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Testosterone deficiency is associated with clinically relevant depression symptoms

Testosterone deficiency is associated with clinically relevant depression symptoms Acta Marisiensis - Seria Medica 2023;69(1):50-54 DOI: 10.2478/amma-2023-0008 RESEARCH ARTICLE Testosterone deficiency is associated with clinically relevant depression symptoms 1* 1 2 2 3 Liliana Vartolomei , Sabin Octavian Tătaru , Andrei Cotruș , Camelia Stanciu , Anca Ileana Sin 1. IOSUD, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania 2. Department of Psychology, Dimitrie Cantemir University, Targu Mures, Romania 3. Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania Objective: To investigate the association between testosterone deficiency and depressive and/or anxiety symptoms. Methods: A cross- sectional study was conducted at the urology outpatient clinic from Ludus County Hospital. A set of validated questionnaires ((International Prostate Symptoms Score (IPSS), Depression Anxiety and Stress Scale (DASS-21), Zung Self-rating Depression Scale (Zung SDS)) were self-administrated. Inclusion criteria: age > 40 years. Exclusion criteria: any relevant psychiatric, cardiovascular, or cancer comorbidity. Sta- tistical analyzes were performed using the statistical software Statistical Package for Social Sciences (SPSS, version 23, Chicago, IL, USA). Results: From the total of 55 participants included in the study, 23 (41.8%) had testosterone deficiency. Most were from the 60-69 years decade, 23 participants (41.8%), and the mean age was 59.3 (SD 9.03) years. Eleven (20%) patients had depressive symptoms according to the depression subscale, of these, 7 had mild symptoms and 4 according to Zung SDS. Testosterone deficiency was associated with an increased DASS-21 global score, p=0.021, and depression score, p=0.047. Conclusions: Patients with testosterone deficiency are pre - senting symptoms of depression. Therefore, these patients need a multi-disciplinary approach that should include a psychological evaluation before making a further management decision. Keywords: testosterone deficiency, depression, anxiety, stress Received 25 October 2022 / Accepted 9 February 2023 Introduction and serum testosterone deficiency (TD) [6]. Men with TD Depression is a common disease worldwide, with a report- present with loss of libido, dysphoria, fatigue, and/or ir- ed incidence of approximately 3.8% of the global popula- ritability symptoms [7] that may correlate with depression tion, with this incidence increasing to 5.0% among adults episodes [8]. A linkage may be because episodes of major and 5.7% among adults over 60 years of age. Thus, accord - depression are increasing with aging [9], while testosterone ing to data from the World Health Organization (WHO), decreases [10]. Consecutively, a correlation between TD approximately 280 million people in the world suffer from and depressive symptoms might increase with age [11]. depression [1]. The most present depressive symptoms in patients with Depression differs from regular mood swings and short- age-related TD are dysthymia, hopelessness and suicidal lived emotional responses to the challenges of everyday life. thoughts [12,13]. In particular when it is recurrent and of moderate or severe Even so, a correlation between TD and major depression intensity, depression can become a serious health problem, is still under investigation, the current literature indicates which influences the individual’s functioning at work, at a link in men with refractory depression, major depression school, and in the family [2]. According to the Diagnostic and/or HIV infection, dysthymia, and/or in elderly (age and Statistical Manual of Mental Disorders, Fifth Edition, >60 years) [14]. Refractory depression or treatment resist- (DSM-5), depressive disorders can embrace many faces ant depression is considered in case of failure to achieve from a major depressive episode to other unspecified mani - remission after treatment with one or two antidepressant festations [3]. of same or different classes [15]. Testosterone represents the main male hormone respon- Thus, our aim was to investigate the association be - sible for sexual development and maintenance of second- tween testosterone deficiency and depressive and/or anxi - ary sexual characteristics [4]. The mechanism of action ety symptoms by conducting a cross-sectional study. involves crossing the cell membrane, binding to specific receptors, and deoxyribonucleic acid (DNA) to facilitate Materials and Methods st both ribonucleic acid (RNA) and protein synthesis. It is in- A cross-sectional study was performed