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Flummoxed by low estrogen levels

Started by EmmaMcAllister, April 05, 2016, 04:49:09 PM

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KayXo

In study provided by you, it is stated at the end

"Further studies in a larger number of patients are needed in order to support this finding."

So, in other, later studies...

J Urol. 1977 Dec;118(6):1019-21.

"Selective adrenal vein catheterization was done on intact and castrated men with prostatic carcinoma. Adrenal to peripheral venous testosterone gradients were observed in all patients, indicating adrenal production of this hormone. No compensatory adrenal production of testosterone was noted during a 17-month period after orchiectomy."

Prostate. 1982;3(2):115-21.

"This study, performed on 40 patients having undergone bilateral subcapsular orchiectomy for prostatic carcinoma, shows that this intervention results in testosterone levels in the female range and that during the year following subcapsular orchiectomy there is no evidence for reactivation of Leydig cells or for increased adrenal androgen secretion as evaluated from plasma testosterone, androstenedione, and dehydroepiandrosterone sulphate levels. In patients treated with estrogens we found no evidence for stimulation of adrenal androgen secretion, whereas in neither group of patients with prostatic carcinoma we found evidence for increased androgen levels at the time of recurrence of the carcinoma."

Urol Int. 1990;45(3):160-3.

"Basal serum levels and ACTH-induced increments ('delta-values') of dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and testosterone and serum albumin levels were studied in patients with prostatic cancer before treatment and after orchidectomy or during estrogen treatment (intramuscular polyestradiol phosphate during the first 3 months, followed by another 3 months with additional oral ethinyl estradiol). Orchidectomy as well as single drug intramuscular or oral + intramuscular estrogens exerted a similar suppressive effect on basal levels of A-4 and 17-OHP."

Prostate. 1989;14(2):177-82.

"Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels."

Urol Res. 1989;17(2):95-8.

"Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone (17OHP), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS) and cortisol were measured before and after 6 months of treatment in prostatic cancer patients treated by orchidectomy (ORX) or with oral + parenteral estrogens (OE), single parenteral estrogens (...), estramustine phosphate (ECYT) or LHRH agonist without (LHRH) or with (LHRH-F) flutamide. Castration values of T and 170HP were reached in all types of treatment (PE at the higher dose).

Int J Androl. 1987 Aug;10(4):581-7.

"Orchidectomy caused a pronounced decrease in 17-OHP levels and minor but significant decreases in the levels of A-4 and DHAS."

"The results further invalidate the hypothesis that there is a 'compensatory' increase in adrenal androgen output following orchidectomy."

In full study...

"Although increased urinary excretion of androgens has been reported after
orchidectomy in several earlier studies (Parker et al., 1984), unchanged or slightly
decreased blood levels of DHA, DHAS and A-4 were reported in more recent
investigations (Luukkarinen et al., 1977; Vermeulen et al., 1982a; Parker ef al.,
1984; Belanger ef al., 1984; Belanger, Brochu & Cliche, 1986). With respect to
oestrogen treatment, modest doses of polyoestradiol phosphate or oestradiol undecylate
administered intramuscularly are reported to cause a slight decrease in A-4
and a slightly decreased, or unchanged, level of DHAS, while the levels of DHA
remained unchanged (Jonsson et al., 1975; Luukkarinen et al., 1977; Leinonen ef
al., 1981; Vermeulen et al., 1982a; Schurmeyer et al., 1986). A dose-dependent
decrease in DHAS levels has also been observed in postmenopausal women during
oral oestrogen replacement therapy (Helgason et al., 1981)."

I am not a medical doctor, nor a scientist - opinions expressed by me on the subject of HRT are merely based on my own review of some of the scientific literature over the last decade or so, on anecdotal evidence from women in various discussion forums that I have come across, and my personal experience

On HRT since early 2004
Post-op since late 2005
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EmmaMcAllister

For what it's worth, 8 months out from my orchiectomy, my free T is 3 pmol/L, or 0.003 nmol/L. I'm not too worried about increased adrenal production. 
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
  •  

KayXo

And more...

J Clin Endocrinol Metab. 1984 Sep;59(3):547-50.

