Stomach medication, high prolactin, and lack of breast growth

[Steph34]

I have been on estradiol for 17 months and have seen no breast growth after the first 4 months. I can't even consider wearing a bra because I have like nothing there. I have tried so many different dosages and types of estradiol, to no avail. I have even tried progesterone, with only temporary swelling. I have sensitivity and soreness frequently, so I know there is developing tissue in there, but they just won't grow! My mother and sister both have big breasts, so I know my problem is not genetic.

So, I was wondering if this lack of progress could be explained by my stomach medication, domperidone. I have been on domperidone for almost 10 years due to gastroparesis. Without it, I suffer from severe nausea and vomiting because my stomach muscles do not contract properly. However, domperidone together with estradiol creates a very high prolactin level, so high that my doctor is afraid I might have a prolactinoma. Could this be impeding the growth of my two little ones? I do get the sense that they shrink when I take a higher dosage of domperidone for my stomach. They also shrink when I exercise; they bounce out of place and disappear!

Could domperidone be stunting their growth?
Would they do better if I wore something to hold them up when they swell and sag?

Help! I really want to grow healthy breasts and would never consider covering them up with shapely plastic.

[RobynD]

Interesting question because that drug does cause an increase in lactation apparently, likely related to the prolactin thing. If your doc does not know, i'd ask around to other docs. Is your doc an endo specialist?

Has your weight changed much on HRT?

[AnonyMs]

I asked my endo about using domperidone to help with breast growth. He didn't say it would do any harm, and I'm pretty sure he would have if it did.

Regarding lack of development have you been doing blood tests and checking the results. Not every doctor knows what they are doing. And is this genetic? Do your female relatives have small breasts?

[KayXo]

De Groot LJ, Beck-Peccoz P, Chrousos G, et al., editors.
South Dartmouth (MA): MDText.com, Inc.; 2000-.

"Prolactin is another anterior pituitary hormone integral to breast development. Prolactin is not only secreted by the pituitary gland but may be produced in normal mammary tissue epithelial cells and breast tumors (14, 15). Prolactin stimulates epithelial cell proliferation only in the presence of estrogen and enhances lobulo-alveolar differentiation only with concomitant progesterone."

so, if anything, prolactin is a good thing...but on domperidone, yes, I think it's wise to check prolactin levels regularly, check for milk letdown, symptoms associated with prolactinoma.

Side effects of domperidone include gynecomastia, a GOOD thing!

Domperidone appears to also INHIBIT CYP1A2 and CYP3A4 enzymes responsible for metabolism of estradiol, hence increasing bioavailability and concentration and half-life of estradiol. Again, more a positive than a negative thing.

Perhaps lack of body fat as you need enough fat to support and help with breast growth. Malnutrition due to malabsorption or not enough nutrients in diet, stress? Stress can strongly affect and negate development.

Have you checked your levels of vitamins, especially B12, fat-soluble vitamins and levels of omega3 relative to omega6? What about your general health? Thyroid, adrenal health? I'm assuming doctors have verified all this.

I'm not a doctor but these are all I can come up with. Perhaps, get the opinions of several doctors on this and something might pop up. Who knows?!

Best of luck.

[calicarly]

High prolactin to the point of worrying about a prolactinoma...

The issue is that estrogen in combination with high prolactin would in almost anyone mean breast growth that is probably more than average because you would be developing your milk ducts and a system in the breasts that would further develop them so I would be focusing on wether or not you are underweight which is often a problem for breast development in all women..

[Steph34]

Is your doc an endo specialist?

Has your weight changed much on HRT?

My doctor is not an endocrinologist but she is much more knowledgeable about transgender medicine than my previous endocrinologist, who made poor decisions to the point of malpractice.

My weight has fluctuated a little, but overall no real change since starting HRT.

I asked my endo about using domperidone to help with breast growth. He didn't say it would do any harm, and I'm pretty sure he would have if it did.

I do wonder because they swell up overnight when my domperidone levels are lower, and seem to shrink when I take too high a dosage. Like I said, I used this medication for my stomach for almost a decade, so I wonder if it caused some kind of desensitization or something.

Regarding lack of development have you been doing blood tests and checking the results. Not every doctor knows what they are doing.

I had monthly blood tests up until November. My estradiol levels have been consistently good and testosterone in the female range.

And is this genetic? Do your female relatives have small breasts?

Like I said, my mother and sister have big ones. My sister said that is one of only two parts of her body that she actually likes. I wish I knew what it felt like to walk around with them on my chest!

De Groot LJ, Beck-Peccoz P, Chrousos G, et al., editors.
South Dartmouth (MA): MDText.com, Inc.; 2000-.

"Prolactin is another anterior pituitary hormone integral to breast development. Prolactin is not only secreted by the pituitary gland but may be produced in normal mammary tissue epithelial cells and breast tumors (14, 15). Prolactin stimulates epithelial cell proliferation only in the presence of estrogen and enhances lobulo-alveolar differentiation only with concomitant progesterone."

Even if prolactin is good at normal female levels, that does not preclude the possibility that a high level, disproportionately high relative to E and P, could be bad because it stimulates something resembling lactation, in which breast contents go away.

so, if anything, prolactin is a good thing...but on domperidone, yes, I think it's wise to check prolactin levels regularly, check for milk letdown, symptoms associated with prolactinoma.

My doctor checks the level routinely, though I have not had symptoms.

Perhaps lack of body fat as you need enough fat to support and help with breast growth.

I think I have enough fat in unwanted places...

Malnutrition due to malabsorption or not enough nutrients in diet, stress? Stress can strongly affect and negate development.

Why would stress matter?

Have you checked your levels of vitamins, especially B12, fat-soluble vitamins and levels of omega3 relative to omega6? What about your general health? Thyroid, adrenal health? I'm assuming doctors have verified all this.