from 1 January to st volved among others in the growth of muscles, bone mass, 31 March 2020. A set of validated questionnaires ((In- penis, and scrotum [5]. ternational Prostate Symptoms Score (IPSS), Depression The term late-onset hypogonadism appeared in 2002, Anxiety and Stress Scale (DASS-21), Zung Self-rating De- defined as a syndrome, characterized by specific symptoms pression Scale (Zung SDS)) were applied to 55 men, aged between 40 and 75 years, who consecutively presented themselves for a specialist urological consultation at the * Correspondence to: Liliana Vartolomei E-mail: liliana.vartolomei17@gmail.com outpatient clinic from Luduş County Hospital. Acta Marisiensis - Seria Medica 2023;69(1) 51 Participants Statistical analysis Inclusion criteria: age > 40 years. Exclusion criteria: any Associations between age, testosterone deficiency with re - relevant psychiatric, cardiovascular or cancer comorbid- sponses to questionnaire items (DASS-21 and Zung SDS) ity. The current study was approved by the local Ethical were quantified using the chi test. Differences between Committee (No. 2441/2019). It was explained to each continuous variables (DASS and Zung SDS score) accord- subject what the applied questionnaires consisted of, how ing to the variables studied, were analyzed using the stu- to complete them, the questionnaire set, and the informed dent t-test. Statistical significance was defined as a p <0.05. consent were handed to each subject. Questionnaires were Statistical analyzes were performed using the statistical completed by the participants and clinical data such as se- software Statistical Package for Social Sciences (SPSS, ver- rum testosterone and prostate specific antigen (PSA) values sion 23, Chicago, IL, USA). were also recorded. The acceptance rate to participate in the study was 91.6 %, 55 participants out of 60 approached. Results Data collection Patients’ characteristics The data completed by the participants were centralized in From the total of 55 participants included in the study, an Excel database that included age as a continuous vari- 23 (41.8%) had testosterone deficiency (TD). Most were able (coded by decades of age), PSA value (ng/dl), pros- from the 60-69 age decade, 23 participants (41.8%) (Table tate gland volume measured with ultrasound, PSA density 1), and the mean age was 59.3 (SD 9.03) years. The mean (calculated as the ratio PSA/prostate volume), testosterone prostate volume measured by ultrasound was 28.7 (SD (ng/dl), testosterone deficiency (TD, coded according to 17.29) cm , the mean value of prostate specific antigen was the recommendations of the American Urology Associa- 1.96 ng/dl (SD 1.69), with a mean PSA density of 0.09 tion: testosterone ≤300 ng/dl on two consecutive determi- (SD 0.15). Regarding lower urinary tract symptoms, 27 nations), followed by the global score of the psychomet- participants reported mild symptoms, 20 moderate symp- ric questionnaires and their interpretation according to toms and 8 patients - severe symptoms (Table 1). the recommended coding and the answers to each item of these questionnaires. Total scores corresponding to the Depression, anxiety, and stress according to DASS-21 scales were calculated by summing the ratings for each re- and Zung SDS sponse according to the rating manuals. The median score at DASS-21 was 9 (interval 0-35) and at Zung SDS was 37.5 (interval 25-56.25). Eleven (20%) Psychometric tests patients had depressive symptoms according to the de- DASS-21 [16] was used to determine symptoms of depres- pression subscale of the DASS-21, of these, 7 had mild sion, anxiety, and stress. This test can evaluate the severity symptoms. Ten (18.2%) patients had anxiety symptoms of behavioral and emotional symptoms that are correlated according to the anxiety subscale of the DASS-21, with with depression, anxiety disorder and stress. We used the 3 that had severe symptoms, all these 3 patients had also 21 items test with specific questions for depression: items moderate or severe depression and stress symptoms, of 3, 5, 10, 13, 16, 17, and 21; anxiety: items 2, 4, 7, 9, which 2 patients (66%) were with TD. Another 6 patients 15, 19, and 20; and stress: items 1, 6, 8, 11, 12, 14, and (10.9%) had symptoms of stress according to the stress 18. Each of the questions was rated from 0 to 3. The final subscale of DASS-21. According to Zung SDS question- score was then converted in a Z-value according to age and naire, 4 (7.3%) patients had a score between 50 and 59, gender, and according to Z-value patients were assigned to which means with mild depressive symptoms (Table 2). one of four categories (normal, mild, moderate, and