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1
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Hutchison E, Eraifej N, Moss J, Rolls S, Wainman H. A guide to prescribing systemic treatments for psoriasis during pregnancy, breastfeeding and in those trying to conceive: what does the current evidence suggest? Clin Exp Dermatol 2024; 49:1316-1329. [PMID: 38769610 DOI: 10.1093/ced/llae209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 04/10/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024]
Abstract
Psoriasis is a common inflammatory skin condition with an estimated prevalence of 1.5% in the UK. Its management has evolved rapidly over the past 15 years as our understanding of its pathogenesis has progressed. Treatment initiation often overlaps with peak reproductive years, posing specific therapeutic challenges for individuals hoping to conceive. Certain systemic agents are well established to be teratogenic during pregnancy, such as methotrexate and acitretin, but data on newer drug classes for psoriasis remain limited. This literature review evaluated recent data on the systemic agents for psoriasis, explicitly considering the context of male and female fertility, pregnancy and breastfeeding. Our goal was to equip clinicians with an accessible, concise summary of up-to-date evidence to help them educate patients and facilitate informed, shared decision-making aligned with their reproductive health.
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Affiliation(s)
- Eliza Hutchison
- University Hospitals Bristol and Weston NHS Foundation Trust, UK
| | | | - Jake Moss
- Gloucestershire Hospitals NHS Foundation Trust, UK
| | - Sophie Rolls
- University Hospitals Bristol and Weston NHS Foundation Trust, UK
| | - Hannah Wainman
- University Hospitals Bristol and Weston NHS Foundation Trust, UK
- University of Bristol, Bristol, UK
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2
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Atas H, Yüksek T, Karakoyunlu AN, Kartal SP, Taş Aygar G. The impact of low-dose methotrexate on erectile dysfunction, sex hormone profile and spermiogram in male patients with psoriasis: a prospective study. Cutan Ocul Toxicol 2024; 43:161-166. [PMID: 38810266 DOI: 10.1080/15569527.2024.2360736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/18/2024] [Accepted: 05/23/2024] [Indexed: 05/31/2024]
Abstract
PURPOSE Psoriasis, affecting approximately 2% of the world's population, often necessitates systemic treatments, with methotrexate (MTX) as a cornerstone therapy. Despite documented systemic side effects of MTX, concerns about its impact on male reproductive health persist. We aim to investigate low-dose MTX effect on hormonal, cellular and functional ability of male reproductive system. MATERIALS AND METHODS Our prospective study on 40 male psoriasis patients receiving low-dose MTX (<15mg/week) comprehensively investigates its effects on erectile function, sex hormones, and spermiogram parameters. RESULTS After six months of MTX treatment, a significant decline in erectile function (p < 0.001) decreased total testosterone levels (p = 0.03) were observed. No significant reduction in sperm count was noted after six months of MTX treatment. CONCLUSIONS Our study highlights a significant decline in erectile function following low-dose MTX therapy, warranting further investigation into this potential side effect. While reassuring for sperm quantity and quality, the findings emphasise the necessity for larger cohorts and longer follow-up times to validate results and comprehend the complex interactions between MTX and male sexual health.
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Affiliation(s)
- Hatice Atas
- Department of Dermatology, Ankara Etlik City Hospital, Ankara, Turkey
| | - Tuğcan Yüksek
- Department of Dermatology, Kyrenia Dr. Akçiçek State Hospital, Kyrenia, Turkish Republic of Northern Cyprus
| | | | | | - Gamze Taş Aygar
- Department of Dermatology, Ankara Etlik City Hospital, Ankara, Turkey
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3
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Zarén P, Turesson C, Giwercman A. Methotrexate use among men-association with fertility and the perinatal health of their children: a Swedish nationwide register study. Fertil Steril 2023; 120:661-669. [PMID: 37395690 DOI: 10.1016/j.fertnstert.2023.05.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 04/28/2023] [Accepted: 05/03/2023] [Indexed: 07/04/2023]
Abstract
OBJECTIVE To study the effect of methotrexate on male fertility and subsequent effects on their children, for which data are scarce and contradictory. DESIGN Nationwide multiregister cohort study. SETTING Not applicable. SUBJECT(S) All children born alive in Sweden between 2006 and 2014 and their fathers. Three cohorts were defined: children to fathers with periconceptional methotrexate exposure (exposed cohort), children whose fathers stopped methotrexate intake ≥2 years before conception (previously exposed cohort), and children to fathers with no methotrexate exposure (control cohort). EXPOSURE(S) The father having at least one dispensed methotrexate prescription from pharmacies 0-3 months before conception, along with at least one more dispensed methotrexate prescription 0-12 months before conception (periconceptional exposure). Previously exposed cohort: the father having no dispensed methotrexate prescriptions in the 2 years before conception, but having at least two dispensed prescriptions before that. MAIN OUTCOME MEASURES Congenital anomalies (major and any; primary outcomes), preterm birth (PTB) and being small for gestational age (SGA; secondary outcomes), as well as need of intracytoplasmic sperm injection (ICSI) to achieve pregnancy (primary outcome in exposed cohort vs. controls, exploratory outcome in previously exposed cohort vs. controls). Outcomes were analyzed using logistic regression. RESULTS A total of 223 children to fathers with periconceptional methotrexate exposure were identified, along with 356 children whose fathers stopped methotrexate intake ≥2 years before conception and 809,706 not methotrexate-treated controls. In children with fathers periconceptionally exposed to methotrexate, the adjusted and unadjusted odds ratios (95% confidence intervals) for major congenital anomalies were 1.1 (0.4-2.6) and 1.1 (0.4-2.4), any congenital anomalies 1.3 (0.7-2.4) and 1.4 (0.7-2.3), PTB 1.0 (0.5-1.8) and 1.0 (0.5-1.8), SGA 1.1 (0.4-2.6) and 1.0 (0.4-2.2), and conception by use of ICSI 3.9 (2.2-7.1) and 4.6 (2.5-7.7). Use of ICSI was not increased among fathers who stopped methotrexate intake ≥2 years before conception, having adjusted and unadjusted odds ratios 0.9 (0.4-1.9) and 1.5 (0.6-2.9). CONCLUSION This study suggests that paternal periconceptional methotrexate use does not increase risk of congenital anomalies, PTB, or SGA in the offspring but may temporarily reduce fertility.
