Psychological and sexual associations of azoospermia in men: a cross-sectional pre-biopsy study

Abstract

Azoospermia can lead to significant psychological distress, low self-esteem, and compromised sexual function. However, the impact of these issues before any invasive diagnostic or treatment procedures is not well studied. We conducted a cross-sectional study involving 134 men diagnosed with azoospermia and 164 age-matched fertile controls. All assessments, including anxiety (Beck Anxiety Inventory [BAI]), depression (Beck Depression Inventory-II [BDI-II]), self-esteem (Rosenberg Self-Esteem Scale [RSES]), and erectile function (International Index of Erectile Function-5 [IIEF-5]), were conducted during the diagnosis visit, prior to any testicular biopsy for infertility treatment. Compared with age-matched fertile controls, men with azoospermia exhibited significantly higher anxiety levels (mean ± standard deviation [s.d.]: 17.3 ± 3.9 vs 9.8 ± 2.8), increased depression scores (mean ± s.d.: 24.1 ± 6.3 vs 12.5 ± 5.1), lower self-esteem (mean ± s.d.: 2.8 ± 0.5 vs 1.8 ± 0.3), and poorer erectile function (mean ± s.d.: 17.2 ± 5.1 vs 21.4 ± 5.2), all with P < 0.001. Importantly, decreased self-esteem was strongly correlated with both depression (r = 0.851) and anxiety (r = 0.843). Additionally, erectile dysfunction showed an inverse correlation with both depression (r = −0.867) and anxiety (r = −0.813), with P < 0.05 for both correlations. The psychological and sexual effects of infertility are often overlooked in the treatment process. Therefore, we advocate that all men with azoospermia receive psychological and sexual support alongside infertility treatment.

INTRODUCTION

Azoospermia is defined as the absence of sperm in the ejaculate across at least two examinations. It accounts for approximately 10%–15% of male infertility cases, representing one of the most severe forms of male-related infertility.1,2

Azoospermia is classified into two types based on its underlying mechanisms, obstructive azoospermia (OA; caused by a physical blockage in the male reproductive tract), and non-obstructive azoospermia (NOA; characterized by the absence of obstruction, with causes related to testicular dysfunction or hormonal abnormalities affecting spermatogenesis and sperm maturation).3 The literature has primarily focused on the treatment and management of azoospermia, with numerous studies addressing this issue.4,5 Regardless of the underlying cause, azoospermia impacts men’s psychosocial and sexual lives.6,7,8 Infertility can lead to feelings of frustration, guilt, and blame within couples, often resulting in individuals feeling inadequate regarding their reproductive capabilities. While most studies have concentrated on the psychosocial stress experienced by women due to infertility, there is a notable lack of research on its effects on men.9 Bendayan et al.6 conducted a cross-sectional study involving 44 men with NOA, finding that a positive testicular sperm extraction (TESE) result correlated with significant improvements in sexual health, couple adjustment, and self-esteem. Conversely, a negative TESE result was linked to significant declines in erectile function, orgasmic function, self-esteem, sexual satisfaction, and various aspects of the couple’s relationship, including affection, satisfaction, cohesion, and consensus.6 Topuz et al.10 assessed anxiety, depression, and quality of life in NOA patients using the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI), and the Short Form of the World Health Organization Quality of Life Questionnaire. They concluded that NOA has profound psychological, social, and biological effects on men.10

Consequently, studies investigating the effects of azoospermia on men have either primarily focused on its relation to infertility or have been limited in scale and scope.11 There is a lack of comprehensive research evaluating the sexual life, self-esteem, anxiety, quality of life, and depression among azoospermic men. Our study aims to fill this gap by examining all these parameters in men with azoospermia. It is an extensive study in the literature to assess the effects of azoospermia on men’s psychological state, quality of life, and sexual health.