B12 deficiency causes anemia so my doctors see no reason to check for that as long as my RBC and hemoglobin remain in the normal female range. My thyroid and adrenal function are normal. I take provitamin A and consume adequate vitamin E so I doubt any deficiency exists. Levels of omega 3 vs. 6 mean nothing as long as there is no deficiency; I consume enough of both.

The issue is that estrogen in combination with high prolactin would in almost anyone mean breast growth that is probably more than average because you would be developing your milk ducts and a system in the breasts that would further develop them so I would be focusing on wether or not you are underweight which is often a problem for breast development in all women..

My BMI is about 21, which is very normal and no one really thinks I am big-boned. I have adequate fat in MALE places like my abdomen, along the waistline... HRT has made little difference, sadly. And my female relatives do not have that problem; only my father does, which makes sense given his obvious lack of E.  I enjoy frequent swelling, itchiness, sensitivity, sometimes pain, but never any lasting growth.

[KayXo]

Even if prolactin is good at normal female levels, that does not preclude the possibility that a high level, disproportionately high relative to E and P, could be bad because it stimulates something resembling lactation, in which breast contents go away.

When women breastfeed/lactate and their prolactin levels are disproportionately high relative to E and P which are very low, their breasts are HUGE, sore and engorged. Ask any ciswoman!

I think I have enough fat in unwanted places...

Cortisol (stress hormone) and insulin tend to stimulate abdominal fat deposition.

Why would stress matter?

Poor blood circulation, cortisol may affect development. I noticed this as when I am under stress, my feminization and especially breast growth suffers vs. when I am more relaxed, calm, breasts suddenly begin to grow again. 10 yrs + taking hormones and I've noticed this pattern consistently. I do not have a full explanation as to why this occurs but it just makes sense to me that a stressed body would respond less optimally than a healthy one.

Levels of omega 3 vs. 6 mean nothing as long as there is no deficiency

It seems that too much omega 6 relative to omega 3 can cause inflammation in the body. Omega 6 is inflammatory, omega 3 is anti-inflammatory. They need to be in balance.

I have adequate fat in MALE places like my abdomen, along the waistline... HRT has made little difference, sadly. And my female relatives do not have that problem; only my father does, which makes sense given his obvious lack of E.

His lack of T; males aren't supposed to have significant levels of E. In females, it is lack of E, especially.

Maturitas. 2012 Mar;71(3):248-56.

"Estradiol stimulates the activity of lipoprotein lipase
(LPL) in femoral adipocytes and lipolysis in abdominal adipocytes
[35], thereby promoting accumulation of gluteo-femoral fat. On
the other hand, estrogen deficiency is associated with enhanced
accumulation of abdominal fat [35]."

"Larger depots of abdominal fat in men are
associated with lower testosterone levels because gonadotropin
secretion is reduced [63], while upon weight loss testosterone levels
and insulin sensitivity return to normal. Furthermore, long-term
treatment of obese men with testosterone causes them to burn fat
and enhances lean body mass [63]. "

The first sentence (second paragraph) may actually clarify one of the recent discussions we had about why T reduces in men who are more obese...GONADOTROPIN SECRETION reduces! And as you see, as weight loss occurs, not only does T increase but INSULIN sensitivity improves. 

[Steph34]

Side effects of domperidone include gynecomastia, a GOOD thing!

Presumably, that occurs mostly in obese patients who are more prone to it to begin with. I was never one of the lucky ones while on domperidone in my pre-transition years. (though they probably feel differently about the 'lucky' part). I did, however, have an occasional stabbing pain in either breast. Such pains are random and more likely to occur when I overeat. They have continued while on HRT. I am not sure if this is good or bad.

Domperidone appears to also INHIBIT CYP1A2 and CYP3A4 enzymes responsible for metabolism of estradiol, hence increasing bioavailability and concentration and half-life of estradiol. Again, more a positive than a negative thing.

I guess that could explain why I have so little trouble maintaining a healthy E level. Still, not really a good thing as I simply adjust my dosage accordingly, and have a harder time coming down when I need to. High E levels, and eating too much while on E, can cause severe scalp fungal flares and resultant hair loss for me.

I asked my endo about using domperidone to help with breast growth. He didn't say it would do any harm, and I'm pretty sure he would have if it did.

It seems to be harmful for my breasts, though. After controlling for food intake, they swell when I take less and shrink when I take more. I wonder if the domperidone is causing breast contents to be diverted to the stomach and digested. It is also a very risky drug because it can cause cardiac arrythmia (QT prolongation), which can be deadly. That is why it is not FDA-approved in the USA. I used to suffer from irregular heartbeats pre-transition. Suppression of T and addition of E have largely eliminated my heart problem and my EKG is normal now.

Cortisol (stress hormone) and insulin tend to stimulate abdominal fat deposition.

I just had my insulin tested and it was so low as to be undetectable, so clearly that is not the culprit. Cortisol is a different matter...

Poor blood circulation, cortisol may affect development. I noticed this as when I am under stress, my feminization and especially breast growth suffers vs. when I am more relaxed, calm, breasts suddenly begin to grow again. 10 yrs + taking hormones and I've noticed this pattern consistently. I do not have a full explanation as to why this occurs but it just makes sense to me that a stressed body would respond less optimally than a healthy one.

Is there any way to suppress cortisol production? My level has consistently been rather high, though still normal, clearly not optimal. Reducing sources of stress in my life does not seem to work as I just stress out more over little problems when I do not focus on big problems.

His lack of T; males aren't supposed to have significant levels of E. In females, it is lack of E, especially.

Does this mean my body still thinks it is 'male' and is accumulating abdominal fat due to lack of T? I have sufficient E. Furthermore, high E due to injections tended to make my abdominal fat problem worse.

