Estradiol transdermal spray for menopausal symptom management: From RCT to real-world evidence

Menopause is a major natural, biological and physiological change in women's lives. It is linked to vasomotor symptoms, sleep problems, mood symptoms, and genitourinary syndrome of menopause, as well as with morbidity, such as osteoporosis and cardiovascular disease. These symptoms and diseases decrease quality of life and burden healthcare systems. Although menopausal hormone therapy is the most effective treatment for climacteric symptoms and recommended as the first treatment choice by leading societies, its use remains limited due to safety concerns, misconceptions, and unequal access. Transdermal estrogen delivery, compared with oral estrogen, is increasingly advised in guidelines because it bypasses first-pass liver metabolism and has a neutral effect on the risk of thromboembolism, and therefore may benefit women with cardiometabolic risk factors. Accordingly, the estradiol transdermal spray offers an efficient, flexible, and user-friendly option. This review summarises evidence from the pivotal randomized controlled trial and four real-world studies in Portugal, Germany, the Nordic countries, and the Czech Republic. The available studies suggest consistent and clinically meaningful improvements in vasomotor symptoms, sleep, mood, sexual health, and genitourinary syndrome of menopause. Severe or very severe hot flushes decreased by 70-90%, usually with one to two sprays daily. Satisfaction and ease-of-use ratings were high (80-90%), and tolerability was favourable, with minimal local reactions. Overall, the evidence supports estradiol transdermal spray as an effective and generally well-accepted treatment option for menopausal symptom management. Its profile is broadly aligned with both current guideline recommendations and informed, patient-centred menopause care.