One of the first rules of medicine is do no harm. If the medic thinks the risks are too get then that is their opinion and a second opinion is warranted. Reducing lifestyle risk is important and acknowledging the risk to the medic as not being relevant to you as the alternative risk of self harm is greater is also important but do not use as a 'blackmail' gambit.

I am at high risk, both sister, mother and grandmother had breast cancer and I am BRACA1 positive. The risk was explained and I accepted it. The endo accepted that and there was no issue.

In summary a second opinion with you being fully aware and explaining your acceptance of the risks is warranted (IMO).

Again, thank you everyone.  I was in a very dark place this afternoon.  Even after I quit crying, I was just laying in bed staring at the wall and Dee was very worried.   You have all helped so, so much.  Thank you from the bottom of my and Dee's heart. 

Quote from: BeverlyAnn on March 08, 2016, 05:17:16 PM
Said I was too old and too many family factors created a risk.  Came home and cried for a while.

Your doctor is incompetent. Find someone else. Read the following on men with prostate cancer treated with high dose estrogen. These men ranged in age from 49 yrs old to 91 yrs old. Median age was 75 yrs old.

Cancer. 2005 Feb 15;103(4):717-23.
Phase II study of transdermal estradiol in androgen-independent
prostate carcinoma.

"Patients with prostate
carcinoma progressing after primary hormonal therapy received (...)"

"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. CONCLUSIONS: 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."

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."

Am J Clin Oncol. 1988;11 Suppl 2:S101-3.
Single drug polyestradiol phosphate therapy in prostatic cancer.

"Serum concentrations of testosterone (T) and estradiol-17 beta (E2) were analyzed in prostatic cancer patients treated with (...) polyestradiol phosphate (PEP) i.m. every fourth week as single drug therapy during a 6 month period."

"Orchidectomy levels of T were reached within 3 weeks (...) and 3 months (...). In the (...) group, mean T levels reached the upper limit of orchidectomy values after 6 months. Accumulation of E2 occurred to mean levels 1,300-2,500 pmol/L at 6 months" (354 - 681 pg/ml)

"No cardiovascular side effects occurred during single-drug PEP treatment."

Tidsskr Nor Laegeforen 1993 Mar 10;113(7):833-5
Endocrine treatment of prostatic cancer. A renaissance for parenteral
estrogen.

"38 patients have been treated at Huddinge Hospital in Stockholm, and
14 patients at Aker Hospital in Oslo, with polyoestradiol phosphate
(Estradurin)(...) injected intramuscularly every 4th week."

"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."

Prostate 1991;18(2):131-7
Cardiovascular and all-cause mortality in prostatic cancer patients treated
with estrogens or orchiectomy as compared to the standard population.

"Four hundred and seventy-seven prospectively randomized patients with
prostatic carcinoma were treated with a combination of intramuscular
polyestradiol phosphate (PEP) and oral ethinyl estradiol, with
intramuscular PEP alone, or with orchiectomy. The cardiovascular and
all-cause mortality of the two estrogen therapy modalities and
orchiectomy were compared with those of the Finnish male population
in general."

"It is concluded that intramuscular PEP monotherapy is associated with
low cardiovascular mortality and with an all-cause and prostatic
cancer mortality equal to orchiectomy."

Int J Technol Assess Health Care 1991;7(2):220-5
Cost comparison of parenteral estrogen and conventional hormonal treatment
in patients with prostatic cancer.

"Twenty-five percent of the patients treated with
oral estrogen suffered cardiovascular complications, compared to none
of the patients treated by orchidectomy or nonoral estrogens."

Prostate 1989;14(4):389-95
Estrogen therapy and liver function--metabolic effects of oral and parenteral
administration.

"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."

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."

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"

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."

Prz Menopauzalny. 2014 Oct;13(5):267-72.

"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)."

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."

Minerva Endocrinol. 1989 Jan-Mar;14(1):41-4.

"In particular, it has been found that estradiol (differently from other estrogens) when administered transdermically is able to relieve menopausal symptoms at doses which do not influence the liver synthesis of proteins."

