Epidemiological investigation of sex hormones and their metabolism-related gene single nucleotide polymorphisms in patients with benign prostatic hyperplasia complicated with late-onset hypogonadism: a retrospective cohort study

Abstract

Background: Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly men, and its etiology is not completely clear. Late-onset hypogonadism (LOH) is a relatively common disease in the aging process of men. BPH is often accompanied by varying degrees of LOH, and the pathogenesis and progression of the two diseases are related. Sex hormone metabolism-related genes affect sex hormone metabolism, to determine androgen, estrogen, androgen/estrogen ratio, and their single nucleotide polymorphisms (SNPs) are common in the population. The relationship between BPH combined with LOH (LOH-BPH) and SNPs in genes related to sex hormone metabolism is still unclear. In this study, the authors hope to clarify the relationship between them through epidemiological investigation.

Objective: To investigate the association between LOH-BPH and SNPs of sex hormone metabolism-related genes.

Materials and methods: A total of 821 middle-aged and elderly men from 1 January 2017 to 31 December 2022, were retrospectively analyzed. According to the diagnosis of LOH-BPH, the patients were divided into LOH-BPH group and non-LOH-BPH group, and the related parameters of the two groups were compared. The parameters included age, total testosterone (tT), estradiol (E2), testosterone/estradiol ratio (T/E), dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), parameters associated with metabolic syndrome, parameters related to BPH, the International Index of Erectile Function 5 (IIEF-5) and erectile dysfunction (ED), and SNPs of genes related to sex hormone metabolism.

Results: Sixty-eight participants were excluded from this study, and 753 eventually completed the study. ED accounted for 48.21%, LOH-BPH accounted for 41.30%, and non-LOH-BPH accounted for 58.70%. tT decreased with age and was negatively correlated with age (r=-0.68, P<0.0001). E2 increased with age and was positively correlated with age (r=0.61, P=0.032). T/E decreased with age and was negatively correlated with age (r=-0.71, P<0.0001). After adjusting for age, LOH-BPH is significantly correlated with tT (r=-0.754, OR=0.071, 95% CI: 0.0048-0.105, P<0.0001), E2 (r=0.765, OR=3.855, 95% CI: 1.828-5.833, P<0.0001), T/E (r=-0.751, OR=0.000, 95% CI: 0.000-0.000, P<0.0001) and ED (r=0.973, OR=5.02, 95% CI: 4.898-6.578, P=0.001). At the same time, the AA genotype of rs1843090 (r=-0.613, OR=0.052, 95% CI: 0.006-0.44, P=0.007), the CC genotype of rs2279357 (r=0.636, OR=20.963, 95% CI: 2.268-93.793, P=0.004), the GG genotype of rs743572 (r=0.681, OR=7.642, 95% CI: 5.005-11.668, P<0.0001), the AA genotype of rs712221 (r=-0.012, OR=0.468, 95% CI: 0.220-0.881, P=0.018), and the TT genotype of rs700518 (r=0.699, OR=26.04, 95% CI: 16.142-42.008, P<0.0001) were significantly associated with LOH-BPH.

Conclusions: The morbidity of LOH-BPH can be associated with SNPs of genes related to sex hormone metabolism.

Figure 1

Flow chart of the study design. AMS, aging male symptoms; BPH, benign prostatic hyperplasia; DHT, dihydrotestosterone; ED, erectile dysfunction; E2, estradiol; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; IIEF-5, international index of erectile function 5; IPSS, international prostate symptom score; LOH, late-onset hypogonadism; MetS, metabolic syndrome; PSA, prostate-specific antigen; PV, prostate volume; Qmax, maximum urinary flow rate; SHBG, sex hormone-binding globulin; SNP, single nucleotide polymorphisms; TG, Triglycerides; tT, total testosterone; WC, Waist circumference.

Figure 2

Schematic representation of possible mechanisms by which SNPs in genes involved in sex hormone metabolism affect sex hormone levels leading to LOH-BPH. AR, androgen receptor; BPH, benign prostatic hyperplasia; CPY, cytochrome C P450 enzyme; DHT, dihydrotestosterone; ER, estrogen receptor; FE, free estrogen; FT, free testosterone; INSL3, insulin-like growth factor-3; LOH, late-onset hypogonadism; SHBG, sex hormone-binding globulin; SRD5A2, Steroid 5-alpha reductase 2; SF-1, steroidogenic factor-1; StAR, steroidogenic acute regulatory proteins; SNP, single nucleotide polymorphisms; TT, total testosterone; TE, total estrogen.

Figure 3

Changes of sex hormones (tT, E2, T/E) with age in patients with BPH with or without LOH. r stands for correlation coefficient for linear correlation analysis; A: P<0.0001; B: P=0.032; C: P<0.0001; BPH, benign prostatic hyperplasia; E2, estradiol; LOH, late-onset hypogonadism; tT, total testosterone; T/E, the ratio of total testosterone to estradiol.