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Interaction between oral estrogen plus progestogen therapy and ABO blood groups on coagulation activation in postmenopausal women

Guimarães, Daniela Amorim Melgaço PhD1,2; dos Santos, Mariana Silva BS1; Gomes, Karina Braga PhD1; van der Bom, Johanna G. MD, PhD3; Rios, Danyelle Romana PhD1,4; Cardoso, Jarbas BS1; Franco, Romerson Martins MD5; Teixeira, George da Silva MD5; Dusse, Luci Maria Sant’Ana PhD1; Carvalho, Maria das Graças PhD1; Fernandes, Ana Paula PhD1

Menopause: The Journal of The North American Menopause Society: March 2012 - Volume 19 - Issue 3 - p 339–345
doi: 10.1097/gme.0b013e31822b721f
Original Articles

Objective The aim of this study was to investigate the effect of postmenopausal hormone therapy on coagulation and whether this effect differs according to ABO blood groups.

Methods This was a prospective observational study to evaluate factor VIII (FVIII) activity, factor von Willebrand (vWF), and D-dimer (D-Di) levels and ABO blood groups in 61 postmenopausal women using oral estrogen plus progestogen therapy (EPT; 2 mg estradiol + 1 mg norethisterone acetate) for 3 months and in 101 women not using EPT. After 3 months, all eligible women who had completed the treatment scheme proposed for the EPT group or those who opted to participate but had not undergone EPT had a blood sample collected for analysis.

Results Significant differences were observed in FVIII activity and vWF levels in the control group between those carrying group O and non–group O blood. For EPT users, significant differences were observed for FVIII activity, vWF, and D-Di levels. After a multivariate regression analysis, FVIII activity and ABO blood groups were independently associated with vWF levels, whereas interaction between ABO blood groups and EPT were independently associated with FVIII activity. Besides diabetes, the ABO × EPT interaction was also noted to be independently associated with D-Di levels.

Conclusions These findings suggest an interactive effect between oral EPT and non-O blood groups, contributing to the mechanism by which estrogen triggers the hypercoagulability state and increased risk for venous thrombosis in women undergoing oral EPT.

These findings suggest an interactive effect between oral estrogen plus progestogen therapy and non-O blood groups. This may contribute to the hypercoagulability state and the increased risk for venous thrombosis in women undergoing oral estrogen and progestogen therapy.

From the 1Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil; 3Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; 4Healthy Science Center, Federal University of São João Del Rey, Divinópolis, Minas Gerais, Brazil; and 5Maternity Otaviano Neves, Belo Horizonte, Minas Gerais, Brazil.

Received April 14, 2011; revised and accepted June 24, 2011.

Funding/support: This study was supported by the Fundação de Amparo à Pesquisa de Minas Gerais and Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Ana Paula Fernandes, PhD, Faculty of Pharmacy, Federal University of Minas Gerais, Av Antonio Carlos, 6627 Belo Horizonte, 31270-901 Minas Gerais, Brazil. E-mail:

©2012The North American Menopause Society