transsexual women and rather than start with ciswomen, I think it would be better to start from scratch (i.e. tabula rasa). Through trial and error, we will find out a range within which transsexual women develop and femininize optimally. If there is anything to be learned from ciswomen, it is that starting at the lowest effective dose is wise and that we may need to gradually increase dose over time to reach at least Stage 4 breasts. We might also realize that adding progesterone allows for full maturation of breasts (to Stage 5) or not, or that it may depend on the individual. As to levels and health risks, we will find out if beyond a certain level, risks do increase or not but according to what studies we have now, it appears they shouldn't and health should actually be kept optimal.

I think this would be the more sensible approach. Whether doctors eventually agree to this approach by persuasion from their patients, through logic and presenting studies, will depend on their willingness to listen, be open-minded and attitude towards change and the unknown. And also depend on how much they really care about our population.

Enough said. :)

Quote from: KayXo on November 19, 2016, 12:32:11 AM
To be fair, I investigated further:

J Clin Endocrinol Metab. 2009 Sep;94(9):3132-54

"Serum estradiol should be maintained at the mean daily level for premenopausal women (<200 pg/ml)"

As I explained, this does not take into account pregnancy (or lactation, or even earlier periods before menses when girls begin developing female characteristics) so that if considered, mean daily levels over the course of the premenopausal period should be quite different. Then, we must ask ourselves: is what we observe in women today natural and the normal course of a woman's hormonal pattern? Probably not. So that at a time when things were more natural, women bore many more children and the mean daily level for premenopausal women would be quite different.

If their goal is to truly mimic ciswomen's pattern, then why not start from the beginning at thelarche, when girls begin to develop breasts and other female traits as this is our goal too. But, as I explained, trying to aim for such levels when growth hormone levels and sensitivity differ so drastically from ours would be wrong and make no sense.

So that really, in the end, we just don't know what is right for transsexual women and rather than start with ciswomen, I think it would be better to start from scratch (i.e. tabula rasa). Through trial and error, we will find out a range within which transsexual women develop and femininize optimally. If there is anything to be learned from ciswomen, it is that starting at the lowest effective dose is wise and that we may need to gradually increase dose over time to reach at least Stage 4 breasts. We might also realize that adding progesterone allows for full maturation of breasts (to Stage 5) or not, or that it may depend on the individual. As to levels and health risks, we will find out if beyond a certain level, risks do increase or not but according to what studies we have now, it appears they shouldn't and health should actually be kept optimal.

I think this would be the more sensible approach. Whether doctors eventually agree to this approach by persuasion from their patients, through logic and presenting studies, will depend on their willingness to listen, be open-minded and attitude towards change and the unknown. And also depend on how much they really care about our population.

Enough said. :)

Really wise advice.

Something else that crossed my mind. Taking an average levels of premenopausal women ignores the fact that levels during premenopause vary from one woman to another so that each women has distinct patterns. Each individual is different. This needs to be, in my opinion, seriously considered in the equation.