Influence of <scp>TNF</scp>‐alpha inhibitors and fumaric acid esters on male fertility in psoriasis patients

Heppt, Franz; Colsman, Andreas; Maronna, Andreas; Uslu, Uğur; Heppt, Markus V.; Kiesewetter, F.; Sticherling, Michael

doi:10.1111/jdv.14364

Cited by 18 publications

(8 citation statements)

References 28 publications

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“…Regarding sperm quality before and after TNF-α inhibitor use, one small randomised control trial (RCT) that included data of 20 men concluded that certolizumab pegol had no adverse event on sperm quality compared to placebo ( Perrier d’Hauterive et al , 2012 ). In studies where a comparison between baseline samples before TNF-α inhibitor exposure and follow-up samples was available, no differences on sperm quality were reported in five studies ( Almeida et al , 2013 ; Micu et al , 2014 , 2019 ; Heppt et al , 2017 ; Grosen et al , 2019a ), while in three studies sperm quality improved after exposure ( Villiger et al , 2010 ; Ramonda et al , 2014 ; Pascarelli et al , 2017 ) and in one study sperm quality worsened after exposure ( Mahadevan et al , 2005 ). A possible positive effect on sperm quality using TNF-α inhibitors could be the result of decreasing disease activity in patients with AS.…”

Section: Discussionmentioning

confidence: 99%

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

Perez-Garcia

Dolhain

Vorstenbosch

et al. 2020

Human Reproduction Update

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BACKGROUND Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment. OBJECTIVE AND RATIONALE The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes. SEARCH METHODS A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data. OUTCOMES A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported. WIDER IMPLICATIONS Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.

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Section: Discussionmentioning

confidence: 99%

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

Perez-Garcia

Dolhain

Vorstenbosch

et al. 2020

Human Reproduction Update

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“…A cross‐sectional study reported a negative impact on sperm parameters, with increased testosterone and SHBG and reduced estrogen, alongside ultrasound evidence of prostatic inflammation in untreated psoriatic patients compared with control 12 . The other 8 studies investigated the effect of retinoid derivatives, 13‐15 MTX, 16‐19 and TNF inhibitors and fumaric acid derivatives 20 on semen quality. The retinoid derivative acitretin showed no effect on sperm parameters in psoriatic patients, 13,14 whereas etretinate and isotretinoin improved sperm motility and morphology, although total sperm count decreased 15 .…”

Section: Resultsmentioning

confidence: 99%

“…Pandhi et al reported the case of a 50‐year‐old man suffering of pustular psoriasis and under treatment with MTX, resulting to be oligoasthenozoospermic after 4 months of treatment 19 . TNF inhibitors (etanercept or adalimumab) showed no effect on semen parameters, whereas fumaric acid derivatives on semen quality reportedly improved genital tract inflammation and seminal PMN elastase in only 4 patients 20 . However, the baseline assessment showed that the semen quality was already compromised in psoriatic patients before starting the treatment, with only 14.8% normozoospermic and increased reporting of leukocytospermia 20 …”

Section: Resultsmentioning

confidence: 99%

The impact of autoimmune systemic inflammation and associated medications on male reproductive health in patients with chronic rheumatological, dermatological, and gastroenterological diseases: A systematic review

