Hum. Reprod. Advance Access originally published online on June 13, 2007
Human Reproduction 2007 22(8):2196-2201; doi:10.1093/humrep/dem153
Use of the etonogestrel-releasing implant is associated with hypoactivation of the coagulation cascade
1 Department of Gynaecology and Obstetrics, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, Brazil 2 Department of Haemostasis, Hospital das Clínicas, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, Brazil 3 Federal University of Rio Grande do Norte, Natal, Brazil
4 Correspondence address. Tel: +55-16-3602-2804; Fax: +55-16-3633-0946; E-mail: carol.sales{at}uol.com.br
BACKGROUND: The role of progestogens in haemostasis is controversial. Our objective is to evaluate the haemostatic effects of an etonogestrel-releasing implant.
METHODS: This open-label, self-controlled, longitudinal study involved 20 healthy women receiving subcutaneous etonogestrel-releasing implants. At baseline, 1, 3 and 6 months, we measured the following: activated partial thromboplastin time; prothrombin time; thrombin time; fibrinogen; coagulation factors II, V, VII, VIII, IX, X and XI; von Willebrand factor; activated protein C (APC); antithrombin; free protein S; plasminogen activator inhibitor type 1 (PAI-1); 
2-antiplasmin; thrombin–antithrombin (TAT) complex; prothrombin fragment 1 + 2 (F1 + 2); D-dimers; APC resistance. Statistical analyses included the Friedman test and ANOVA.
RESULTS: Levels of APC (P < 0.01), factor II (P = 0.02), factor VII (P = 0.006), factor X (P = 0.01) and F1 + 2 (P < 0.001) were reduced, whereas those of PAI-1 (P = 0.01) and factor XI (P = 0.006) were transitory increased. All of these values, however, remained within normal ranges. Surprisingly, TAT concentrations fell below the normal range (P < 0.001).
CONCLUSIONS: Our findings suggest that the etonogestrel-releasing implant does not induce a prothrombotic pattern during the first six months of use, and that its use is associated with a reduction in thrombin generation.
Key words: etonogestrel/progestogens/haemostasis/coagulation/contraception
Submitted on January 16, 2007; resubmitted on May 4, 2007; accepted on May 9, 2007.