I see plenty of women in my clinic that come from other clinics that are on hormone replacement therapy, and when I ask them what their estradiol levels are, they have no clue. They tell me that their healthcare provider never checks their estradiol levels. Some say, "I have asked about it, and their healthcare providers tell them that there is no need to check your estradiol levels.“ The problem with that statement is that it's just not true. Their providers might not know that it's not true, and they might be sincere with their answer. However, there is plenty of scientific evidence that is contrary to that statement.

Let's be crystal clear: the research exists, the optimal ranges are established, and the silence is a choice born of ignorance and not malice.

Medical schools don't teach hormone optimization, and most residencies, to include OBGYN residencies and endocrinology residencies, don't teach hormone optimization. Some health care providers reading that statement might disagree, but I will tell you how I know because when I go to these conferences and I go to these courses, which I've been doing for the last 14 or 15 years, I'm sitting next to an endocrinologist or an OB/GYN physician along with many other specialists. These courses are taught by endocrinologists and OB/GYNs and other scientists, and they will say we didn't learn this in residency.

Now, there might be some residencies that teach hormone optimization, but for the most part, most do not. There is over three decades of Pharma co kinetic studies, randomized controlled trials, and observational data: the optimal serum Estradiol range for most menopausal women on hormone replacement therapy is 65 to 150 pg/mL. This is not my opinion. This isn't functional medicine voodoo or nonsense. This is hard science published in the most prestigious medical journals in the world.

Vasomotor Symptoms

A landmark randomized, prospective, double-blind study published in 1985 assessed the ability of transdermal estradiol to suppress hot flashes and vasomotor symptoms in symptomatic menopausal women. They found a dose-response relationship, meaning that relief of hot flashes was directly proportional to the amount of estradiol the women were taking.

The dose-response relationship is brutal in its clarity:

  • Estradiol serum level of 61 pg/mL: 50% reduction of hot flashes.
  • Estradiol serum level of 122 pg/mL: 100% reduction of hot flashes.

Contemporary studies have generally confirmed these findings (ish). In a 2014 study, women taking 0.5 mg/ day of oral estradiol experienced a 52.9% reduction in vasomotor symptoms, compared to 28.6% with placebo. They didn’t report the serum estradiol levels in this study, but other studies confirm that 0.5 mg oral estradiol gives you a serum estradiol level of about 25 pg/ml. This suggests that even lower doses of estrogen may begin to improve vasomotor symptoms in some women.

Bone Health

Bone Protection (Preventing Further Loss): Requires serum estradiol levels of 30-60 pg/mL. While studies suggest that serum estradiol levels as low as 30-50 pg/mL are needed to put the brakes on bone loss, most studies suggest that a serum estradiol level of 60+ pg/mL is where a significant reduction in bone resorption is achieved.

Bone Building (Actually Growing New Bone): Requires serum estradiol levels of 65-150+ pg/mL. Anabolic bone effects (building new bone tissue rather than just preventing loss) require higher estradiol levels than simply preventing bone loss. If you have osteoporosis and your doctor put you on a "bone-building" dose of estrogen and your serum level is 40 pg/mL, you're not building anything.

Cardiovascular Protection

Thus far, the positive randomized controlled trials showing that estrogen prevents cardiovascular disease have all been done using oral forms of estrogen (either oral conjugated equine estrogen or oral estradiol).

Oral estradiol at doses achieving 65+ pg/mL provides cardiovascular protection when started within 10 years of menopause.

The studies are as follows:

ELITE Trial: 1 mg oral estradiol daily (achieving ~66 pg/ mL) significantly reduced progression of atherosclerosis when initiated within 6 years of menopause.

Danish Osteoporosis Prevention Study: 2 mg oral estradiol daily (~108 pg/mL) produced:

  • 52% reduction in cardiovascular disease over 10 years
  • 39% reduction in cardiovascular events over 16 years
  • 34% reduction in all-cause mortality

EPAT Trial: 1 mg oral estradiol daily reduced the rate of plaque progression on Carotid Intimal Media Thickness (CIMT) testing compared to placebo.

However, here's the kicker: transdermal estradiol at standard “mid-range” doses provided no cardiovascular protection in the single randomized controlled trial where it has been studied.

The KEEPS trial showed zero cardiovascular benefit with 50 mcg transdermal patches (achieving only ~50-55 pg/mL). Zero. Zilch. Nada.

Now, it’s quite possible that transdermal estradiol also protects the heart, as long as it’s dosed high enough. Observational studies support this idea, but randomized controlled trials on transdermal estradiol are lacking to confirm it definitively.

So let's be clear: estradiol levels matter. All hormone levels matter. If you're using hormone replacement therapy and your levels aren't being checked or they're checked but they don't meet the levels in this article, you need to have a serious discussion with your provider to see if they'll increase your estradiol levels.