Quote from: BoroTrans on March 30, 2016, 04:54:42 PM
I am getting ready to start hormones but am frightened about the blood clot risks. How real is this risk? I know every drug has risks but has anyone had any problems in this area? It concerns me because heart disease runs in my family and am over 50 and somewhat overweight. What are y'alls thoughts?
The risk of blood clots and of stroke was only found in women who took non bio-identical hormones such as Premarin (CEE or conjugated equine estrogens) and medroxyprogesterone acetate (Provera). Cyproterone acetate also slightly increases this. If you stick with bio-identical estradiol (or estradiol valerate), especially non-orally, the risks are negligible.
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]."
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"
In studies on transsexual women taking high doses of bio-identical estradiol orally and not orally, in studies on men with prostate cancer (aged 49-91) taking high doses of estrogen, either transdermally or by injections, no cardiovascular complications were noted and neither were the occurrence of DVT (deep vein thrombosis) or pulmonary embolism.
Prostate 1989;14(4):389-95"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."
Please note the synthetic estrogens mentioned are ethinyl estradiol, not bio-identical estradiol.
J Urol. 2005 Aug;174(2):527-33; discussion 532-3.
Transdermal estradiol therapy for prostate cancer reduces
thrombophilic activation and protects against thromboembolism."These results suggest that transdermal estradiol reduces
thrombophilic activation in men with advanced prostate cancer, and
protects against the risk of thrombosis."
Pregnant women produce high concentrations of estradiol and progesterone, up to 75,000 pg/ml estradiol (at most, we can 4,000-5,000 but usually in the hundreds, in the majority of women). Despite this, the risk of DVT is around 0.05% - 0.2%, higher after giving birth!
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.« 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)
Cas Lek Cesk. 1997 Jul 30;136(15):468-72."This data supports the concept that the decreased serum levels of cytoadhesive molecules of sP-selectin and sE-selectin are dependent on serum estrogen levels and together with a new, estrogen induced, equilibrium of the fibrinolytic system suggest an explanation for the relatively low incidence of thromboembolic events in pregnancy. Decrease of cytoadhesive molecules may be one of explanations of favourable effects of estrogens on the development of atherosclerotic vascular changes."
J Pharm Pract. 2014 Apr 17;27(3):243-252.
Pregnancy-Related Venous Thromboembolism."Risk factors include advanced maternal age, obesity, smoking, and cesarian section."
"Additionally, the presence of concomitant thrombophilia, particularly factor V Leiden (homozygosity), prothrombin gene mutation (homozygosity), or antiphospholipid syndrome (APS), increases the risk of pregnancy-related VTE"
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)"
Remember, this is in pregnant women with extremely high levels of estradiol and the risk is VERY very low.
Regarding cardiovascular health:
. Ciswomen are reported to be much less affected than men by cardiovascular complications despite pregnancy levels of estradiol and levels of up to 650 pg/ml every menstrual cycle. Their risks increase (and approach that of males) post-menopause when estrogen levels DROP. Studies have strongly suggested a protective role for estrogen. I can provide these studies.
Cardiovasc Res. 2006 Mar 1;69(4):777-80."There is an
abundance of scientific evidence for the protective effect of estrogen against atherosclerosis, such as short-term vasodilating effects as well as long-term vascular protective and anti-atherosclerotic effects [2]. Epidemiological evidence shows that pre-menopausal women have a reduced risk for mortality from cardiovascular diseases [3] and that women are at a lower risk for the development of heart failure [4] and have enhanced cognitive function and reduced neurodegeneration associated with Alzheimer's disease and stroke [5]. Further proof for the protective effect of female gender is the fact that post-menopausal women have a similar or even increased risk for cardiovascular disease compared to men [3] and have an increased risk for adverse outcome after myocardial infarction and acute coronary syndromes, despite similar treatment with thrombolysis and percutaneous interventions [6]. It was therefore postulated that estrogen replacement would be beneficial in preventing cardiovascular diseases in post-menopausal females."
"The cardioprotective effect of estrogen is further supported by the findings that ovariectomy caused a loss of cardioprotection, which was regained by chronic estrogen replacement therapy."
"The vascular protective effects of estrogen and their mechanisms are thus fairly well-established."
Ann Clin Res. 1983;15 Suppl 38:1-121."Estradiol-17 beta substitution decreased the systolic and diastolic blood pressure in normotensive, hypertensive and borderline hypertensive postmenopausal women."
"Irrespective of the pretreatment blood pressure levels, heart rate decreased during estradiol-17 beta substitution"
. Randomized controlled trials (the most reliable type of study), the Danish and WHI studies have shown estrogen taken alone or without medroxyprogesterone acetate (known to have deleterious effects on cardiovascular markers and oppose estrogen's beneficial effects on cardiovascular health) to DECREASE the cardiovascular complications (and death from). The Danish study (bio-identical estradiol w/progestin other than medroxyprogesterone acetate) did not observe an increase in stroke nor DVT/PE (deep vein thrombosis/pulmonary embolism) incidence.
. Transdermal and even oral bio-identical estradiol in women have shown to positively impact blood pressure with transdermal having an overall beneficial effect on several cardiovascular markers and negligibly affecting coagulation. Studies to support this.
J Lipid Res. 2006 Feb;47(2):349-55."This prospective pilot study of 18 men with androgen-independent prostate cancer receiving ADT measured effects of TDE on lipid and inflammatory CVD risk factors before and after 8 weeks of TDE (...). During treatment, estradiol levels rose 17-fold; total cholesterol, LDL cholesterol, and apolipoprotein B levels decreased. HDL2 cholesterol increased, with no changes in triglyceride or VLDL cholesterol levels. Dense LDL cholesterol decreased and LDL buoyancy increased in association with a decrease in HL activity. Highly sensitive C-reactive protein levels and other inflammatory markers did not worsen. Compared with ADT, short-term TDE therapy of prostate cancer improves lipid levels without deterioration of CVD-associated inflammatory markers and may, on longer-term follow-up, improve CVD and mortality rates."
TDE = transdermal estradiol
ADT = androgen deprivation therapy
Horm Mol Biol Clin Investig. 2014 May;18(2):89-103."The cardiovascular protection observed in females has been attributed to the beneficial effects of estrogen on endothelial function."
"estrogen alone or combined with progesterone has been associated with decreased blood pressure"
"Estrogens physiologically stimulate the release of endothelium-derived vasodilator factors and inhibit the renin-angiotensin system."
Rev Prat. 1993 Dec 15;43(20):2631-7."This favourable effect of estrogens is completed by other mechanisms which modify platelet aggregation, prostacyclin/thromboxane equilibrium, endothelin, etc., and which improve arterial wall morphology and vasoactive reactions. Some synthetic progestogens, given with oestrogens for endometrium control, may compromise these spectacular vascular benefits, but this is not the case with natural progesterone."
So, if you stick to the natural bio-identical hormones, you should be fine and even better.