Thromb Haemost. 2001 Apr;85(4):619-25.

"In summary, oral estradiol increased markers of fibrinolytic activity, decreased serum soluble E-selectin levels and induced potentially antiatherogenic changes in lipids and lipoproteins. In contrast to these beneficial effects, oral estradiol changed markers of coagulation towards hypercoagulability, and increased serum CRP concentrations. Transdermal estradiol or placebo had no effects on any of these parameters."

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."

Biochem Pharmacol. 2013 Dec 15;86(12):1627-42.

"Cardiovascular disease (CVD), such as coronary heart disease (CHD) and hypertension, is less common in premenopausal women (Pre-MW) than in men of the same age, suggesting vascular benefits of estrogen [1,2]. Also, the risk of CVD increases with age in postmenopausal women (Post-MW) compared with Pre MW, partly due to decreased plasma estrogen levels."

"Earlier observational studies, such as the Nurses' Health Study (NHS) in the mid 1970s, suggested that estrogen therapy in Post-MW reduced the risk of CVD by 35% to 50% [1]. Also, a meta-analysis of observational studies showed  33% reduction in fatal CVD among MHT users compared with nonusers [3]. Experimental studies supported vascular benefits of estrogen. Acute administration of estrogen in female or male patients improves vasodilator responses and ameliorates myocardial ischemia [4]. Also, acute administration of estrogen in dogs and isolated rat and rabbit hearts lowers coronary vascular resistance and enhances coronary blood flow [5]. Estrogen modulates vascular function by targeting estrogen receptor (ER) in endothelial cells (ECs) and vascular smooth muscle (VSM) [1,2]. Estrogen also enhances the release of vasodilator substances such as nitric oxide (NO) and prostacyclin (PGI2), and decreases the production and effects of vasoconstrictors such as endothelin (ET-1) and angiotensin II (AngII) [1,2]."

J Am Coll Cardiol. 2000 Dec;36(7):2154-9.

"This is a randomized controlled primary prevention trial, in which
16,608 postmenopausal women aged 50–79 years with an
intact uterus received conjugated equine estrogens (CEE), plus MPA, or placebo.
The primary outcomes were nonfatal myocardial infarction and coronary
heart disease (CHD) death, with invasive breast cancer as
the primary adverse outcome. While the planned duration of
the treatment was 8.5 years, the CEE+MPA treatment arm
was stopped prematurely after 5.2 years, due to apparent increases
in cardiovascular events and breast cancer incidence
[7]. The evaluation of the CEE-alone treatment arm (women
without a uterus) is still ongoing, due to the absence of such
apparent increases in hazard. This is strongly suggestive
of a potentially harmful effect of the progestin used in the
study (MPA)."

Menopause. 2014 Jan 6.

"Menopause is accompanied by a dramatic rise in the prevalence
of hypertension (HTN) in women, suggesting a protective
role for endogenous estradiol in BP regulation"

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"

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 (high dose)
ADT = androgen deprivation therapy

Oral estrogen in the above studies most often refers to ethinyl estradiol, conjugated equine estrogens (or DES), which pose greater risks than oral estradiol. Studies have shown this quite unequivocally. I can provide you these as well, if you want.

Your doctor may be worried about breast cancer risk but remind him that breast cancer is most common in women after the age of 40-50, when estrogen levels DROP.

Also,

Journal of Clinical & Translational Endocrinology 2 (2015) 55-60

"Although studies are small, overall cancer incidence in transgender men and transgender women to-date has not been found to be different than their respective male and female controls [5]. There are no reports of change in breast cancer specific risk among transgender individuals on estrogen compared to secular trends of male breast cancer incidence. Rates are lower relative to secular trends of female breast cancer rates."

"Additionally, there are ten case reports of breast cancer development among MTF individuals on estrogen since 1968"

Despite several decades of aggressive estrogen treatment.

