Sex-Based Evaluation of Lipid Profile in Postoperative Adjuvant Mitotane Treatment for Adrenocortical Carcinoma

Abstract

Background: A wide interindividual variability in mitotane concentrations and treatment-related dyslipidemia have been reported. Here, we aimed to underline the sex-related differences in the lipid profile in patients that underwent radical surgery of adrenocortical carcinoma during treatment with adjuvant mitotane. Methods: A chromatographic method was used to quantify the drug in plasma collected from adult patients with complete tumor resection, also considering active metabolite o,p’-DDE. Results: We observed different lipid profiles between males and females and between pre- and post-menopausal women. Considering the mitotane-related effects on lipid levels, we observed that higher drug concentrations were correlated with higher HDL in all the considered groups (p < 0.001), with total cholesterol both in males (p = 0.005) and females (p = 0.036), with triglycerides in postmenopausal females (p = 0.002) and with LDL in male patients (p < 0.001). Increases in o,p’-DDE were positively correlated with HDL levels in all the groups (p < 0.001) and negatively with LDL in all the groups (males p = 0.008, pre- and post-menopausal females p < 0.001), with total cholesterol in pre- (p = 0.016) and post-menopausal women (p = 0.01) and with triglycerides in premenopausal females (p = 0.005). Conclusions: This is the first study designed to evaluate sex differences in lipoprotein and lipid levels during mitotane adjuvant treatment; the results suggest that a gender and personalized approach could be useful to prevent and manage alterations in the lipid profile.

Keywords: cholesterol; dyslipidemia; gender; menopause; o,p’-DDD; o,p’-DDE; safety; sex; side effect; triglycerides.

Figure 1

Influence of sex on total-cholesterol levels (mg/dL). Box plot of sex’s influence on total-cholesterol levels (mg/dL): The black lines in the boxes show the interquartile ranges (IQRs): quartile 1, median values and quartile 3; the open dots and stars describe the outlier values. The p-value is shown.

Figure 2

Influence of sex on HDL levels (mg/dL). Box plot of sex’s influence on HDL levels (mg/dL): The black lines in the boxes show the interquartile ranges (IQRs): quartile 1, median values and quartile 3; the open dots and stars describe the outlier values. Symbols (star and circle) indicate outliers of the study sample. The p-value is shown.

Figure 3

Influence of sex on triglyceride levels (mg/dL). Box plot of sex’s influence on triglyceride levels (mg/dL): The black lines in the boxes show the interquartile ranges (IQRs): quartile 1, median values and quartile 3; the open dots and stars describe the outlier values. The p-value is shown.

Figure 4

Influence of menopause on total-cholesterol levels (mg/dL). Box plot of sex’s influence on total-cholesterol levels (mg/dL): The black lines in the boxes show the interquartile ranges (IQRs): quartile 1, median values and quartile 3; the open dots and stars describe the outlier values. The p-value is shown.

Figure 5

Influence of sex on HDL levels (mg/dL). Box plot of sex’s influence on HDL levels (mg/dL): The black lines in the boxes show the interquartile ranges (IQRs): quartile 1, median values and quartile 3. The p-value is shown.

Figure 6

Influence of sex on LDL levels (mg/dL). Box plot of sex’s influence on LDL levels (mg/dL): The black lines in the boxes show the interquartile ranges (IQRs): quartile 1, median values and quartile 3; the open dots and stars describe the outlier values. The p-value is shown.

Figure 7

Influence of sex on triglyceride levels (mg/dL). Box plot of sex’s influence on triglyceride levels (mg/dL): The black lines in the boxes showed the interquartile ranges (IQRs): quartile 1, median values and quartile 3; the open dots describe the outlier values. The p-value is shown.