severe symptoms) [17]. Testosterone deficiency and depression Zung SDS [18] contains 20 items and was designed A statistically significant association was identified be - based on the specific diagnostic criteria for depression. Par - tween DASS-21 global score and TD, p=0.021 and DASS ticipants rate each item using a 4-point Likert scale. The Depression and testosterone deficiency, p=0.047 (Table scores of the Zung SDS ranges from 20 to 80 but results 3). The item analysis demonstrated a statistically signifi - are converted to a SDS Index to a 100 points scale. cant association between TD and agitation: 60.9% vs. Table 1. Patients’ characteristics Characteristic Patients Percentage Age (years) 40-49 9 16.4 50-59 17 30.9 60-69 23 41.8 70-75 6 10.9 Testosterone deficiency <300 ng/dl 23 41.8 International Prostate Symptoms Score 1-7 27 49.1 8-19 20 36.4 20-35 8 14.5 52 Acta Marisiensis - Seria Medica 2023;69(1) Table 2. DASS-21 and Zung SDS interpretation Questionnaire subscale Interpretation Patients Percentage DASS-21 depression No symptoms 44 80 Mild symptoms 7 12.7 Moderate symptoms 2 3.6 Severe symptoms 2 3.6 DASS-21 anxiety No symptoms 45 81.8 Mild symptoms 3 5.5 Moderate symptoms 4 7.3 Severe symptoms 3 5.5 DASS-21 stress No symptoms 49 89.1 Mild symptoms 3 5.5 Moderate symptoms 3 5.5 Zung SDS No symptoms 51 92.7 Moderate symptoms 4 7.3 Table 3. Association of testosterone deficiency (TD) with depression, anxiety and stress symptoms according to DASS-21 TD DASS-21 DASS-21 Depression DASS -21 Anxiety DASS -21 Stress no Mean 8.31 2.97 2.63 2.72 Std. Deviation 6.029 2.192 2.511 2.275 Median 8.00 3.00 2.00 3.00 Minimum 0 0 0 0 Maximum 30 10 11 9 Patients 32 32 32 32 yes Mean 12.83 4.48 4.13 4.22 Std. Deviation 8.721 2.952 3.415 2.969 Median 11.00 4.00 4.00 3.00 Minimum 1 1 0 0 Maximum 35 12 13 12 Patients 23 23 23 23 total Mean 10.20 3.60 3.25 3.35 Std. Deviation 7.543 2.622 2.989 2.668 Median 9.00 3.00 2.00 3.00 Minimum 0 0 0 0 Maximum 35 12 13 12 Patients 55 55 55 55 P value 0.021 0.047 0.073 0.060 21.9% (p=0.012), and lower self-esteem: 47.8% vs. 12.5% tosterone value than those without depressive symptoms (p=0.014). [22,23]. Likewise, 3 other studies have identified a cor - relation between testosterone levels and severity of depres- Discussion sion [24–26]. Kong et al. instead demonstrated a positive In our study, patients with testosterone deficiency were correlation between Aging Males Symptoms (AMS) and more likely to have higher DASS-21 scores (overall for BDI scores, r=0.5, p<0.01 [27]. Contrary, a study that in- depression, anxiety, and stress symptoms) and a statisti- cluded 3413 men from the Norwegian city of Tromsø did cally significant association was found also with depression not identify a correlation between testosterone levels and symptoms scores. When present, severe anxiety symp- mental disorder defined by a score > 1.85 on the Hopkins toms are associated with moderate and severe depression Symptom Checklist-10 scale [28]. This may be due to gen - and stress symptoms and with TD. Similarly, three stud- eral population characteristics in this specific geographical ies identified an increased prevalence of depression among area [29]. men with TD compared with those without TD. Using We found that one out of five patients investigated is an 11-point reference value of the Beck Depression Inven- presenting with depressive symptoms according to DASS- tory (BDI) scale, Rotter et al. [19] reported a prevalence 21 depression subscale. On the other hand, when using of 30.9% vs. 26.4%, and Boeri et al. [20] a prevalence Zung SDS scale less than 10% presented clinically rele- of 52.4% vs. 23.8%. In contrast, Jankovska et al. used a vant depression symptoms. However, when using a lower reference value of 16 on the BDI scale to define depres - cut-off the percentage may increase [30]. Taking together, sive symptoms and identified that in the group of patients DASS-21 can be used as a screening tool in adult males with depressive symptoms, 31% also had testosterone defi - as was previous proved in other populations [31–33], and ciency, compared to 12% in the group without depressive this must be doubled by another specific psychometric test symptoms [21]. [34] and clinical interview to conclude if the patients are Furthermore, other studies have identified that pa - meeting the DSM-V criteria [3] and if they are needing any tients with depressive symptoms have a lower average tes- kind of intervention or pharmacological treatment [35]. Acta Marisiensis - Seria Medica 2023;69(1) 53 As current literature advocate that depression represents Conclusion a combination of genetic, biological, environmental, and