Quote from: Dena on November 24, 2016, 11:12:50 PMEstradiol Valerate has a different chemical structure that's suppose to survive the first pass and latter it's cleaved by the body turning it into estradiol. If this is true, there is little advantage to avoiding the first pass as the liver will leave it alone.
Incorrect Dena.
Maturitas, 4 (1982) 315-324"It has also been demonstrated in man that, following oral administration of (...) oestradiol [ 14C]valerate the fatty acid is split from the steroid during the absorption process and/or the first passage through the liver."
"As a result of metabolic processes in the gastrointestinal tract, the intestinal wall and the liver (during the first passage), not only does cleavage of the fatty acid take place very quickly, but the free 178-oestradiol from the greater part of the dose undergoes further metabolic changes. A comparison of the areas under the curve representing the 17B-oestradiol levels following intravenous and oral administration of oestradiol valerate in man made it possible to estimate the bioavailability: an average of about 3% of an orally administered dose of 2 mg becomes bioavailable as metabolically unchanged 17B-oestradiol and can exerts its effect in the target tissues"
M. Notelovitz et al. (eds.), The Climacteric in Perspective
© MTP Press Limited 1986"Estradiol valerate is also split after oral administration during the absorption process and the first liver passage."
"The systemic availability of estradiol after oral administration of the steroid ester is greatly limited. As a result of the metabolic process in the gastrointestinal tract, the intestinal wall and the liver, not only does cleavage take place very rapidly, but the free estradiol is subject to further metabolic changes"
Quote from: Xirafel on November 24, 2016, 11:24:54 PMFrom what I read, like 90% of it is destroyed in the liver which means that your dosage could go up by ten times and wreck havoc on your body.
QuoteOne possible side-effect of overdosing for my pills is sudden death, likely from a blood clot.
At most, levels will go up to 2,000-3,000 pg/ml sublingually. Compare this to levels achieved during intramuscular injections of estradiol in transsexual women (mine are 1,000-4,000 pg/ml, clotting times remain normal, health remains good) or levels in women during pregnancy (up to 75,000 pg/ml) when risk of DVT is 0.1% and PE is 0.01% or consider these studies where very high levels were attained with minimal side-effects.
Horm Metab Res. 1994 Sep;26(9):428-31."Thirteen osteopenic women received (...) estradiol valerate (...) 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."
"We have experience with therapeutic pseudopregnancy in about 200 patients with mammahypoplasia (Lauritzen 1992). Its rate of objective and subjective tolerance is excellent."
"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."
AND
Adolesc Pediatr Gynecol (1995) 8:20-23"This consisted of a combined intramuscular injection (...) of estradiol valerate (...) and (...) hydroxyprogesterone caproate (Proluton Depot , Schering Company, Germany) given weekly for 6 months."
Ages 16-30.
Estradiol levels (range, between 3 and 6 months):
920 – 6789 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."
There have also been studies on sublingual administration with good results.
Am J Med. 1995 Aug;99(2):119-22.
Estrogen acutely increases peripheral blood flow in postmenopausal women."Eleven normotensive, post-menopausal female volunteers (mean age 53 +/- 6 years) were studied. Six women were in natural menopause and 5 had had a hysterectomy (mean age of the menopause 49 +/- 3 years). We used a double-blind, randomized protocol to assess the acute response to sublingual estradiol-17 beta (...) on the forearm resistance vessels, compared with sublingual placebo."
"Subjects were given, in double-blind, randomized fashion, a sublingual placebo tablet (Mead Johnson Laboratories, Evansville, Indiana) on 1 day and
sublingual estradiol-17B (Estrace (...), Mead Johnson Laboratories) on the other."
"Estradiol-17B plasma concentrations increased from 112 +/- 38 to 3,234 +/- 411 pmol/L (P <0.0001) after administration of sublingual estradiol-17B (normal postmenopausal plasma concentration less than 200 pmol/L; normal premenopausal physiologic ranges: luteal 368 to 1,100 pmol/L, midcycle 785 to 1,840 pmolIL, follicular 74 to 368 pmol/L).
No subjects reported any adverse symptoms after administration of either estradiol-178 or placebo."
3,234 pmol/L = 881 pg/ml, 40 minutes after sublingual administration
J Clin Psychiatry. 2001 May;62(5):332-6.
Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study.1)
Estrofem sublingually 3 to 8 times daily for weeks.Most women recovered and did not have any depressive symptoms following treatment. There was rapid improvement in symptoms within first week and recovery thereafter. Neither psychotherapy or anti-depressants worked.Also this,
Obstet Gynecol. 2015 Mar;125(3):605-10."In transgender women, estrogen therapy, with or without antiandrogen therapy, was associated with lower BP."
"Transgender women were treated with estrogens.
Fourteen (88%) were given sublingual micronized 17-beta estradiol (...) twice daily."
"one subject received estradiol valerate (...) intramuscular every 2 weeks"
"Transgender women (persons assigned male at birth, but who identify as females and who use estrogens with or without an anti-androgen to develop female secondary sex characteristics) had normal median baseline and 6 month body mass index (24.8 kg/m2 (IQR=4.3) and 23 kg/m2 (IQR=4.5) respectively).
