Cardiovascular Outcomes in Women on Oral vs Transdermal Estrogen

Introduction to Estrogen Therapy

Transdermal estrogen therapy is significantly safer than oral estrogen for cardiovascular outcomes in women, with substantially lower risk of venous thromboembolism and no increased risk of stroke compared to oral formulations 1

Transdermal estrogen does not increase the risk of venous thromboembolism, with odds ratio of 0.9 (95% CI, 0.4-2.1) compared to 4.2 (95% CI, 1.5-11.6) for oral estrogen preparations in postmenopausal women 1

Transdermal estrogen formulations were not associated with a clear risk of stroke, especially at low doses 2

Blood pressure levels in women with premature ovarian insufficiency treated with transdermal 17β-estradiol were statistically lower than after combined oral contraceptives, likely due to more physiological impact on the renin-angiotensin-aldosterone axis 1
17β-estradiol reduces LDL levels and increases HDL, while ethinyl estradiol has a negative impact on insulin tolerance 1

Transdermal estradiol and vaginal progesterone had more beneficial effects on lumbar spine bone mineral density than standard hormone replacement therapy using oral ethinyl estradiol and oral norethisterone 3
In a randomized study of 30 women, 17β-estradiol 2 mg daily with levonorgestrel 75 μg showed more favorable effects on lumbar spine bone mineral density compared to ethinyl estradiol 30 μg with levonorgestrel 150 μg 3

The American College of Cardiology recommends that transdermal estrogen should be preferred over oral estrogen for most women requiring hormone therapy, particularly those with cardiovascular risk factors including hypertension 1, 4
The Menopause Society recommends estrogen-based hormone therapy may be most appropriate using the lowest effective dose of estrogen in women <60 years of age with low cardiovascular, thromboembolic, and breast cancer risk profiles 2
The American College of Cardiology states that hormone therapy is not recommended for primary prevention of cardiovascular disease in women 4

The National Comprehensive Cancer Network recommends that women with history of hormone-dependent cancers should generally avoid hormone therapy 5
The National Comprehensive Cancer Network states that for women with intact uterus requiring hormone therapy, progestin must be added to prevent endometrial hyperplasia and cancer 5