Quote from: Kaylee on November 29, 2013, 08:42:56 AM
I take my E sublingually, not for the effect on the bloodstream but to help bypass the first pass through the liver which it can have quite an effect on.
I think it does lead to increased levels because it is bypassing the stomach and liver. I don't have any evidence to hand, but I forgot to not take my meds before my last blood test and my E levels were through the roof, like 6000+ (looking back I'm a little upset that they weren't over 9000! 
)
OK.... Not trying to derail an important thread, but here is a post with lots of info/links for sublingually.....
"
I've been reading a little about how 17beta-estradiol (E2) works, from injestion and metabolism to gene transcription.
A few things:
1) E2 is more potent than its metabolite etrone (E1) and has greater affinity with the ERalpha and ERbeta receptors. E1 and E2 compete for the same receptors which would mean less estrogenic action if there is less E2
2) Swallowing estradiol leads to first pass in the liver and conversion to estrone. Sublingual or buccal estradiol leads to a rapid spike in free 17beta-estradiol and a greater E2/E1 ratio (which is desirable for the reason above).
A comparison of the pharmacokinetic parameters of oral and sublingual
administration of micronized estradiol to post menopausal women revealed
that the time to the maximal concentration of estradiol was significantly
different by the two routes of administration, being 1 hr or less for sublingual
administration and 6.5-7.6 hr for oral administration. The maximal plasma
concentration, terminal half life, area under the curve for the integral of the
serum concentration over time (area under the curve) and oral clearance
were also different with the two routes of administration. For example, after
sublingual administration of 1 mg micronized estradiol, the maximal plasma
estradiol concentration was 451 pg/mL, the terminal half life was 18 hr, the
area under the curve was 2109 pg/mL per hr and the oral clearance was 7.6
L/hr per kg bw; after oral administration, these values were 34 pg/mL, 20.1 h,
823 pg/mL per hr and 27.2 L/hr per kg bw, respectively. The concentrations
of estrone were not dependent on route of administration. Sublingual
administration resulted in a significantly lower ratio of estrone to estradiol
than oral administration during the 24 hr period.[IARC. Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World
Health Organization, International Agency for Research on Cancer, 1972-
PRESENT. (Multivolume work). Available at:
http://monographs.iarc.fr/index.php, p. V72 476 (1999)] **PEER
REVIEWED**
3) Free estrone can and is converted back to E2 when needed but is then metabolized by the liver again (second pass...). This circular process is repeated until the estrogen metabolite is evacuated from the body. Estrone can be thought of estrogen storage in this respect and it is the reason that oral estrogen can feminize.
Oral mucosal administration of estradiol
Sublingual and buccal treatment is a non-invasive
and simple route of administration. Owing to the
high vascularization of the oral mucosa, estradiol
is rapidly absorbed and enters directly the
circulation. Although the oral mucosa contains
degrading enzymes, the inactivation is much less
than after enteral administration, and the avoid-
ance of the gastrointestinal metabolism and the
first-pass effect in the liver results in serum levels
of estradiol 10-fold higher than after oral inges-
tion, and the bioavailability is about five times
higher 123,124.
Pharmacokinetics
The sublingual administra-
tion of a tablet with 0.25 mg micronized
estradiol caused a rise in the level of estradiol up
to a maximum of about 300 pg/ml and of estrone
of 60 pg/ml within 1 h. The application of 1 mg
estradiol led to a serum maximum of 450 pg/ml
estradiol and 165 pg/ml estrone. Thereafter, the
estradiol level decreased rapidly to 85 pg/ml
within 3 h, while that of estrone declined much
slower, reaching a value of 80 pg/ml after 18 h
123.
After the buccal administration of 0.25 mg
estradiol in postmenopausal women, a steep rise
in the serum concentration of estradiol occurred,
reaching a maximum of 500 pg/ml within 1 h.
Thereafter, the estradiol level declined rapidly to
70 pg/ml after 4 h. Treatment for 2 weeks with
0.25 mg estradiol each twice a day resulted in
peak levels at steady state of 620 pg/ml 125.
Pharmacodynamics
The method was well toler-
ated, and no taste or other sensation was reported.
In postmenopausal women with coronary artery
disease, a single sublingual administration of 1 or
2 mg estradiol caused vasodilation, improved
ischemia and augmented blood flow. The clinical
effect occurred some minutes after dosing and
suggested a rapid non-genomic effect of estradiol
on the arterial wall
126. In patients with severe postnatal depression,
daily sublingual treatment with 1 mg estradiol 3–8
times daily resulted in a rapid improvement of
depression symptoms with-in 1 week 127.
After 4 weeks of buccal treatment of postmeno-
pausal women with daily 400mg estradiol, hot
flushes had significantly decreased by 80% (from
0.8 to 0.15 hot flushes per hour) and the vaginal
epithelium (maturation index) was normalized.
There were no unusual or severe adverse effects,
and mastodynia was reported by only one out of
18 women 128
4) Estrone is carcinogenic (women on HRT are given progesterone to avoid cancers involving ERalpha receptors).
5) Even when E2 enters the blood directly (eg., buccal administration), most of it is bound to SHGB and only 1-2% is free to exert its estrogenic effect in the relevant cells.
6) Androgens do not bind to E receptors and estrogens do not bind to AR androgen receptors. However, both estrogens and androgens do bind to SHBG sex hormon binding globulin.
7) Reducing SHBG should mean more free estrogen (and more androgens, which is also why they should be suppressed when on estrogen).
SHBG drops when insulin is increased. That is, taking E2 (sublingual/buccal/transdermal ...but not orally) immediately after a meal should mean more E2 molecules reaching E receptors as less of it is bound. (Incidentally, a similar reasoning is established in the bodybuilding comunity for testosterone...)
9) Some testosterone is necessary for estrogen to properly exert its estrogenic effect at the E receptors (for poorly understood reasons).
10) While M2Fs take estrogen once or twice in the day, which rapidly falls as it is processed out of the body, females secrete estrogen (converted from testosterone in the ovaries) continually with diurnal and monthly rythms.
...I welcome your thoughts. I have included the papers and references below. They are really worth reading.
Technical papers
http://actor.epa.gov/actor/GenericChemi ... rn=50-28-2
http://www.ncbi.nlm.nih.gov/pubmed/9052581http://www.cenegenicsfoundation.org/lib ... ration.pdf
http://faculty.washington.edu/andchien/ ... trogen.pdf
http://www.ijbmb.org/files/IJBMB1104006.pdfGood introductory site
http://www.news-medical.net/health/Estrogen-Types.aspxInteresting info
http://www.sciencedaily.com/releases/20 ... 161246.htm
http://psychcentral.com/news/2011/10/22 ... 30629.html
"