"Prostatic carcinoma is androgen dependent and, therefore, treated by orchiectomy. However, adrenal androgen secretion remains intact after orchiectomy, and several investigators even reported an increase in serum adrenal androgen concentrations after orchiectomy. Such an increase in androgen secretion theoretically could promote tumor recurrence. To investigate this question, we obtained multiple blood samples from 10 men before, within 1 week after, and up to 6 months after orchiectomy for prostatic carcinoma. Serum testosterone concentrations became unmeasurable (less than 40 ng/dl) after orchiectomy. Three of the 10 patients had transient increases of at least 50% in both serum dehydroepiandrosterone (DHA) and cortisol after orchiectomy, presumably due to surgical stress, but mean serum DHA and DHA sulfate (DHAS) did not increase in the group as a whole. Subsequently, serum DHA and DHAS concentrations were similar to preoperative values in all patients. Therefore, we find no evidence to support the hypothesis that adrenal androgen concentrations increase after orchiectomy."

Perhaps, some transwomen who are especially stressed due to the surgery or change in their lives may be more prone to produce higher levels of adrenal androgens so that adrenal output is not increased in response to low T (or low sex hormones) as Laura suggested but in response to stress, which follows a life changing surgery, which may be more significant in some vs others. This makes much more sense, in my opinion and would account for why some men experienced increased adrenal output of androgens, post-op while others didn't.

I am not a medical doctor, nor a scientist - opinions expressed by me on the subject of HRT are merely based on my own review of some of the scientific literature over the last decade or so, on anecdotal evidence from women in various discussion forums that I have come across, and my personal experience

On HRT since early 2004
Post-op since late 2005
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KayXo

To conclude:

Only 2 out of 8 studies showed orchiectomy to result in increased levels of adrenal androgen output. In those two studies, 37% of men and 30% of men had increased output, less than 50% (about 1 in 3 men) AND in one study, the increase was transient, perhaps correlated with stress (higher cortisol) and not low T.

On the other hand, these studies were not in transsexual women who take E post-op. Studies have shown E to actually sometimes reduce adrenal androgen output in men and in women which would suggest that taking E post-op would help counter the rise in adrenal androgen output, if it occurs, perhaps due to stress.

There could be other explanations as well for why androgenic symptoms increase post-op in some transwomen.
I am not a medical doctor, nor a scientist - opinions expressed by me on the subject of HRT are merely based on my own review of some of the scientific literature over the last decade or so, on anecdotal evidence from women in various discussion forums that I have come across, and my personal experience

On HRT since early 2004
Post-op since late 2005
  •  

EmmaMcAllister

So, an update. After a little more than a month taking my estradiol buccally (which I find easier than sublingual) my estradiol levels have gone from 100 pmol/L (27.24 pg/mL) to 2763 pmol/L (752.65 pg/mL). So now it seems that I have the OPPOSITE problem. I suspect my doctor will want to cut my dosage, but honestly, I've been progressing amazingly in this past month. So unless this high of a level is incredibly dangerous, I'd rather not go down.
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
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Dena

If you took your dosage the same day you were tested, those number could be misleading. It's possible that within a few hours, your levels could drop to more normal ranges as your blood passes through your liver. Remember that you have only eliminated the first pass problem but sooner or latter, all the estradiol will pass through the liver and be processed. The time between the last dose and the blood test is very important in determining your true levels.
Rebirth Date 1982 - PMs are welcome - Use [email]dena@susans.org[/email] or Discord if your unable to PM - Skype is available - My Transition
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EmmaMcAllister

I took my night dose at approximately 11pm on Thursday, and had my blood drawn at approximately 10am on Friday before I took my day dose. So, shouldn't it have dropped sufficiently by then?
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
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Dena

I was told not to take it a day before being tested. I hear all sorts of numbers for half lives, but I suspect another 12 hours would have quartered your levels and they might have dropped even more. The information I have can't directly be applied to the way you are taking your hormones so my answer is somewhat of a guess as to what your true levels would be. Needless to say, if your levels are that high after 24 hours, possibly a level reduction should be considered but after 11 hours it's hard to say.
Rebirth Date 1982 - PMs are welcome - Use [email]dena@susans.org[/email] or Discord if your unable to PM - Skype is available - My Transition
If you are helped by this site, consider leaving a tip in the jar at the bottom of the page or become a subscriber
  •  

KayXo

Quote from: EmmaMcAllister on May 21, 2016, 12:24:45 PM
So, an update. After a little more than a month taking my estradiol buccally (which I find easier than sublingual) my estradiol levels have gone from 100 pmol/L (27.24 pg/mL) to 2763 pmol/L (752.65 pg/mL). So now it seems that I have the OPPOSITE problem. I suspect my doctor will want to cut my dosage, but honestly, I've been progressing amazingly in this past month. So unless this high of a level is incredibly dangerous, I'd rather not go down.