Patients with testosterone deficiency are presenting symp - psychological factors, everything must be taking into ac- toms of depression. Consequently, these patients need a count [36]. Furthermore, particular in elderly may co-exist multi-disciplinary approach that should include a psycho- with other serious medical conditions, such as cancer, car- logical evaluation prior to any decision making regarding dio-vascular diseases, diabetes, or Parkinson’s disease, with further management. a reported incidence of up to 28% among the elderly with such comorbidities, according to the latest meta-analysis. Authors’ contribution In young men, it can be associated with erectile dysfunc- LV - Study design, data analysis, critical revision and edit- tion [37]. These comorbidities are often exacerbating in ing of manuscript, final approval for publication; SOT - the presence of depression and frequently drugs that are Study design, research implementation, drafting of manu- taken for these ailments can produce side effects that favor script, data collection, final approval for publication; AC depression manifestation. - Study design, study validation and supervision, critical In our cohort more than 40% of patients had TD, review of manuscript, final approval for publication; CS - which represent a quite large number when compared to Study design, data analysis, critical review of manuscript, the current literature, which establish a prevalence up to final approval for publication; AIS - Study design, data 10% in western countries [38], similar in Asian cohorts, analysis, critical review of manuscript, final approval for in a Indian cohort 22% [39] or 5.8% in a population from publication; Korea [40]. Similar findings were reported by the Hypog - onadism In Men study, which reported a prevalence of TD Conflicts of interest of 38.7% [41], therefore the prevalence might be heteroge- None to declare neous among different populations. Lower baseline levels of testosterone were also shown References 1. Depression. (WHO). Retrieved May 26, 2022, from https://www.who.int/ to be associated with a longer durations of positive COV- news-room/fact-sheets/detail/depression. ID-19 testing and thus viral clearance in males hospitalized 2. Dinesh AA, Helena Pagani Soares Pinto S, Brunckhorst O, et al. Anxiety, depression and urological cancer outcomes: A systematic review. Urol for COVID-19 infection [42]. In case of prostate cancer Oncol. 2021;39:816–828. (PCa) diagnosis, lower baseline testosterone levels were as- 3. Diagnostic and Statistical Manual of Mental Disorders: DSM 5. 5th ed., sociated with unfavorable prognosis in patients undergo- American Psychiatric Association, 2013. 4. 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Testosterone deficiency is associated with clinically relevant depression symptoms

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Abstract

Acta Marisiensis - Seria Medica 2023;69(1):50-54 DOI: 10.2478/amma-2023-0008 RESEARCH ARTICLE Testosterone deficiency is associated with clinically relevant depression symptoms 1* 1 2 2 3 Liliana Vartolomei , Sabin Octavian Tătaru , Andrei Cotruș , Camelia Stanciu , Anca Ileana Sin 1. IOSUD, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania 2. Department of Psychology, Dimitrie Cantemir University, Targu Mures, Romania 3. Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania Objective: To investigate the association between testosterone deficiency and depressive and/or anxiety symptoms. Methods: A cross- sectional study was conducted at the urology outpatient clinic from Ludus County Hospital. A set of validated questionnaires ((International Prostate Symptoms Score (IPSS), Depression Anxiety and Stress Scale (DASS-21), Zung Self-rating Depression Scale (Zung SDS)) were self-administrated. Inclusion criteria: age > 40 years. Exclusion criteria: any relevant psychiatric, cardiovascular, or cancer comorbidity. Sta- tistical analyzes were performed using the statistical software Statistical Package for Social Sciences (SPSS, version 23, Chicago, IL, USA). Results: From the total of 55 participants included in the study, 23 (41.8%) had testosterone deficiency. Most were from the 60-69 years decade, 23 participants (41.8%), and the mean age was 59.3 (SD 9.03) years. Eleven (20%) patients had depressive symptoms according to the depression subscale, of these, 7 had mild symptoms and 4 according to Zung SDS. Testosterone deficiency was associated with an increased DASS-21 global score, p=0.021, and depression score, p=0.047. Conclusions: Patients with testosterone deficiency are pre - senting symptoms of depression. Therefore, these