I was reading a pamphlet recommended to me by a regional PP clinic  and in this brochure PDF from a university in Minnesota is the following statements:

QuoteFor reasons that aren't understood, estrogen seems to cause blood clots less when it is taken through the skin rather than by pills or injections.

and

QuoteThe risk of blood clots may be reduced by taking estrogen via skin patch, cream, or gel (rather than pill/injection) and also by using a lower dose of estrogen

Is there any truth to these statements?

All my Dr's have recommended the safest way to take E is via Patches or gels....Implants are great but are losing favour rapidly where I live. I think a lot is your age and overall health as well.

I have read several articles and reports about the safest way to take E and that is always through the skin and a pellet is pretty much the same as it is absorbed into the skin layers(I think).

Pills and Injection are the least favourable forms of delivery due to health concerns, someone may even be able to point you in the way of a good study...

A number of studies have shown the injectable E2 is quite safe at appropriate doses. DVT is a higher risk with pills taken orally, taking them sublingually appears to mitigate this risk. The main DVT issue was non-bioidentical estrogens which were used in the past, 17β-Estradiol doesn't have those issues.

The other issue with oral pills is they lead to an undesired E1:E2 ratio, which can hamper feminisation. This doesn't seem to happen when taken sublingually or via other delivery methods.

Quote from: ElizabethK on January 04, 2018, 12:51:48 AM
All my Dr's have recommended the safest way to take E is via Patches or gels....Implants are great but are losing favour rapidly where I live. I think a lot is your age and overall health as well.

I have read several articles and reports about the safest way to take E and that is always through the skin and a pellet is pretty much the same as it is absorbed into the skin layers(I think).

Pills and Injection are the least favourable forms of delivery due to health concerns, someone may even be able to point you in the way of a good study...

Injections are unfavoured as they are only available from a compounding pharmacy and most Australian medical providers have little to no idea how to dose it. Using the recommendations of Australian docs is a farce - you know some Aussie docs are still prescribing Premarin or ethinylestradiol? These are known to cause issues.

Quote from: Izzy Grace on January 04, 2018, 12:16:09 AM
I was reading a pamphlet recommended to me by a regional PP clinic  and in this brochure PDF from a university in Minnesota is the following statements:

and

Is there any truth to these statements?

This seems way off base to me -- yes oral estrogen has risks higher than either transferral or injected estrogen, however recommendation of my endo due to my age and hence higher DVT risk  was for injected as a first choice and transdermal as a second.

Just a note on pellets. They are implanted in the fat layer (subdermal) and are slowly absorbed into the bloodstream.

Sent from my SM-G930V using Tapatalk

According to my doctor, the risk of blood clots come from processing the estrogen through the liver (taken orally). If you bypass the liver (patch, injection, or sublingual - how I take it) you negate the risk.

Quote from: Izzy Grace on January 04, 2018, 12:16:09 AMIs there any truth to these statements?

No. Several studies have shown that high dose E2 IM injections in transsexual women, in ciswomen (even past their prime) and in older cismen with prostate cancer, with levels as high as 3,000 pg/ml, did not result in any DVT complications. I can send you those studies, if you want.

Three such studies:

Horm Metab Res. 1994 Sep;26(9):428-31.

"Thirteen osteopenic women received (...) estradiol valerate and (...) hydroxyprogesterone caproate by intramuscular injections once a week for 6 months (so called "pseudopregnancy")."

"Six patients were peri- or postmenopausal (49.5 +/- 4.8 years of age, group A)"

"The duration of the therapy was 6, and in 4 patients 9 months"

"Estradiol increased from 34.8 +/- 7.5 pg/ml to 3226 +/- 393 pg/ml after 3 months and to 2552 +/- 254 pg/ml after 6 months, respectively, in group A."

"In group B estradiol increased from 27.8 +/- 6.5 pg/ml to 3028 +/- 728 after 3 and to 2491 +/- 684 pg/ml after 6 months."

"The treatment was well tolerated. No adverse effects were seen, the patients expressed a feeling of particular well being, 3 of them wanted to have the injections repeated and none of them wanted to stop treatment because of troubles or side effects."

"Three of our osteopenic patients received this therapy for 9 months with resulting stabilization of lumbar spine bone density, without any severe side effects."

"Investigations of lipids, liver enzymes and haemostasiology to be published later will show the absence of unwanted metabolic effects of this regimen."

"In conclusion, our data show, that the treatment (...) by means of high parenteral estrogen-progestogen depot injections is effective. Virtually no side effects occurred. The therapy is well accepted by the patients."

