Pregnant women's estradiol levels can go as high as 75,000 pg/ml.
http://cebp.aacrjournals.org/cgi/content-nw/full/12/5/452/T1 These levels were obtained just before labor/delivery, at the end of pregnancy which lasted on average, 38 weeks.
Mean estradiol levels (E2): 24,000 pg/ml, Range: from 800-75,000 pg/ml
http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf"Normal estradiol levels are lowest at menses and into the early follicular
phase (25-75 pg/mL) and then rise in the late follicular phase to a peak
of 200-600 pg/mL just before the LH surge, which is normally followed
immediately by ovulation. As LH peaks, estradiol begins to decrease
before rising again during the luteal phase (100-300 pg/mL)."
"
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"
Pregnancy lasts 9-10 months.
Neuropsychobiology. 2014;69(3):147-53.In 95 women. Late pregnancy.
Average Estradiol levels:
89.3 nmol/L (+/- 33.3), 56 – 122,6 nmol/L
89,300 pmol/L (+/- 33,300), 56,000 - 122,600 pmol/L
24,326 pg/ml (+/- 9,071), 15,255 - 33,397 pg/mlWomen have been pregnant for millions of years, traditionally women bore many children during a lifetime, at times, in excess of 10. Risk of blood clots in pregnant women is VERY low.
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."
In other words, a risk of 0.05-0.2 %. Very small.
Also,
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)
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.
Breast cancer is also lower in women who have more children.
Same with men with prostate cancer, aged 49-91 yrs old, given estradiol in high doses, to help with cancer. Levels ranged from 300-700 pg/ml. And yet, no complications. Studies confirmed this.
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)."
Am J Obstet Gynecol. 1993 Dec;169(6):1549-53."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."
Hum Reprod. 2002 Mar;17(3):825-9."We examined metabolic parameters in cohorts of women with and without subcutaneous estrogen therapy with concomitant supra-normal concentrations of estradiol (SE)."
"Women with SE have similar triglyceride and HDL cholesterol levels but lower LDL cholesterol concentrations compared with post-menopausal women not taking ERT. The observations that the SE group showed reduced fasting insulin and WHR suggest that supra-normal circulating concentrations of estradiol, delivered subcutaneously, may beneficially influence insulin metabolism."
I, myself, have had levels as high as 4,000 pg/ml with no negative impact on my health since the two years on injections. I'm supervised by three doctors. My clotting factors are normal, so is my liver, lipids, insulin, etc. I've had several blood tests done.
The issue appears to be not so much levels, but rather the type of estrogen and less importantly, route of administration. Bio-identical estradiol seems fairly safe.
And just recently,
JAMA. 2016 Jul 19;316(3):300-12."Among women undergoing fertility treatment in the Netherlands between 1980 and 1995, IVF treatment compared with non-IVF treatment was not associated with increased risk of breast cancer after a median follow-up of 21 years. Breast cancer risk among IVF-treated women was also not significantly different from that in the general population. These findings are consistent with absence of a significant increase in long-term risk of breast cancer among IVF-treated women."
http://www.nytimes.com/2016/07/20/health/ivf-breast-cancer-risk.html?_r=0"Women undergoing in vitro fertilization have long worried that the procedure could raise their risk for breast cancer.
After all, the treatment requires temporarily increasing levels of certain sex hormones to five or 10 times the normal. Two of those hormones, estrogen and progesterone, can affect the course of certain kinds of breast cancer.
A series of studies over the past decade suggested that these former patients may have little to worry about. Experts remained cautious, however, because women who had undergone I.V.F. in the 1980s had not yet reached menopause by the time of the research.
But the largest, most comprehensive study to date, published Tuesday, provides further reassurance: It finds no increased risk among women who have undergone I.V.F."
"Perhaps the study's most surprising finding was that breast cancer risk was significantly lower among those women who underwent seven or more cycles of I.V.F., compared with those who received one or two cycles.
"That's reassuring, because you would think if you did I.V.F. 10 times, your risk would be higher," said Dr. Owen K. Davis, the president of the American Society for Reproductive Medicine."
"Mia Gaudet, the strategic director of breast and gynecologic cancer research at the American Cancer Society, applauded the study for adding a "significant amount of evidence that there is no link between I.V.F. and breast cancer.""
