Quote from: Naomi71 on November 11, 2016, 01:47:32 AMshe told me that the risk for trombosis, or a brain seizure is still there.
Because she is thinking of studies where non bio-identical estrogens are used. In the case of bio-identical estrogen, especially taken non-orally, studies have shown these risks to be negligible.
Just take the case of men with prostate cancer who were prescribed a very high dose of transdermal patches.
Cancer. 2005 Feb 15;103(4):717-23."Patients with prostate carcinoma progressing after primary hormonal therapy received TDE (...) per 24 hours"
TDE = transdermal estradiol
"The mean (+/-95% CI) serum estradiol level increased from 17.2
pg.mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL
(range,
334.6-586.7 pg/mL)."
"No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed."
"In patients with APIC, TDE was well tolerated and produced a modest response rate, but
was not associated with thromboembolic complications or clinically important changes in several coagulation factors."
Median age of patients was 75 (49-91).
J Urol. 2005 Aug;174(2):527-33; discussion 532-3.
Transdermal estradiol therapy for prostate cancer reduces
thrombophilic activation and protects against thromboembolism."Levels of VIIa and XIIa were unaffected by transdermal estradiol therapy. Although levels of TAT III were increased in some patients at 12 months, the increase was markedly less than that observed historically with equivalent doses of oral estrogens. Levels of the inhibitory and fibrinolytic factors including protein C, protein S, APC-R, TPA and PAI-1 remained stable. Reductions in F1+F2, fibrinogen and D-Dimer levels represented a normalization from increased levels to the physiological range."
"These results suggest that
transdermal estradiol reduces thrombophilic activation in men with advanced prostate cancer, and protects against the risk of thrombosis."
Prostate 1989;14(4):389-95"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."
Fertil Steril. 2010 Mar 1;93(4):1267-72."Standard MtF cross-sex hormone therapy at our department includes transdermal 17ß-estradiol"
"Activated protein C resistance was detected in 18/251 patients (7.2%), and protein C deficiency was detected in one patient (0.4%). None of the patients developed VTE under cross-sex hormone therapy during a mean of 64.2 +/- 38.0 months."
Biochem Pharmacol. 2013 Dec 15;86(12):1627-42.
Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease."There was no increase in VTE risk with the use of transdermal estrogen,
even in patients with pre-existing thrombophilia [15]."
Climacteric. 2012 Apr;15 Suppl 1:11-7. "There is a wealth of evidence to suggest that, unlike oral estrogens, transdermal estradiol does not increase the risk of venous thromboembolism, probably due to its lack of effect on the coagulation cascade, including thrombin generation and resistance to activated protein C, and does not increase the risk of stroke. It is cardioprotective, significantly reducing the incidence of myocardial infarction compared with non-users"
Maturitas. 2008 Jul-Aug;60(3-4):185-201."Non-orally administered estrogens, minimizing the hepatic induction of clotting factors and others proteins associated with the first-pass effect, are associated with potential advantages on the cardiovascular system. In particular, the risk of developing deep vein thrombosis or pulmonary thromboembolism is negligible in comparison to that associated with oral estrogens. In addition, recent indications suggest potential advantages for blood pressure control with non-oral estrogens."
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."
Pregnant levels have very high levels, up to
75,000 pg/ml (275,000 pmol/L)http://cebp.aacrjournals.org/cgi/content-nw/full/12/5/452/T1 and yet...
Ann Intern Med. 2005 Nov 15;143(10):697-706."Women with deep venous thrombosis or pulmonary embolism first diagnosed between 1966 and 1995, including women with venous thromboembolism during pregnancy or the postpartum period (defined as delivery of a newborn no more than 3 months before the deep venous thrombosis or pulmonary embolism event date, including delivery of a stillborn infant after the first trimester)."
« The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to 5.22;P < 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100,000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs.
95.8 per 100,000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100,000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (
10.6 vs. 159.7
per 100,000). "
Risk of DVT: 0.1%
Risk of pulmonary embolism: 0.01%
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)."
"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"
"The mean serum oestradiol level of the 1388 women attending the clinic in 1988 was 767 pmol/l (
range 78-2925 pmol/l), 66% had serum oestradiol levels <1000 pmol/l and 3% (38 women) had levels >1750 pmol/l (Fig 1)."
Horm Metab Res. 1994 Sep;26(9):428-31."Six patients were peri- or postmenopausal (
49.5 + 4.8 years of age, group A)"
"The duration of the therapy was 6, and in 4 patients 9 months"
"Estradiol increased from 34.8 +/- 7.5 pg/ml to
3226 +/- 393 pg/ml after 3 months and to
2552 +/- 254 pg/ml after 6 months, respectively, in group A."
"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."
In transsexual women...
Archives of Sexual Behavior, Vol. 27, No. 5, 1998"The incidence of thromboembolic events during cross-gender hormone treatment in our patients was
zero."
"None of our patients developed deep vein thrombosis or embolism during cross-gender hormone therapy performed in our clinic."
Despite 17 patients receiving high dose intramuscular estradiol.
Exp Clin Endocrinol Diabetes. 2011 Feb;119(2):95-100"84 male-to-female transsexuals (MtFs) were treated with (...) oestradiol-17β valerate every 10 days." This was intramuscular.
"We observed one case of deep vein thrombosis in a 49 years old MtF who had uneventful medical history prior hormone therapy.
No further side effects or other complications were observed during the study."
Estradiol levels ranged from 340.5 pmol/L to 1,362.4 pmol/L, measured on the last day, just before the next injection so lowest levels (trough).
So, taking these two studies, out of a total of 101 women taking high doses of estrogen intramuscularly (non-orally), there was only one thromboembolic complication (1%) which could be due to just chance, have nothing to do with treatment.
One especially striking is this study in women with advanced breast cancer who were treated with moderate and VERY high dose oral bio-identical estrogen.
JAMA. 2009 August 19; 302(7): 774–780."We therefore conducted a randomized phase 2 trial in postmenopausal women with hormone receptor-positive, AI-resistant advanced disease to compare (...) estradiol daily (...) with (...) daily (...)"
"the mean [standard deviation] trough levels of estradiol at one month were
302 [519] pg/mL on the (...) arm and
2403 [2268] pg/mL on the (...) arm (P <.001)"
"The rate of thrombosis was low with
one event on each arm of the study." Both Grade 4/5
Median age: 54.7 yrs old (36.3-83.8 ); 59.5 yrs old (39.4-77.7)Sharing these with your doctor could be helpful.