PARTICIPANTS AND METHODS

This cross-sectional study utilized prospectively collected data from Fatih Sultan Mehmet Training and Research Hospital (Istanbul, Türkiye) and was conducted between April 2023 and September 2024. A total of 298 men were enrolled, divided into two groups: an azoospermia group of 134 men who diagnosed with azoospermia, and a control group of 164 fertile men who had fathered a child within the past year. Approval was obtained from the local ethics committee of University of Health Sciences, Hamidiye School of Medicine, Fatih Sultan Mehmet Training and Research Hospital (Istanbul, Türkiye; Approval No. FSMEAH-KAEK 2020/151). All participants provided informed consent after the nature and purpose of the study were explained. Couples seeking assistance at Fatih Sultan Mehmet Training and Research Hospital due to difficulties in conceiving were assessed for male factors. Men with azoospermia were included in the study after confirmation through at least two semen analyses conducted more than 2 weeks apart. The female partners of these men underwent gynecological evaluations and were found to be fertile.

We gathered data on participants’ ages, medical histories, education levels, and durations of infertility. The exclusion criteria were as follows: (1) diagnosed psychiatric disorders (e.g., major depression, schizophrenia, or post-traumatic stress disorder [PTSD]); (2) use of medications with known psychological or sexual side effects (e.g., Selective Serotonin Reuptake Inhibitors [SSRIs] or antipsychotics); (3) chronic systemic illnesses such as cancer, diabetes, lupus, or organ failure; (4) ongoing infertility treatment; and (5) lack of consent to complete the study questionnaires.

The control group consisted of healthy men of similar age who had fathered a child within the last year and had no history of infertility. A pilot study involving 12 individuals was conducted for power analysis, which indicated the need for at least 143 participants per group. To account for potential dropouts, more participants were initially recruited. After excluding incomplete responses (23 from the azoospermia group and 22 from the control group), the final analysis included 134 participants in the azoospermia group and 164 in the control group.

All questionnaires were reviewed and evaluated by a licensed psychiatrist experienced in male sexual health and psychological assessment. They were administered during the visit when the diagnosis was disclosed and before any invasive diagnostic or therapeutic procedures.

BAI, a self-reported tool, consists of 21 items that assess common symptoms of anxiety over the past week. Each item is scored on a 0–3 scale, with higher scores indicating greater anxiety severity. The Turkish version of the BAI Scale has been previously validated by Ulusoy et al.,12 confirming its appropriateness for use in local populations. RSES was developed by Morris Rosenberg in the 1960s. The Rosenberg Self-Esteem Scale (RSES) assesses personal self-worth through items that evaluate both positive and negative self-perception. Lower total scores indicate higher self-esteem. The Turkish validated version of RSES was carried out by Cuhadaroglu13 in 1986. The Turkish validated version BDI-II consists of 21 items designed to measure the intensity of depressive symptoms, encompassing emotional, behavioral, and physical aspects of depression. Higher scores reflect more severe depression. Its reliability and validity in Turkish populations have been confirmed by Kapci et al.14 The International Index of Erectile Function (IIEF) is a validated questionnaire with 15 questions that explore five domains of sexual function: erectile function, orgasmic function, sexual desire, satisfaction with sexual intercourse, and overall sexual satisfaction.15 It aims to standardize terminology across studies on the prevalence of erectile dysfunction (ED) in various populations and countries.16 A simplified 5-item version of the IIEF (IIEF-5) has been developed for ease of use,11 proving to be specific, valid, and sensitive for clinical applications.17,18 The Turkish version of the IIEF-5 scale has demonstrated strong psychometric properties in a previous study.19

Statistical analyses

A pilot study involving 12 participants was conducted to perform a power analysis using G*Power software (version 3.01; Kiel University, Franz Faul, Germany). Based on the estimated effect size derived from the pilot data, the analysis indicated that a minimum sample size of 143 participants per group was required to achieve a statistical power of 95% (1−β = 0.95) with a Type I error rate of α = 0.05. Data from the pilot study were included in the final analysis. Statistical analyses were performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). The normality of data distribution was assessed with the Kolmogorov–Smirnov test. Descriptive statistics were computed for the study variables. Independent samples t-tests were used to compare the mean scores between the NOA and control groups for RSES, IIEF-5, BDI-II, and BAI. The Pearson correlation test assessed the relationships between the variables. Furthermore, a multivariate linear regression analysis was conducted to identify the independent predictors of depression (BDI-II) scores, considering azoospermia, age, body mass index (BMI), comorbidities, and smoking status as covariates. All statistical tests were two-sided, and a Type I error rate of α = 0.05 was considered statistically significant.

RESULTS

There were no significant differences in age, education level, smoking rates, chronic disease prevalence, past psychiatric history, or duration of infertility between the groups (Table 1).

