We are firmly in our health testing era. Thank you Bryan Johnson.
We can now test how long we might live.
So why is it so bloody hard to test hormones in menopause?
If you weren’t well aware of that, welcome to the menopuzzle.
But first, let’s get one thing out of the way. If you aren’t ovulating or menstruating, you aren’t producing measurable hormones. We simply have nothing meaningful to interpret. If you, like many women, ask their doctors to “please measure my hormones” when you don’t bleed then we’re out of luck.
The exception here is if you’re actively taking hormone replacement therapy. Now we got something to sink our teeth into.
A little herstory.
The classic dosage for giving hormones is based on the prevention of bone loss (osteoporosis). We used to give a synthetic Estrogen called CEE at 0.625 mg per day. We learned in 2002 it’s not the best option so switched to creams, gels and patches. Each has its own equivalent dosage to prevent bone loss. Here’s a little taste of what it takes to match the CEE:
Estrogel 1.25 mg 1-2 pumps per day.
Estrogen patch 50 mcg twice per week.
Oral Estradiol 1-2 mg per day.
There are many other options, too many to list here. But you get the point, there are rough equivalents.
What is a healthy blood level of Estrogen?
It depends on the intention and the evidence we have available for that intention.
If you’re trying to prevent bone loss the level is somewhere over 200 pmol/L, probably around level of 220 pmol/L (60 pg/mL).
1 pump of Estrogel gives you 110 pmol/L (30 pg/mL)
2 pumps of Estrogel gets 294 pmol/L (80 pg/ml)
If you’re trying to prevent heart attacks and strokes the level may be somewhere around 70 pmol/L.
But it’s not that clear.
In another study women were given 50 mcg patches or 0.45 mg CEE. They were also given 200 mg of progesterone 12 days per month. The 50 ug estradiol patches did NOT reduce heart disease. This corresponded to a serum E2 level of 165-202 pmol/L (45-55 pg/ml).
Another study where women received oral estrogen 1 mg per day. The primary outcome was the rate of change in carotid-artery intima–media thickness (CIMT), which was measured every 6 months.
Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause.
Even though we have these few studies, we don’t have as robust evidence for heart disease as we do for bone health.
What about hot flashes? Are hot flashes too hot to measure?
Among women reporting complete relief of hot flashes, those randomized to topical estrogen had a mean E2 level of 161 pmol/L (44 pg/mL). This is helpful because it defines a clinically effective window of E2 levels when using estrogen creams. Except, many women show clinically that they need very low levels of estrogen replacement to actually help resolve their symptoms. Contradiction, I know.
It begs the question, can we trust blood tests for hormones?
We have some flaws to discuss.
Women who use the gel and women younger than 50 tend to have greater variance in their blood levels.
In one 2024 study, 25% of women using the highest dose of estrogen had levels less than the goal of 200 pmol/L. Meanwhile, women above 50 and women using the estrogen patch had the lowest levels, even though the dosages were equivalent.
You see, it’s not straightforward.
Where do these goal numbers come from?
It is thought that estrogen blood levels in menopause should be similar to those in the early follicular phase of the menstrual cycle in premenopausal women. With standard HRT doses, like 1 mg of oral estradiol or a 50 mcg patch, estradiol levels usually fall between 150 and 370 pmol/L, which is about the same as the follicular phase.
The drug monograph for Estrogel affirms this measurement should be similar to the serum estradiol level normally produced by the ovary before menopause during the middle part of the follicular phase of the menstrual cycle (150-400 pmol/L).
Why are we copying the follicular phase?
The follicular phase is a natural state during the menstrual cycle when estrogen levels rise steadily without the influence of high progesterone levels. This phase represents a hormonal baseline that supports numerous essential body functions.
Studies show that achieving estrogen levels within a follicular-phase range (approximately 40-250 pmol/L or 10-68 pg/mL) reduces symptoms of menopause while minimizing risks associated with higher or erratic levels of estrogen.
What are the other cons of measuring Estrogen? There are a few to consider:
- Serum estradiol may underestimate tissue levels because these routes bypass the liver and create more stable tissue delivery but less systemic fluctuation.
- Estradiol levels in the serum may not reflect estrogen receptor activation in tissues (e.g., brain, bone, skin).
- Symptom improvement (e.g., hot flashes, mood, sleep) often does not correlate directly with specific serum estradiol thresholds.
- Variability in how individuals metabolize and absorb estradiol can lead to different serum levels for the same dose.
- Polymorphisms in estrogen metabolism pathways (e.g., CYP1A1, COMT) can further influence estradiol levels.
- Estradiol levels can vary throughout the day and with dosing schedules (e.g., after transdermal gel application).
- Timing relative to the last dose significantly impacts serum measurements, especially for short-acting formulations.
- Estradiol metabolizes into estrone and other estrogen metabolites, which contribute to overall estrogenic activity but are not reflected in estradiol serum levels.
- If serum estradiol measurement is necessary, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is preferred for accuracy.
Even if we knew the number we needed to achieve, would the test be reliable enough to show us your true estrogen level?
IF you’re going to measure estrogen, when is it best to measure estrogen?
Midway between dosing ie) mid day if Estrogen applied in the morning.
Factors that affect Estradiol levels
Concurrent acute alcohol ingestion with oral estradiol has been found to cause a threefold rise in serum estradiol concentrations, apparently by slowing the metabolism of estradiol.
Does doubling estrogen dose double the serum level? No.
The serum estradiol level with estradiol 2 mg (107.6 pg/mL) was significantly higher by 60% than with estradiol 1 mg (65.8 pg/mL) or CE 0.45 mg (60.1 pg/mL), and it was also significantly higher than with CE 0.625 mg (76.8 pg/mL). Our findings suggest that serum estradiol level is NOT directly proportional to estrogen dose.
What do the “authorities” say about testing hormones in menopause?
The Menopause Society writes: the use of serum testing to guide hormone therapy dosing is considered unreliable because of differences in hormone pharmacokinetics and absorption, diurnal variation, and interindividual and intraindividual variability.
The drug company writes: Because of the variable absorption of Estrogel between individuals due to the technique of self administration on the skin, it is recommended to obtain measurement of serum estradiol level after initiation of treatment. This measurement should be done when the patient has developed her technique for Estrogel application.
Measure none, slather twice.
In my practice, I don’t routinely recommend testing hormones after menopause unless you ask for them and know the pitfalls. This is true whether you aren’t taking hormone replacement or you are and want to know if you’re in a specific menozone.
We don’t have the science yet to chase a specific number value.
I prefer to dose most women in the most tolerable middle range of hormones or until they have very few symptom complaints. Having said that, if you want to test, let’s do it. There’s no gatekeeping here.
Dr. Bobby Parmar
Naturopathic Physician