Eur J Cancer. 2013 Jan;49(1):52-9. (In women with previous breast cancer)

The Stockholm study was controlled, randomized, and progestins were only given at 3 month intervals for 14 days. What they found was no increased breast cancer risk. The trial lasted 6 years and after follow-up of 10.8 yrs, there was still no increased risk.

"After 10.8 years of follow-up, there was no difference in new breast cancer events: 60 in the HRT group versus 48 among controls (hazard ratio (HR)=1.3; 95% confidence interval (CI)=0.9-1.9). Among women on HRT, 11 had local recurrence and 12 distant metastases versus 15 and 12 for the controls. There were 14 contra-lateral breast cancers in the HRT group and four in the control group (HR=3.6; 95% CI=1.2-10.9; p=0.013). No differences in mortality or new primary malignancies were found."

"The number of new events did not differ significantly between groups, in contrast to previous reports. The increased recurrence in HABITS has been attributed to higher progestogen exposure. As both trials were prematurely closed, data do not allow firm conclusions. Both studies found no increased mortality from breast cancer or other causes from HRT."

There was no increase in mortality due not only to breast cancer but other causes as well, like stroke or DVTs.

BMJ. 2012 Oct 9;345 (British Medical Journal) (a randomized controlled study)

Women treated with bio-identical estradiol vs not.

(during intervention, 10 yr study)
"The occurrence of any cancer did not differ significantly (39 in control group v 36 in treated group; 0.92, 0.58 to 1.45; P=0.71) or breast cancer (17 in control group v 10 in treated group, 0.58, 0.27 to 1.27; P=0.17; fig 4). The occurrence of other cancers did not differ significantly (25 in control group v 26 in treated group; 1.04, 0.60 to 1.80; P=0.88): three women in the control group had a diagnosis of both breast cancer and other cancer. The composite endpoint mortality or breast cancer applied to 40 women in the control group and 22 in the treated group (0.54, 0.32 to 0.91, P=0.020)."

(6 yrs after intervention, follow-up)
"The groups did not differ significantly for breast cancer (26 in control group v 24 in treated group; 0.90, 0.52 to 1.57; P=0.72) or for other cancers (43 in control group v 52 in treated group; 1.21, 0.81 to 1.82; P=0.35, fig 6)."

"A significant interaction was found between hormone replacement therapy and age at baseline for the composite endpoint mortality or breast cancer (P=0.028) with the younger women (<50 years) receiving hormone therapy having a significantly reduced risk (0.49, 0.28 to 0.87, P=0.015, fig 6). Women who had undergone hysterectomy (n=192) and received oestrogen alone had a decreased risk of death or breast cancer compared with women in the control group (0.42, 0.18 to 0.97; P=0.043; fig 6)."

Interestingly,

"During the intervention period 41 women died (26 in control group v 15 in treated group; 0.57, 0.30 to 1.08; P=0.084). Heart failure was diagnosed in eight participants (7 in control group v 1 in treated group; 0.14, 0.02 to 1.16; P=0.07) and myocardial infarction was diagnosed in five participants (4 in control group v 1 in treated group; 0.25, 0.03 to 2.21; P=0.21)"

"Stroke rates did not differ between the groups (14 in control group v 11 in treated group; 0.77, 0.35 to 1.70; P=0.70). The rate of venous thromboembolism was low and did not differ significantly between groups. Three women had confirmed deep vein thrombosis (1 in control group v 2 in treated group; 2.01, 0.18 to 22.16) and only one woman (control group) was admitted to hospital with pulmonary embolism."

16 yrs later,

"During the 16 years 67 women died (40 in control group v 27 in treated group; 0.66, 0.41 to 1.08; P=0.10; fig 5). Heart failure was diagnosed in 11 participants (8 in control group v 3 in treated group; 0.37, 0.10 to 1.41; P=0.15) and myocardial infarction was diagnosed in 16 participants (11 in control group v 5 in treated group; 0.45, 0.16 to 1.31; P=0.14)."