patients need a multi-disciplinary approach that should include a psychological evaluation before making a further management decision. Keywords: testosterone deficiency, depression, anxiety, stress Received 25 October 2022 / Accepted 9 February 2023 Introduction and serum testosterone deficiency (TD) [6]. Men with TD Depression is a common disease worldwide, with a report- present with loss of libido, dysphoria, fatigue, and/or ir- ed incidence of approximately 3.8% of the global popula- ritability symptoms [7] that may correlate with depression tion, with this incidence increasing to 5.0% among adults episodes [8]. A linkage may be because episodes of major and 5.7% among adults over 60 years of age. Thus, accord - depression are increasing with aging [9], while testosterone ing to data from the World Health Organization (WHO), decreases [10]. Consecutively, a correlation between TD approximately 280 million people in the world suffer from and depressive symptoms might increase with age [11]. depression [1]. The most present depressive symptoms in patients with Depression differs from regular mood swings and short- age-related TD are dysthymia, hopelessness and suicidal lived emotional responses to the challenges of everyday life. thoughts [12,13]. In particular when it is recurrent and of moderate or severe Even so, a correlation between TD and major depression intensity, depression can become a serious health problem, is still under investigation, the current literature indicates which influences the individual’s functioning at work, at a link in men with refractory depression, major depression school, and in the family [2]. According to the Diagnostic and/or HIV infection, dysthymia, and/or in elderly (age and Statistical Manual of Mental Disorders, Fifth Edition, >60 years) [14]. Refractory depression or treatment resist- (DSM-5), depressive disorders can embrace many faces ant depression is considered in case of failure to achieve from a major depressive episode to other unspecified mani - remission after treatment with one or two antidepressant festations [3]. of same or different classes [15]. Testosterone represents the main male hormone respon- Thus, our aim was to investigate the association be - sible for sexual development and maintenance of second- tween testosterone deficiency and depressive and/or anxi - ary sexual characteristics [4]. The mechanism of action ety symptoms by conducting a cross-sectional study. involves crossing the cell membrane, binding to specific receptors, and deoxyribonucleic acid (DNA) to facilitate Materials and Methods st both ribonucleic acid (RNA) and protein synthesis. It is in- A cross-sectional study was performed from 1 January to st volved among others in the growth of muscles, bone mass, 31 March 2020. A set of validated questionnaires ((In- penis, and scrotum [5]. ternational Prostate Symptoms Score (IPSS), Depression The term late-onset hypogonadism appeared in 2002, Anxiety and Stress Scale (DASS-21), Zung Self-rating De- defined as a syndrome, characterized by specific symptoms pression Scale (Zung SDS)) were applied to 55 men, aged between 40 and 75 years, who consecutively presented themselves for a specialist urological consultation at the * Correspondence to: Liliana Vartolomei E-mail: liliana.vartolomei17@gmail.com outpatient clinic from Luduş County Hospital. Acta Marisiensis - Seria Medica 2023;69(1) 51 Participants Statistical analysis Inclusion criteria: age > 40 years. Exclusion criteria: any Associations between age, testosterone deficiency with re - relevant psychiatric, cardiovascular or cancer comorbid- sponses to questionnaire items (DASS-21 and Zung SDS) ity. The current study was approved by the local Ethical were quantified using the chi test. Differences between Committee (No. 2441/2019). It was explained to each continuous variables (DASS and Zung SDS score) accord- subject what the applied questionnaires consisted of, how ing to the variables studied, were analyzed using the stu- to complete them, the questionnaire set, and the informed dent t-test. Statistical significance was defined as a p <0.05. consent were handed to each subject. Questionnaires were Statistical analyzes were performed using the statistical completed by the participants and clinical data such as se- software Statistical Package for Social Sciences (SPSS, ver- rum testosterone and prostate specific antigen (PSA) values sion 23, Chicago, IL, USA). were also recorded. The acceptance rate to participate in the study was 91.6 %, 55 participants out of 60 approached. Results Data collection Patients’ characteristics The data completed by the participants were centralized