%201.avif)
What our latest survey found about estradiol absorption and symptom control
The background
In 2023, several UK professional organisations – including the British Menopause Society (BMS), Faculty of Sexual & Reproductive Healthcare (FSRH), Royal College of General Practitioners (RCGP), Royal College of Obstetricians & Gynaecologists (RCOG), Society for Endocrinology (SfE), and the Royal College of Nursing (RCN) Women’s Health Forum – issued a joint safety alert advising that estrogen should not routinely be prescribed above licensed dose limits, and emphasising the importance of using the 'lowest effective dose' for symptom control. The statement highlighted that higher-than-licensed doses fall outside established safety evidence and should generally only be used in exceptional circumstances.
However, in 2024, the BMS later acknowledged that some women may require higher doses of estrogen outside licensing guidelines when care is appropriately individualised. The statement also noted that there is no evidence to justify stopping HRT at a certain age and that dose adjustment should be based on individual clinical need; a statement that many lack the guidance or experience to put into practice.
The current upper licensed limits for transdermal estrogen preparations were established decades ago in the 1980s, based on clinical trials that used pharmacokinetics (blood levels rather than clinical symptoms) and small dose-finding studies that fall short of the regulatory standard that would be expected of any new medicine today. In addition, the maximum dose was chosen on a practical basis of patch size or gel volume instead of any efficacy plateau or observed safety issues.
Real-world experience since has shown a large variability in transdermal estradiol absorption, with a significant number of women on the highest licensed dose achieving lower than expected blood levels.
A woman who absorbs estradiol poorly is not failing to respond to treatment, she may just need a higher dose to reach the same blood level that an average absorber gets from a standard dose. Crucially, a higher gel or patch dose to compensate for poor absorption does not mean more estradiol is reaching the bloodstream: it means the body is finally receiving an adequate amount.
Therefore, increasingly, clinicians and researchers are questioning whether these limits adequately reflect the wide variation in how women absorb and respond to hormones in real-world clinical practice today.
Against this backdrop, we conducted a survey exploring women’s experiences of symptom control, estradiol absorption, blood testing and access to treatment. Nearly 800 women from the UK and internationally responded.
Why does this happen?
Skin is not a simple, uniform barrier. How well estradiol passes through it depends on many individual factors including skin thickness, hydration, body composition, age, and even where on the body the gel or patch is applied.
Some people's skin is simply much less permeable than others. This is not unique to estradiol: it’s a known feature of all medicines delivered through the skin, including nicotine and fentanyl patches, where the product labels already acknowledge this variability.
There is also a second layer of variation that happens after the estradiol enters the bloodstream. Estradiol is mostly carried around the body bound to proteins. Only the tiny ‘free’ fraction – typically 1 to 2% – is actually available to act on cells. The level of these binding proteins varies considerably between women, meaning that two women with the same total estradiol reading in a blood test may actually have very different amounts of estradiol available to their bodies.
What did we find?
Among the 612 women who gave a definite yes/no response to the question 'Have you been able to achieve adequate symptom control using the highest licensed dose of transdermal estradiol?':
• 324 women (53%) reported that they had not been able to achieve adequate symptom control despite using the highest licensed dose of transdermal estradiol.
We also found:
• Over 70% of women on a range of estradiol doses reported that their symptoms were either only partially controlled or not controlled at all on their current dose
• Nearly half of respondents had discussed increasing their dose above the licensed maximum with a healthcare professional. Of these women, more than half reported being refused a higher dose
• 43% reported switching between different types or brands of estradiol due to lack of effectiveness
• Among women who had their estradiol blood levels measured, more than half reported levels that were lower than expected for their dose
• 67% of women were advised to reduce or stop treatment due to concerns around safety and 44% because of prescribing limits, which was happening despite ongoing symptoms and, in some cases, low blood estradiol levels.
Some women described feeling pressured to reduce doses that they felt were helping their symptoms. Comments included:
‘[My GP said it’s] not safe to prescribe, even though I'd been on higher [dose] for three years.’
'I see a private menopause specialist who put me on high doses to achieve symptom control. But every time I see an NHS provider for anything, not even hormone related, it’s queried and I’m made to feel stupid for being on such a high dose. Constantly told to try and reduce.’
‘I was told lowest dose for shortest time, and that “when” I get cancer, I will have to come off it anyway.’
Why does this matter?
HRT is highly effective for many women, and standard doses work well for most women. However, research has shown that there is variation in how women absorb and respond to transdermal estradiol.
It has been known for many years that some women need higher doses that others for adequate absorption of estradiol through their skin into their bloodstream. These results show that many women are struggling to be prescribed the dose of estradiol they need to improve both their symptoms and their future health.
Collectively, these findings add to growing discussion around whether current dosing frameworks and guidelines actually reflect the wide variation in women’s responses to transdermal estradiol, and highlight how more evidence-based and individualised approaches are needed for some women to achieve adequate symptom control with hormones.
