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This thesis explores the impact of immune-mediated inflammatory diseases, particularly inflammatory arthritis, on male sexual and reproductive health. Using a holistic approach, multiple studies were conducted to address critical clinical questions: How do immune-mediated inflammatory diseases and their pharmacological treatments affect male sexual and reproductive health outcomes? Is fertility impaired in males diagnosed with inflammatory arthritis? How does inflammatory arthritis impact male sexual health? Is methotrexate safe for men with immune-mediated diseases who wish to conceive? The chapters of this thesis delve into these questions, offering comprehensive insights into the intricate relationships between these diseases and male health. Through detailed analysis and rigorous research, this work sheds light on the often-overlooked aspects of male reproductive health in the context of inflammatory conditions. The findings underscore the importance of considering these factors in clinical practice to improve patient outcomes.

Objective European Alliance of Associations for Rheumatology (EULAR) task forces (TF) requires participation of ≥2 junior members, a health professional in rheumatology (HPR) and two patient research partners for the development of recommendations or points to consider. In this study, participation of these junior and representative members was compared with the one of traditional TF members (convenor, methodologist, fellow and expert TF members). Methods An online survey was developed and emailed to previous EULAR TF members. The survey comprised multiple-choice, open-ended and 0-100 rating scale (fully disagree to fully agree) questions. Results In total, 77 responded, 48 (62%) women. In total, 46 (60%) had participated as a junior or representative TF member. Most junior/representative members reported they felt unprepared for their first TF (10/14, 71%). Compared with traditional members, junior/representative members expressed a significantly higher level of uncertainty about their roles within the TF (median score 23 (IQR 7.0-52.0) vs 7 (IQR 0.0-21.0)), and junior/representative members felt less engaged by the convenor (54% vs 71%). Primary factors that facilitated interaction within a TF were experience, expertise and preparation (54%), a supportive atmosphere (42%) and a clear role (12%). Conclusion Juniors, patients and HPR experience various challenges when participating in a EULAR TF. These challenges differ from and are generally less pronounced than those experienced by traditional TF members. The convenor should introduce the participants to the tasks, emphasise the value of their contributions and how to prepare accordingly for the TF meeting.

Introduction Current scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS). Methods In a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods. Results In total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. Discussion Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.

Objectives The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems. Methods We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak). Results In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31-40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years. Conclusions This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.

Objectives Sexual health is defined as a state of physical, emotional, mental and social well-being in relation to sexuality. The impact of inflammatory arthritis (IA) on male sexual health has been mainly studied focusing on erectile function, one of the physical components of sexual health. Our objective was to describe the viewpoints among men with IA in the Netherlands on the overall impact of IA on their sexual health. Methods Q-methodology, a mixed methods approach to systematically study subjectivity was used. Adult men diagnosed with IA ranked 34 opinion statements about potential impacts of IA on their sexual health and were interviewed. By-person factor analysis was used to identify common patterns in the rankings, which were interpreted as viewpoints. Data from the interviews were used to verify and adjust the interpretations. Results 30 men (22-77 years) with IA were included. The analysis revealed three viewpoints. Men with the viewpoint â € Arthritis negatively affects my sexual health' experience a dramatic impact on all components of sexual health. In viewpoint â € I am keeping up appearances', IA negatively impacts sexual health but a distinguishing coping mechanism could mask a more serious negative impact. Men with the viewpoint â € I am satisfied with my sexual health'' experience no significant impact of IA on their sexual health. Conclusions We identified three viewpoints on the impact of IA on male sexual health, two revealed a negative influence that goes beyond the physical act of sex. IA can severely affect the emotional, mental and social components of sexual health.