Comparative Evidence Between Transdermal and Oral Menopausal Hormone Therapy

Key Message

• Hormone therapy may be prescribed to support individuals experiencing symptoms of menopause due to a decline in estrogen in the body. Menopausal symptoms may vary in frequency and intensity, and commonly include vasomotor symptoms (VMS) (often referred to as hot flashes or night sweats), sleep disruption, and mood changes, and may include impacts to bone or heart health and overall quality of life.
• For individuals seeking support managing these symptoms, menopausal hormone therapy (MHT) with estrogen (or a combination of estrogen and progesterone) is an established treatment.
• Various routes of administration (ways to take estrogen) are available for MHT with estrogen, including oral (taken as a pill) or transdermal (absorbed through the skin), but the comparative clinical efficacy, effectiveness, and safety of these administration routes are unclear.
• Decision-makers are interested in whether transdermal estrogen should be considered for public reimbursement (funding) as a first treatment option (first-line option), as an alternative to oral estrogen for MHT.
• We evaluated the evidence of the clinical efficacy, effectiveness, safety, and cost-effectiveness (value from a human or health system perspective) of transdermal versus oral estrogen in MHT using a rapid review approach.
• We searched for evidence-based guidelines on the use of transdermal or oral estrogen in MHT.
• We identified 7 systematic reviews, 4 primary studies, and 3 clinical practice guidelines relevant to this review. No relevant health technology assessment (HTA) reports or cost-effectiveness studies were identified.
• The included studies suggest that transdermal estrogen may reduce VMS, improve sleep, and have a lower risk of blood clots compared to oral estrogen. Both transdermal and oral MHT may improve bone health and have similar safety risk profiles for breast and gynecological cancers. Furthermore, transdermal MHT may be a safer choice for those at risk of developing blood clots; however, there are inconsistent results related to the risk of heart disease and stroke.
• The included studies suggest oral MHT is more effective at improving cholesterol levels but may raise triglyceride levels. In contrast, transdermal MHT has mixed effects on cholesterol levels, though it also raises triglyceride levels.
  Guideline recommendations consider transdermal MHT over oral MHT for addressing specific individual concerns related to sexual well-being and reducing risk for gallstones, blood clots, stroke, and heart disease.
• There is limited evidence comparing transdermal and oral MHT, particularly for managing VMS, health-related quality of life, and sleep quality. However, some studies suggest transdermal MHT may have a lower risk of venous thromboembolism (VTE) (blood clots in the veins).
• Given these safety considerations, policymakers may consider reimbursement for transdermal MHT, but additional research is needed to inform consideration for efficacy and cost-effectiveness.