Table 1.

Demographic characteristics of the participants

Demographic characteristic	Azoospermia group (n=134)	Control group (n=164)	P
Age (year), mean±s.d.	33.2±3.1	33.3±3.2	0.396
Education (year), mean±s.d.	12.5±4.1	12.4±3.9	0.152
Duration of infertility (month), mean±s.d.	21.7±6.3	NA	NA
Unemployment, n (%)	5 (3.7)	6 (3.7)	0.452
History of depression, n (%)	4 (3.0)	4 (2.4)	0.181
Smoking, n (%)	53 (39.6)	62 (37.8)	0.373
Chronic disease (DM, HT, and CHD), n (%)	18 (13.4)	26 (15.9)	0.244

NA: not applicable; s.d.: standard deviation; DM: diabetes mellitus; CHD: coronary heart disease; HT: hypertension

Table 2 compares the psychological well-being and sexual function of the two groups. The azoospermia group had significantly lower self-esteem, as indicated by higher RSES values (mean ± standard deviation [s.d.]: 2.8 ± 0.5 vs 1.8 ± 0.3, P < 0.001). Additionally, this group exhibited significantly greater depression scores compared to the controls (mean ± s.d.: 24.1 ± 6.3 vs 12.5 ± 5.1, P < 0.001), according to the BDI-II.

Table 2.

Self-esteem, depression, anxiety, and erectile function of participants

Assessment	Azoospermia group (n=134), mean±s.d.	Control group (n=164), mean±s.d.	P
RSES	2.8±0.5	1.8±0.3	<0.001
BDI-II	24.1±6.3	12.5±5.1	<0.001
BAI	17.3±3.9	9.8±2.8	<0.001
IIEF-5	17.2±5.1	21.4±5.2	<0.001

IIEF-5: International Index of Erectile Function-5; RSES: Rosenberg Self-Esteem Scale; BDI-II: Beck Depression Inventory-II; BAI: Beck Anxiety Inventory; s.d.: standard deviation

Anxiety levels, measured by the BAI, were also statistically higher in the azoospermia group (mean ± s.d.: 17.3 ± 3.9) than those in the control group (mean ± s.d.: 9.8 ± 2.8; P < 0.001). Furthermore, erectile function, assessed using the IIEF-5, was significantly lower in the azoospermia group (mean ± s.d.: 17.2 ± 5.1) compared to that in the control group (mean ± s.d.: 21.4 ± 5.2, P < 0.001).

Pearson correlation analyses revealed significant relationships among psychological variables and IIEF-5 scores. Self-esteem, as measured by the RSES, showed a strong positive correlation with BDI-II scores (r = 0.851, P < 0.05) and BAI scores (r = 0.843, P < 0.05), while it had a strong negative correlation with IIEF-5 scores (r = −0.845, P < 0.05). Depression scores were positively correlated with anxiety (r = 0.864, P < 0.05) and negatively correlated with erectile function (r = −0.867, P < 0.05). A similar negative correlation was found between anxiety and erectile function (r = −0.813, P < 0.05). In contrast, age and duration of infertility did not show significant correlations with any psychological or sexual function measures (all P > 0.05; Table 3).

Table 3.

Correlations among continuous variables

Variable	Age	DOI	RSES	BDI-II	BAI	IIEF-5
Age	1
DOI	−0.003	1
RSES	−0.082	0.007	1
BDI-II	−0.073	−0.012	0.851*	1
BAI	−0.076	−0.016	0.843*	0.864*	1
IIEF-5	0.071	0.021	−0.845*	−0.867*	−0.813*	1

^*Correlation is significant at the 0.05 level (two-tailed). DOI: duration of infertility; IIEF-5: International Index of Erectile Function-5; RSES: Rosenberg Self-Esteem Scale; BDI-II: Beck Depression Inventory-II; BAI: Beck Anxiety Inventory

To further investigate whether azoospermia independently predicted depressive symptoms, a multivariate linear regression analysis was conducted, adjusting for age, BMI, comorbidities, and smoking status. The results indicated that azoospermia significantly predicted higher depression scores (β = 3.25, P < 0.001). These data suggest that even after accounting for potential confounding factors, males with azoospermia reported significantly higher levels of depressive symptoms compared to fertile controls.