The lack of a clear explanation for my lack of growth further contributes to my suspicion that someone in my family is giving me something to inhibit feminization.

[KayXo]

I wonder if the domperidone is causing breast contents to be diverted to the stomach and digested.

Contents of the breast digested? What? When breasts shrink, there is simply cellular apoptosis (cells die) of the glandular and adipose tissue.

It is also a very risky drug because it can cause cardiac arrythmia (QT prolongation), which can be deadly. That is why it is not FDA-approved in the USA.

From motilium monograph

"The QT prolongation observed in this study when domperidone was administered according to the recommended dosing is not clinically relevant."

"This lack of clinical relevance is corroborated by pharmacokinetics and QTc interval data from two older
studies"

"It was therefore concluded that concentrations of domperidone (...) daily had no clinically significant effect on QTc in healthy subjects."

"Co-administration with potent CYP3A4 inhibitors has been shown to increase domperidone
concentrations to the point where QT interval prolongation may occur."

"Examples of potent CYP3A4 inhibitors include some azole antifungals (eg, intraconazole, voriconazole,
posaconzazole), some macrolide antibiotics (eg, clarithromycin, telithromycin), and some
protease inhibitors (ritonavir, saquinavir, telaprevir)."

"Use of MOTILIUM and other drugs which prolong QTc intervals requires that caution be exercised in
patients who have existing prolongation of cardiac conduction intervals, particularly QTc, patients
with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart
failure. Other risk factors for sudden cardiac arrest include a family history of coronary artery
disease, high blood pressure, high blood cholesterol, obesity, diabetes, smoking and excessive
alcohol consumption. It is desirable to optimise electrolyte levels prior to starting domperidone."

"Caution should be exercised when domperidone is co-administered with drugs which have been
shown to cause QT interval prolongation"

"Very rare case reports of QTc prolongation, ventricular arrhythmia, and sudden death have occurred
with domperidone use. Although most reported cases have occurred in patients receiving the
intravenous form of domperidone, or in patients with other risk factors, an association with oral
domperidone cannot be completely ruled out. Therefore, domperidone should be used with caution
in patients with other risk factors for QTc prolongation including hypokalaemia, severe
hypomagnesaemia, structural heart disease, the concomitant administration of QTc prolonging
medicines, or an underlying genetic predisposition."

In summary, it seems the risk is very low if taken alone at normal doses, in a person without medical or genetic predispositions without other drugs that increase its concentrations or have an effect on QT prolongation. I would exercise caution if Spiro were also taken as it affects electrolytes.

I just had my insulin tested and it was so low as to be undetectable, so clearly that is not the culprit.

Good news! I'm happy for you.

The lack of a clear explanation for my lack of growth further contributes to my suspicion that someone in my family is giving me something to inhibit feminization.

LOL. I doubt it.

[Steph34]

When women breastfeed/lactate and their prolactin levels are disproportionately high relative to E and P which are very low, their breasts are HUGE, sore and engorged. Ask any ciswoman!

Cis women breastfeed after going through pregnancy, a 9-month period when their E and P are extremely high. It makes sense that they would have bigger breasts after exposure to such high levels of E and P during pregnancy. Again, this does not mean that high prolactin is good or even necessarily harmless.

Cortisol (stress hormone) and insulin tend to stimulate abdominal fat deposition.

I was wondering if my higher than ideal cortisol level could be due to my long walks, sometimes 5 hours or 10 miles. Walking alone *is* a little stressful, after all. I do get the sense that my breasts shrink when I walk. Then when I have dinner and relax, they swell again.

Contents of the breast digested? What? When breasts shrink, there is simply cellular apoptosis (cells die) of the glandular and adipose tissue.

And why would my cells be dying? I am only in my second year of HRT; my breasts should still be growing!

"The QT prolongation observed in this study when domperidone was administered according to the recommended dosing is not clinically relevant."

Therein lies the catch. When I overeat (and even when I do not, albeit to a lesser extent), I usually exceed the recommended dosage for reasons of efficacy.

In summary, it seems the risk is very low if taken alone at normal doses, in a person without medical or genetic predispositions without other drugs that increase its concentrations or have an effect on QT prolongation. I would exercise caution if Spiro were also taken as it affects electrolytes.

I did have some bad irregularity when I used spironolactone, but thankfully I got off of it before it did too much harm to any part of me other than my skin. I am careful to avoid those other medications. When I had an infected finger, they wanted to put me on ciprofloxacin, but I declined because my stomach doctor told me the combination could lead to "sudden death" from QT prolongation. Still, I must quote my stomach doctor who told me, "Either drug (domperidone or ciprofloxacin) alone is risky. Together they are deadly." So I am inclined to believe my stomach doctor about it being a risky medication that I need to watch my usage of.

LOL. I doubt it.

I wouldn't rule it out. Twice in my adult life, I was given a steroid without my consent. The first time was done directly by my father after he got angry at me and I lacked the will to resist because I was scared of him and misled to believe the drug had a legitimate medical purpose. The second time, I stood up for myself BUT it was done through my mother after my father made angry threats and again lied by claiming medical necessity. I did not find out until my mother confessed several years later after I came out as trans. So, it has happened before. How can I ever trust my parents again after that? And yes, I still live with them for reasons of finances and companionship.

[KayXo]

Cis women breastfeed after going through pregnancy, a 9-month period when their E and P are extremely high. It makes sense that they would have bigger breasts after exposure to such high levels of E and P during pregnancy

Despite E and P levels dropping after pregnancy, their breasts remain big and can even become more so due to engorgement of milk as a result of high prolactin levels. It is only after prolactin levels drop for good, that breasts finally shrink and sag. Prolactin is an important hormone involved in the etiology of breast growth.