"Stroke rates did not differ between groups, with 21 cases in the control group and 19 in the treated group (0.89, 0.48 to 1.65; P=0.71). The rate of venous thromboembolism and pulmonary embolism was low and there was no significant difference between groups (fig 6⇓). Nine women had confirmed deep vein thrombosis (5 in control group v 4 in treated group; 0.80, 0.22 to 2.99; P=0.74), and only four women were admitted to hospital with pulmonary embolism (3 in control group v 1 in treated group; 0.33, 0.04 to 3.21; P=0.34)."

"In the control group 23 deaths were due to cardiovascular causes and 17 to non-cardiovascular causes. In the treatment group six deaths were due to cardiovascular causes and 21 to non- cardiovascular causes."

J Natl Cancer Inst. 2005 Apr 6;97(7):533-5.

"the Women's Health Initiative recently reported (9) no increase in the risk of breast cancer associated with an average of 7 years of treatment with estrogen alone but rather a statistically non-significant trend toward a reduced risk (RH = 0.77, 95% CI = 0.59 to 1.01)."

Of 10,000 women/year,

10 more incidences of breast cancer and coronary heart disease in women NOT on estrogen VS those on estrogen alone. (source: Menopause. 2014 Jan 6.)

Lancet. 2012 Jun 23;379(9834):2322-3.

"MacMahon and colleagues3 were
the first investigators to make a formal link with parity,
showing, in 1970, that parous women had a decreased
risk of breast cancer compared with nulliparous women.
Parous women receive further protection if they have
their first child at a young age, bear more children, and
if they breastfeed."

The more pregnancies (during which estrogen levels peak at as much as 75,000 pg/ml), the lower the risk of breast cancer.

BMC Women's Health 2005;5:12

"the highest breast cancer incidence is in post-menopausal women, when endogenous E2 levels are much lower than before menopause"

"This pattern of increased risk for breast cancer immediately following full-term pregnancies is well-documented [140-142]. E2 concentrations increase steadily during pregnancy, peaking at about 100 times normal cycling levels [3]. In the days around parturition, these concentrations drop precipitously to levels below those of normal cycling females, where they are maintained for at least a month and potentially much longer (depending on suckling suppression) [143]. We postulate that the observed increase in breast cancer risk may be accounted for by the concurrent decrease in E2."

"The failure of low levels of E2 to inhibit cancer growth is also reflected in patterns of tumor development within the estrous cycle. In mice, breast tumor growth occurs primarily in diestrus (when E2 is low), and tumor size is maintained or shrinks when E2 levels are high [137]."

CONCLUSION:

Estradiol may favorably impact cardiovascular markers, negligibly impacts coagulation (may even be protective) and seems to be inversely associated with breast cancer risk.

Bev, my endo gave me the same crap and I have no limiting familial issues. I've been trying to find someone else but I may have to drive three hours or more to see someone who has real experience in trans issues. I've been without any hormones for 12 years now and it has given me osteoporosis. No one locally will lift a finger to help me with this. I'm really upset.

Cindi

Quote from: JLT1 on March 08, 2016, 07:41:02 PM
The risk of stroke and heart attack are higher for individuals on HRT

An increase in risk of stroke was found in women who were taking non bio-identical hormones in the WHI study of 2003. In those taking estrogen alone, the increase in risk was 0.01% per year. In those taking estrogen with progestin, increase in risk was 0.02-0.04% per year. This finding was not duplicated in the Danish study where women were given BIO-IDENTICAL estradiol. There was no increase in stroke risk.

In the WHI study, only estrogen combined with progestin increased coronary heart disease incidence. Estrogen alone decreased it. In the Danish study, there were less cardiovascular complications in women ON HRT. Regardless of smoking status.

Women, in general, before menopause (when estrogen levels are highest), have a lower risk of heart disease relative to men. After menopause (when estrogen levels drop), this changes and risk becomes the same or greater.

We seriously need to better inform our doctors. I get the impression they know very little in this matter and rely mostly on the WHI study without having delved into the details of it. It is unacceptable. They should be the experts on the matter!