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Affiliation(s)
- Peter Zarén
- Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Reproductive Medicine Centre, Skåne University Hospital, Malmö, Sweden.
| | - Carl Turesson
- Rheumatology, Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Rheumatology, Skåne University Hospital, Malmö, Sweden
| | - Aleksander Giwercman
- Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Reproductive Medicine Centre, Skåne University Hospital, Malmö, Sweden
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4
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Neema S, Kothari R, Rout A, Mani S, Bhatt S, Sandhu S. Systemic treatment of psoriasis in special population. Indian J Dermatol Venereol Leprol 2023; 0:1-8. [PMID: 37317756 DOI: 10.25259/ijdvl_7_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/21/2023] [Indexed: 06/16/2023]
Abstract
Psoriasis is a common skin disorder affecting approximately 1% of the general population. The treatment of psoriasis depends on the body surface area involvement, quality of life impairment and associated co-morbidities. Special population comprising of pregnant women, lactating mothers, elderly individuals and children, is more vulnerable. They are not included in drug trials; rendering the data for use of systemic treatment scant and is mainly based on anecdotal evidence. In this narrative review, we discuss systemic treatment options in this special population. Though couples planning a family are not considered a special population, they form a subset that require special therapeutic consideration and have also been included in this review.
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Affiliation(s)
| | - Rohit Kothari
- Department of Dermatology, Command Hospital Air Force, Bengaluru, Karnataka, India
| | | | - Siddharth Mani
- Department of Dermatology, INHS Sanjivani Kochi, Kerala, India
| | - Siddharth Bhatt
- Department of Dermatology, INHS Asvini, Mumbai, Maharashtra, India
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5
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Boussaid S, Makhlouf Y, Rekik S, Jammali S, Cheour E, Sahli H, Elleuch M, Ben Saad H. The effects of autoimmune rheumatic-related diseases on male reproductive health: A systematic review. J Reprod Immunol 2022; 150:103472. [PMID: 34998078 DOI: 10.1016/j.jri.2021.103472] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 11/24/2021] [Accepted: 12/30/2021] [Indexed: 11/26/2022]
Abstract
Autoimmune rheumatic-related diseases (ARRDs) have physical and psychological impact on patients, including their sexual life. While many studies have investigated fertility problems in females, data on males-related fertility are scarce, which explains the lack of guidance. The main objective of this systematic review was to evaluate the reproductive health in males with ARRDs. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until September 16, 2021, and tackling the effects of ARRDs and/or ARRDs treatments on male fertility and/or pregnancy outcomes, were included. A total of twenty-five studies met the inclusion criteria. They were published between 1981 and 2018. The studied ARRDs were spondyloarthritis (n = 9), systematic lupus erythematosus (SLE, n = 6), Behcet disease (BD, n = 5), rheumatoid arthritis (RA, n = 5), antiphospholipid syndrome (n = 1), and dermatomyositis (n = 1). The most reported effects of ARRDs on fertility are i) high levels of reproductive hormones, mainly in RA and SLE; ii) impaired semen quality in SLE, spondyloarthritis, and BD; and iii) higher rate of varicocele in BD and spondyloarthritis. Regarding the treatments effects, i) conventional synthetic disease-modifying anti-rheumatic drugs (e.g.; methotrexate and salazopyrine) increase testosterone level, ii) cyclophosphamide impairs fertility, iii) anti-tumor necrosis factor agents are associated with improvement in semen quality, and iv) no increased number of miscarriages or congenital abnormalities in children fathered by BD was reported. To conclude, both ARRDs and their treatments alter fertility in males with ARRDs. In practice, in addition to the conventional semen analysis, screening for infertility seems legitimate in males with ARRDs.
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Affiliation(s)
- Soumaya Boussaid
- Rheumatology Department, Rabta Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia; Research Unit LR 05 SP 01, la Rabta Hospital, Tunisia.
| | - Yasmine Makhlouf
- Rheumatology Department, Rabta Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia.
| | - Sonia Rekik
- Rheumatology Department, Rabta Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia; Research Unit LR 05 SP 01, la Rabta Hospital, Tunisia.
| | - Samia Jammali
- Rheumatology Department, Rabta Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia; Research Unit LR 05 SP 01, la Rabta Hospital, Tunisia.
| | - Elhem Cheour
- Pain Treatment center, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia; Research Unit LR 05 SP 01, la Rabta Hospital, Tunisia.
| | - Hela Sahli
- Rheumatology Department, Rabta Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia; Research Unit LR 05 SP 01, la Rabta Hospital, Tunisia.
| | - Mohamed Elleuch
- Rheumatology Department, Rabta Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University Tunis el Manar, Tunis, Tunisia.
| | - Helmi Ben Saad
- Université de Sousse, Faculté de Médecine de Sousse, Service de Physiologie et Explorations Fonctionnelles, Sousse, Tunisie; Université de Sousse, Hôpital Farhat HACHED, Service de Physiologie et Explorations Fonctionnelles, Sousse, Tunisia; Université de Sousse, Hôpital Farhat HACHED, Laboratoire de recherche LR12SP09 «Insuffisance cardiaque», Sousse, Tunisia.
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6
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El Miedany Y, Palmer D. Rheumatology-led pregnancy clinic: men perspective. Clin Rheumatol 2021; 40:3067-3077. [PMID: 33449229 PMCID: PMC8289755 DOI: 10.1007/s10067-020-05551-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 12/12/2020] [Accepted: 12/14/2020] [Indexed: 10/26/2022]
Abstract
The birth of reproductive rheumatology as a subject of interest in rheumatology has led to improvement of clinical care for patients living with autoimmune rheumatic diseases and paved the way towards setting a specialized pregnancy service within the standard rheumatology practice. In contrast to women, where there has been wealth of literature regarding pregnancy, lactation, and birth outcomes, there is not as much focusing on male sexual health and outcomes among inflammatory arthritis patients. Challenges such as decrease ability to conceive, impaired fertility, erectile dysfunction, and other sexual problems have been raised by male patients living with autoimmune rheumatic diseases. This broad scope gives the reproductive health concept in men another expansion with views to include sexual health problems screening among men attending the standard outpatient rheumatology clinics. This article adds to the paucity of real-life experience and aims at discussing the sexual health from the men perspective and provides a practical approach towards screening, and assessment of men living with autoimmune diseases in standard day to day practice.
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Affiliation(s)
| | - Deborah Palmer
- Rheumatology Department, North Middlesex University Hospital, London, England
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7
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Perez-Garcia LF, Dolhain RJEM, Vorstenbosch S, Bramer W, van Puijenbroek E, Hazes JMW, Te Winkel B. The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review. Hum Reprod Update 2021; 26:961-1001. [PMID: 32743663 PMCID: PMC7600290 DOI: 10.1093/humupd/dmaa022] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/17/2020] [Accepted: 05/01/2020] [Indexed: 12/11/2022] Open
Abstract
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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Affiliation(s)
- L F Perez-Garcia
- Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - R J E M Dolhain
- Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - S Vorstenbosch
- Netherlands Pharmacovigilance Centre Lareb, 5237 MH 's-Hertogenbosch, The Netherlands
| | - W Bramer
- Medical Library, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - E van Puijenbroek
- Netherlands Pharmacovigilance Centre Lareb, 5237 MH 's-Hertogenbosch, The Netherlands.,Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology and Economics, University of Groningen, 9712 CP Groningen, The Netherlands
| | - J M W Hazes
- Department of Rheumatology, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands
| | - B Te Winkel
- Netherlands Pharmacovigilance Centre Lareb, 5237 MH 's-Hertogenbosch, The Netherlands
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8
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Jensen NB, Justesen SD, Larsen A, Ernst E, Pedersen LH. A systematic overview of the spermatotoxic and genotoxic effects of methotrexate, ganciclovir and mycophenolate mofetil. Acta Obstet Gynecol Scand 2021; 100:1557-1580. [PMID: 33755191 DOI: 10.1111/aogs.14151] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 02/23/2021] [Accepted: 03/14/2021] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants. MATERIAL AND METHODS The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies. RESULTS A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded. CONCLUSIONS Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.
