Quote from: Laura_7 on April 05, 2016, 11:51:38 AM
Clin Endocrinol (Oxf). 1995 May;42(5):445-50.
An audit of oestradiol levels and implant frequency in women undergoing subcutaneous implant therapy.
Buckler HM1, Kalsi PK, Cantrill JA, Anderson DC.
On the grounds that the aim is to restore premenopausal serum E2 levels, our declared clinical policy is not to repeat implants even in the presence of symptoms if serum E2 levels are > 400 pmol/l.
In other words, if a woman experiences menopausal symptoms but has levels above 400 pmol/L, additional implant insertion is denied. Why? Because they say supraphysiological levels may result. I question this for the following three reasons:
1) According to
https://en.wiktionary.org/wiki/supraphysiological, supraphysiological means
"Of or pertaining to amounts greater than normally found in the body." I seriously doubt that levels above 275,000 pmol/L, found in the bodies of ciswomen during pregnancy, can be achieved with subsequent insertion of pellets upon return of symptoms. They don't truly understand the meaning of supraphysiological.
2) What is so wrong with achieving higher levels? Studies in men with prostate cancer (with levels up to 2,500 pmol/L), studies in transsexual women probably experiencing much higher levels with high dose injectables and observations in pregnant women with extremely high levels have shown that despite these levels, the risk of cardiovascular and embolism complications is NEGLIGIBLE. Also, from this study
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)."
3) Women during a cycle achieve levels as high as 649 pg/ml (2,382 pmol/L).
http://www.specialtylabs.com/clients/outreach/web/site/details.asp?tid=44312&cid=301&keyword=Hence, additional implants are denied upon return of symptoms for no good reason and aren't justified. Some women end up suffering unnecessarily.
Some women may need more to feel good as the above study suggests...
"Complete withdrawal of oestrogen therapy as suggested by Gangar et al. (1989), to allow levels to return to 200 pmol/L is wrong and in severely depressed patients may be
dangerous. Supraphysiological oestradiol levels are an uncommon consequence of oestradiol implants occurring most frequently in women with a history of depression or surgical castration. These high serum oestradiol levels were not associated with any deleterious effects and
may be necessary for the control of symptoms in specific women."
Although the threshold mentioned here is lower, this observation nonetheless applies to the policy earlier stated because these women did best with levels much higher than 400 pmol/L, in excess of 1,750 pmol/L. Not all women respond the same, some being less sensitive than others and doctors treating transwomen should learn a thing or two from this study, realizing that one size fits all levels is perhaps not the best way to go about treating us.
QuoteTherapy was with (...) E2 implants inserted subcutaneously in the lower abdominal wall.
Dosages aren't allowed, Laura! Oops!
QuoteThere appears to be no justification for giving E2 implants more frequently as this policy achieves satisfactory (physiological) premenopausal E2 levels and good symptomatic relief without any evidence for accumulation of E2 or 'tachyphylaxis'.
If one delves deeper into the study, one notes that not all women had "good symptomatic relief" as is asserted by authors in the conclusion. In fact, at 50 months implant therapy, 15 % of women complained of hot flushes, 5% of irritability, 3 % of either lassitude/lethargy, 3% of anxiety and 2% of low libido which are symptoms typically associated with too low estrogen and which improved for the most part in women after implant therapy.
Also, upon further review, one notes that 16 women discontinued treatment because they preferred other forms of HRT and 3 saw no benefit, perhaps because some of these women were getting menopausal symptoms well before the level of 400 pmol/L was reached.
Did these women experience desensitization OR instead just needed higher levels to feel good as opposed to some others who do well on lower levels and whose threshold to experiencing symptoms is much lower? Who knows? But, certainly, tachyphylaxis cannot be written off as the authors seem to do. It could well be that some women experienced desensitization and there may be evidence for tachyphylaxis.
The last statement from the original study which I disagree with based on the findings that not all women were symptom free:
"The policy of implanting, purely based on perceived return of symptoms without regard to the plasma oestradiol level, is illogical and may lead to accumulation and supra-physiological oestradiol levels."
This seems very wrong to me for the reasons cited above. These are NOT supraphysiological levels (far from), there appears to be no harmful effects that result from higher levels and not all women respond the same level due to varying sensitivity and this is shown in the fact that not all women showed good symptomatic relief as is implied by the conclusions of this study.
Further investigations are warranted to determine whether desensitization occurs in certain women or whether the return of symptoms may simply mean that some women need higher levels to feel best.
