Objective: To investigate the effect of sex on substantia nigra (SN) echogenicity in young-to-middle aged adults with a history of methamphetamine use.

Background: The sonographic appearance of the SN is abnormally enlarged (hyperechogenic) in adults with a history of methamphetamine use. It is unclear if the SN vulnerability differs between male and female methamphetamine users. We hypothesised that the area of SN echogenicity is greater in male methamphetamine users than in female methamphetamine users because testosterone is toxic to dopaminergic neurons undergoing oxidative stress¹, and oxidative stress occurs in dopaminergic neurons exposed to amphetamine and/or methamphetamine².

Methods: The area of SN echogenic signal was measured in abstinent human amphetamine users (n=15 males aged 34±8 years and n=12 females aged 32±8 years) and non-drug-using controls (n=18 males aged 27±9 years and n=22 females aged 22±3 years) with a Philips iU22 machine. The right and left SN was measured ipsilateral to the transducer (1-5 MHz, placed over the pre-auricular acoustic bone window).

Results: There was a significant effect of group (F_1,63=29.438, P<0.001) and gender (F_1,63=10.302, P=0.002), and a group-by-gender interaction (F_1,63=5.397, P=0.023), on the area of SN echogenicity (largest side). The area of SN echogenicity did not differ between males (0.196±0.053 cm²) and females (0.182±0.056 cm²) in the control group. However, in the methamphetamine group, males exhibited a significantly larger area of SN echogenicity (0.314±0.074 cm²) than females (0.229±0.063 cm², P=0.013), even though methamphetamine consumption (occasions of use) was comparable between the sexes (males: 583±815, females: 726±951). Male methamphetamine users also had a significantly larger area of SN echogenicity than male controls (P<0.001), but the comparison between female methamphetamine users and female controls did not reach statistical significance (P=0.062).

Conclusions: Methamphetamine use in males is associated with more pronounced changes in SN echomorphology than in females. The abnormal SN echomorphology in males may be associated with the toxic effects of testosterone on dopaminergic neurons undergoing oxidative stress.

References: 1 Holmes et al 2016 Endocrinology 157:2824-35 2 Yamamoto et al 2010 Ann N Y Acad Sci 1187:101-121

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MDS Abstracts - https://www.mdsabstracts.org/abstract/substantia-nigra-hyperechogenicity-in-male-methamphetamine-users/