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[Hurdity]

Here is a study detailing estrogen application intravaginally.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354766/

Rigg and colleagues measured the levels of estradiol, estrone, LH, and FSH after application of 2 g of vaginal cream containing either 0.2 mg estradiol (E2), 2.0 mg estradiol (E2), or 1.25 mg conjugated equine estrogen (CEE) in six postmenopausal women.23 Each participant rotated treatment with each type of cream. With the low dose estradiol (0.2 mg), an increase in serum estradiol was seen in 30 minutes with a peak of 80 ± 19 pg/ml reached at 4 hours. In comparison, the high dose estradiol cream (2.0 mg) led to an increase in serum estradiol that occurred in 15 minutes with its peak occurring in 4 hours at 527 ± 45 pg/ml. CEE cream showed a much slower rise of estradiol level, with a significant increase occurring after 3 hours and a peak reached at 6 hours of 33 ± 6.6 pg/ml.

What's interesting is when you look at the graph, you notice how levels remain quite stable over 24 hours. I have the entire study of this (N Engl J Med 1978; 298:195-197, DOI: 10.1056/NEJM197801262980406)

Also,

Intravaginal estradiol is also utilized in women undergoing embryo transfer. Tourgeman et al. studied oral versus vaginal estrogen administered to women preparing for embryo transfer.27 The women were given leuprolide, inducing a temporary menopausal state, and then administered either oral micronized estradiol (2mg bid orally or vaginally) during days 15-21 of their cycle. Two hours after the final dose of oral estradiol, mean serum levels were 279 pg/ml compared to mean serum levels following vaginal estradiol (2344 pg/ml).

And,

In a study by Martin et al.28 postmenopausal women were given 0.5 mg vaginal micronized estradiol as a one time dose. Another group was given 0.5 mg vaginally with alternate day dosing for 14 days. The levels of estradiol, estrone, and gonadotropins were analyzed at 2, 4, 6, 8,10 and 24-hours post application. With the one time dose, estradiol reached a mean peak level of 1105 ± 160 pg/ml at 4 hours. At 10 hours, the estradiol level was 24 times baseline levels. In contrast, estrone reached 11 times baseline after 8 hours (exact values not given, approximately 400 pg/ml vs 0). There was a significant decrease in both FSH and LH during the first 10 hours (FSH approximately 90 to 70 mIU/ml, and LH 40 to 25 mIU/ml).28 These data were compared to an earlier study in which 2 mg oral estradiol was used. Use of vaginal estradiol 0.5 mg resulted in a peak serum estradiol 10 times higher than 2 mg oral estradiol (0.5mg of vaginal estradiol resulted in mean peak levels of 1105 pg/ml at 4 hours as noted above vs 2.0 mg oral estradiol esulted in peak level of 110 pg/ml at 2 hours ). Estrone levels were 25% higher with the vaginal application. Oral delivery of estradiol yielded serum levels of estrone which significantly exceeded levels of serum estradiol secondary to hepatic “first pass” metabolism. However, vaginal administration of estradiol results in higher serum levels of estradiol compared to estrone because the vaginally administered estradiol is not subject to “first pass” metabolism. 28, 29

With estradiol tablets taken vaginally, levels fluctuate more. There is quite a rapid peak and then drop so that by 24 hours, levels are back to where they were before taking the tablet. Cream results in much steadier levels.


I have all 3 studies as pdfs. I work at a university, this is why.

Thanks for the links Erika28 but I don't see their relevance to what was being discussed? Yes it is well known that transdermal and especially vaginal absorption (though mucous membranes) is an effective way of getting a drug into the system but these studies do not alter the point that estradiol gel developed for transdermal application and absorption through the skin of the abdomen or trunk, should not be applied to/into the vagina - not least because of the unknown range of systemic levels attained which can have drastic consequances for the womb lining. The estradiol levels attained in one of these studies are absurdly high anyway!  I would have thought that if you are a university researcher (as you have access to the full studies) you would know that these studies were not designed to test or provide support to vaginal use of estradiol gel as an ongoing part of HRT? Only trials using the available products and carried out for the same length of time as (or similar to) the existing trials ( prior to launching the HRT products ie the gel) - should be used. Any oestrogen product designed to provide a systemic dose of HRT would have been developed and tested extensively for this purpose.

I think maybe there used to be an oestrogen cream designed for systemic HRT in US - Estrace - but might be wrong about this? The current formulation of Estrace is as a vaginal cream.

Of course you can do what you like "regardless of what is proven and what is not" - but like I said - the information on this website about HRT and products is all bona fide based on medical and scientific research and endorsed by BMS - so it is important on this forum (which is an adjunct of the main website) to challenge "advice" given that advocates considerable departure from current medical recommendations (in the broadest sense).

Hurdity x

[Erika28]

I'm not a university researcher. I just work at the university as an administrator and was a former student there.

I supplied those studies just for information, nothing more. It's an interesting read.

Why don't more women in the UK use pellets containing estradiol? These seem to be quite effective, last a long time (4-6 months) and have been advocated by some like John Studd.