in From the total of 55 participants included in the study, an Excel database that included age as a continuous vari- 23 (41.8%) had testosterone deficiency (TD). Most were able (coded by decades of age), PSA value (ng/dl), pros- from the 60-69 age decade, 23 participants (41.8%) (Table tate gland volume measured with ultrasound, PSA density 1), and the mean age was 59.3 (SD 9.03) years. The mean (calculated as the ratio PSA/prostate volume), testosterone prostate volume measured by ultrasound was 28.7 (SD (ng/dl), testosterone deficiency (TD, coded according to 17.29) cm , the mean value of prostate specific antigen was the recommendations of the American Urology Associa- 1.96 ng/dl (SD 1.69), with a mean PSA density of 0.09 tion: testosterone ≤300 ng/dl on two consecutive determi- (SD 0.15). Regarding lower urinary tract symptoms, 27 nations), followed by the global score of the psychomet- participants reported mild symptoms, 20 moderate symp- ric questionnaires and their interpretation according to toms and 8 patients - severe symptoms (Table 1). the recommended coding and the answers to each item of these questionnaires. Total scores corresponding to the Depression, anxiety, and stress according to DASS-21 scales were calculated by summing the ratings for each re- and Zung SDS sponse according to the rating manuals. The median score at DASS-21 was 9 (interval 0-35) and at Zung SDS was 37.5 (interval 25-56.25). Eleven (20%) Psychometric tests patients had depressive symptoms according to the de- DASS-21 [16] was used to determine symptoms of depres- pression subscale of the DASS-21, of these, 7 had mild sion, anxiety, and stress. This test can evaluate the severity symptoms. Ten (18.2%) patients had anxiety symptoms of behavioral and emotional symptoms that are correlated according to the anxiety subscale of the DASS-21, with with depression, anxiety disorder and stress. We used the 3 that had severe symptoms, all these 3 patients had also 21 items test with specific questions for depression: items moderate or severe depression and stress symptoms, of 3, 5, 10, 13, 16, 17, and 21; anxiety: items 2, 4, 7, 9, which 2 patients (66%) were with TD. Another 6 patients 15, 19, and 20; and stress: items 1, 6, 8, 11, 12, 14, and (10.9%) had symptoms of stress according to the stress 18. Each of the questions was rated from 0 to 3. The final subscale of DASS-21. According to Zung SDS question- score was then converted in a Z-value according to age and naire, 4 (7.3%) patients had a score between 50 and 59, gender, and according to Z-value patients were assigned to which means with mild depressive symptoms (Table 2). one of four categories (normal, mild, moderate, and severe symptoms) [17]. Testosterone deficiency and depression Zung SDS [18] contains 20 items and was designed A statistically significant association was identified be - based on the specific diagnostic criteria for depression. Par - tween DASS-21 global score and TD, p=0.021 and DASS ticipants rate each item using a 4-point Likert scale. The Depression and testosterone deficiency, p=0.047 (Table scores of the Zung SDS ranges from 20 to 80 but results 3). The item analysis demonstrated a statistically signifi - are converted to a SDS Index to a 100 points scale. cant association between TD and agitation: 60.9% vs. Table 1. Patients’ characteristics Characteristic Patients Percentage Age (years) 40-49 9 16.4 50-59 17 30.9 60-69 23 41.8 70-75 6 10.9 Testosterone deficiency <300 ng/dl 23 41.8 International Prostate Symptoms Score 1-7 27 49.1 8-19 20 36.4 20-35 8 14.5 52 Acta Marisiensis - Seria Medica 2023;69(1) Table 2. DASS-21 and Zung SDS interpretation Questionnaire subscale Interpretation Patients Percentage DASS-21 depression No symptoms 44 80 Mild symptoms 7 12.7 Moderate symptoms 2 3.6 Severe symptoms 2 3.6 DASS-21 anxiety No symptoms 45 81.8 Mild symptoms 3 5.5 Moderate symptoms 4 7.3 Severe symptoms 3 5.5 DASS-21 stress No symptoms 49 89.1 Mild symptoms 3 5.5 Moderate symptoms 3 5.5 Zung SDS No symptoms 51 92.7 Moderate symptoms 4 7.3 Table 3. Association of testosterone deficiency (TD) with depression, anxiety and stress symptoms according to DASS-21 TD DASS-21 DASS-21 Depression DASS -21 Anxiety DASS -21 Stress no Mean 8.31 2.97 2.63 2.72 Std. Deviation 6.029 2.192 2.511 2.275 Median 8.00 3.00 2.00 3.00 Minimum 0 0 0 0 Maximum 30 10 11 9 Patients 32 32 32 32 yes Mean 12.83 4.48 4.13 4.22 Std. Deviation 8.721 2.952 3.415 2.969 Median 11.00 4.00 4.00 3.00 Minimum 1 1 0 0 Maximum 35 12 13 12 Patients 23 23 23 23 total Mean 10.20 3.60 3.25 3.35 Std. Deviation 7.543 2.622 2.989 2.668 Median 9.00 3.00 2.00 3.00 Minimum 0 0 0 0 Maximum 35 12 