Quote from: Cindi Jones on March 09, 2016, 10:24:53 AM
Bev, my endo gave me the same crap and I have no limiting familial issues. I've been trying to find someone else but I may have to drive three hours or more to see someone who has real experience in trans issues. I've been without any hormones for 12 years now and it has given me osteoporosis. No one locally will lift a finger to help me with this. I'm really upset.

Cindi

I know you're in a remote area but no one will help?  I think I would do the drive.  Dee's doctor took her off estrogen several years ago and she ended up telling him he had a choice.  Give her back the estrogen or testify at her murder trial.   But after they found the blood clot in her leg while she was in the hospital in 2011, of course no more estrogen.  She has handled it better emotionally this time.  I haven't worried about her shooting me at all.  LOL

I texted with my therapist this morning and she has faxed my letter to Dr. Tangpricha plus we are meeting tomorrow.  So now I just need to make an appointment for that second opinion. 

Quote from: JLT1 on March 08, 2016, 09:07:13 PM
If not, consider an orchi followed by HRT using estradiol  (KayXo calls it bioidentical).  Think patches, sublingual, injections, implants or coated pills.....

Your doctor is not only relying on the WHI study in women but on other studies in transsexual women that have used non bio-identical forms of estrogen such as ethinyl estradiol and conjugated equine estrogens, sometimes in very high doses.

This one study denotes the difference between ethinyl estradiol and bio-identical estradiol

J Clin Endocrinol Metab. 2003 Dec;88(12):5723-9.
Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people

"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)."

"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."

Study denoting differences between non bio-identical forms and bio-identical E.

J Clin Endocrinol Metab. 2012 Dec;97(12):4422-8.
Predictive Markers for Mammoplasty and a Comparison of Side Effect Profiles in Transwomen Taking Various Hormonal Regimens

"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"

"Thromboembolism occurred in 1.2% of individuals,
with a statistically significant increase in the incidence of
thromboembolism in those treated with CEE"

"Finally, the important safety finding that the incidence
of thromboembolism is 8 times more common with CEE"

And another one

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. These findings need replication and suggest that various oral estrogen drugs may be associated with different levels of cardiovascular risk."

And...

J Am Osteopath Assoc. 2011 Mar;111(3):153-64.

"17β-Estradiol is FDA approved for menopausal symptoms, may have cardioprotective effects, and may have fewer adverse effects on blood pressure than conjugated equine estrogens."

And...

Biochem Pharmacol. 2013 Dec 15;86(12):1627-42.

"In effect, the term CEE may obscure the fact that it does not contain E2. CEE and E2 have different chemical structures, pharmacological properties, metabolic products, and ER binding affinity, selectivity, and agonistic properties [1]. Because both ER-dependent and ER-independent mechanisms play a role in mediating the cardiovascular actions of E2, CEE may not mimic the cardiovascular effects of E2. In monkeys, CEE show no effect on intimal hyperplasia after balloon injury [23]. In human aortic VSM cells (VSMCs), some components of CEE such as E1, E3 and E1-sulfate are less potent than E2 in inhibiting mitogeninduced VSMC growth and MAPK activity [1]. Thus estrogens other than E2 may be less effective in CVD, contributing to the lack of vascular protective actions of MHT."

"In Post-MW, treatment with esterified estrogen shows lower risk of ischemic stroke and MI, and no increase in VTE risk compared to CEE [13]. Also, treatment of ovariectomized (OVX) hypertensive rats with E2-valerate increases serum vascular endothelial growth factor (VEGF)."

And one last study on the differences...(there are many more)

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."


Also, there are two studies in transsexual women, showing bio-identical estradiol, either taken orally or not, sometimes in very high doses (Intramuscular, parenteral) not to have increased cardiovascular complications.

1) Exp Clin Endocrinol Diabetes. 2005 Dec;113(10):586-92.

"Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS."

"Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented."

2) Archives of Sexual Behavior, Vol. 27, No. 5, 1998 (high dose intramuscular E or oral estradiol, low to medium doses, only two people taking non bio-identical forms)

"None of our patients developed deep vein thrombosis or embolism during cross-gender hormone therapy performed in our clinic." No cardiovascular complications noted in study either.