I was wondering if my higher than ideal cortisol level could be due to my long walks, sometimes 5 hours or 10 miles. Walking alone *is* a little stressful, after all. I do get the sense that my breasts shrink when I walk. Then when I have dinner and relax, they swell again.

Exercise may be good up to a certain point and it depends on the individual. Too much exercise may actually stress the body and for some people who are already stressed, this threshold is reduced. I think it's best to not do more than you can. Know your limits.

And why would my cells be dying? I am only in my second year of HRT; my breasts should still be growing!

Cell death could be due to a drop in E levels, perhaps an increase in stress leading to other hormonal changes, it could be due to weight/fat loss, etc.

I did have some bad irregularity when I used spironolactone, but thankfully I got off of it before it did too much harm to any part of me other than my skin.

Dehydration due to sodium/water loss.

Still, I must quote my stomach doctor who told me, "Either drug (domperidone or ciprofloxacin) alone is risky. Together they are deadly." So I am inclined to believe my stomach doctor about it being a risky medication that I need to watch my usage of.

It's important to be proactive in one's treatment and read the actual studies, data as sometimes doctors are not familiar with them fully. Doctors are not infallible. I should know.

[JessicaSondelli]

Hi Steph,

My blood work also showed a high (33) Prolactin level pre-HRT and I will have to do another test after 1 month on HRT. He wants to make sure my prolactin doesn't boost over 100 with added estrogen.

After doing some reading I found out that a high protein diet can boost your prolactin and since I'm on the slow carb diet for almost a year it could explain this.

Are u on a similar diet?

Cheers
-J


Sent from my iPad using Tapatalk

[KayXo]

My blood work also showed a high (33) Prolactin level pre-HRT and I will have to do another test after 1 month on HRT. He wants to make sure my prolactin doesn't boost over 100 with added estrogen.

He is afraid that a prolactinoma, a tumor of the pituitary will develop. High prolactin levels alone aren't proof that there is a prolactinoma.

My prolactin levels are between 87 and 130 ng/ml. This is perfectly normal given my E values, which range from 1,000-4,000 pg/ml. My doctors aren't concerned. Prolactin levels in pregnant women can go up to 350 while they remain quite high during breastfeeding. The incidence of prolactinoma in women is 0.1%. E naturally stimulates prolactin synthesis and has not been found to cause prolactinomas in humans.

Consider the following:

1)

Journal of Endocrinological Investigation
June 1995, Volume 18, Issue 6, pp 450-455

"Observations that a high proportion of patients with prolactinoma had previously used estrogen containing oral contraceptives"

"A large multicenter controlled case study found no evidence suggesting that estrogen containing oral contraceptive users were more likely to develop a prolactinoma (4) than non-users. Another study (5) did not find an increased risk of prolactinomas in users of estrogen containing oral contraceptives for the purpose of birth control. However, the latter study did find that women who had taken estrogen containing oral contraceptives or non contraceptive estrogens (as conjugated estrogen or ethinyl estradiol) for menstrual regulation had approximately an 8 and 16 fold greater likelihood respectively of developing a prolactinoma."

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

"autopsies of patients treated with pharmacological doses of estrogen do not show an increased number of prolactinomas (15), and case control studies have not demonstrated an association between estrogen use and prolactinoma formation (16)."

Hence, so far, causation has not been established between the use of non-bio-identical estrogens (which you are likely NOT taking) and prolactinoma.

2) There only have been 8 cases reported in transsexual women in the literature, despite decades of sometimes aggressive dosages of E. Of these 8 cases, all were taking some form of non-bio-estrogen with sometimes a non-bio-identical progestogen. There has not been one report of transsexual woman developing a prolactinoma under treatment with exclusively bio-identical hormones.

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

"Prolactinomas in oestrogen-treated MtoF persons are
rare."

"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."


3) Even those with hyperprolactinemia or a small prolactinoma rarely, if ever, show a deterioration of the condition when treated with non-bio-identical estrogens or during pregnancy (when E levels go up to 75,000). Pregnancy has even shown to have a favorable effect on pre-existing prolactinomas. Hence, pregnancy and HRT use is NOT contraindicated in women with high prolactin levels or small pituitary tumors as they rarely, if ever, make things worse.

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

"no evidence of tumor growth was seen in premenopausal women with microadenomas or women with idiopathic hyperprolactinemia treated with conjugated estrogen or oral contraceptives for 2–6 yr (14, 17, 18). Additional information supporting the safety of estrogen in women with prolactinomas is the observation that microprolactinomas rarely increase in size during pregnancy (10)."

"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)."

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.'

"women presenting microprolactinoma should be allowed to use current contraceptive pills"

Contraception. 1998 Aug;58(2):69-73.

"In conclusion, although the number of observations is limited, the data suggest that after 2 years of follow-up, no harmful effect of OC use was observed in these patients."

Pituitary. 2005;8(1):31-8.

"We followed 71 term pregnancies in women bearing microprolactinomas. Of the 22 patients with previous surgery, none presented symptoms of tumor growth. Of the 41 pregnant patients treated with bromocriptine alone, only one (2.4%) presented with headaches, which regressed with drug reintroduction."

To resume, HRT has not been shown to cause prolactinoma, is very rare in transsexual women and never been associated with the use of bio-identical estrogen AND women with preexisting condition such microadenomas are allowed to go through with HRT or pregnancy as these have rarely, if ever cause a deterioration.

[Steph34]

My blood work also showed a high (33) Prolactin level pre-HRT and I will have to do another test after 1 month on HRT. He wants to make sure my prolactin doesn't boost over 100 with added estrogen.

My prolactin level started at 16 pre-HRT, which is relatively high, but yours was 33? That is extraordinary and I would definitely think you should ask a doctor whether you need to be screened for prolactinoma. My prolactin never reached 100, although it did get fairly close when I used injections. I no longer inject estrogen.