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Affiliation(s)
| | | | - Agnete Larsen
- Department of Biomedicine, Aarhus University, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Erik Ernst
- Department of Biomedicine, Aarhus University, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Laboratory for Reproduction, Institute of Anatomy, Aarhus University, Aarhus, Denmark
| | - Lars H Pedersen
- Department of Biomedicine, Aarhus University, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
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9
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Nast A, Smith C, Spuls P, Avila Valle G, Bata‐Csörgö Z, Boonen H, De Jong E, Garcia‐Doval I, Gisondi P, Kaur‐Knudsen D, Mahil S, Mälkönen T, Maul J, Mburu S, Mrowietz U, Reich K, Remenyik E, Rønholt K, Sator P, Schmitt‐Egenolf M, Sikora M, Strömer K, Sundnes O, Trigos D, Van Der Kraaij G, Yawalkar N, Dressler C. EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – Part 2: specific clinical and comorbid situations. J Eur Acad Dermatol Venereol 2021; 35:281-317. [DOI: 10.1111/jdv.16926] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022]
Affiliation(s)
- A. Nast
- Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Department of Dermatology, Venereology and Allergology Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
| | - C. Smith
- St John’s Institute of Dermatology London UK
| | - P.I. Spuls
- Academic Medical Centre Amsterdam Amsterdam Netherlands
| | - G. Avila Valle
- Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Department of Dermatology, Venereology and Allergology Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
| | | | - H. Boonen
- Office‐Based Dermatology Practice Geel Belgium
| | - E. De Jong
- Radboud University Medical Centre Nijmegen Nijmegen Netherlands
| | - I. Garcia‐Doval
- Unidad de Investigación. Fundación Piel Sana AEDV Madrid Spain
| | | | | | - S. Mahil
- Guy's and St Thomas' NHS Foundation Trust London UK
| | - T. Mälkönen
- Helsinki University Central Hospital Helsinki Finland
| | - J.T. Maul
- Department of Dermatology University Hospital of Zürich Zürich Switzerland
| | - S. Mburu
- International Federation of Psoriasis Associations (IFPA)
| | - U. Mrowietz
- Universitätsklinikum Schleswig‐Holstein Kiel Germany
| | - K. Reich
- Translational Research in Inflammatory Skin Diseases Institute for Health Services Research in Dermatology and Nursing University Medical Center Hamburg‐Eppendorf Hamburg Germany
| | | | | | - P.G. Sator
- Municipal Hospital Hietzing Vienna Austria
| | - M. Schmitt‐Egenolf
- Dermatology Department of Public Health & Clinical Medicine Umeå University Umeå Sweden
| | - M. Sikora
- Department of Dermatology Medical University of Warsaw Warsaw Poland
| | - K. Strömer
- Office‐Based Dermatology Practice Mönchengladbach Germany
| | | | - D. Trigos
- International Federation of Psoriasis Associations (IFPA)
| | | | - N. Yawalkar
- Department of Dermatology, Inselspital Bern University HospitalUniversity of Bern Bern Switzerland
| | - C. Dressler
- Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Department of Dermatology, Venereology and Allergology Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany
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10
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Finelli R, Leisegang K, Finocchi F, De Masi S, Agarwal A, Damiani G. 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. Am J Reprod Immunol 2021; 85:e13389. [PMID: 33420722 DOI: 10.1111/aji.13389] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/04/2021] [Indexed: 01/13/2023] Open
Abstract
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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Affiliation(s)
- Renata Finelli
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Kristian Leisegang
- School of Natural Medicine, University of the Western Cape, Cape Town, South Africa
| | - Federica Finocchi
- Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy
| | | | - Ashok Agarwal
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Giovanni Damiani
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.,Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
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11
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Anton C, Ciobica A, Doroftei B, Maftei R, Ilea C, Darii Plopa N, Bolota M, Anton E. A Review of the Complex Relationship between Irritable Bowel Syndrome and Infertility. ACTA ACUST UNITED AC 2020; 56:medicina56110592. [PMID: 33172048 PMCID: PMC7694637 DOI: 10.3390/medicina56110592] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/04/2020] [Accepted: 11/04/2020] [Indexed: 11/16/2022]
Abstract
Irritable bowel syndrome (IBS) is a gastrointestinal disease that negatively affects up to 20% of the population. Infertility is defined as a disorder of the reproductive system described by lack of success in achieving pregnancy after more than a year of regular unprotected sexual intercourse. The main purpose of our review was to analyze the available literature regarding the IBS-infertility connection. Another secondary purpose of the present paper was to find out if oxidative stress may be the missing puzzle that may explain this possible correlation. After analyzing the available literature we concluded that oxidative stress is a plausible mediator of the connection between both female and male fertility and IBS. However, the data lacks in direct evidence to confirm this hypothesis. Nevertheless, it is recommended that certain levels of oxidative stress should not be exceeded in order to decrease IBS symptoms and increase the odds of conception given that generation of reactive oxygen species (ROS) is an aftermath of metabolically active cells. Therefore, reducing the oxidative stress by living a healthier lifestyle with a balanced diet, rich in micronutrients, limited in caffeine and alcohol, avoiding smoking and maintaining a normal body mass index with regular physical exercise may promote fertility and help diminishing IBS symptomatology. Studies with measurements of biological samples are needed in order to assess the complex relationship between oxidative stress, IBS and infertility.
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Affiliation(s)
- Carmen Anton
- Department of Gastroenterology, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 6th University Street, 700490 Iasi, Romania;
| | - Alin Ciobica
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700490 Iasi, Romania
- Department Center of Biomedical Research, Romanian Academy, Iasi Branch, Nr. 8, Carol I Avenue, No. 8, 700490 Iasi, Romania
- Department of Biology, Academy of Romanian Scientists, Splaiul Independentei Nr. 54, Sector 5, 050094 Bucuresti, Romania
- Correspondence:
| | - Bogdan Doroftei
- Department of Obstetrics and Gynecology, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 6th University Street, 700490 Iasi, Romania; (B.D.); (C.I.); (E.A.)
| | - Radu Maftei
- Clinical Department, Origyn Fertility Center, Palace Street, No 3C, 700032 Iasi, Romania;
| | - Ciprian Ilea
- Department of Obstetrics and Gynecology, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 6th University Street, 700490 Iasi, Romania; (B.D.); (C.I.); (E.A.)
| | - Natalia Darii Plopa
- Department of of Obstetrics and Gynecology, Grand Hôpital De Charleroi, Avenue du Centenaries 73, 6061 Charleroi, Belgium;
| | - Maria Bolota
- Department of Obstetrics and Gynecology, Spitalul Clinic de Obstetrică și Ginecologie Cuza Vodă, 700032 Iasi, Romania;
| | - Emil Anton
- Department of Obstetrics and Gynecology, Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 6th University Street, 700490 Iasi, Romania; (B.D.); (C.I.); (E.A.)
