Is hormone replacement therapy (HRT) with estradiol plus sequential norethisterone (Novofem) contra

Fråga: Is hormone replacement therapy (HRT) with estradiol plus sequential norethisterone (Novofem) contraindicated in a patient with coagulation factor VII deficiency? A perimenopausal woman with factor VII deficiency has previously been denied substitution treatment with tibolone (Livial), since this drug could aggravate the coagulation defect.

Sammanfattning: There is no evidence of sequential hormone replacement therapy causing anticoagulant effects or aggravating a pre-existing factor VII deficiency.

Svar: No specific information on the use of HRT in women with coagulation factor deficiencies was identified in Medline or standard pharmacological literature.

The influences of tibolone treatment on the coagulation system are complex, and dominated by an enhanced fibrinolysis. In addition, it has been associated with decreased levels of several procoagulant factors, including activated factor VII (fVIIa) (1,2). Similar but less pronounced effects have been observed in patients treated with continuous combined HRT. In a 24 weeks´ randomised comparison between tibolone and continuous estrogen/gestagen combination therapy, the plasma levels of fVIIa dropped 18 and 8 percent in the two groups, respectively (2).

In contrast to continuous combined HRT, sequential HRT (e.g. Novofem) has been associated with over-all procoagulant effects and unaltered or even increased plasma levels of fVIIa (2,3). Furthermore, haemorrhage (other than genital bleeding) is not a known side effect of Novofem, speaking against clinically relevant anticoagulant properties of the drug (4). In the Swedish adverse drug reactions database, there is a single report of haematoma with a possible connection to sequential HRT with estrogen

orethisterone. However, this patient was also treated with other drugs, including ibuprofen, and the clinical presentation was more suggestive of vasculitis than a coagulative disorder (5).