After doing some reading I found out that a high protein diet can boost your prolactin and since I'm on the slow carb diet for almost a year it could explain this.

Are u on a similar diet?

No. I have been on a plant-based diet for over 9 years and I usually get more than 50 percent of my calories from carbs. I do make sure I include enough protein, but it is never excessive. Furthermore, my creatinine is low, which usually indicates a diet with less protein than average.

[Steph34]

Despite E and P levels dropping after pregnancy, their breasts remain big and can even become more so due to engorgement of milk as a result of high prolactin levels. It is only after prolactin levels drop for good, that breasts finally shrink and sag. Prolactin is an important hormone involved in the etiology of breast growth.

I would not be producing milk, though, right?

Exercise may be good up to a certain point and it depends on the individual.

True. A total lack of exercise definitely increases my stress.

Too much exercise may actually stress the body and for some people who are already stressed, this threshold is reduced. I think it's best to not do more than you can. Know your limits.

I love food too much to eat only a normal amount. Prolonged exercise, even pushing my limit sometimes, is the only way to prevent unwanted weight gain. And yes, I have tried gaining weight, up to a BMI of 24 last year, and it had no benefit for my breasts. The weight came on all over the body, but my breasts did not grow.

Cell death could be due to a drop in E levels, perhaps an increase in stress leading to other hormonal changes, it could be due to weight/fat loss, etc.

I think I suffer from all of those problems. My dosage of E is inconsistent. I try to bring my E level down sometimes to reduce side effects. I only sometimes use P. I have a high level of DHEA. And my weight and body fat have been fairly steady over the long-term but can fluctuate significantly in the short-term. I wonder if those inconsistencies could be preventing my girls from developing properly.
They are my second favorite part of feminizing and I want nothing but the best for them.

Dehydration due to sodium/water loss.

Perhaps, but my sodium intake is usually above average.

It's important to be proactive in one's treatment and read the actual studies, data as sometimes doctors are not familiar with them fully. Doctors are not infallible. I should know.

I should know, too. My first HRT doctor, a board-certified endocrinologist, was actually a total quack who permanently masculinized my face by starting me on Lupron without an anti-androgen. With that said, cardiac arrest is NOT something to mess around and I HAVE had some irregular heartbeats when I exceed my prescribed dosage of domperidone.

There has not been one report of transsexual woman developing a prolactinoma under treatment with exclusively bio-identical hormones.

Very few trans women use domperidone, though. Domperidone has prolactinoma as a rare, but potentially serious, side effect. Domperidone and estradiol both raise prolactin levels. Together, the two may cause problems that neither one causes alone.

Hence, pregnancy and HRT use is NOT contraindicated in women with high prolactin levels or small pituitary tumors as they rarely, if ever, make things worse.

I have noticed a strong correlation between my E level and my prolactin level. On the one hand, that reassured my doctor that I do not need screening for a prolactinoma. On the other hand, my prolactin levels have consistently been much higher than one would expect based on my E dosage. My prolactin level has consistently been abnormally high when compared to the cis female range, sometimes greatly so, even though the same cannot be said of my E level. That would seem to suggest a hypersensitivity to E in stimulating prolactin production.

[KayXo]

I would not be producing milk, though, right?

High prolactin can lead to galactorrhea. Progesterone inhibits this though but can also increase prolactin production.

Prolonged exercise, even pushing my limit sometimes, is the only way to prevent unwanted weight gain

More exercise  =  burning more calories = increased hunger = eating more. Everything balances out in the end.

I have a high level of DHEA.

What about your free/bio-available T levels? Are you taking an anti-androgen? I don't remember...

And my weight and body fat have been fairly steady over the long-term but can fluctuate significantly in the short-term. I wonder if those inconsistencies could be preventing my girls from developing properly.

Doubtful.

Domperidone has prolactinoma as a rare, but potentially serious, side effect.

I read that a prolactinoma is a contraindication to using domperidone but nowhere, have I come across domperidone causing a prolactinoma. Can you point to where this is stated and/or studies supporting this?

Domperidone and estradiol both raise prolactin levels. Together, the two may cause problems that neither one causes alone.

Maybe, maybe not. I would wager, very unlikely.

I have noticed a strong correlation between my E level and my prolactin level. On the one hand, that reassured my doctor that I do not need screening for a prolactinoma. On the other hand, my prolactin levels have consistently been much higher than one would expect based on my E dosage. My prolactin level has consistently been abnormally high when compared to the cis female range, sometimes greatly so, even though the same cannot be said of my E level. That would seem to suggest a hypersensitivity to E in stimulating prolactin production.

I will give you some numbers that could be an eye-opener for you.

E levels in pregnant women: 1,000 pg/ml-75,000 pg/ml (based on various sources)
Prolactin levels (based on my lab's ranges) in pregnant women: 9-349 ng/ml

More specifically:

1st trimester E levels (normal range in women): 1,000-5,000 pg/ml
1st trimester prolactin levels (normal range in women): 8.9-191.2 ng/ml

My levels range from 1,000-4,000. Prolactin levels were 130 on day 3 after injection, 87 on day 5 when E levels dropped. So, the raise in prolactin levels is deemed normal considering my E levels. Also, when E levels drop on day 5, so do prolactin levels. This indicates everything is as expected and the absence of a prolactinoma.

By the way, I have carefully studied each and every case of prolactinoma reported in transsexual women, except one. Prolactin levels ranged from 68 to 1,887 ng/ml! With bilateral galactorrhea being present 4 times out of 7.

[Steph34]

High prolactin can lead to galactorrhea. Progesterone inhibits this though but can also increase prolactin production.

I have never had any external discharge. Is it possible for discharge to occur internally?

More exercise  =  burning more calories = increased hunger = eating more. Everything balances out in the end.

