Treatment with a GnRH analogue: effects on hemostatic risk factors for thrombo-embolic disease.
OBJECTIVE
Steroid hormones, especially estrogens, are known to affect hemostatic risk factors for thromboembolism, cardiovascular disease, and stroke. We examined these risk factors during depression of the serum estradiol concentration by a GnRH analogue.


METHODS
Patients were treated with a GnRH analogue, goserelin (Zoladex), 3.6 mg/inj monthly, for a period of 6 months. Blood samples were collected during and after treatment and in a control group. In ten patients a blood sample was also drawn before treatment. Measurements were made of serum estradiol, and the plasma concentrations of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen, antithrombin III (AT III) and protein C activity, factor VII (FVII) antigen, and fibrinogen.


METHODS
Outpatient clinics at the Departments of Obstetrics and Gynecology at two university hospitals in southern Sweden.


METHODS
Twenty-seven women with endometriosis were consecutively included. A control group comprised 20 women with normal menstrual cycles.


METHODS
The concentrations of the hemostatic components during depression of the serum estradiol concentrations, as compared to those during normal ovulatory cycles.


RESULTS
Serum estradiol concentrations during treatment were comparable to those of postmenopausal women (mean, 23.2 pmol/L), and both AT III and protein C activity were significantly increased (P < .005 and P < .02, respectively). As compared to controls, plasma concentrations of PAI-1 and t-PA of patients were significantly higher both during and after treatment. In the subgroup also studied prior to treatment, there were no differences in hemostatic components, when comparing pretreatment and posttreatment values.


CONCLUSIONS
Treatment with this type of GnRH analogue for 6 months is safe with regard to its effect on hemostatic risk factors. The similar responses of t-PA and its inhibitor, PAI-1, to alterations in estrogen levels as well as inflammatory reactivity presumably constitute a balance mechanism preserving fibrinolytic defenses.
Lindoff
C
C
Department and Research Laboratory of Obstetrics and Gynecology, University Hospital Lund, Sweden.
Petersson
F
F
Samsioe
G
G
Astedt
B
B
D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D004715:Endometriosis / Q000097:blood / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D005167:Factor VII / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D017273:Goserelin / Q000009:adverse effects* / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010960:Plasminogen Activators / Q000097:blood; D011486:Protein C / Q000032:analysis; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology*
D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D017273:Goserelin; D004958:Estradiol; D000990:Antithrombin III; D005167:Factor VII; D005340:Fibrinogen; D010960:Plasminogen Activators