Vaginal estradiol use and the risk for cardiovascular mortality

• Published in: Human reproduction (Oxford) 2016-04, Vol.31 (4), p.804-809
• Main Authors: Mikkola, Tomi S., Tuomikoski, Pauliina, Lyytinen, Heli, Korhonen, Pasi, Hoti, Fabian, Vattulainen, Pia, Gissler, Mika, Ylikorkala, Olavi
• Format: Article
• Language: English
• Subjects: Aged; Cardiovascular Agents - administration & dosage; Cardiovascular Agents - therapeutic use; Cohort Studies; Coronary Disease - epidemiology; Coronary Disease - mortality; Coronary Disease - prevention & control; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - therapeutic use; Drug Prescriptions; Estradiol - administration & dosage; Estradiol - therapeutic use; Estrogens - administration & dosage; Estrogens - therapeutic use; Female; Female Urogenital Diseases - drug therapy; Finland - epidemiology; Follow-Up Studies; Humans; Middle Aged; Postmenopause; Registries; Risk Factors; Stroke - epidemiology; Stroke - mortality; Stroke - prevention & control; Vaginal Creams, Foams, and Jellies
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dew014

Abstract STUDY QUESTION Does the use of post-menopausal vaginal estradiol (VE) affect the mortality risk for coronary heart disease (CHD) and stroke. SUMMARY ANSWER The use of VE reduces the risk for cardiovascular mortality. WHAT IS KNOWN ALREADY A growing number of women use VE for post-menopausal genitourinary symptoms. Although this therapy is intended to have only local effects, estrogen is absorbed into the blood circulation and thus VE use may also have systemic effects. STUDY DESIGN, SIZE, DURATION We studied a nationwide cohort in Finland 1994–2009 during which post-menopausal women (n = 195 756) initiated the use of VE (age [mean ± SD] 65.7 ± 10.9 years). Follow-up data gathered 1.4 million women-years and we assessed the mortality risk due to CHD (n= 9656) or stroke (n = 4294). PARTICIPANTS/MATERIALS, SETTING, METHODS The mortality risk in VE users was compared with that in the age-matched background population (standardized mortality ratio; [SMR]; 95% confidence interval) and related to various durations of exposure to VE (1 to ≤3, >3 to ≤5, >5 to ≤10 and >10 years). MAIN RESULTS AND THE ROLE OF CHANCE The use of VE was accompanied by decreases in the risk for CHD and stroke death. The risk reduction for CHD death was highest for >3 to ≤5 years exposure (SMR 0.64; 0.57–0.70) and for stroke for >5 to ≤10 years exposure (SMR 0.64; 0.57–0.72). The risk reductions for both CHD and stroke mortality were detected in all age groups with the highest risk reduction being in women aged 50–59 years (SMR 0.43; 0.19–0.88 and SMR 0.21; 0.06–0.58, respectively). LIMITATIONS, REASONS FOR CAUTION Our series lack a placebo arm and thus, may harbor a healthy woman bias. Moreover, data on clinical variables such as weight, smoking, blood pressure and family background were unobtainable for this study. Women using both VE and systemic hormone therapy (HT) were included in the comparator background population. This should not cause any significant error because the proportion of women using VE or other HT was modest (