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Yu B, Darves-Bornoz AL, Brannigan RE, Halpern JA. Acute anejaculation, hypogonadism, and fertility preservation in the setting of neurosarcoidosis: case report and literature review. F S Rep 2020; 1:317-325. [PMID: 34223263 PMCID: PMC8244293 DOI: 10.1016/j.xfre.2020.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 09/23/2020] [Accepted: 09/26/2020] [Indexed: 11/26/2022] Open
Abstract
Objective To examine fertility preservation techniques in the setting of neurosarcoidosis, and to review the impact of corticosteroid and methotrexate therapy on fertility. Design Case report of a patient with infertility secondary to anejaculation associated with spinal neurosarcoidosis, treated with systemic corticosteroids and methotrexate. Setting Academic tertiary-care hospital. Patient(s) A 39-year-old man presented with neurosarcoidosis complicated by acute anejaculation, erectile dysfunction, and hypogonadism. He underwent fertility consultation and sperm cryopreservation before initiating methotrexate therapy. His pretreatment total testosterone was low, at 157 ng/dL. Intervention(s) Unsuccessful pharmacologic therapy and penile vibratory stimulation (PVS) were followed by microdissection testicular sperm extraction (microTESE). Clomiphene was administered for optimization of spermatogenesis before microTESE. Main Outcome Measure(s) Vials of cryopreserved sperm, testis histopathology, and serum testosterone levels. Result(s) Eight vials of viable sperm were harvested by means of micro-TESE and cryopreserved. Despite intraoperative appearance of hypospermatogenesis, 90% of seminiferous tubules had active germ cell sloughing. Total testosterone increased to 278 ng/dL 2 months after initiating clomiphene. Conclusion(s) Conventional fertility preservation techniques may be effective in the setting of neurosarcoidosis-induced infertility owing to largely intact spermatogenesis. PVS, though not effective for this patient, should be considered along with electroejaculation, given high success rates in other patients with neurogenic anejaculation. Corticosteroid-mediated hypogonadism also must be considered in these patients, because it can negatively affect downstream spermatogenesis. In addition, evidence for the impact of paternal methotrexate exposure on fertility is limited and requires further investigation. As such, fertility consultation before initiating methotrexate is highly recommended.
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Affiliation(s)
- Benjamin Yu
- Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Anne L Darves-Bornoz
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Robert E Brannigan
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Joshua A Halpern
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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13
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Perez-Garcia LF, Dolhain R, Te Winkel B, Carrizales JP, Bramer WM, Vorstenbosch S, van Puijenbroek E, Hazes M, van Doorn MBA. Male Sexual Health and Reproduction in Cutaneous Immune-Mediated Diseases: A Systematic Review. Sex Med Rev 2020; 9:423-433. [PMID: 32883623 DOI: 10.1016/j.sxmr.2020.07.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/13/2020] [Accepted: 07/17/2020] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Information about the possible effects of cutaneous immune-mediated diseases (cIMDs) on male sexual function and reproduction is scarce. Factors known to impair sexual health and reproduction, such as inflammation, medication use, and hypogonadism, can be present in a significant proportion of male patients with cIMD. OBJECTIVES To systematically review the literature for the influence of paternal cIMD on many aspects of male sexual and reproductive health, such as sexual function, reproductive hormones, fertility, and pregnancy and offspring outcomes. METHODS A systematic literature search was performed. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes, and offspring's health with a list of cIMDs. RESULTS The majority of the identified studies included patients with psoriasis (22 of 27), and sexual function was the most common outcome of interest (20 of 27). For patients diagnosed with psoriasis, the prevalence of male sexual dysfunction reported in these studies ranged from 34 to 81%. Hypogonadism in patients with psoriasis was reported in 2 of 3 studies. Sperm analysis abnormalities in patients with psoriasis were reported in 3 of 4 studies. No information about the effect of paternal disease on pregnancy and offspring outcomes was identified. CONCLUSIONS Disease activity in psoriasis might play an important role in the development of sexual dysfunction, hypogonadism, and abnormal sperm quality. For the other cIMD included in this review, there is insufficient information regarding male sexual and reproductive health to draw firm conclusions. More research is needed to understand the association between cIMD and impaired male sexual and reproductive health. Perez-Garcia LF, Dolhain R, te Winkel B, et al. Male Sexual Health and Reproduction in Cutaneous Immune-Mediated Diseases: A Systematic Review. Sex Med Rev 2021;9:423-433.
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Affiliation(s)
- Luis F Perez-Garcia
- Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Radboud Dolhain
- Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Bernke Te Winkel
- Netherlands Pharmacovigilance Centre Lareb, 's-Hertogenbosch, the Netherlands
| | - Juan P Carrizales
- Servicio de Reumatología, Universidad Autónoma de Nuevo León, Hospital Universitario, Monterrey, Mexico
| | - Wichor M Bramer
- Medical Library, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Saskia Vorstenbosch
- Netherlands Pharmacovigilance Centre Lareb, 's-Hertogenbosch, the Netherlands
| | - Eugene van Puijenbroek
- Netherlands Pharmacovigilance Centre Lareb, 's-Hertogenbosch, the Netherlands; Research Institute of Pharmacy, PharmacoTherapy, Epidemiology and Economics, University of Groningen, Groningen, the Netherlands
| | - Mieke Hazes
- Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Martijn B A van Doorn
- Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
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14
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Cacciapuoti S, Scala E, Megna M, Gallo L, Fontanella G, Ruggiero A, Savastano S, Fabbrocini G. Impact of current antipsoriatic systemic treatments on male and female fertility: what endocrinologists need to know. Minerva Endocrinol (Torino) 2020; 46:350-362. [PMID: 32720503 DOI: 10.23736/s2724-6507.20.03236-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Fertility is a function of the body that is often overlooked as a site for the expression of the side effects of certain drugs. With the approval of new drugs with a totally innovative mechanism of action, the risk assessment on fertility both in male and female is more difficult. This is particularly true in psoriasis, an invalidating inflammatory skin disease. The estimated prevalence of psoriasis in adults ranged from 0.51% to 11.43%, and in children from 0% to 1.37%, with frequent diagnosis in young patients of childbearing age. With the increasing use of new, predominantly immunosuppressive or biologic drugs for psoriasis, questions frequently arise in clinical practice as to their safety in men and women wishing to procreate. Both psoriatic patients and their physicians are concerned about adverse effects of the disease and its treatment on their future fertility, causing additional concerns in the therapeutic management of these patients. Among antipsoriatic drugs, conventional therapies are mainly involved in the onset of infertility in both sexes, exerting in some cases toxic effects against reproductive organs. Conversely, biologic agents appear to improve male and female fertility especially when gonadal impairment is related to inflammatory phenomena. There is a lack of review articles of commonly used medications in psoriasis with respect to their potential effects on fertility. The aim of this paper was to provide a practical guide for both dermatologist and endocrinologist in therapeutic management of psoriatic patients of childbearing age, considering the impact of prescribed drugs on their current and future fertility.
