Yup. Still in the menopause-sucks-should-we-do-estrogen cycle. I have been in the rabbit hole of PubMed, which lists all the different scientific journal articles from all specialties. It kills me that we as doctors tend to stay in our field alone, and cross pollinating would help a ton. So my latest article was looking at a review article on “Systemic Estradiol Levels with Low-dose Vaginal Estrogens.” This was published in The Journal of the North American Menopause Society in 2019.
The basic question-When you use low dose vaginal estrogen, does it get absorbed? What does it look like? For women who are at higher risk for estrogen supplementation (ie dense breast tissue, breast cancer risk, blood clotting risk), is it safe to use vaginal estrogen? How much does it change your blood estradiol levels?
They defined low dose vaginal estrogen as less than 25ug estradiol or 0.3mg conjugated equine estrogen. Estradiol levels at baseline and during treatment and maximum estradiol concentrations were summarized by dose within assay type. They then pooled the studies to try to show a proposed range of systemic estradiol levels for normal, untreated postmenopausal women.
Study:
- mean basal estradiol levels were 3.1 -4.9 pg/cc (range undetectable to 10.5) for untreated postmenopausal women
- systemic estradiol levels with vaginal estrogens
- 25 ug insert:
-
- 7.1-9.1 pg/ml with 25ug softgel capsule insert and
- 16.7-22.7 pg/ml with a 25 ug tablet insert
- 10 ug insert
- 4.6-7.4 pg/ml with softgel
- 6.6 – 14.8 pg/ml with tablet
- 4 ug insert
- 3.6-3.9 pg/ml with softgel
- Systemic estradiol absorption may be influenced by placement of estradiol higher (as with an applicator) vs. lower in the vagina
- Some studies showed that theickness of the vaginal wall affected absorption, with thicker walls over time causing less absorbption. (one study showed 47% less absorption at day 14 than at day 1)
- They discuss the difficults of measuring estradiol levels, with older assays not being as specific, so they would report a normal level of 20-30 pg/ml in postmenopausal women, but these had more cross reaction. They dsicuss there should be a standardized assay to measure low levels of estraodiol.
Conclusion:
Serum estradiol concentrations were generally lower when measured with more specific and sensitive assays.
Estradiol absorption was dose dependent and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow dose vaginal estrogens may decrease adverse events associated with higher doses of vaginal estrogen.
They conclude, “Our review of systematic absorption of estradiol with use of low dose and ultralow dose vaginal estrogen therapies found low to negligible amounts of circulating estradiol that may be influenced by product formulation and vaginal placement.” They also propose a more updated base level of estradiol in normal, untreated post menopausal women.
My thoughts?
Your body absorbs things through the skin and mucosa. The lining of the vagina is mucosa and likely absorbs more through it than the skin (with its thicker tougher outer layer) does. So the question is, if you want to really get estrogen into you, is it a good method? And if you are doing vaginal estrogen because you really want it to be a local treatment to your vaginal area to help with menopausal changes there, how much are you absorbing and getting a systemic effect? Many of these studies used vaginal estrogen specifically because the women had issues with pain during sex.
This review was good, as it looked at recent studies, only low dose vaginal estrogen therapy, and compared to normal post menopausal women. They found across the studies the level of estradiol in post menopausal women was consistent.
They show many studies which show the absorption of vaginal estrogen goes down over time, as the treatment helps to “thicken up” the vaginal mucosa again. Clearly the tablet has better absorption, as does using an applicator to place it up higher.
So is it safe? Particularly the lower doses 4ug and 10ug don’t lift the estrogen levels above what was seen as the standard base level for untreated post menopausal women. So likely yes. But I wouldn’t start willy nilly doing any of this without checking your baseline level and discussing this with your doctor.
Interesting.