Tidsskr Nor Laegeforen 1993 Mar 10;113(7):833-5

"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"

"The only side effect of significance is gynaecomastia. Follow-up of the patients does not indicate any increased risk of thrombosis or cardiovascular disease."

Med Clin (Barc). 1999 Oct 23;113(13):484-7. (translation from Spanish)

"The population included in this study had a mean age (ED) of 30.2 (7.4) years, between 18 and 44 years, comprising 31 male transsexuals (VaM) and 26 female transsexuals (MaV )."

"All patients had undergone hormonal self-therapy at different doses and guidelines for at least 6 months and a maximum of 10 years. Treatment of transsexual VaM consisted of estrogens in the form of estradiol enanthate (...). This compound is usually associated in the same preparation (...) of a progestogen (algestone) (...). In addition, the treatment is completed with (...) of an antiandrogen such as cyproterone acetate (...). Some were patched to different regimens and doses of estradiol preparations (n = 4)."

"Estrogenic treatment in males has also been associated with an increase in the incidence of thromboembolic complications 3. We have not objectified, through anamnesis and detailed clinical examination and ultrasound, this complication in any of our patients."


And, to conclude,

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

"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."

"Indeed, when native estrogens are given parenterally, the effects on liver-derived plasma proteins, coagulation factors, lipoproteins, and triglycerides are very weak or completely abolished [17,18,20,28-30,431. Recent studies have demonstrated that the same principle is valid also during estrogen treatment for prostatic cancer. The native hormone estradiol-17B, when given as intramuscular injections of polyestradiol phosphate, can clearly provide a suppression of testosterone equal to that following orchidectomy [28,44,45]. In spite of this, there is only a minimal influence on liver metabolism as expressed by plasma protein synthesis [24]."

Thank you for the info.  My doctor was pushing for the injections but time and funds were tight so I'm going to probably go that route in a few weeks depending on how things go now.

Just noting the above quoted studies are based on relatively small patient cohorts, decidedly too small for a DVT risk assessment.

The very high estrogen levels experienced during pregnancy are associated with a 4-fold increased risk of DVT.

Quote from: SadieBlake on January 04, 2018, 12:46:44 PM
Just noting the above quoted studies are based on relatively small patient cohorts, decidedly too small for a DVT risk assessment.

The very high estrogen levels experienced during pregnancy are associated with a 4-fold increased risk of DVT.

They wouldn't have been the studies I used to make the point, there's always someone who complains about sample size.. This has result been repeated several times in several different studies,

I read many medical, scientific and cultural articles on this subject specifically, but I have not found agreed conclusions and there conflicting scientific research in this regard and there is no confirmed information on this subject specifically so far

*Read more


http://worldlinkmedical.com/transdermal-vs-oral-e2-estradiol/

&


https://transcare.ucsf.edu/article/information-estrogen-hormone-therapy

Quote from: SadieBlake on January 04, 2018, 12:46:44 PM
Just noting the above quoted studies are based on relatively small patient cohorts, decidedly too small for a DVT risk assessment.

There are many more studies and when you combine the findings of these studies with those of others where high levels were attained on pellets, patches, etc. in even high-risk populations and where no such complications arise (or at the very least, the incidence is VERY low), one can start to assess with more certainty.

QuoteThe very high estrogen levels experienced during pregnancy are associated with a 4-fold increased risk of DVT.

Indeed but the absolute risk remains low (around 0.1% for DVT, 0.01% for pulmonary embolism) despite significantly higher levels than those attained on IM E2 (at most, 4,000-5,000 pg/ml, levels go up and down, don't remain that high), up to 75,000 pg/ml during pregnancy. The risk actually even increases post-partum, when E2 levels drop to close to zero.

The risk is only 0.1% during pregnancy, when levels are VERY high and sustained vs up and down in us and much lower levels.

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)

Risk of venous thromboembolism during pregnancy: 0.1%
Risk of pulmonary embolism during pregnancy: 0.01%

Thank you everyone.

I'm just trying to do my due diligence and I'd rather error on caution and explore every question. My intention was to use E to suppress my T, and I believe those are higher doses, though i dont believe they are anywhere near the levels during pregnancy.

I appreciate the responses, I'm not terribly good at medical research and I thought I'd call on the collective knowledge here.

A few more studies...

J Adolesc Health. 2017 Oct 19.

"Follow-up physiologic data were available for 59 youth (34 transmasculine and 25 transfeminine participants)."