And more...

Eur J Endocrinol. 2014 Mar 10.

"The incidence of heart disease increases with age, but is lower in women than in men up to 75 years. A protective effect of female sex hormones or, alternatively, acceleration in male heart disease by testosterone at younger ages, could explain this sex difference."

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."

Lancet. 1993 Jul 17;342(8864):133-6.

"Acute administration of oestradiol-17 beta therefore has a beneficial effect on myocardial ischaemia in women with coronary artery disease. This effect may be due to a direct coronary-relaxing effect, to peripheral vasodilation, or to a combination of these mechanisms. Oestradiol-17 beta may prove to be a useful adjunct to the treatment of angina in postmenopausal women with coronary heart disease."

Quote from: AnonyMs on March 08, 2016, 11:02:10 PM
I don't know how much these concerns are due to weight, but you might find my experience helpful.

I have had medical issues due to weight, and one specialist told me I should stop taking estrogen. That wasn't going to happen. To cut a long story short, I increased it instead and felt so much better I managed to get my weight under control, and now I don't have medical issues anymore.

Estradiol may HELP with weight management in a healthy manner.

Menopause. 2013 May;20(5):554-60.
Conjugated equine estrogens and estradiol benzoate differentially modulate the natriuretic peptide system in spontaneously hypertensive rats.

"Estradiol decreased the body weight and parametrial adipose tissue mass of SHRs."

Maturitas. 2012 Mar;71(3):248-56.

""Ovariectomy of rats increases food intake and, concomitantly,
body weight [11] and these effects can be reversed by restoring
physiological levels of estradiol [11]"

"estradiol potentiates the effect of the satiating CCK peptide released from the small
intestine in response to food intake [14,15], while attenuating the
appetite-stimulating potency of the gastric hormone ghrelin [16].
Furthermore, estradiol stimulates anorexigenic POMC/CART activity
and inhibits orexigenic NPY/AgRP neurons in the ARC [17,18]."

"both female rodents and primates eat less
during the estrus phase prior to and following ovulation, when they
are more sexually receptive and active [10]."

"Similarly in the case of women, food intake during the different
phases of the menstrual cycle varies (Fig. 3). Thus, a meta-analysis
revealed that mean food intake is lowest during the periovulatory
phase of the menstrual cycle, when estradiol levels are high [23]."

"Moreover, binge-eating may be more pronounced during
the premenstrual period [29], a process which may involve low levels
of serotonin in the brain [25]."

"Estradiol stimulates the activity of lipoprotein lipase
(LPL) in femoral adipocytes and lipolysis in abdominal adipocytes
[35], thereby promoting accumulation of gluteo-femoral fat. On
the other hand, estrogen deficiency is associated with enhanced
accumulation of abdominal fat [35]."

"most such investigations conclude
that HRT actually lowers weight gain and body fat [76,80,81].
In addition, HRT prevents the shift in fat deposition from the normal
female condition to the more unhealthy central fat depots associated
with the menopausal transition (Fig. 5) [76,82,83]."

"treatment of postmenopausal
women with estrogen enhances LPL activity in the
femoral region and at the same time lipolysis in the abdominal
region, which might promote fat accumulation in the former region
and fat loss from the abdomen [84]."

"Interestingly, the route of estrogen
administration may be an important factor in this context, since
one crossover study found less fat gain with transdermal than with
oral administration [85]."

Quote from: Cindy on March 08, 2016, 11:49:54 PM
I am at high risk, both sister, mother and grandmother had breast cancer and I am BRACA1 positive. The risk was explained and I accepted it. The endo accepted that and there was no issue.

Just looking at studies and associations, it appears that estrogen may be protective of breast cancer, its use having either reduced the incidence (sometimes significantly) or not affected it all, in three randomized controlled trials (the strongest form of study) one of which included women who had previous breast cancer.

We find a greater risk in nulliparous women than in parous women exposed to much higher levels of E due to the presence of pregnancies. The presence of cycles vs no cycles seems important too. Transsexual women do not usually cycle their hormones.