In addition, BMI (β = 0.15, P = 0.033) and the presence of comorbidities (β = 1.10, P = 0.028) were positively associated with BDI-II scores, while age (P = 0.063) and smoking status (P = 0.175) did not reach statistical significance. The regression model confirmed that azoospermia significantly contributes to the variance in depressive symptom scores, independent of demographic and health-related factors (Table 4).

Table 4.

Multivariate regression analysis of azoospermia as an independent predictor of depression scores (Beck Depression Inventory-II)

Predictor	Co-efficient ( β )	s.e.	P	95% CI	95% CI
Azoospermia	3.25	0.85	<0.001	1.58 to 4.92	1.58 to 4.92
Age	0.02	0.01	0.063	0 to 0.04	0 to 0.04
BMI	0.15	0.07	0.033	0.02 to 0.28	0.02 to 0.28
Comorbidities	1.10	0.50	0.028	0.12 to 2.08	0.12 to 2.08
Smoking status	0.75	0.55	0.175	-0.32 to 1.82	−0.32 to 1.82

BMI: body mass index; CI: confidence interval; s.e.: standard error

DISCUSSION

Azoospermia is the most severe form of male infertility and has various psychological effects beyond the inability to have children, including anxiety, depression, low self-esteem, and social stigma.20 This study demonstrates that azoospermia significantly impacts men’s psychological and sexual well-being. Compared to fertile men, those diagnosed with azoospermia exhibit higher levels of anxiety and depression, along with lower self-esteem and poorer erectile function.

Our findings align with previous literature, indicating that infertility in men is not only a biological issue but also a threat to masculine identity. Swierkowski-Blanchard et al.7 found that many infertile men associate sperm production with sexual adequacy and self-worth. Their participants expressed feelings of shame and inadequacy regarding their infertility, especially within romantic relationships. Men with NOA often experience shame, inadequacy, and psychosocial withdrawal. Similarly, a systematic review by Biggs et al.11 confirmed that male-factor infertility is linked to lower self-esteem, poorer quality of life, and increased symptoms of depression and anxiety, particularly when compared to fertile men. Like our study, they found a negative correlation between depression and anxiety levels and self-esteem.

In the multivariate regression analysis, azoospermia remained an independent factor associated with higher depression scores, even after adjusting for age, BMI, comorbidities, and smoking. This finding indicates that the psychological impact of azoospermia cannot be solely attributed to general health or demographic characteristics; it is intrinsically related to the condition itself. Therefore, regular psychological evaluation and early counseling should be considered the essential components of care for men diagnosed with azoospermia.

The broader literature supports the clinical significance of these observations. Fisher and Hammarberg,21 along with Wischmann and Thorn,8 highlighted that men often endure infertility challenges in silence due to stigma, societal expectations, and the perception that fertility is primarily a “women’s issue”. Consequently, men with infertility are at risk of unrecognized psychological issues, including depression, isolation, and sexual avoidance. Our study further confirmed this, revealing that participants with azoospermia consistently scored lower on all psychosocial measures compared to fertile men.

Consistent with earlier findings by Kızılay et al.,22 who identified a positive correlation between sperm parameters and erectile function, our results indicated a strong relationship between IIEF-5 and RSES scores, as well as poor self-esteem, depressive symptoms, and sexual dysfunction. Yıkılmaz et al.23 found that men with NOA often experience sexual function issues, particularly related to erection and orgasm. This underscores the close connection between sexual health and emotional well-being in infertile men. A systematic review of sexual dysfunction and infertility revealed that infertility adversely affects sexuality in both men and women.24 Male infertility not only impacts the individual but also significantly affects their partner. Kulaksız et al.25 found that women whose partners were diagnosed with male-factor infertility exhibited higher rates of depression, anxiety, and sexual dysfunction compared to fertile controls. However, these outcomes were more pronounced in women facing female-factor infertility. These findings, along with our results, reinforce the notion that infertility-related distress is shared between partners, and male infertility should not be considered in isolation. Bendayan et al.6 noted that unsuccessful TESE operations can negatively impact psychological and sexual health, while successful procedures can enhance self-esteem and relationship quality. In a similar vein, Akbal et al.26 found that unsuccessful TESE interventions adversely affect sexual function. Kocamanoglu et al.27 demonstrated that men with idiopathic NOA often experience more depressive symptoms than those with Klinefelter syndrome, despite the latter group facing more severe hormonal disruptions.

