Sex Hormone Levels And Their Associated Influences In Gender-specific Alcohol Use Disorder Patients

Objective: Alcohol use disorder(AUD)has become one of the serious social and medical problems in the world today,and alcohol is a central nervous system depressant and is by far the most commonly used and recognised addictive substance.Sex hormones,which are steroid hormones that interact with steroid hormone receptors in the body,play an important role in establishing gender-specific structural and functional changes in the brain that may le AUDto gender differences in drinking behaviour.Previous studies have also shown significant gender differences in susceptibility,progression and complications of alcohol use disorders.Sex hormone levels are also influenced by a variety of factors,including genetic,biological,psychiatric,pharmacological,age and gender.Gender is one of the most important factors affecting sex hormone levels.There are few reports on the factors associated with sex hormones and their gender differences in patients with alcohol use disorders in China,and even fewer in inpatients.Therefore,this study included inpatients with alcohol use disorder in psychiatric hospitals to investigate the prevalence of sex hormone abnormalities and to explore the gender differences in sex hormone levels in patients with alcohol use disorder and their heterogeneous correlates.Methods: 377 inpatients with alcohol use disorder were included in this study from April 2021 to December 2022 and the analysis of the study data was a secondary analysis of a clinical research trial.A systematically developed questionnaire was used to collect socio-demographic information such as gender,age and years of education and clinical information such as age at first drink,years of drinking and daily drinking from the enrolled subjects.The 10-item Alcohol use disorder identification test(AUDIT)was used to assess each patient’s alcohol use.The patient’s level of alcohol craving was assessed using a visual analogue scale(VAS).Patients’ impulsiveness was assessed using the Chinese version of the Barratt Impulsiveness Seale(BIS-11)questionnaire.Plasma levels of the six sex hormones were measured by fluorescent immunoassay in all subjects.To compare the differences in general demographic data,blood indicators and alcohol use between male and female patients and to analyse the gender differences in sex hormone levels and their heterogeneous correlates in inpatients with alcohol use disorders.Results:(1)General data of the enrolled subjects: a total of 377 inpatients with alcohol use disorder(including,among them,327 males and 50 females)were included,with an overall age of 21-73(41.69±9.63)years,a mean of 9(5,9)years of education,an age of first drinking of 11-62(21.65±6.39)years,and a drinking history of 2 to 43(20.04±8.87)years.(2)Comparison of general information and clinical characteristics between the male and female groups: patients in the female group had significantly better marital status than men,and patients in the female group had higher levels of estradiol(E2),luteinizing hormone(LH)and prolactin(PRL)than patients in the male group(P<0.05);while body mass index(BMI),smoking problems,testosterone(Tes)levels,age at first drink,daily alcohol consumption,and drinking years were all lower than in the male group(P<0.05).The differences in impulsivity,follicle stimulating hormone(FSH)and progesterone(Pro)between the two groups were not significant(P>0.05).(3)Prevalence of abnormal sex hormone levels: The overall abnormality rate of E2 levels in alcohol-dependent patients was 28.7%,of which elevation was predominant(21.0%),and the incidence of elevation was 16.5% in male patients and 50.0% in female patients,with a significant difference(P<0.001);the overall abnormality rate of FSH levels was 14.3%,both higher than normal,and the incidence of elevation was11.6% in male patients and 32.0% in female The overall abnormality rate of LH level was 9.8%,which was higher than the normal value,and the incidence of elevation was5.2% in male patients and 40.0% in female patients,which was significant(P<0.001);the overall abnormality rate of Tes level was 22.3%,which was mainly decreased(16.2%),but in The overall abnormality rate of Tes level was 22.3%,with a predominant decrease(16.2%),but in the male and female groups,the performance was opposite,with an increase in male patients(7.0%)and a decrease in female patients(100.0%),with a significant difference(P<0.001);the abnormal Pro level was elevated(74.5%),with a predominant increase in male patients(75.5%)and in female patients(68.0%),with a non-significant difference(P=0.255);the overall abnormality rate of PRL level was mainly elevated(42.4%),33.6% in male patients and 100% in female patients,and the difference was significant(P<0.001).(4)Factors related to sex hormone levels in overall patients: estradiol(E2)was positively correlated with gender and age at first drinking in overall patients hospitalized in the acute phase of alcohol use disorder(P<0.05).Folliculopoietin(FSH)was negatively correlated with age,behavioral impulse score in impulsivity trait,alcohol use level,and years of drinking(P<0.05);luteinizing hormone(LH)was positively correlated with gender and negatively correlated with age,smoking,behavioral impulse score in impulsivity trait,alcohol use level,consequences of alcohol use problems,and years of drinking(P<0.05).Testosterone(Tes)was positively(P<0.05)and negatively(P<0.05)correlated with gender,body mass index,smoking,behavioral impulsivity score in impulsivity trait,alcohol use level,problematic consequences of alcohol use,and years of drinking.Prolactin(PRL)was positively correlated with gender,age at first drinking,cognitive impulse score and unplanned impulse score in impulsivity trait(P<0.05),and negatively correlated with body mass index,smoking,action impulse score,alcohol use level,years of drinking as a consequence of alcohol use problems,and daily drinking(P<0.05).Progesterone(Pro)was positively correlated with the level of thirst(P<0.05).(5)Correlation factors of the six levels of sex hormones in different genders:correlation analysis yielded different correlation factors for different genders and levels of different sex hormones.a.PRL levels in the male group were negatively correlated with drinking levels(AUDIT-C,)and daily drinking(P<0.05),and PRL levels in the female group were negatively correlated with age,age at first drinking,and thirst level(P<0.05).b.E2 levels in the male group were negatively correlated with patient’s education(P<0.05)and positively correlated with age at first drinking(P<0.05).c.Tes levels in the female group were positively correlated with thirst level and BMI(P<0.05).d.Pro levels in the female group were negatively correlated with age and marital status(P<0.05).Pro levels were positively correlated with thirst level in men(P<0.05).e.FSH levels were negatively correlated with age and years of drinking in men(P<0.05).f.LH levels were negatively correlated with age,AUDIT-C score and years of drinking in men(P<0.05).(6)Analysis of factors influencing the levels of the six sex hormones: Dichotomous logistic regression analysis indicated that among men with alcohol use disorders,a higher AUDIT-C score(OR=0.932,95% CI: 0.872~0.997,P=0.041)negatively predicted PRL levels,a higher BMI(OR=1.082,95% CI: 1.006~1.164,P=0.034)could positively predict E2 levels,higher age could negatively predict FSH levels(OR=0.953,95% CI: 0.927~0.981,P=0.001),higher thirst could positively predict Pro levels(OR=1.041,95% CI: 1.001~1.119,P=0.023),higher age(OR= 0.968,95% CI:0.941~0.995,P=0.021)and a higher AUDIT-C score(OR=0.922,95% CI: 0.862~0.987,P=0.019)negatively predicted LH.In the female group,a higher BMI(OR=1.451,95%CI: 1.085 ~1.942,P= 0.012)positively predicted Tes levels.Conclusion: Sex hormone levels in patients with alcohol use disorders have significant gender differences,and different sex hormone indicators are influenced by different factors,so more attention should be paid to them during clinical treatment,care and prognosis and rehabilitation.In addition,body mass index and alcohol consumption levels are risk factors for sex hormone abnormalities.However,more and better designed clinical studies are needed to further elucidate the relationship between sex hormone levels and alcohol use disorders,the gender differences and the factors that influence them,in order to provide a biological reference in the development of recommendations for individual assessment and treatment of alcohol use disorders.