Pregnant women have levels up to 75,000 pg/ml, clotting incidence is less than 0.2%. In men with prostate cancer, levels up to 700 pg/ml have not been found to cause health problems, namely cardiovascular and clotting. These men ranged in age from 49-91 yrs old. My estradiol levels are 1,000-4,000 pg/ml, I'm healthy, clotting factors are normal so is C-reactive protein. I'm supervised by three doctors.

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


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

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

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

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

Prostate 1989;14(4):389-95
Estrogen therapy and liver function--metabolic effects of oral and parenteral
administration.


"Oral estrogen therapy for prostatic cancer is clinically effective
but also accompanied by severe cardiovascular side effects.
Hypertension, venous thromboembolism, and other cardiovascular
disorders are associated with alterations in liver metabolism. The
impact of exogenous estrogens on the liver is dependent on the route
of administration and the type and dose of estrogen. Oral
administration of synthetic estrogens has profound effects on
liver-derived plasma proteins, coagulation factors, lipoproteins, and
triglycerides, whereas parenteral administration of native estradiol
has very little influence on these aspects of liver function.
"

No sense in measuring levels as there is neither an ideal level for feminization, is not a good gauge of health risks and fluctuates in 24 hours.

Quote from: Dena on May 21, 2016, 12:49:33 PM
If you took your dosage the same day you were tested, those number could be misleading. It's possible that within a few hours, your levels could drop to more normal ranges as your blood passes through your liver. Remember that you have only eliminated the first pass problem but sooner or latter, all the estradiol will pass through the liver and be processed. The time between the last dose and the blood test is very important in determining your true levels.

Much less estradiol will pass through the liver and the small amount that eventually circulates through the portal vein is so small as to negligibly affect clotting or liver. Estradiol is easily metabolized and eliminated by the liver so there is no second and third pass like non bio-identical estrogens.

There is no such as true or normal level as levels fluctuate so much and normal in women can be anywhere from 20-75,000 pg/ml.
I am not a medical doctor, nor a scientist - opinions expressed by me on the subject of HRT are merely based on my own review of some of the scientific literature over the last decade or so, on anecdotal evidence from women in various discussion forums that I have come across, and my personal experience

On HRT since early 2004
Post-op since late 2005
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EmmaMcAllister

I really wish there was some universal consensus on these matters. I expect my doctor will try to bring my levels down to a max of 400 pg/mL, but I'm just not sure what the best thing to do would be. My breasts are just now starting to bud significantly, so I don't want to take a step backwards.
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
  •  

KayXo

Quote from: EmmaMcAllister on May 23, 2016, 03:54:42 PM
I really wish there was some universal consensus on these matters.

There should be but doctors are simply misinformed or uninformed. Doctors need to be better educated. And take the time to read the studies that are out there.
I am not a medical doctor, nor a scientist - opinions expressed by me on the subject of HRT are merely based on my own review of some of the scientific literature over the last decade or so, on anecdotal evidence from women in various discussion forums that I have come across, and my personal experience

On HRT since early 2004
Post-op since late 2005
  •  

Richenda

Quote from: EmmaMcAllister on April 06, 2016, 12:52:41 PM

One other thing I'm curious about is the timing of my blood work. My mother is a phlebotomist and she always takes my blood early in the morning before she goes to work. I take my dosage later when I get out of bed, so invariably she ends up taking my blood before my daily dosage and long after my last dosage. Would this suggest that my results are artificially low, or should I still expect much higher levels in the morning before I've taken my dose?


Hi Emma, I had the same issue with a low E reading after being told not to take my meds: Estradiol  E2 74.2 pg/ml after being nearly 300 in December (https://www.susans.org/forums/index.php?topic=209373.new;topicseen#new ). So I laid off E for over 12 hours before the result and, guess what, it came back low. So I'm pretty certain that's the reason with yourself.

