Low dose transdermal hormone replacement therapy is recommended over oral treatment for hot flushes and night sweats, when pharmacological treatment is needed.
Transdermal dosing has lower risk for stroke and venous thromboembolism, and about similar effect on postmenopausal symptoms than oral treatment, and is recommended for women with migraine, diabetes, and patients using drugs for epilepsy. Contraindications and balance between benefits and harms should be carefully discussed.
A population based nested case-control database (United Kingdom's General Practice Research Database) study 1 included all women in the database aged 50-79 years (n=955 582) in years 1987- 2006. Exposure to hormone replacement therapy (HRT) was categorised into oestrogens only, oestrogens plus progestogen, progestogen only, and tibolone. Oestrogens were further subdivided according to the route of administration (oral vs transdermal) and dose (low vs high): low dose oral products contained ≤ 0.625 mg of equine oestrogen or≤ 2 mg of estradiol and; transdermal low dose products contained ≤ 50 μg of oestrogen. There were 15 710 cases of stroke matched to 59 958 controls. The rate of stroke in the cohort was 2.85 per 1000 per year. The adjusted rate ratio of stroke associated with current use of transdermal HRT was 0.95 (95% CI 0.75 to 1.20) relative to no use. The rate of stroke did not increase with the addition of a progestogen to the transdermal oestrogens. The risk of stroke was not increased with use of low oestrogen dose patches (RR 0.81, 95% CI 0.62 to 1.05) compared with no use, whereas the risk was increased with high dose patches (RR 1.89, 95 % CI 1.15 to 3.11). Current users of oral HRT had a higher rate of stroke than non-users (RR 1.28, 95% CI 1.15 to 1.42) with both low dose and high dose.
A meta-analysis 2 assessing the risk of vascular events included 15 observational studies at moderate risk of bias with follow-up of 3 to 20.25 years. When compared to transdermal oestrogen therapy (ET), oral ET was associated with increased risk of a first episode of venous thromboemolism (RR 1.63; 95% C, 1.40 to 1.90; I² 53%), deep venous thrombosis (RR 2.09; 95% CI 1.35 o 3.23; I² 0 %), and possibly stroke (RR 1.24; 95% CI,1.03 to 1.48; a single case-controlled study), but not myocardial infarction (RR 1.17; 95% CI 0.80 to 1.71; I² 74%).
A national Danish registry based cohort study 3 included 980 003 women, 20 199 suffered a stroke (78% ischemic, 12% hemorrhagic, and 10% subarachnoid hemorrhage). In total, 36% of women used hormone therapy. Current use conferred a relative rate of 1.16 (95% CI 1.12 to 1.22). Compared with never users, the increased rate ratio of all stroke with continuous, cyclic combined estrogen/progestin, and estrogen only oral therapies were 1.29 (95% CI 1.21 to 1.37), 1.11 (95% CI 1.04 to 1.20), and 1.18 (95% CI 1.10 to 1.26), respectively. Transdermal application of hormone therapy was not associated with risk of stroke.
Date of latest search: 2020-10-22
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