"The mean estradiol level at 24 months is higher than expected with standard dosing (286.04 pg/mL) with a very large range (5–1,993 pg/mL). For those youth taking estradiol via oral route, the levels at follow-up have a smaller range than those getting intramuscular injections (19– 331 pg/mL and 5–1,933 pg/mL respectively), and lower mean at follow-up (135.3 vs. 577.6 pg/mL)."

"Among this cohort of youth reported here, there were several statistically significant changes in mean values of physiologic parameters over time, but these did not translate to clinical safety concerns. Hormone levels were impacted as anticipated, and reflect the therapeutic goals of the care. These data indicate that gender-affirming hormone therapy is safe over a time period of approximately two years."

Adolesc Pediatr Gynecol (1995) 8:20-23

Estradiol levels (range, between 3 and 6 months):
920 – 6789 pg/ml

Averages at 3 and 6 months: 3028 pg/ml; 2800 pg/ml

"High-dose intramuscular injections of estrogen and progestogen were well tolerated. We have experience with more than 200 patients treated for mammahypoplasia using this regime with minimal side effects. 18 All six patients completed the treatment and some were eager to continue therapy."

Prostate 1991;18(2):131-7

"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."

"The combination estrogen therapy group consisted of 146 patients (mean age 72.7 yr), the parenteral estrogen group of 124 patients (mean age 69.8 yr), and the orchiectomy group of 207 patients (mean age 72.0 yr)."

"In the PEP monotherapy group, the total follow-up time of 124 prostatic cancer patients was 334.0 yr. Two cardiovascular deaths and 32 all-cause deaths were reported. The age-standardized rate ratio was 0.17 (95% confidence interval 0.05-0.57) for cardiovascular mortality and 1.50 (95% confidence interval 1.06-2.11) for all-cause mortality."

"In a previous report [10], which included patients of the present study, no cardiovascular mortality or clinical thromboembolic complications were observed in the first 6 mon of follow-up, when intramuscular PEP alone was given (...). In the study of Henriksson et al. [23], where 38 patients with prostatic cancer were treated with monthly PEP injections, there were no cardiovascular complications during a mean follow-up time of 12.9 mon. In the present study, cardiovascular mortality was very low in patients receiving intramuscular PEP monotherapy, by far lower than among the standard male population. It seems possible that intramuscular PEP treatment protects prostatic cancer patients from cardiovascular deaths."

Archives of Sexual Behavior, Vol. 27, No. 5, 1998

"Transsexual patients were seen by the authors in the Endocrinological Outpatient Clinic of the Max-Planck-Institute between 1991 and 1995 inclusively."

"The incidence of thromboembolic events during cross-gender hormone treatment in our patients was zero."

"None of our patients developed deep vein thrombosis or embolism during cross-gender hormone therapy performed in our clinic."

Despite 17 individuals, ranging from less than 20 yrs old up to 60 yrs old +, being on high to very high doses of estradiol injected IM.

Exp Clin Endocrinol Diabetes. 2011 Feb;119(2):95-100

"84 male-to-female transsexuals (MtFs) were treated with (...) oestradiol-17β valerate every 10 days." (IM injection)

"We observed one case of deep vein thrombosis in a 49 years old MtF who had uneventful medical history prior hormone therapy. No further side effects or other complications were observed during the study."

Estradiol levels ranged from 340.5 pmol/L to 1,362.4 pmol/L "at the nadir immediately prior the oestradiol-17 β valerate injection whenever possible."
93 pg/ml – 371 pg/ml

Mean age of 36.3 years (SD 11.3).

Quote from: Izzy Grace on January 04, 2018, 02:41:49 PM
Thank you everyone.

I'm just trying to do my due diligence and I'd rather error on caution and explore every question. My intention was to use E to suppress my T, and I believe those are higher doses, though i dont believe they are anywhere near the levels during pregnancy.

I appreciate the responses, I'm not terribly good at medical research and I thought I'd call on the collective knowledge here.

And here's where you find that you need a doctor onboard.. The dose required to do what you want is going to depend in part on you, and balancing it out requires a doc or endo.. It may be "higher" than some, or you may find that a "standard" dose is fine..

As always, consult your doctor..

Quote from: kelly_aus on January 04, 2018, 05:18:19 PM
And here's where you find that you need a doctor onboard.. The dose required to do what you want is going to depend in part on you, and balancing it out requires a doc or endo.. It may be "higher" than some, or you may find that a "standard" dose is fine..

As always, consult your doctor..

Well, dang, lol... If there is anything I have noticed is that there is a huge disparity in doctors. I'm just worried I'm going to get a doctor who has no idea or is winging it or playing it SO safe they let it affect my care/result.