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Affiliation(s)
- Sara Cacciapuoti
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy -
| | - Emanuele Scala
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Matteo Megna
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Lucia Gallo
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Giuseppina Fontanella
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Angelo Ruggiero
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Silvia Savastano
- Unit of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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15
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Bermas BL. Paternal safety of anti-rheumatic medications. Best Pract Res Clin Obstet Gynaecol 2020; 64:77-84. [DOI: 10.1016/j.bpobgyn.2019.09.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 09/12/2019] [Indexed: 12/18/2022]
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16
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Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence. Semin Arthritis Rheum 2019; 48:911-920. [DOI: 10.1016/j.semarthrit.2018.07.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/18/2018] [Accepted: 07/23/2018] [Indexed: 12/31/2022]
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17
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Park YE, Kim TO. Sexual Dysfunction and Fertility Problems in Men with Inflammatory Bowel Disease. World J Mens Health 2019; 38:285-297. [PMID: 30929327 PMCID: PMC7308231 DOI: 10.5534/wjmh.190007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 01/29/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is usually diagnosed in young individuals. Crohn's disease and ulcerative colitis are the 2 principal forms of IBD. Patients with IBD demonstrate varying degrees of disease activity and sometimes need to undergo bowel surgery such as proctocolectomy with ileal pouch-anal anastomosis that involves removal of the entire colon and rectum with consequent sexual dysfunction. Several studies have shown that sulfasalazine, affects male fertility. Additionally, many men with IBD are unable to control their smoking, drinking, and eating habits, which can cause worsening of disease activity and fertility. Therefore, infertility and sexual dysfunction are important issues in young patients diagnosed with IBD because they are related to optimal management of the disease and patients' quality of life. Only a few studies have reported sexual dysfunction and infertility in men with IBD. Therefore, this study reviewed the current literature describing male sexual dysfunction scales and evaluated the causes of sexual dysfunction and infertility in men with IBD.
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Affiliation(s)
- Yong Eun Park
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
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18
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Kumar P, Das A, Lal NR, Jain S, Ghosh A. Safety of important dermatological drugs (retinoids, immune suppressants, anti androgens and thalidomide) in reproductively active males with respect to pregnancy outcome: A brief review of literature. Indian J Dermatol Venereol Leprol 2018; 84:539-546. [PMID: 29998864 DOI: 10.4103/ijdvl.ijdvl_77_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Paternally transmitted damage to offspring is recognized as a complex issue. Each parent contributes 23 chromosomes to a child; hence, it is necessary to know the effects of both maternal and paternal pre-and peri-conceptional exposure to drugs on pregnancy outcome. While there are many studies on the effects of maternal drug exposure on pregnancy outcome, literature on paternal exposure is scarce. Of late however, paternal exposure has been receiving increasing attention. We present a brief review on the safety of commonly used drugs in dermatology, focused on retinoids, immune suppressants, anti androgens and thalidomide.
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Affiliation(s)
- Piyush Kumar
- Department of Dermatology, Katihar Medical College, Katihar, Bihar, India
| | - Anupam Das
- Department of Dermatology, KPC Medical College and Hospital, Kolkata, West Bengal, India
| | - Niharika Ranjan Lal
- Department of Dermatology, ESI-PGIMSR and ESIC Medical College, Kolkata, West Bengal, India
| | - Sourabh Jain
- Department of Dermatology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Anupama Ghosh
- Department of Dermatology, CGHS, Kolkata, West Bengal, India
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19
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Abstract
Male fertility can be impaired by a multitude of factors. In addition to environmental and life style factors, such as stress, noise, smoking and overweight, diverse diseases can also have a negative effect on the ability to father a child and the hormone balance, particularly the testosterone level. In many diseases the currently available data do not go beyond observations of limited fertility. In this article the focus is on diseases in the treatment field of dermatology. Special attention is paid to chronic inflammatory and autoimmune skin diseases. Data from recent years show that the excessive inflammatory reaction that these diseases have in common, most probably also has an influence on fertility and interacts with the testosterone concentration in serum. In addition, the impact of hereditary skin diseases on male fertility is discussed, which can have a direct influence on the ability to father a child due to disruption of the hypothalamus-pituitary-gonad axis.
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Affiliation(s)
- William Grobe
- Klinik und Poliklinik für Dermatologie und Allergologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Deutschland
| | - Jean-Pierre Allam
- Klinik und Poliklinik für Dermatologie und Allergologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Deutschland
| | - Gerhard Haidl
- Klinik und Poliklinik für Dermatologie und Allergologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Deutschland.
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20
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Zakhem GA, Motosko CC, Mu EW, Ho RS. Infertility and teratogenicity after paternal exposure to systemic dermatologic medications: A systematic review. J Am Acad Dermatol 2018; 80:957-969. [PMID: 30287313 DOI: 10.1016/j.jaad.2018.09.031] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 09/12/2018] [Accepted: 09/16/2018] [Indexed: 11/25/2022]
Abstract
BACKGROUND This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark. OBJECTIVE To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men. METHODS Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure. RESULTS A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications. LIMITATIONS We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects. CONCLUSIONS Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better-quality studies are required in this area, particularly studies assessing potential teratogenicity.
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Affiliation(s)
- George A Zakhem
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
| | - Catherine C Motosko
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
| | - Euphemia W Mu
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York; Department of Dermatologic Surgery, Mount Sinai Beth Israel, New York, New York
| | - Roger S Ho
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York.
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Abstract
Infertility affects up to 12% of all men, and sexual dysfunction occurs frequently in men of reproductive age, causing infertility in some instances. In infertile men, hypoactive sexual desire and lack of sexual satisfaction are the most prevalent types of sexual dysfunction, ranging from 8.9% to 68.7%. Erectile dysfunction and/or premature ejaculation, evaluated with validated tools, have a prevalence of one in six infertile men, and orgasmic dysfunction has a prevalence of one in ten infertile men. In addition, infertile men can experience a heavy psychological burden. Infertility and its associated psychological concerns can underlie sexual dysfunction. Furthermore, general health perturbations can lead to male infertility and/or sexual dysfunction. Erectile dysfunction and male infertility are considered proxies for general health, the former underlying cardiovascular disorders and the latter cancerous and noncancerous conditions. The concept that erectile dysfunction in infertile men might be an early marker of poor general health is emerging. Finally, medications used for general health problems can cause sperm abnormalities and sexual dysfunction. The treatment of some causes of male infertility might improve semen quality and reverse infertility-related sexual dysfunction. In infertile men, an investigation of sexual, general, and psychological health status is advisable to improve reproductive problems and general health.