I disagree. My binge eating has more to do with pleasure seeking than with hunger taming. I will overeat whether I exercise or not, perhaps slightly more when I exercise but not enough to offset the calories burned while exercising. Given my high calorie intake, exercise is the main reason I am not overweight like my female relatives.

What about your free/bio-available T levels? Are you taking an anti-androgen? I don't remember...

My free T was up to 3, as of last month. I no longer use any anti-androgens. My doctor tells me they are not necessary now that I have had my orchiectomy. They are also expensive and/or have bad side effects. However, I have read that high DHEA has androgenic effects (masculinizes appearance) in women, and my doctor tells me it causes female pattern hair loss. I fear that my problems, including lack of breast growth, are due to high DHEA. Sadly, I have no idea how to suppress it.

I read that a prolactinoma is a contraindication to using domperidone but nowhere, have I come across domperidone causing a prolactinoma. Can you point to where this is stated and/or studies supporting this?

Not really, but it stands to reason that anything that raises prolactin levels would be a risk factor.

Maybe, maybe not. I would wager, very unlikely.

I have read about numerous cases of symptomatic hyperprolactinemia in women taking domperidone, but much less so in men, suggesting that this is a bigger problem when domperidone is combined with estradiol. That makes sense, since both increase prolactin.

I will give you some numbers that could be an eye-opener for you.

E levels in pregnant women: 1,000 pg/ml-75,000 pg/ml (based on various sources)
Prolactin levels (based on my lab's ranges) in pregnant women: 9-349 ng/ml

More specifically:

1st trimester E levels (normal range in women): 1,000-5,000 pg/ml
1st trimester prolactin levels (normal range in women): 8.9-191.2 ng/ml

I already knew that levels during pregnancy are incredibly high. They are also irrelevant, since 1)I cannot become pregnant, 2)pregnancy is not required for normal breast growth or any other aspect of feminization in cis women, and 3)many women report unpleasant side effects of high hormone levels during pregnancy. Those are clearly not desirable levels for trans women.

My levels range from 1,000-4,000. Prolactin levels were 130 on day 3 after injection, 87 on day 5 when E levels dropped. So, the raise in prolactin levels is deemed normal considering my E levels. Also, when E levels drop on day 5, so do prolactin levels. This indicates everything is as expected and the absence of a prolactinoma.

My doctor's concern was that my prolactin is disproportionately high relative to E, but I am not worried because that is to be expected based on my domperidone use. My prolactin level (always under 100 on E injections and always under 70 on E patches) is not high enough to suggest a prolactinoma, especially given its tight correlation with my E level.

By the way, I have carefully studied each and every case of prolactinoma reported in transsexual women, except one. Prolactin levels ranged from 68 to 1,887 ng/ml!

My doctor said she has seen "problems" with prolactin levels as low as 60.

[KayXo]

I have never had any external discharge. Is it possible for discharge to occur internally?

When prolactin levels are high, there will be increased production of milk in breast glands so there will be "discharge" inside, as in milk inside the breasts. If breasts aren't well-developed, then perhaps engorgement with milk will be much less.

Given my high calorie intake, exercise is the main reason I am not overweight like my female relatives.

Have you stopped exercising for one full year and compared weight? Perhaps, there is another reason you don't gain as much weight as them. Healthier eating habits? Less refined carbs?

My free T was up to 3, as of last month.

If in ng/dl, it's close to low end of male range and above female range.
If in pg/ml, well within female range.
If in pmol/L, low to under female range.

It's important to indicate units of measure. I'm assuming it's pg/ml or perhaps pmol/L.

I fear that my problems, including lack of breast growth, are due to high DHEA. Sadly, I have no idea how to suppress it.

DHEA is a precursor to potent androgens such as T and DHT. DHEA in and of itself, if T and DHT are low, is not a problem as it is a very weak androgen and acts mostly as a precursor.

If your free T is indeed within female range or even low end to lower than (I don't know what units your levels are), I wouldn't be concerned. If T is low, then DHT is low too as T is a precursor to DHT.

Not really, but it stands to reason that anything that raises prolactin levels would be a risk factor.

So far, no prolactinoma has been observed from domperidone, used since 1974 (42 yrs existence) despite this drug raising prolactin levels. Pregnancy and breastfeeding increase prolactin levels significantly but have never been observed to cause/induce prolactinoma. Same for oral contraceptives and HRT in ciswomen, the association is strongly in favor of a reverse causation. In transwomen, there have been occurrences with non-bio-identical forms, at higher doses BUT causation remains to be established and one can argue that many more prolactinomas should have occurred given the tens of thousands exposed to such treatment. I'D still not take a chance using them since there have indeed been prolactinomas with them and there are many other potential side-effects as well.

In other words, it doesn't *necessarily* stand to reason. 

I have read about numerous cases of symptomatic hyperprolactinemia in women taking domperidone, but much less so in men, suggesting that this is a bigger problem when domperidone is combined with estradiol. That makes sense, since both increase prolactin.

Hyperprolactinemia in and of itself, is not a problem. It is a problem when a prolactinoma is present. In women, there are more cases of it because prolactin levels are more often high due to estradiol, as you state. But, like I stated earlier, higher prolactin levels don't necessarily mean more prolactinoma. No such incidence in the history of domperidone use in women or in men.

I already knew that levels during pregnancy are incredibly high. They are also irrelevant, since 1)I cannot become pregnant, 2)pregnancy is not required for normal breast growth or any other aspect of feminization in cis women, and 3)many women report unpleasant side effects of high hormone levels during pregnancy. Those are clearly not desirable levels for trans women.