13 12 Patients 55 55 55 55 P value 0.021 0.047 0.073 0.060 21.9% (p=0.012), and lower self-esteem: 47.8% vs. 12.5% tosterone value than those without depressive symptoms (p=0.014). [22,23]. Likewise, 3 other studies have identified a cor - relation between testosterone levels and severity of depres- Discussion sion [24–26]. Kong et al. instead demonstrated a positive In our study, patients with testosterone deficiency were correlation between Aging Males Symptoms (AMS) and more likely to have higher DASS-21 scores (overall for BDI scores, r=0.5, p<0.01 [27]. Contrary, a study that in- depression, anxiety, and stress symptoms) and a statisti- cluded 3413 men from the Norwegian city of Tromsø did cally significant association was found also with depression not identify a correlation between testosterone levels and symptoms scores. When present, severe anxiety symp- mental disorder defined by a score > 1.85 on the Hopkins toms are associated with moderate and severe depression Symptom Checklist-10 scale [28]. This may be due to gen - and stress symptoms and with TD. Similarly, three stud- eral population characteristics in this specific geographical ies identified an increased prevalence of depression among area [29]. men with TD compared with those without TD. Using We found that one out of five patients investigated is an 11-point reference value of the Beck Depression Inven- presenting with depressive symptoms according to DASS- tory (BDI) scale, Rotter et al. [19] reported a prevalence 21 depression subscale. On the other hand, when using of 30.9% vs. 26.4%, and Boeri et al. [20] a prevalence Zung SDS scale less than 10% presented clinically rele- of 52.4% vs. 23.8%. In contrast, Jankovska et al. used a vant depression symptoms. However, when using a lower reference value of 16 on the BDI scale to define depres - cut-off the percentage may increase [30]. Taking together, sive symptoms and identified that in the group of patients DASS-21 can be used as a screening tool in adult males with depressive symptoms, 31% also had testosterone defi - as was previous proved in other populations [31–33], and ciency, compared to 12% in the group without depressive this must be doubled by another specific psychometric test symptoms [21]. [34] and clinical interview to conclude if the patients are Furthermore, other studies have identified that pa - meeting the DSM-V criteria [3] and if they are needing any tients with depressive symptoms have a lower average tes- kind of intervention or pharmacological treatment [35]. Acta Marisiensis - Seria Medica 2023;69(1) 53 As current literature advocate that depression represents Conclusion a combination of genetic, biological, environmental, and Patients with testosterone deficiency are presenting symp - psychological factors, everything must be taking into ac- toms of depression. Consequently, these patients need a count [36]. Furthermore, particular in elderly may co-exist multi-disciplinary approach that should include a psycho- with other serious medical conditions, such as cancer, car- logical evaluation prior to any decision making regarding dio-vascular diseases, diabetes, or Parkinson’s disease, with further management. a reported incidence of up to 28% among the elderly with such comorbidities, according to the latest meta-analysis. Authors’ contribution In young men, it can be associated with erectile dysfunc- LV - Study design, data analysis, critical revision and edit- tion [37]. These comorbidities are often exacerbating in ing of manuscript, final approval for publication; SOT - the presence of depression and frequently drugs that are Study design, research implementation, drafting of manu- taken for these ailments can produce side effects that favor script, data collection, final approval for publication; AC depression manifestation. - Study design, study validation and supervision, critical In our cohort more than 40% of patients had TD, review of manuscript, final approval for publication; CS - which represent a quite large number when compared to Study design, data analysis, critical review of manuscript, the current literature, which establish a prevalence up to final approval for publication; AIS - Study design, data 10% in western countries [38], similar in Asian cohorts, analysis, critical review of manuscript, final approval for in a Indian cohort 22% [39] or 5.8% in a population from publication; Korea [40]. 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Journal

Acta Marisiensis - Seria Medica – de Gruyter

Published: Mar 1, 2023

Keywords: testosterone deficiency; depression; anxiety; stress

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