Risk of Venous Thromboembolism Associated With Local and Systemic Use of Hormone Therapy in Peri- and Postmenopausal Women and in Relation to Type and Route of Administration Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Wednesday, July 13, 2016

Risk of Venous Thromboembolism Associated With Local and Systemic Use of Hormone Therapy in Peri- and Postmenopausal Women and in Relation to Type and Route of Administration


 Risk of Venous Thromboembolism Associated With Local and Systemic Use of Hormone Therapy in Peri- and Postmenopausal Women and in Relation to Type and Route of Administration
 Menopause. 2016;23(6):593-599

Objective. The aim of the study was to assess the risk of venous thromboembolism (VTE) associated with systemic hormone therapy according to type and to route of administration and the risk of VTE associated with locally administered estrogen.

  • Comparisons with Previous RCTs (HT vs Placebo)

  • Comparisons with Previous Studies (Estrogens Plus Progestogens vs Estrogens Only)

    (Comparisons include data from WISDOM, WHI, HERS, Million Womens Study trials)


Strengths and Limitations

  Our study is the first to highlight both local and systemic use, route of administration, and the importance of the progestogen component. The strengths of this study is the population-based design, the detailed and standardized data collection through interviews, and the possibilities to assess several intrinsic and extrinsic risk factors in the same population including known risk factors for VTE. It was possible to study various estrogen treatment preparations. The diagnostic classification based on presence of both a verified radiological examination of VTE and commenced anticoagulant therapy reduces the risk of misclassification.[18] Potential limitations include the possibility of selection bias, the limited sample size, and the lack of laboratory data to define menopause status. Also recall—bias cannot be ruled out as the information on exposure was collected retrospectively, however we tried to minimize this by sending all participants a letter with a memory support catalogue and a time schedule to fill in before the interview. Our study was an observational study of VTE cases and selected controls and not a randomized study. We could therefore only estimate relative risks (or relative odds) of VTE in women with and without a particular exposure and not directly estimate disease risk. As only 5% of our study population had a previous arterial disease, excluding these women from the analyses would not have influenced the results.


The VTE risk is higher among users of combined estrogen– progestogen treatment than among users of estrogen only. Orally administered estrogen only generated greater risk than transdermal preparations. Transdermal estrogen treatment and estrogen for local effect seem not to be related to an increased risk of VTE. No statistically significant difference in VTE risk by type of progestogen was found.


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