Zou et al.28 reported that family function and self-efficacy play mediating roles in anxiety and depression among infertility patients, suggesting that interpersonal relationships and cognitive strengths contribute to psychological resilience. Wu et al.29 noted that men undergoing infertility treatment frequently feel marginalized, which can lead to emotional detachment and the discontinuation of treatment. The European Society of Human Reproduction and Embryology (ESHRE) recommendations advocate for integrated psychosocial treatment within fertility services, emphasizing the importance of regular emotional assessments for both partners. However, men are often overlooked in therapeutic settings, despite this guidance. Our findings support this observation, revealing that participants with NOA exhibited significantly lower self-esteem and higher anxiety levels, indicating an unmet need in clinical practice.30 While we utilized validated Turkish versions of BAI, the RSES, the BDI-II, and the IIEF scales, cultural factors may have influenced how participants interpreted certain items. In Türkiye, fatherhood and fertility are closely linked to male identity, and infertility is often viewed as a personal or social failure. Aksoy Derya et al.31 found that infertile men frequently experience feelings of inadequacy, shame, and social stigma within this cultural context. These dynamics may help explain the heightened psychological distress observed in our samples. Collectively, these findings underscore the necessity for multidisciplinary and inclusive infertility care that addresses the psychological, relational, and identity-related aspects of male infertility.

The strengths of our study include a focus exclusively on azoospermia patients, creating a homogeneous group, and a substantial number of participants, along with a control group. Unlike the study by Topuz et al.,10 our research involved a larger sample size and included a comparison with a fertile control group. Additionally, we employed a variety of scales, allowing for a comprehensive comparison of psychological distress, self-esteem, and sexual function.10 It is crucial to note that all assessments were conducted prior to any testicular biopsy or infertility treatment, as invasive procedures may exacerbate psychological burdens. We intentionally conducted evaluations in the pre-intervention period to avoid confounding effects from such procedures.

Limitations

One limitation of this study is that participants completed the questionnaires independently, which may have led to misunderstandings or response bias. Another limitation is the lack of inclusion of partners’ emotional or psychological reactions, which could provide a more comprehensive understanding of infertility impact. Additionally, we did not differentiate between OA and NOA regarding psychological outcomes.

To isolate the psychological outcomes from the effects of medical procedures or treatments, all assessments were conducted during the pre-biopsy period, treating participants as a single ‘azoospermia’ group. This approach was necessary because the distinction between OA and NOA is typically confirmed only after advanced diagnostic procedures or interventions. Consequently, a systematic classification was not applied in this study. Men with OA and NOA may exhibit differences in hormonal profiles, clinical backgrounds, and emotional responses to infertility, which could have influenced the observed results. Although distinguishing these groups generally requires invasive diagnostic procedures, psychological outcomes may vary between them. Therefore, we were unable to assess potential differences between OA and NOA subgroups. Future studies that stratify participants based on azoospermia type could provide a more nuanced understanding of how these subgroups experience and cope with infertility-related stress. Longitudinal research is needed to explore how azoospermia impacts sexual and psychological functioning over time, particularly before and after diagnostic or therapeutic procedures. Couple-based studies that include both partners would also enrich our understanding of how infertility affects relationship dynamics and emotional well-being.

CONCLUSIONS

Infertility, particularly due to azoospermia, has a significant impact on men’s self-esteem, mental health, sexual life, and overall quality of life. The results of this study underscore the importance of a multidisciplinary approach that integrates emotional support into infertility treatment. Clinical care should encompass psychological screening, family counseling, and interventions aimed at enhancing self-efficacy and coping skills.

AUTHOR CONTRIBUTIONS

SYK, TT, DK, BA, and MY contributed to the conceptualization of the study. TT, BA, A Garayev, and EO developed the methodology. SYK and TT carried out the investigation. A Garayev, MOO, and MY performed the data curation. BA, DK, A Guzel, and EO conducted the formal analysis. SYK, TT, DK, RBD, EO, and IB wrote the original manuscript draft. SYK, TT, DK, IB, and MY performed the manuscript review and editing. TT, MB, SYK, RBD, and MY managed the project administration. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.