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Affiliation(s)
- Francesco Lotti
- Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
| | - Mario Maggi
- Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
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22
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Ding J, Shang X, Zhang Z, Jing H, Shao J, Fei Q, Rayburn ER, Li H. FDA-approved medications that impair human spermatogenesis. Oncotarget 2018; 8:10714-10725. [PMID: 27801671 PMCID: PMC5354694 DOI: 10.18632/oncotarget.12956] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 10/17/2016] [Indexed: 01/14/2023] Open
Abstract
We herein provide an overview of the single-ingredient U.S. Food and Drug Administration (FDA)-approved drugs that affect human spermatogenesis, potentially resulting in a negative impact on male fertility. To provide this information, we performed an in-depth search of DailyMed, the official website for FDA-approved drug labels. Not surprisingly, hormone-based agents were found to be the drugs most likely to affect human spermatogenesis. The next category of drugs most likely to have effects on spermatogenesis was the antineoplastic agents. Interestingly, the DailyMed labels indicated that several anti-inflammatory drugs affect spermatogenesis, which is not supported by the peer-reviewed literature. Overall, there were a total of 65 labels for drugs of various classes that showed that they have the potential to affect human sperm production and maturation. We identified several drugs indicated to be spermatotoxic in the drug labels that were not reported in the peer-reviewed literature. However, the details about the effects of these drugs on human spermatogenesis are largely lacking, the mechanisms are often unknown, and the clinical impact of many of the findings is currently unclear. Therefore, additional work is needed at both the basic research level and during clinical trials and post-marketing surveillance to fill the gaps in the current knowledge. The present findings will be of interest to physicians and pharmacists, researchers, and those involved in drug development and health care policy.
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Affiliation(s)
- Jiayi Ding
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Xuejun Shang
- Department of Andrology, Jinling Hospital/Nanjing General Hospital Affiliated with Nanjing University School of Medicine, Nanjing, China
| | - Zhanhu Zhang
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Hua Jing
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Jun Shao
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | - Qianqian Fei
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
| | | | - Haibo Li
- Department of Reproductive Medicine, Nantong Maternity and Child Health Hospital, Nantong, China
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Rademaker M, Agnew K, Andrews M, Armour K, Baker C, Foley P, Frew J, Gebauer K, Gupta M, Kennedy D, Marshman G, Sullivan J. Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration. Australas J Dermatol 2017; 59:86-100. [PMID: 28543445 DOI: 10.1111/ajd.12641] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 01/28/2017] [Indexed: 12/20/2022]
Abstract
The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.
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Affiliation(s)
- Marius Rademaker
- Department of Dermatology, Waikato Clinical Campus, Auckland Medical School, Auckland, New Zealand
| | - Karen Agnew
- Department of Dermatology, Greenlane Clinical Centre, Auckland, New Zealand.,Starship Children's Hospital, Auckland, New Zealand
| | - Megan Andrews
- The Skin and Cancer Foundation of Victoria, Melbourne, Victoria, Australia
| | - Katherine Armour
- The Skin and Cancer Foundation of Victoria, Melbourne, Victoria, Australia
| | - Chris Baker
- Department of Medicine (Dermatology), University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia.,University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Peter Foley
- Department of Medicine (Dermatology), University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia.,University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - John Frew
- Department of Dermatology, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - Kurt Gebauer
- Department of Dermatology, University of Western Australia, Freemantle, Western Australia, Australia
| | - Monisha Gupta
- Department of Dermatology, Liverpool Hospital, Skin Hospital, Sydney, New South Wales, Australia.,University of New South Wales, Sydney, New South Wales, Australia
| | - Debra Kennedy
- Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Gillian Marshman
- Flinders Medical Centre and Repatriation General Hospital, Adelaide, South Australia, Australia
| | - John Sullivan
- Holdsworth House Medical Practice, Sydney, New South Wales, Australia
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The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure. Inflamm Bowel Dis 2017; 23:561-569. [PMID: 28267049 DOI: 10.1097/mib.0000000000001064] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. METHODS A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. RESULTS In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. CONCLUSIONS This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.
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Immunosuppressants and Male Reproduction. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1034:179-210. [PMID: 29256132 DOI: 10.1007/978-3-319-69535-8_12] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Prolonged use of immunosuppressant medications is occasionally seen in infertile men with chronic inflammatory conditions; autoimmune disorders; or an organ or hematopoietic stem cell transplant. Chronic inflammation impacts negatively on male reproductive endpoints, so immunosuppressant therapy can produce improvements. Corticosteroids have been used to treat antisperm antibodies and even as an empirical treatment for male infertility in general. Trials of these methods have provided mixed results on semen quality and fertility, with improvement, no change and negative effects reported by different investigators. In a substantial number of observational studies, patients on long-term therapy with prednisone for chronic inflammatory disease, testosterone levels were lower compared to untreated controls, though randomized controlled trials have not been conducted. Similarly decreases in testosterone have been reported in men receiving corticosteroids to minimize transplant rejection; however, most were treated with multiple immunosuppressive medications that may have contributed to this effect. A large number of trials of healthy men treated with corticosteroids have shown some disruption in reproductive hormone levels, but other studies reported no effect. Studies in monkeys, rats (at human equivalent dose), cattle, sheep, and horses have shown endocrine disruption, including low testosterone with dexamethasone treatment. Of the cytostatic immunosuppressives, which have high potential for cellular damage, cyclophosphamide has received the most attention, sometimes lowering sperm counts significantly. Methotrexate may decrease sperm numbers in humans and has significant negative impacts in rodents. Other chemotherapeutic drugs used as immunosuppressants are likely to impact negatively on male fertility endpoints, but few data have been collected. The TNF-α Inhibitors have also received little experimental attention. There is some evidence that the immunophilin modulators: cyclosporine, sirolimus, and everolimus cause endocrine disruption and semen quality impairment. As we review in this chapter, results in experimental species are concerning, and well-designed studies are lacking for the effects of these medications on reproductive endpoints in men.
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Gutierrez JC, Hwang K. The toxicity of methotrexate in male fertility and paternal teratogenicity. Expert Opin Drug Metab Toxicol 2016; 13:51-58. [PMID: 27590039 DOI: 10.1080/17425255.2017.1230198] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION There is a high prevalence of methotrexate (MTX) use in males of reproductive age. The scope of this paper reviews what is known regarding risks to fertility and partners' pregnancy outcomes with regard to MTX use in men. Areas covered: This paper reviews the evidence for current recommendations for MTX use and male fertility and aims to educate professionals regarding MTX use in reproducing males so that patients may be counseled appropriately. A literature search included peer-reviewed sources from PubMed searches and the literature referenced within. Expert opinion: There is a lack of evidence regarding effects of MTX on male fertility. The recommendation to stop MTX three months prior to conception is safe, but is not evidenced by an understanding of the impact of MTX on spermatogenesis or paternal-mediated teratogenicity but rather the timeframe of spermatogenesis. Given the unclear evidence, patients treated with MTX must be counseled on the likelihood of adverse effects of MTX and role of sperm cryopreservation. Future studies are needed to help elucidate the unclear evidence of MTX effects on male fertility and pregnancy outcomes.