I'm currently in my first week of IM estradiol valerate. I can't in all honesty say that I'm enjoying it very much and will almost certainly return to sublingual. However, under the guidance of the clinic, I'm going to mix up the types of oestrogen a little each day with 2 x estradiol valerate and 1 x straight oestrogen. I always take them sublingually. I'm also going to be more strict about taking those every 8 hours. I don't know if this will help but I would definitely recommend the sublingual route.
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Richenda

Sorry, I've just read your updates on this page. Wow!!!! I'm so pleased for you. Go girl :)

Interesting about your buccal delivery. I'm a big fan of sublingual / buccal.
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EmmaMcAllister

Yup, the difference is pretty staggering. I really don't know why anyone would bother with oral administration. I know my individual experience can't be universalized, but oral seems so ineffectual. I'm still wondering if injections might be the best way to go though, because the peaks and valleys might better mimic the natal female cycle.
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
  •  

Richenda

I'm at the end of day 5 of my first week of injection and it's likely to be my last. In fact, scrub that, it is my last. I haven't found the experience at all pleasant. I felt pretty rough for the first three days: hot flashes, rushes, then alternating periods of virtual narcolepsy. I've felt completely out of it at times. It really was horrible.

So I'm returning to my tried and trusted sublingual, just nudging the dosage up a touch and varying the pills between estradiol valerate straight oestrogen. I can't say more on that because although I won't mention dosage the frequency might break the rules.

What I'm going to focus on now more is my anti androgen, starting bicalutamide to go alongside the finasteride.

I'm writing all the above because I guess everyone really is different and you need to follow what's right for you Emma imho. I'm thrilled for you at the way your estrogen level has shot up. Continue to work with your body: it's yours and no-one else's.
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KayXo

Quote from: EmmaMcAllister on May 27, 2016, 09:20:07 AM
I'm still wondering if injections might be the best way to go though, because the peaks and valleys might better mimic the natal female cycle.

I think the female cycle isn't natural and is only a recent phenomena due to modernization. Cycles lead to constant proliferation and apoptosis which can increase the likelihood of cancerous cells. They also lead to mood swings. I personally see no reason to mimic this.

Traditionally, women would spend most their lives being pregnant and nursing with hormone levels being much more steady.

Quote from: Richenda on May 27, 2016, 09:51:00 AM
I'm at the end of day 5 of my first week of injection and it's likely to be my last. In fact, scrub that, it is my last. I haven't found the experience at all pleasant. I felt pretty rough for the first three days: hot flashes, rushes, then alternating periods of virtual narcolepsy. I've felt completely out of it at times. It really was horrible.

Your dose is likely too low. Estrogen load is less now.

QuoteSo I'm returning to my tried and trusted sublingual, just nudging the dosage up a touch and varying the pills between estradiol valerate straight oestrogen.

No difference between estradiol valerate and estradiol.

Maturitas. 1982 Dec;4(4):315-24

"After oral or parenteral administration, oestradiol valerate, the synthesis compound contained in various commercially available preparations, is completely converted into the natural substances 17 beta-oestradiol and valeric acid. The 17 beta-oestradiol produced on cleavage of the ester behaves in the organism like the endogenous steroid hormone. Oestradiol valerate and 17 beta-oestradiol are virtually dose-equivalent. No differences in the spectrum of action of the oestrogen and its ester have been found either in animal experiments or man. The pharmacokinetic behaviour and the biotransformation of the 17 beta-oestradiol originating from oestradiol valerate are no different from those of natural 17 beta-oestradiol."

I personally found no difference between taking E sublingually vs orally. Same results and orally, was more convenient with less ups and downs.
I am not a medical doctor, nor a scientist - opinions expressed by me on the subject of HRT are merely based on my own review of some of the scientific literature over the last decade or so, on anecdotal evidence from women in various discussion forums that I have come across, and my personal experience

On HRT since early 2004
Post-op since late 2005
  •  

EmmaMcAllister

So, my doctor cut my dose in half, as I expected he would. Beyond my estradiol levels, he was concerned about my hemoglobin. So, back to once a day, retest in a few weeks.
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
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Richenda

Hi Emma,

Am I allowed to ask what the haemoglobin result was? I had a low result too and have been taking iron supplements and watching my diet. Don't know yet if that will help.
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EmmaMcAllister

128 g/L, down from 135 g/L the month before.
Started HRT in October, 2014. Orchiectomy in August, 2015. Full-time in July, 2016!

If you need an understanding ear, feel free to PM me.
  •  

Richenda

Ah okay. Mine was 140 g/L at last checkup. I was low on protein, sodium and chloride so have changed my diet and added protein which I think raises haemoglobin?

I'm starting on bicalutamide today but that's another story.
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