Finelli

Leisegang

Finocchi

et al. 2021

American J Rep Immunol

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Autoimmune disorders currently affect 5%‐8% of the global population, characterized by an aberrant chronic inflammatory response to self‐antigens. The aim of this study was to systematically review the current available evidence investigating the impact of systemic autoimmune diseases and associated immunosuppressive treatment on fertility parameters of adult men. Clinical trials, observational studies, and case reports written in English and reporting semen analysis, evaluation of seminal oxidative stress, and/or sperm DNA fragmentation in patients affected by psoriasis and psoriatic arthritis, celiac disease, inflammatory bowel diseases, systemic lupus erythematosus, ankylosing spondylitis, hidradenitis suppurativa, uveitis, dermatomyositis, and rheumatoid arthritis were collected by searching on PubMed, EMBASE, OVID, Scopus, and Cochrane Library databases, with no limit of time. The study quality and the extent of bias in design, methods, and outcome assessment were evaluated by applying the Joanna Briggs Institute Critical Appraisal tools. Evidence suggested that various autoimmune diseases or relevant medications can adversely affect male fertility parameters and that patients may benefit of counseling and sperm cryopreservation. Clinical trials further investigating any adverse effect of autoimmunity and related thereby on male infertility are warranted, to develop appropriate guidelines for males diagnosed and treated for autoimmune disorders.

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“…Oxidative stress has been shown to decrease spermatogenesis, sperm motility, and membrane integrity of testicular somatic cells [10,29]. Therefore, genital tract inflammation has been described as a significant comorbidity in psoriasis patients [30].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of sex hormone profiles and seminal fluid analysis in psoriatic patients and their correlation with psoriasis severity

Alzubi¹,

Seetan²,

Jarrar³

et al. 2021

J. Mens. Health

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Background and objective: Psoriasis is a chronic inﬂammatory skin condition characterized by thick silvery plaques, commonly involving the elbow, knees, lower back, and scalp. Psoriasis also affects the reproductive systems of patients. Males with untreated psoriasis are at risk of impaired fertility due to chronic systemic inﬂammation, which might affect the hormonal proﬁle and sexual accessory glands. In females, having psoriasis does not affect the chances of getting pregnant. This study aims to assess the effect of psoriasis, as a chronic inﬂammatory condition, on sex hormone proﬁles and seminal ﬂuid parameters. Methods: 87 male patients aged 18−50 with psoriasis who fulﬁlled the inclusion criteria were included in the study and matched with healthy controls. Demographic and clinical data, including age, severity, duration, and body mass index (BMI) were recorded. All patients underwent a complete physical exam, including a skin and andrological exam, in addition to ultrasound scrotum and seminal ﬂuid analysis. Blood sample tests were conducted for a complete hormonal proﬁle, including luteinizing hormone (LH), follicular stimulating hormone (FSH), testosterone, and estradiol. Results: The mean age of the case group was 39.5 ± 5.6 years, and the mean BMI was 24.0 ± 2.2. The mean duration of psoriasis was 6.5 ± 3.5 years. The mean levels of testosterone and LH of cases were lower than those of controls, whereas FSH and estradiol were abnormally higher among case groups. Sperm concentration, normal sperm motility, and normal sperm morphology were also found to be lower than in the case group. Age, psoriasis area, and severity index (PASI) scores were signiﬁcant predictors of sperm concentration (P = 0.000). The BMI was negatively correlated with sperm concentration (−0.249, P = 0.01), motility (−0.198, P = 0.05), and morphology (−0.205, P = 0.05). A negative correlation was found between the PASI score and sperm concentration (−0.519, P = 0.01). Conclusion: The evaluation of seminal ﬂuid analysis and hormone proﬁles among psoriasis patients showed marked variability. However, it was evident that the levels of sex hormones and seminal parameters were lower among patients with psoriasis than the healthy controls; this may indicate the possibility of developing sexual dysfunction and infertility among patients with untreated psoriasis. The level of estradiol was found to be abnormally high among psoriasis cases, which may account for a possible compensatory mechanism in ongoing sexual dysfunction among psoriasis patients.

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Influence of TNF‐alpha inhibitors and fumaric acid esters on male fertility in psoriasis patients

Cited by 18 publications

References 28 publications

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review

The impact of autoimmune systemic inflammation and associated medications on male reproductive health in patients with chronic rheumatological, dermatological, and gastroenterological diseases: A systematic review

Evaluation of sex hormone profiles and seminal fluid analysis in psoriatic patients and their correlation with psoriasis severity

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