Relevant if you have levels comparable to pregnant women so that you can see how prolactin levels rise in relation to estradiol levels, like me and some other women who are on injectable/pellets and who find they

1) have better breast growth and feminization (latter in my case)
2) feel better (also my case)

Some women feel especially good during pregnancy (my mom and many others). It depends. It's important not to generalize and assume pregnant levels are not required for any transwoman to feel good, have decent feminization and breast growth. My experience proves this to be wrong and that of many other women I have come into contact during my 10 yrs+ of exploring this matter.

Remember that ciswomen developed at a time when growth hormone levels were very high and genetic ageing did not begin so that lower levels sufficed, on top of no prior masculinization. Hence, most of us, being older, may indeed need quite high levels for good results. It DEPENDS.

My doctor said she has seen "problems" with prolactin levels as low as 60.

What problems? In which population?

[Steph34]

When prolactin levels are high, there will be increased production of milk in breast glands so there will be "discharge" inside, as in milk inside the breasts. If breasts aren't well-developed, then perhaps engorgement with milk will be much less.

Is milk production good or bad for growth?

Have you stopped exercising for one full year and compared weight? Perhaps, there is another reason you don't gain as much weight as them. Healthier eating habits? Less refined carbs?

I could never stop exercising for one full year, but I have noticed a correlation between short-term weight and exercise. It is not water weight since I really do not sweat much. It could be in part due to my higher metabolic heat production with prolonged exposure to cool air. Also, I use laxatives that may facilitate the flow of calories into the large intestine. Plus I consume less saturated fat, a nutrient that increases ghrelin levels. I also avoid sweets most of the time and never eat active yeast.

If in ng/dl, it's close to low end of male range and above female range.
If in pg/ml, well within female range.
If in pmol/L, low to under female range.

It's important to indicate units of measure. I'm assuming it's pg/ml or perhaps pmol/L.

It is in pg/ml, so within female range. That makes sense, since my total T and SHBG are also within female range.

DHEA is a precursor to potent androgens such as T and DHT. DHEA in and of itself, if T and DHT are low, is not a problem as it is a very weak androgen and acts mostly as a precursor.

My doctor told me that 1)DHEA is the hormone that causes female pattern hair loss, which runs in my family, and 2)Taking estradiol raises DHEA levels. Worrisome, indeed...

Hyperprolactinemia in and of itself, is not a problem.

It is a problem when women report side effects such as dizziness, etc.

Relevant if you have levels comparable to pregnant women so that you can see how prolactin levels rise in relation to estradiol levels, like me and some other women who are on injectable/pellets and who find they

1) have better breast growth and feminization (latter in my case)
2) feel better (also my case)

High estradiol will make people feel really great in the short term of a few months, but like anything else that produces a sensation of being high, tolerance will occur and then it will require a high level to maintain a normal mood. Not healthy. I did see somewhat of a tolerance effect from my past use of injections. Thankfully I got off of them before I became totally desensitized to its emotional effects. I also did not see any breast growth nor did I feminize any better on the injections, despite E levels 4 times as high as on patches. I DID however, have increased side effects, including scalp fungus, nausea/bloating, and extreme moodiness. More is not necessarily better.

Some women feel especially good during pregnancy (my mom and many others). It depends.

There are other explanations for feeling good during pregnancy besides high hormone levels. Excitement about having a baby, perhaps working less or not at all... so there is not necessarily a causative effect.

It's important not to generalize and assume pregnant levels are not required for any transwoman to feel good, have decent feminization and breast growth.

Breast growth or breast swelling? It is important to distinguish between the two. If breasts require constant exposure to hormones to maintain their size, that is swelling and is not sustainable over the long-term.

Remember that ciswomen developed at a time when growth hormone levels were very high and genetic ageing did not begin so that lower levels sufficed, on top of no prior masculinization. Hence, most of us, being older, may indeed need quite high levels for good results. It DEPENDS.

I don't necessarily disagree, but sometimes I get the sense that you think higher levels could help most people with poor feminization, when clearly that was not true for me. Just saying.

What problems? In which population?

I would have to ask.

[KayXo]

Is milk production good or bad for growth?

I think neither. What matters is estrogen and progesterone. And of course, that androgens are low and/or inhibited to allow for growth.

Plus I consume less saturated fat, a nutrient that increases ghrelin levels.

Saturated fat actually makes one less often hungry IF not eaten with very carby foods. People on high fat (moderately saturated), low carb diets end up eating much less. I should know. Eating bacon, eggs and butter (+ macadamias) in the morning, I sometimes don't get hungry until the next day. This is one of the benefits of eating this way. It's very satiating.

Eur J Nutr. 2013 Feb;52(1):1-24.

"The observational evidence does not support the hypothesis that dairy fat or high-fat dairy foods contribute to obesity or cardiometabolic risk, and suggests that high-fat dairy consumption within typical dietary patterns is inversely associated with obesity risk."

My doctor told me that 1)DHEA is the hormone that causes female pattern hair loss

Because it can convert peripherally to testosterone and eventually to DHT (through 5 alpha-reductase) in tissues.

which runs in my family

You could ask to be put on finasteride which reduces DHT levels. Even if T levels in the blood are low, DHT levels can be much higher in tissues and people like you, who are sensitive genetically, may still experience side-effects from this amount.

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

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

2)Taking estradiol raises DHEA levels.

From a purely chemical standpoint, estradiol cannot convert back to DHEA (or T). DHEA can, however, raise estradiol levels because it converts to T which then can convert to estradiol. If indeed estradiol raised DHEA (and T) levels, mine should be quite high instead of near the low end of the female range, considering my E levels are VERY high. My androgen levels have actually been the lowest they've ever been since being on pregnancy levels of estradiol. My body hair is more sparse, thinner, grows slower while my head hair might be slightly thicker and more dense than before. Imagine the repercussions in pregnant women and in men with prostate cancer who are prescribed high dose estrogen whose lives depend on how much androgens are inhibited.