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Affiliation(s)
| | - Kathleen Hwang
- b Division of Urology , Rhode Island Hospital , Providence , Rhode Island , USA
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Abstract
Male fertility can be affected by a variety of organs diseases, including the skin. Several genodermatoses affect the skin and several other organs including the male reproductive system, commonly in the form of cryptorchidism and hypogonadism. The most relevant syndromes are associated with dyschromias, such as deSanctis-Cacchione, poikiloderma congenital, LEOPARD, and H syndrome; others with ichthyosis, such as Rud, and trichothiodystrophy; or a group of unrelated genodermatoses, such as ablepharon macrostomia, Coffin-Siris, Gorlin-Goltz, and Werner. Acquired skin diseases may also affect male fertility usually in the form of orchitis or epididymal obstruction or androgen antagonists. These include infections (leprosy and HIV), autoimmune (erythema nodosum leprosum), granulomatous (sarcoidosis, Langerhans cell histiocytosis), nutritional deficiency (zinc), and malignancy. Several therapeutics of skin diseases are notorious for their effects on male fertility, most notably are the cytotoxic drugs (methotrexate), irradiation, and antiandrogens (spironolactone, finasteride). Although the prevalence of these skin diseases is low, the associated male infertility represents a challenge due to the difficulty of its management. Clinical management of the skin diseases should include consideration of their effects not only on the diseases but also on the male reproductive system.
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Affiliation(s)
- M Badawy Abdel-Naser
- Department of Dermatology, Andrology and STIs, Ain Shams University, 4 Al Rahman Tower, El Sawah Square, Cairo, 11281, Egypt.
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
| | - Christos C Zouboulis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany
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Najafi G, Atashfaraz E, Farokhi F. Attenuation of Methotrexate-Induced Embryotoxicity and Oxidative Stress by Ethyl Pyruvate. INTERNATIONAL JOURNAL OF FERTILITY & STERILITY 2016; 10:232-8. [PMID: 27441057 PMCID: PMC4948076 DOI: 10.22074/ijfs.2016.4914] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Accepted: 08/01/2015] [Indexed: 01/24/2023]
Abstract
Background Methotrexate (MTX), as an anti-folate agent, is widely used in the
treatment of rheumatic disorders and malignant tumors, however it damages reproductive sys-
tem in mice. The aim of this research was to study the effects of ethyl pyruvate (EP) on embryo
development and oxidative stress changes in the testis of mice treated with MTX.
Materials and Methods In this experimental study, thirty-two adult male Naval
Medical Research Institute mice, with average weight of 26 ± 2 g, were divided into
four groups. The first group (control) received distilled water (0.1 ml/mice/day), while
the second group was intraperitoneally (IP) treated with 20 mg/kg MTX once per
week. The third group was IP treated with 40 mg/kg/day EP, and the fourth group was
IP treated with both 20 mg/kg MTX and 40 mg/kg/day EP for 30 days. At the end of
treatment fertilization rate and embryonic development were evaluated. Differences
between these groups were assessed by ANOVA using the SPSS software package for
Windows with a Tukey-Kramer multiple post-hoc comparison test. Results MTX treatment caused significant (P<0.05) increase in malondialdehyde
(MDA) and reduced catalase (CAT), as well as leading to in vitro fertilization (IVF) and
embryonic development. The improved effects of EP on the IVF were determined by the
reduced level of MDA (index of oxidative stress) and significant increased level of CAT
(a key antioxidant). We observed significant increase in fertilization rate and embryonic
development in the treated group with both MTX and EP. Conclusion It is suggested that EP can be useful in ameliorating testicular
damages and embryotoxicity induced by MTX. These effects could be attributed to its
antioxidant properties.
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Affiliation(s)
- Gholamreza Najafi
- Department of Basic Sciences (Anatomy and Embryology), Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Elham Atashfaraz
- Department of Biology, Faculty of Science, Urmia University, Urmia, Iran
| | - Farah Farokhi
- Department of Biology, Faculty of Science, Urmia University, Urmia, Iran
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30
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Krause ML, Makol A. Management of rheumatoid arthritis during pregnancy: challenges and solutions. Open Access Rheumatol 2016; 8:23-36. [PMID: 27843367 PMCID: PMC5098768 DOI: 10.2147/oarrr.s85340] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Rheumatoid arthritis, a chronic inflammatory autoimmune disease with significant physical disability, affects women three times more frequently than men, often in their childbearing years. Parenthood decisions can be challenging, often affected by perceptions of their disease state, health care needs, and complex pharmacological treatments. Many women struggle to find adequate information to guide them on pregnancy planning, lactation, and early parenting in relation to their chronic condition. The expanded availability and choice of pharmacotherapies have supported optimal disease control prior to conception and enhanced physical capabilities for women to successfully overcome the challenges of raising children but require a detailed understanding of their risks and safety in the setting of pregnancy and breastfeeding. This review outlines the various situational challenges faced by rheumatologists in providing care to men and women in the reproductive age group interested in starting a family. Up to date evidence-based solutions particularly focusing on the safe use of disease-modifying antirheumatic drugs and biologic response modifiers to assist rheumatologists in the care of pregnant and lactating women with RA are reviewed.
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Affiliation(s)
- Megan L Krause
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, MN, USA
| | - Ashima Makol
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, MN, USA
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31
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Yiu ZZN, Warren RB, Mrowietz U, Griffiths CEM. Safety of conventional systemic therapies for psoriasis on reproductive potential and outcomes. J DERMATOL TREAT 2015; 26:329-34. [PMID: 25424052 DOI: 10.3109/09546634.2014.991673] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The effects of conventional systemic therapies for psoriasis on pregnancy outcomes, lactation, male fertility and mutagenicity are common concerns in the clinical setting. There is relatively little evidence to guide clinician and patient. In this study, we review the safety profile of the commonly used conventional systemic therapies used for psoriasis in individuals of reproductive potential. Safety data are derived from large-scale registries, adverse-event reporting databases, clinical trials and case reports. We assess the effect of each therapy on adverse pregnancy outcomes, including congenital malformations, and lactation with maternal administration. We also assess the effect of the therapies on male fertility and potential mutagenicity with paternal administration. We provide applicable guidance to inform clinician and patient before and after conception.
