Thirty patients were treated with aminoglutethimide 250 mg four times per day together with cortisone acetate 50 mg twice per day for the first 2 weeks, followed by aminoglutethimide 250 mg four times per day with cortisone acetate 25 mg twice per day.
Pretreatment values for plasma tHcy in the group treated with aminoglutethimide are shown in Fig.
Three patients in the group treated with formestane, two patients in the aminoglutethimide group, one patient in the exemestane group, and three patients in the megestrol acetate group had tHcy above the value defined as the upper health-related limit for postmenopausal women in our laboratory (18 [micro]mol/L; see Patients and Methods).
Treatment with aminoglutethimide was associated with a significant change in plasma tHcy (Fig.
The selectivity of the increase in plasma tHcy during aminoglutethimide treatment was further documented by an increase in the tHcy/tCys ratio with no increase in tCys.
Thus, data for patients treated with aminoglutethimide were re-analyzed after exclusion of the five patients who had received tamoxifen as their last treatment modality before aminoglutethimide.
To evaluate whether the increase in plasma tHcy caused by treatment with aminoglutethimide could be the result of reduced cobalamin or folate, which are cofactors in Hcy metabolism, we determined serum cobalamin and folate and RBC folate before and during aminoglutethimide therapy.
Previous findings suggested that an increased risk of cardiovascular diseases (14) associated with aminoglutethimide adjuvant treatment may be partly the result of an increase in plasma cholesterol and triglycerides (26).
The possibility that alterations in tHcy during treatment with aminoglutethimide could be secondary to alterations in blood lipids may be considered.
We found that treatment with aminoglutethimide caused a significant and substantial increase in plasma tHcy and the ratio of tHcy to tCys.
It is difficult from our data to identify the mechanism by which aminoglutethimide increases plasma tHcy.
In summary, our data show that aminoglutethimide treatment increases plasma tHcy in breast cancer patients.