Alterations in Pattern Baldness According to Sex: Hair Metabolomics Approach

Abstract

Pattern baldness has been associated with the male hormone, dihydrotestosterone. In this study, we tried to determine how the overall metabolic pathways of pattern baldness differ in patients and in normal controls. Our study aimed to identify alterations in hair metabolomic profiles in order to identify possible markers of pattern baldness according to sex. Untargeted metabolomics profiling in pattern baldness patients and control subjects was conducted using ultra-performance liquid chromatography-mass spectrometry. To identify significantly altered metabolic pathways, partial least squares discriminant analysis was performed. Our analysis indicated differences in steroid biosynthesis pathway in both males and females. However, there was a remarkable difference in the androgen metabolic pathway in males, and the estrogen metabolic and arachidonic acid pathways in females. For the first time, we were able to confirm the metabolic pathway in pattern baldness patients using hair samples. Our finding improves understanding of pattern baldness and highlights the need to link pattern baldness and sex-related differences.

Keywords: female; hair metabolomics; male; pattern baldness; ultra-performance liquid chromatography-mass spectrometry.

Figure 1

Partial least squares discriminant analysis (PLS-DA) score plots showing discriminant different patterns in controls (red circles) and pattern baldness patients (green circles). (a) PLS-DA in positive mode with male groups, (b) PLS-DA in negative mode with male groups, (c) PLS-DA in positive mode with female groups, and (d) PLS-DA in negative mode with female groups.

Figure 2

Permutation test to validate partial least squares discriminant analysis score. Permutation numbers were set to 100. X-axis showed the permuted class labels and Y-axis shows optimal number of components by cross validation in (a) male groups and (b) female groups.

Figure 3

The top 20 scores of variable importance in projection (VIP) values. On the left part of the graph, significant difference of metabolites are indicated. The main graph represents the VIP scores. On the right part of the graph, dark red indicates high abundance and dark blue indicates low abundance, respectively. (a) Male groups and (b) female groups; c, normal controls; p, pattern baldness patients.

Figure 4

Differentiated metabolic pathways between patient groups and controls can be visually confirmed. Dark red indicates that the pathways were significantly different, with red circles indicating more significance than yellow circles. Light yellow means a less significant than yellow. The Y-axis represents the –log p values, whereas the X-axis represents the pathway impact values. (a) Pathway analysis based on 42 metabolites in male groups from an untargeted analysis and (b) pathway analysis based on 26 metabolites in female groups from an untargeted analysis.

Figure 5

Metabolites with differences between male groups in steroid metabolic pathway. (a) Metabolites in red indicate significant differences between groups and (b) the pathway mapping of metabolites and relative quantitation between male pattern baldness patients and male controls. The larger the circle, the larger the relative quantitative value. Red circles indicate higher metabolite concentrations in the patient group and blue circles indicate higher metabolite concentrations in the control group.

Figure 6

Metabolites with differences between female groups in steroid metabolic pathway. (a) Metabolites in red indicate significant differences between groups and (b) the pathway mapping of metabolites and relative quantitation between female pattern baldness patients and female controls. The larger the circle, the larger the relative quantitative value. Red circles indicate higher metabolite concentration in the patient group and blue circles indicate higher metabolite concentration in the control group.