Non-oral bio-identical estradiol is best as it is the least likely to affect coagulation (can even protect) and have an interaction with oral medications such as coumadin.
J Urol. 2005 Aug;174(2):527-33; discussion 532-3. (Men with prostate cancer were treated with high dose transdermal estrogen)
"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."
Tidsskr Nor Laegeforen 1993 Mar 10;113(7):833-5
Endocrine treatment of prostatic cancer. A renaissance for parenteral
estrogen(Men with prostate cancer were treated with high dose intramuscular estrogen)
"Morbidity and mortality from cancer are
the same as may be achieved by surgical orchidectomy. The only side
effect of significance is gynaecomastia. Follow-up of the patients
does not indicate any increased risk of thrombosis or cardiovascular
disease."
J Lipid Res. 2006 Feb;47(2):349-55."Transdermal estrogen therapy (TDE) has a lower thrombosis risk than oral estrogen and may improve CVD risk 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."
Obstet Gynecol Clin North Am. 1987 Mar;14(1):269-98."The amount of estradiol leaving the liver following oral administration is substantially less than that which enters it through the portal vein. The systemic administration of estradiol avoids this initial hepatic metabolism. Furthermore, only 25 per cent of nonorally administered estrogen will go to the liver at each pass, and nonhepatic tissues would be exposed to a greater extent than after oral administration. Thus, peripheral administration of estradiol reduces the exaggerated hepatic responses in comparison to nonhepatic actions."
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; it significantly reduces the incidence of new-onset diabetes, a risk factor for myocardial infarction. Micronized progesterone has also been shown not to increase the risk of venous thromboembolism and further reduced the incidence of new-onset diabetes when combined with transdermal estrogen. Micronized progesterone has a neutral effect on the vasculature, including a neutral or beneficial effect on blood pressure. Therefore, experimental and clinical data indicate that transdermal estradiol and micronized progesterone could represent the optimal HRT, particularly in women at risk of adverse events."
Rev Prat. 1993 Dec 15;43(20):2631-7."Until now, the possible risk of thrombo-embolism has limited the prophylactic use of hormonotherapy and imposed contraindications. This risk is due to imbalance in hepatic (procoagulant effect) and peripheral (fibrinolytic effect) stimulations and therefore is to be feared specifically with oral oestrogens and their hepatic first-pass effect."
"On the other hand,
there is no known theoretical risk when oestradiol is given parenterally, which in France is the favoured method. This type of replacement therapy with oestradiol should be more often prescribed to subjects with atherogenic hyperlipidaemia, arterial hypertension or ischaemic coronary disease: not only it is not contraindicated, but it should soon become an indication."
Int J Pharm Compd. 2013 Jan-Feb;17(1):74-85."Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women. Cardiovascular biomarkers, inflammatory factors, immune signaling factors, and health outcomes were favorably impacted, despite very high life stress, and home and work strain in study subjects. The therapy did not adversely alter the net prothrombotic potential, and there were no associated adverse events. This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in populations with high perceived stress and a history of stressful life events prior to, or during the menopausal transition."
Prz Menopauzalny. 2014 Oct;13(5):267-72."Menopausal hormone therapy (MHT) is the most effective method of treating vasomotor symptoms and other climacteric symptoms related to estrogen deficiency in peri- and postmenopausal period. In addition to estrogen replacement, women with preserved uterus require the addition of progestagen in order to ensure endometrial safety. One of rare but severe complications of MHT is venous thromboembolism (VTE). The incidence of VTE rises in parallel to women's age and body weight. The condition is also linked to hereditary and acquired risk factors. Oral estrogens increase the risk of venous thromboembolic complications to varying extents, probably depending on their type and dose used. Observational studies have not found an association between an increased risk of VTE and transdermal estrogen treatment regardless of women's age and body mass index (BMI). Micronized progesterone and pregnanes, including dydrogesterone, have no effect on the risk of VTE, whereas norpregnane progestagens cause an additional increase in risk. Among hormonal preparations which are commercially available in Poland, the combination of transdermal estradiol with oral dydrogesterone appears to be the optimum choice, as it does not elevate the risk of VTE (compared to patients not using MHT), and dydrogesterone seems to be the progestagen of choice."
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. To the same extent, a growing literature suggests that the progestins used in association with estrogens may not be equivalent. Recent evidence indeed shows that natural progesterone displays a favorable action on the vessels and on the brain, while this might not be true for some synthetic progestins."
Cancer Epidemiol Biomarkers Prev. 2003 May;12(5):452-6.
http://cebp.aacrjournals.org/cgi/content-nw/full/12/5/452/T1 In pregnant women, levels can go as high as 75,000 pg/ml. Levels measured just before delivery (end of pregnancy)
http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf "If conception occurs, estradiol levels continue
to rise, reaching levels of 1,000-5,000 pg/mL during the first trimester,
5,000-15,000 pg/mL during second trimester, and 10,000-40,000 pg/mL
during third trimester. 6-8"
Neuropsychobiology. 2014;69(3):147-53."The mean age of the women was 30.7 ± 4.5 years and 55
(57.3%) were nulliparous (pregnant with their first child).
The assessments were made in gestational week 38.2 ± 0.6
and the median number of days until parturition was 13.5
days (range 1–32 days)."
In 95 women. Late pregnancy.
Average Estradiol levels:
24,326 pg/ml (+/- 9,071), 15,255 - 33,397 pg/ml (after conversion to units)
Despite high levels, pregnant women who get their estradiol secreted internally,
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."
...have a risk of 0.05-0.02% of having a thromboembolism.
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). "
Hence, most cases of DVT and PE, already quite low, are present post-partum, not during pregnancy.
PLEASE KEEP ALL THIS INFO CLOSE TO YOU. You can use this to persuade doctors to prescribe you estradiol despite your condition.
Cyproterone acetate (Androcur), medroxyprogesterone acetate (Provera), birth control pills, conjugated equine estrogens whether orally or not tend to increase coagulation and thus increase risk of DVT and pulmonary embolism.
Bio-identical progesterone (oral or not), non-oral bio-identical estradiol (gel, patch, injections, pellets), oral dydrogesterone, oral spironolactone, LhRh agonists appear to
not affect coagulation and not increase risks. I'm not sure about the rest. Check with doctors/pharmacists. But, some of these oral medications may affect intestinal and hepatic CYP enzymes metabolizing coumadin (I think CYP3A4 for instance) so check for interactions, always with health professionals.
Best of luck.
