The advantages of transdermal estrogens

Hello from sunny Barcelona, we’re very excited to be sharing the latest studies and data with you from the ESG Congress 2017. The conference started with a fantastic opening session on Climacteric and Menopause: from symptoms to therapies, from security to efficacy.

One of the key themes in this session was looking at the use of transdermal estrogens. Eswald started his session on the advantages of transdermal estrogens by re-iterating that Menopause hormone therapy (MHT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause and highlighted that it is agreed amongst most societies and guidelines that for women aged younger than 60 years or within 10 years of menopause onset, that have no contraindications, the benefit-risk ratio is most favourable for treatment of VMS, and for preventing bone loss and fractures in women at elevated risk.

From the data published by the WHI back in 2002, we know that the only significant findings in the “adjusted” results were for a reduction in total fracture risk and an increased risk of venous thromboembolism (VTE). So what are the true benefits and risks? Benefits include reduction in risk of bone fractures, hip fractures and colorectal cancer whilst risks include increased prevalence of VTE, ischemic stroke and coronary heart disease.

Transdermal estrogen and VTE

Below the age of 60, the risk of VTE is very rare, however risk of VTE events increases with use of oral MHT and age in addition to the presence of other risk factors such as congenital or acquired thrombophilic disorders.  As oral estrogen therapy is contra-indicated in women with a personal history of VTE, transdermal estrogen therapy should be the first choice in obese women suffering from climacteric symptoms.  This is further supported by the ESTHER study which showed that transdermal estrogen also significantly reduces risk of VTE when you have a BMI between 25 and 30 or over 30.  

Transdermal estrogen and Cardiovascular risk.

The use of transdermal compared with oral estrogen may also be less likely to produce thrombotic risk, risk of stroke and coronary artery disease risk.  41% of all death due to major causes in European women are cause by cardiovascular disease so reducing this risk is crucial. The Danish national registry study showed significantly lower risk with the transdermal route rather than oral for cardiovascular diseases. Although previously key markers of CVD: LDL cholesterol and HDL cholesterol seem more beneficial for oral (lower LDL and higher HDL) more sophisticated markers such as proinflammatory HDL is decreased in transdermal but increased in oral. Triglycerides are also increased in oral but decreased in transdermal. Simon JA et al. Menopause, 2017 Jun; 23(6):600-10 shows women receiving transdermal estradiol therapy have significantly lower incidences of CVD event compared to those receiving oral estradiol therapy and also had significantly lower healthcare costs.

Transdermal estrogen and Stroke risk

Whilst the oral route leads to increased risk of stroke, this is not true for the transdermal route. The French National Health Insurance database study (Canonico M et al. Stroke 2016 July; 47(7) 1734-41.) shows risk increases with dose even with the transdermal approach however in the case of stroke, transdermal has significantly lower risk.

So are transdermal estrogens better?

Data shows that transdermal estrogen are as effective as oral estrogens regarding the treatment of VMS and the prevention of osteoporosis and fractures.  The potential benefit of transdermal is related to the opportunity of avoiding the first liver passage. As a result transdermal estrogens don’t result in increased risk of VTE or stroke and is safer to use in obese women suffering from climacteric symptoms.