Both systolic and diastolic median blood pressures in this group dropped significantly from baseline to 6 months (130.5 mmHg (IQR 11.5) to 120.5 mmHg (IQR 15.5) p=.006; 78 mmHg (IQR 21) to 67 mmHg (IQR 12), p=.001 respectively)."
"All transgender women had estradiol levels at least in the physiologic female – range at 6 months, with
3/16 (19%) having supraphysiologic levels > 1000pg/dl (including the one transgender woman using intramuscular estradiol valerate). At 6 months, free testosterone was in the female physiologic range in 14/15 (93%), however only 10/15 (66%) had total testosterone levels in the female physiologic range (Table 4)."
Mean age: 29 yrs old
Minimum: 19 yrs old
Maximum: 50 yrs old
AND
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)."
"Increased levels of oestradiol may be beneficial, not only for their anti-depressant effect, but also in their effect upon bone density. The latter is greater after implant therapy than after oral therapy and is related to the greater plasma oestradiol levels achieved in women with implants. None of the 38 patients complained of alleged symptoms 01 oestrogen excess, such as breast tenderness, fluid retention or nausea."
"Supraphysiological oestradiol levels are an uncommon consequence of oestradiol implants occurring most frequently in women with a history of depression or surgical castration.
These high serum oestradiol levels were not associated with any deleterious effects and may be necessary for the control of symptoms in specific women"
Finally,
Lancet. 1993 Jul 17;342(8864):133-6.
Beneficial effect of oestrogen on exercise-induced myocardial ischaemia in women with coronary artery disease."We have studied
the acute effect of sublingual oestradiol-17 beta on exercise-induced myocardial ischaemia in eleven women (mean age 58 [SD 8] years) with coronary artery disease."
"
Plasma oestradiol-17 beta concentrations were confirmed to be higher after sublingual oestradiol-17 beta than after placebo (2531 [1192] vs 155 [168] pmol/L, p < 0.001). Oestradiol-17 beta increased both time to 1 mm ST depression (456 [214] vs 579 [191] s, p < 0.004; difference of medians 92 [95% CI 46-254]) and total exercise time (569 [249] vs 658 [193] s, p < 0.01; difference 54 [10-212]).
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."
Eur Heart J. 1998 Jul;19(7):1019-26."To evaluate the effects of (...)
sublingual 17 beta-oestradiol on exercise capacity, exercise-induced myocardial ischaemia and circulating levels of endothelin-1 in post-menopausal women with stable coronary artery disease."
"The mean serum levels of oestradiol increased from a control level of 72 +/- 28 pmol.l-1 to
3557 +/- 1731 pmol.l-1 after 30 min and to 5028 +/- 3971 pmol.l-1 after 60 min with a gradual decline thereafter. Sublingual 17 beta-oestradiol did not induce any improvement in exercise duration when compared with nitroglycerin and placebo (500 +/- 112 s, 505 +/- 107 s, 498 +/- 157 s), and did not influence time to onset of ST-segment depression (358 +/- 89 s, 436 +/- 93 s, 384 +/- 116 s). The plasma levels of endothelin-1 did not change after administration of 17 beta-oestradiol, nitroglycerin or placebo."
No improvement but no adverse effects either.
Menopause. 1998 Summer;5(2):79-85."The administration of (...)
sublingual estradiol to 24 postmenopausal women (aged 48-58 years) was followed 60 min post-dose by a surge in mean estradiol serum levels (
1759 +/- 704 pg/ml)."
"At rest a slight drop in systolic and diastolic blood pressure was measured after estrogen ingestion: 132 +/- 24 mm Hg versus 127 +/- 21 mm Hg, p < 0.05; 83 +/- 11 mm Hg versus 78 +/- 10 mm Hg, p < 0.02. There were no changes in resting heart rate, double product, or vascular resistance. The left heart cavities became smaller: the left atrium diameter decreased from 33.7 +/- 4 mm to 32.3 +/- 4 mm, p < 0.01; the end-systolic diameter decreased from 24.9 +/- 3 mm to 23.6 +/- 4 mm, p < 0.01; the end-diastolic diameter decreased from 44.5 +/- 4 mm to 42.7 +/- 4 mm, p < 0.01. The peak aortic blood flow velocity fell from 120 +/- 19 cm/s to 116 +/- 22 cm/s (p < 0.05), and the flow velocity integral fell from 26.3 +/- 4 cm to 24.9 +/- 5 cm (p < 0.01); the cardiac output underwent a small change, with borderline significance: 7 +/- 2 L/min versus 6.7 +/- 2 L/min, p = 0.06. Only minor changes in the hemodynamic and echocardiographic parameters were recorded after estrogen for both isometric and dynamic exercises. Analyses were also made for two subgroups: 13 normotensive women were compared with 11 hypertensive women. The post-estrogen decreases in resting blood pressure and in peak blood velocity were observed only in the hypertensive subjects, whereas the changes in heart dimensions and in flow velocity integral were the same in both subgroups."