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Affiliation(s)
- Zenas Z N Yiu
- The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre , Manchester , UK and
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Palomba S, Sereni G, Falbo A, Beltrami M, Lombardini S, Boni MC, Fornaciari G, Sassatelli R, La Sala GB. Inflammatory bowel diseases and human reproduction: a comprehensive evidence-based review. World J Gastroenterol 2014; 20:7123-36. [PMID: 24966584 PMCID: PMC4064059 DOI: 10.3748/wjg.v20.i23.7123] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 02/13/2014] [Accepted: 02/26/2014] [Indexed: 02/06/2023] Open
Abstract
To evaluate the effects of inflammatory bowel diseases (IBDs) on human reproduction, we reviewed the current literature using a systematic search for published studies (articles and/or abstracts) without limits for English language. We searched on Medline (through PubMed), the Institute for Scientific Information, the Web of Science and the websites for the registration of controlled trials (http://controlled-trials.com/). Bibliographies of retrieved articles, books, expert opinion review articles and reviewed bibliographies from subject experts were manually searched. Titles and abstracts were screened initially, and potential relevant articles were identified and reviewed. Whenever possible, data were analyzed by comparing IBD patients vs healthy controls, and patients with active IBDs vs those with disease in remission. The effects of IBDs on female fertility, fertility in infertile couples, pregnancy and male infertility were examined separately. Patients with IBDs in remission have normal fertility. At the moment, there is no established guideline for the preservation of fertility in women with IBD undergoing surgery. Further data are needed regarding guidelines for the management of these patients. Data regarding IBDs and infertility are currently completely lacking. Considering the prevalence of intestinal pathology in young adults of childbearing age, this field is of great scientific and clinical interest, opening up important future perspectives. Another important and as yet unexplored point is the response to treatments for infertility in patients with IBDs. In particular, the question is whether the reproductive outcomes (clinical and biological) can be influenced by the IBD of one of the partners. The goals for successful reproductive outcomes in IBD population are correct counseling and disease remission. IBDs significantly affect several reproductive aspects of human (female, male, couple) reproduction. Further data are needed to develop guidelines for the clinical management of subjects of reproductive age with IBDs.
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Millsop JW, Heller MM, Eliason MJ, Murase JE. Dermatological medication effects on male fertility. Dermatol Ther 2013; 26:337-46. [DOI: 10.1111/dth.12069] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
| | | | - Mark J. Eliason
- Department of Dermatology; University of Utah; Salt Lake City; Utah
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Wakefield D, El-Asrar AA, McCluskey P. Treatment of Severe Inflammatory Eye Disease in Patients of Reproductive Age and during Pregnancy. Ocul Immunol Inflamm 2012; 20:277-87. [DOI: 10.3109/09273948.2012.684736] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Sartorius GA, Handelsman DJ. Testicular Dysfunction in Systemic Diseases. Andrology 2010. [DOI: 10.1007/978-3-540-78355-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Affiliation(s)
- C A Wallace
- University of Washington, and Children's Hospital and Medical Center, Seattle, USA
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38
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Handelsman DJ. Testicular Dysfunction in Systemic Diseases. Andrology 1997. [DOI: 10.1007/978-3-662-03455-2_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Affiliation(s)
- H Zachariae
- Department of Dermatology, Marselisborg Hospital, University of Arhus, Denmark
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40
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Morris LF, Harrod MJ, Menter MA, Silverman AK. Methotrexate and reproduction in men: case report and recommendations. J Am Acad Dermatol 1993; 29:913-6. [PMID: 8408841 DOI: 10.1016/0190-9622(93)70270-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Methotrexate has been used in the treatment of recalcitrant psoriasis for more than 35 years. We examined the significance of impaired spermatogenesis in a young man undergoing methotrexate treatment for severe psoriasis with associated arthritis. A medical geneticist was consulted and a review of the literature was performed. Genetic abnormalities that could lead to mutagenesis include chromosomal abnormalities and single-gene mutations. These aspects are considered and recommendations are made for counseling men undergoing methotrexate therapy so that risks and options can be considered.
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Affiliation(s)
- L F Morris
- Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas
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Abstract
Over recent years radical improvements in the treatment of malignant disease have resulted in the cure of patients in or approaching reproductive age, and with that cure, the effects on gonadal function have become apparent. Gonadal failure is particularly important in Hodgkin's disease, germ cell tumours, choriocarcinoma, and leukaemia, diseases of young people which are largely curable. Premature ovarian and testicular failure are easily missed by doctors concerned primarily with the erradication or arrest of a life-threatening disease, but for the patient the hormonal, psychological and social sequelae of treatment may be devastating. In this article we review the effects of chemotherapy on gonadal function and discuss the management of gonadal failure.
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Affiliation(s)
- C Barton
- Department of Clinical Oncology, Hammersmith Hospital, London, UK
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42
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Stockton DL, Paller AS. Drug administration to the pregnant or lactating woman: a reference guide for dermatologists. J Am Acad Dermatol 1990; 23:87-103. [PMID: 2195076 DOI: 10.1016/0190-9622(90)70192-k] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Dermatologists are occasionally faced with the problem of appropriate systemic drug administration to the lactating or pregnant woman. The physician's responsibility is to be aware of the potential risk of prescribing a specific therapeutic agent, to inform the mother of this risk, and to administer an alternate, less deleterious drug, if available. The purpose of this review is to provide guidelines for dermatologists who must consider the risks to the fetus or neonate of drug administration to the pregnant woman or lactating mother.
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Affiliation(s)
- D L Stockton
- Department of Dermatology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL
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44
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45
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Roenigk HH, Auerbach R, Maibach HI, Weinstein GD. Methotrexate in psoriasis: revised guidelines. J Am Acad Dermatol 1988; 19:145-56. [PMID: 3042816 DOI: 10.1016/s0190-9622(88)80237-8] [Citation(s) in RCA: 215] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- H H Roenigk
- Northwestern University Medical School, Chicago, IL 60611
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Abstract
Although methotrexate is frequently employed as an antimetabolic chemotherapeutic agent for childhood cancer, it is rarely used for dermatologic disorders in children. In the pediatric patient whose skin disease is recalcitrant to more conservative treatment, a trial of methotrexate is often appropriate. There are few reports of the drug's use for skin disorders in childhood upon which to base rational therapeutic management, however. In setting guidelines for use in children, we must consider pharmacokinetic studies and methotrexate toxicity observed in managing pediatric cancer.
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48
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50
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El-Beheiry A, El-Mansy E, Kamel N, Salama N. Methotrexate and fertility in men. ARCHIVES OF ANDROLOGY 1979; 3:177-9. [PMID: 518200 DOI: 10.3109/01485017908985067] [Citation(s) in RCA: 65] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The possible deleterious effects of folic acid antagonist methotrexate on the fertility potential have been investigated in 26 male psoriatic patients. Examination for semen, testicular histology, and spermatogenic function using radioactive phosphorus revealed that methotrexate had no unfavorable effect on male fertility. A long follow up of the patients and their offspring is needed to exclude the possible teratogenic effect of the drug.
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