Then, we find that older women, with less E have an increased risk vs pre-menopausal.

Did you know that estrogen has been used in women to treat breast cancer since the 1960's?

And finally, the incidence in transsexual woman is VERY low despite decades of aggressive E doses and is said to be equal to men not on HRT, therefore no increase at all.

Hence, the idea that estrogen is conducive to breast cancer is not supported by data.

Quote from: BeverlyAnn on March 09, 2016, 11:11:55 AM
after they found the blood clot in her leg while she was in the hospital in 2011, of course no more estrogen.

What estrogen was she taking? Orally or not orally? Did the doctors differentiate between types of estrogen and route of administration?

When you consider that high doses of non-oral estrogen did not increase the incidence of thrombosis amongst men with prostate cancer whose median age was 75, all the studies indicating transdermal estrogen to not increase this risk in post-menopausal women, it is a strange conclusion to come at, depriving her of estrogen.

I, myself, am on a high dose of E non-orally, with levels between 1,000-4,000 pg/ml. Clotting factors were tested twice, both times normal. DVT incidence is very low (less than 0.02%) in pregnant women whose levels go up to 75,000 pg/ml.

There are several health risks from stopping E like depression/anxiety, cognitive deficits, osteoporosis, increased risk of Alzheimer's, of diabetes, of weight gain, of blood pressure problems, cardiovascular problems, increased risk of colon cancer. Estrogen also protects against prostate cancer. 

KayXO you're amazing. 

I sure wish doctors would get up to speed.  When my wife started menopause her doctor prescribed her conjugated estrogen and medroxyprogesterone (non-bioidentical progesterone).  I knew both were the wrong choice but talking to her about hormones is tricky to say the least.   Anyway surprise they didn't work very well.

This doesn't just happen with trans people and doctors.  My sister has a heart birth defect that she knows more about than most cardiologists.  A friend found a solution to his prostate cancer that his local specialist weren't even aware was an option at the time.  Now it's a pretty standard treatment.  I have a very common blood disorder that I'm always explaining to medical professionals.   Sometimes I think the medical profession is a little like the wizard of OZ behind the curtain.

Anyway I just needed to rant.
Take care,
Paige

Quote from: KayXo on March 09, 2016, 11:48:11 AM
What estrogen was she taking? Orally or not orally? e levels go up to 75,000 pg/ml.

Dee was taking, IIRC, low dosage of Estradiol once a day orally. 

It's so crazy that some doctors say one thing and some another.  Dee had her regular checkup with our Primary Care today and our P.C. was even confused as to why I was turned down.  She thought the second opinion was a good idea.

Quote from: BeverlyAnn on March 09, 2016, 02:23:50 PM
Dee was taking, IIRC, low dosage of Estradiol once a day orally.

You aren't supposed to state doses but given this was bio-identical estradiol at such a low dose, I would be very hesitant before saying that this caused the clot considering all the findings I've come across with higher doses of E. Establishing causation is not an easy task and one should not jump to conclusions.

PLEASE read all of what I provided today in detail, understand it, keep it close to you. It might be very helpful in helping you get the treatment you deserve and that is best for your health.

Take care, BeverlyAnn.




*No Dosages Please*

Quote from: KayXo on March 09, 2016, 02:37:42 PM
 

You aren't supposed to state doses but given this was bio-identical estradiol at such a low dose, I would be very hesitant before saying that this caused the clot considering all the findings I've come across with higher doses of E. Establishing causation is not an easy task and one should not jump to conclusions.

PLEASE read all of what I provided today in detail, understand it, keep it close to you. It might be very helpful in helping you get the treatment you deserve and that is best for your health.

Take care, BeverlyAnn.

Stupid me for putting dosage.  I used to gig people for that years ago as a moderator.  LOL

Thank you.  I'm going to print out all that info and go over it thoroughly.

I also just got reprimanded for reposting your post with dose included. Stupid me TOO!  Sorry moderators!