1132 SHORT COMMUNICATION
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Advances in dermatology and venereology Acta Dermato-Venereologica
Methotrexate-associated Sexual Dysfunction : Two Case Reports
Grigorios THEODOSIOU and Åke SVENSSON Department of Dermatology and Venereology , Skåne University Hospital , SE-205 02 Malmö , Sweden . E-mail : gregtheodosiou @ yahoo . com ; Grigorios . Theodosiou @ skane . se Accepted May 30 , 2017 ; Epub ahead of print May 31 , 2017
Methotrexate ( MTX ) is a potent competitive inhibitor of the enzyme dihydrofolate reductase . MTX is widely used in dermatology practice for psoriasis and many other conditions , including bullous disorders , autoimmune connective tissue diseases , pityriasis rubra pilaris ( PRP ), sarcoidosis , and miscellaneous other dermatoses .
The most common adverse effects of MTX include nausea , fatigue , dizziness , headache , stomatitis and abdominal pain . Serious adverse effects include hepatotoxicity , pulmonary toxicity , nephrotoxicity , myelosuppression and increased risk of lymphoproliferative disorders .
We report here 2 cases of sexual dysfunction during MTX therapy . To the best of our knowledge , there have been only 2 cases in the literature of this rare side-effect in patients with psoriasis treated with MTX ( 1 ). There are also some reports of sexual dysfunction in patients treated with MTX for rheumatological conditions ( 2 – 4 ).
CASE REPORTS Patient 1
A 58-year-old man with a 32-year history of plaque psoriasis was started on a regimen of oral MTX at a weekly dosage of 12.5 mg and folic acid supplement . The patient was otherwise healthy and took no other medications . At the follow-up visit the patient reported that the drug was generally well tolerated . However , 2 weeks after the initiation of treatment the patient began to experience reduced libido and difficulty in obtaining an erection . His treatment was switched to acitretin and , within 4 weeks , complete resolution of the sexual dysfunction was reported .
Patient 2
A 68-year-old man with psoriasis vulgaris , previously treated with narrow-band ultraviolet B ( UVB ) phototherapy and acitretin , was started on weekly oral MTX 12.5 mg and folic acid 5 mg . The patient had hypertension and diabetes mellitus type 2 and was on losartan and metformin . At follow-up 6 months later , the patient reported loss of libido and erectile dysfunction . The symptoms were noticed 3 weeks after the initiation of treatment . On account of the excellent response to MTX , the patient chose not to discontinue the treatment . Four months later , however , treatment was discontinued due to elevated liver function tests . The patient reported that his sexual dysfunction resolved within 3 weeks on discontinuation of MTX .
Neither of these patients had history of depression or had previously experienced reduced libido or difficulty in obtaining an erection . No signs of depression had been assessed at the initial or follow-up visits .
DISCUSSION
These 2 patients reported onset of sexual dysfunction only a few weeks after initiation of MTX and resolution of the symptoms within 3 – 4 weeks after discontinuation of the drug , in agreement with the cases reported by Wylie et al . ( 1 ). A case of MTX-associated sexual dysfunction has been reported in a patient with erythroderma treated with MTX , where impotence was noticed 9 months after the initiation of the treatment and subsided 2 weeks after discontinuation of MTX . Re-administration of MTX elicited the same symptom 2 months later ( 5 ).
The exact mechanism of this adverse effect of MTX remains unknown . It has been assumed that impaired pituitary function , as result of interleukin-1 blockage , as well as an inhibitory effect on the production of nitric oxide by MTX , that leads to reduced activity against vascular smooth muscle , may play a role ( 1 ). This type of adverse effect may also be idiosyncratic .
Although reduced libido and impotence are rare side-effects of MTX according to the manufacturers , MTX-associated sexual dysfunction is seldom mentioned in textbooks and rarely reported in the literature . The detection of drug-induced adverse sexual effects is challenging ; patients are often reluctant to report sexual dysfunction and there are often several overlapping aetiologies , including cardiovascular disorders , depression or mood disorders . We assume , therefore , that MTXassociated sexual dysfunction may be under-reported .
We report here 2 cases of MTX-induced sexual dysfunc tion in order to raise the awareness of this adverse effect . Taking into consideration that patients with psoriasis have a higher risk of sexual dysfunction irrespective of treatment , compared with the general population . It is important to make a careful assessment of sexual function both at the initial and follow-up visits ( 1 , 6 – 9 ).
The authors declare no conflicts of interest .
REFERENCES
1 . Wylie G , Evans D , Gupta G . Reduced libido and erectile dysfunction : rarely reported side-effects of methotrexate . Clin Exp Dermatol 2009 ; 34 : 234 . doi : 10.2340 / 00015555-2714 Acta Derm Venereol 2017 ; 97 : 1132 – 1133
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica .