Quote from: Richenda on June 22, 2016, 09:33:44 PM
I'm gobsmacked that you've never heard of the connection Kay. Maybe a little more time on MSM would help. I travel widely and have been married to a medic and a pilot is my best friend, but anyone who follows the news would have picked up the connection between HRT and DVT when flying.
I am well aware of the connection between flying and DVT but not aware of any transwoman who stopped their hormones due to this or who were told by their doctors to stop them due to these circumstances. Think of the millions of women worldwide who take birth control pills which pose greater risks than what we typically take and who fly back and forth without even stopping them or being told by their doctors to stop them. Should these women stop their pills? Perhaps but if doctors don't advise against cessation of birth control pills before a flight, why would they in the case of transwomen who typically are on HRT that is less risky?
QuoteThere is a clear risk associated between HRT and DVT
It's important to make the distinction between different types of HRT. The link found was in those taking birth control pills or conjugated equine estrogen or DES (sometimes with progestins) which are all non bio-identical forms and have shown to have greater impact on coagulation than bio-identical estradiol, more so if the latter is taken non-orally in which case the impact on coagulation is negligible as the studies above show as it mimics the way in which ciswomen get their estrogen.
J Clin Endocrinol Metab. 2012 Dec;97(12):4422-8"Historically, high-dose estrogen in the form
of ethinyloestradiol or conjugated equine estrogen (CEE) was
used to suppress testicular function and induce feminization.
In
view of the procoagulant nature of these older estrogens and the
inability to use plasma estradiol levels to guide treatment, this
protocol was changed in 2004 to oral estradiol valerate"
JAMA Intern Med. 2014 Jan 1;174(1):25-31."In an observational study of oral hormone therapy users, CEEs use was associated with a higher risk of incident venous thrombosis and possibly myocardial infarction than estradiol use. This risk differential was supported by biologic data."
Biochem Pharmacol. 2013 Dec 15;86(12):1627-42. "There was no increase in VTE risk with the use of transdermal estrogen, even in patients with pre-existing thrombophilia [15]."
J Thromb Haemost. 2014 Mar 15."Compared with E2 users, CEE users had greater thrombin generation peak values, endogenous thrombin potential, and lower total protein S (multivariate adjusted differences of 49.8 nM (95%CI: 21.0, 78.6); 175.0 nMxMin (95%CI: 54.4, 295.7); and -13.4% (95%CI: -19.8, -6.9), respectively)."
"The hemostatic profile of women using CEE is more prothrombotic than that of women using E2. These findings provide further evidence for a different thrombotic risk for oral CEE and oral E2."
Maturitas. 2015 Mar 9."In an observational study of oral HT users, CEE was associated with a significantly higher risk of incident venous thrombosis (OR, 2.08; 95% CI, 1.02–4.27), significantly higher activated protein C resistance (OR 1.68; 95% CI, 1.24–2.28), and a nonsignificant elevation in myocardial infarction risk (OR, 1.87; 95% CI, 0.91–3.84) when compared with estradiol use [56]."
"The hemostatic profile of women taking CEE was shown to be more prothrombotic than that of women using oral estradiol, including significantly higher thrombin generation peak value and decreased total protein S (P = 0.001 and P ≤ 0.001, respectively) [57]. In an oophorectomized pig model, both estradiol and CEE reduced aggregation of platelets, but only estradiol increased platelet secretion of nitric oxide, and platelets from estradiol-treated animals caused relaxation of coronary arteries [58]. »
Minerva Med. 2013 Apr;104(2):161-7."New kinds of COC without EE but with Estradiolvalerat or Estradiol showed a much lower degree of coagulation activation than "classical" COC containing EE."
"Estradiol itself has a lower impact on estrogen-hepatic proteins, and is more readily metabolized by the liver than ethinyl estradiol, the ethinyl group on which slows down that process. The structure increases the bioavailability of ethinyl estradiol compared with E2, but may also contribute to an increased likelihood of estrogen-related adverse events.40 »
"The authors reported a procoagulatory shift in levels of these markers in women taking levonorgestrel–ethinyl estradiol. In contrast, they reported significantly smaller changes from baseline in these markers among women taking NOMAC-E2. One outcome was a change in activated protein C resistance. This marker, which has been proposed as an independent risk factor for venous thromboembolism, increased to a greater degree in levonorgestrel–ethinyl estradiol users than in NOMAC-E2 users (0.46 versus 0.20, P < 0.01). »
"Agren et al evaluated multiple coagulatory and thrombolytic indices over six cycles of oral contraceptive use in a randomized study comparing NOMAC-E2 with levonorgestrel–ethinyl estradiol (...). They reported that NOMAC-E2 had minimal influence on markers of hemostasis, and caused less change in these parameters than the pill containing ethinyl estradiol 30 μg.33 »
Andrologia. 2014 Sep;46(7):791-5.« Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer"
"Cessation of use of ethinyl oestradiol and peri-operative thrombosis prophylaxis for surgery have reduced prevalence rate of VTE."
Journal of Clinical & Translational Endocrinology 2 (2015) 55-60"Other compelling data suggest that
the incidence of venous thromboembolism (VTE) among transgender
women appears associated with the presence of a hypercoaguable
risk factor, including the use of an especially
thrombogenic estrogen (ethinyl estradiol) which is no longer used
[3]. Gooren et al. (2008), reported no increase in VTE among 2236
male-to-female (MTF) transgender individuals on HT from 1975 to
2006 compared with controls, with the exception of those who used
ethinyl estradiol, for which there was a 6-8% incidence [4]."
Menopause. 2006 Jul-Aug;13(4):643-50."Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis."
Fertil Steril. 1997 Sep;68(3):449-53.« Compared with placebo, oral E2 replacement therapy resulted in a significant decrease in fibrinogen and apo B and a significant increase in plasminogen."
J Clin Endocrinol Metab. 2003 Dec;88(12):5723-9."The large differential effect of oral EE and oral E(2) indicates that the prothrombotic effect of EE is due to its molecular structure rather than to a first-pass liver effect (which they share). Moreover, these differences may explain why M-->F transsexuals treated with oral EE are exposed to a higher thrombotic risk than transsexuals treated with td E(2)."
"In conclusion, we have shown that treatment of MtF transsexuals with sex steroid hormones (CPA combined with E2 or EE) affects the hemostatic balance with a very pronounced difference in the effects of oral EE compared with the effects of both td E2 or oral E2. Oral EE induces a clinically relevant prothrombotic state."
QuoteThere are thousands of online articles about the link, some academic, others less so. It is evidential that women on contraceptive pills and HRT have an increased risk of DVT when flying
Certainly. But a distinction must be made. Not all forms are equally thrombogenic and when taken non-orally, bio-identical estradiol has very little effect.
QuoteBy the way, the DVT risk is precisely why surgeons performing GRS usually insist patients stop taking hormones for up to 3-4 weeks prior to surgery.
Indeed. But, many don't grasp the differences between the different forms of estrogen and are unaware of the scientific literature re: bio-identical estradiol taken non-orally or even the very low (absolute) incidence of DVT in pregnant women despite VERY high levels of estradiol. I repeat. I take estradiol parenterally and my clotting times remain normal.
If estrogen were ALWAYS a risk for DVT regardless of form or route of administration, then explain why ciswomen are allowed to have surgery or at the very least, not asked to take something (i.e. LhRh agonist) to temporarily suspend their production of endogenous estrogen? The answer: because the estrogen is bio-identical and secreted directly into the blood. Levels in ciswomen can go as high as 650 pg/ml during a menstrual cycle and I doubt doctors would only admit women into surgery during their menses.
QuoteGeneral risk factors for VTE include the following:
Estrogen use (hormonal contraceptives or hormone replacement therapy)'
Hormonal contraceptives contain ethinyl estradiol and sometimes a progestin (not bio-identical progesterone which has no effect on coagulation) that further increases that risk like drospirenone or even cyproterone acetate.
Hormone replacement therapy with a link comprised of conjugated equine estrogens and often a progestin, medroxyprogesterone acetate which both increase risk of DVT, to a much greater degree than bio-identical estradiol with bio-identical progesterone.
Again, one needs to differentiate between forms.
Quote'Oral contraceptives
Oral contraceptive use has been incriminated as a risk factor for venous thromboembolism during long-haul flights. This gives rise to questions about the type of oral contraceptive and whether stopping or changing to an alternative form of contraception will lower the risk of venous thromboembolism.
Here, we see that no decision has been made as to whether women should be told to stop these pills prior to long haul flights so women do indeed continue taking them and they pose greater risks than what transwomen typically take.
QuoteThe increased risk of venous thromboembolism is mainly associated with the combination of oestrogen and progestogen. Later 'generation' formulations have not been associated with a lower risk. After stopping a combined oral contraceptive pill the risk of venous thromboembolism gradually returns to baseline, although this takes the equivalent of 2–3 menstrual cycles. Progestogen-only preparations have less risk of venous thromboembolism, but there is still a 2–3 month delay before the increased risk subsides if the woman switches to them from a combined pill.'
Here oestrogen and progestogen refer to non bio-identical forms.
Quotehttp://www.bupa.com.au/health-and-wellness/health-information/az-health-information/deep-vein-thrombosis
'Causes of DVT
You are more likely to get a DVT if you:
are pregnant or have recently had a baby.
The actual absolute risk of DVT is 0.05 - 0.2% for pregnant and post-partum women, the incidence being greater post-partum. Despite estradiol levels reaching levels of 75,000 pg/ml and dropping to very low levels post-partum.
Curr Opin Obstet Gynecol. 2014 Dec;26(6):469-75.« Venous thromboembolism is, in the developed world, a major cause of maternal morbidity and mortality during pregnancy or early after delivery, with a reported incidence ranging from 0.49 to 2.0 events per 1000 deliveries."
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). "
"Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during
the postpartum period." (When estrogen levels drop and are low)
Hence,
most cases of DVT and PE, already quite low, are present post-partum, not during pregnancy. And those cases present during pregnancy are associated with certain specific conditions.
VOL. 118, NO. 3, SEPTEMBER 2011 OBSTETRICS & GYNECOLOGY
Thromboembolism in Pregnancy"The most important individual risk factor for venous
thromboembolism in pregnancy is a personal history of
thrombosis."
"The next most important individual risk factor for venous
Thromboembolism in pregnancy is the presence of a thrombophilia
(3, 23)."
"Both acquired and inherited thrombophilias increase the risk
of venous thromboembolism (26)"
"other risk factors for the development of pregnancy-associated
venous thromboembolism include the physiologic
changes that accompany pregnancy and childbirth,
medical factors (such as obesity, hemoglobinopathies,
hypertension, and smoking), and pregnancy complications
(including operative delivery) (3, 6–8, 17, 27, 28). »
Some of these factors either don't apply to transsexual women or are quite rare occurrences such as previous thrombosis or thrombophilia. Also, transwomen will never attain such high estradiol levels, at most, 4-5,000 pg/ml.
It's important to keep things in perspective.