If indeed estradiol raised DHEA levels and thus raised T and DHT levels, we should be observing many more cases of women experiencing hair loss during their reproductive years. Women actually experience hair thinning/loss to a far greater extent after menopause, when E levels drop.

Androstenediol is the only androgen that can convert back to DHEA.

(notice the direction of the arrows)
http://www.angelfire.com/sc3/toxchick/images/S/steroidogenesis.gif
http://www.genome.jp/kegg/pathway/hsa/hsa00140.html
http://tau.amegroups.com/article/viewFile/2762/3634/49844

There is one way, however, that I could possibly see estradiol raising DHEA levels, now that I come to think of it. Estradiol, especially if taken orally or non-orally at higher levels, will stimulate the production of transcortin as it circulates through the portal vein. Transcortin binds cortisol (especially) and aldosterone. As a result, the levels of free circulating cortisol and aldosterone drop, negative feedback to ACTH drops and ACTH output increases, resulting in an increase in DHEA/DHEA-S. But, like I said, despite my high levels of estradiol, my DHEA and DHEA-S levels have remained low, more towards the low end of the female range and my T VERY low (free T undetectable, probably due to high SHBG). I even noticed that on the day when my E is the highest, my DHEA-S is the lowest. I think this could potentially happen when non bio-identical estrogens are taken as they circulate through the portal vein to a far greater extent due to the body's difficulty in metabolizing them so would stimulate transcortin to a far greater extent as well. In the end though, I think this is a non-issue because in both cases where DHEA levels may rise, either due to non bio-identical forms or VERY VERY high levels of estradiol during the second and third trimester of pregnancy, SHBG which is also very high would offset the potential androgenic effects of DHEA converting to T and DHT as the latter two bind strongly to SHBG.

It is a problem when women report side effects such as dizziness, etc.

How is dizziness a side-effect of hyperprolactinemia? This would be indeed quite a problem for pregnant and breastfeeding women which I don't think it is.

High estradiol will make people feel really great in the short term of a few months, but like anything else that produces a sensation of being high, tolerance will occur and then it will require a high level to maintain a normal mood.

I think many, many women (trans and cis) will testify that being on estradiol for several years has not suddenly desensitized them to the mood-enhancing effects of E. There is some degree of fluctuation, especially on injections, which keeps cells responsive. In the case of pellets, levels may be indeed too steady and cause desensitization.

To illustrate just how much levels fluctuate on injections, my estradiol levels went from 2,500 pg/ml to 1,300 pg/ml in just 2 days!!! No possible desensitization from this.

I did see somewhat of a tolerance effect from my past use of injections. Thankfully I got off of them before I became totally desensitized to its emotional effects.

I can attest to the fact that I've been on high levels for 2 yrs now (on injectables) and my mood is still perfectly fine. I see no deterioration whatsoever. The same can be said of several other women on this board and women I've come into contact with who have been on injectables for years! You seem to be the odd case.

I also did not see any breast growth nor did I feminize any better on the injections, despite E levels 4 times as high as on patches.

I must admit to seeing less breast growth on injections vs pills (I was taking a high dose orally) BUT as far as the rest of me, I've found I've feminized to a far greater extent than ever before and FEEL better and look HEALTHIER.

I DID however, have increased side effects, including scalp fungus, nausea/bloating, and extreme moodiness.

Moodiness will occur IF you don't inject frequently enough as levels may drop too much after a certain time. Usually, 7 days is best. The other symptoms, I've personally never experienced, thank goodness and have rarely, VERY rarely come across when reading about other women on injectables. Like I said, you may be the odd case.

More is not necessarily better.

Sometimes, yes, sometimes, no. It depends. In my case, it turned out alright.

There are other explanations for feeling good during pregnancy besides high hormone levels. Excitement about having a baby, perhaps working less or not at all... so there is not necessarily a causative effect.

I agree but I wouldn't discount the mood-enhancing effects of hormones either. I believe hormones, by improving mood, increase the odds of the mother's survival and hence her baby's survival. From an evolutionary standpoint, it makes a whole lot of sense. It's no coincidence that progesterone, a hormone found in high concentrations in pregnant women, converts to allopregnanolone, found to have a calming effect on the organism. Estradiol also positively impacts serotonin.

Maturitas. 1996 May;24(1-2):37-41.

"Serotonin, known for its beneficial action on mood and well-being, is also involved in cardiovascular functions. Thus the current work was undertaken to study the effect of hormone replacement therapy on serotonin turnover in postmenopausal women. Eighteen women received estradiol transdermally and 17 women estradiol valerate orally for 4 weeks. The serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) was determined in the urine before, and after 2 and 4 weeks' estradiol treatment. With both administration routes estradiol produced a significant increase in urinary 5-HIAA excretion, greatest with transdermal estradiol after 28 days of treatment. The enhancement of serotonin turnover may contribute not only to an improvement of mood and well-being but also to a cardioprotective effect of estradiol observed after hormone substitution in postmenopausal women."

J Clin Psychiatry. 2001 May;62(5):332-6.
Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study

"Most women recovered and did not have any depressive symptoms following treatment. There was rapid improvement in symptoms within first week and recovery thereafter. Neither psychotherapy or anti-depressants worked."

Breast growth or breast swelling? It is important to distinguish between the two. If breasts require constant exposure to hormones to maintain their size, that is swelling and is not sustainable over the long-term.

Breast glands will also shrink (cell apoptosis) in response to a drop in estrogen. In order to maintain glandular tissue and firmness, a certain amount of estrogen is usually needed. Increase in milk in the breast glands, and increase in water concentration can indeed temporarily cause breast swelling. Same with fat, if one gains or loses adipose tissue.

sometimes I get the sense that you think higher levels could help most people with poor feminization, when clearly that was not true for me. Just saying.

It can help at times, yes. But there are many other factors as well. I'm not ignoring these factors at all.