Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies

Abstract

Summary:Erectile dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg of sildenafil orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant.

Synergetic effect of testosterone and phophodiesterase-5 inhibitors

“…24 Despite the lack of a clear definition of PDI-5 inhibitor failure, the main indications to start combination therapy were failure of PDE-5 inhibitors and low-borderline testosterone. [16][17][18][22][23][24]29,30 The remaining studies reported good response with other indications, like ED and hypogonadism unresponsive to testosterone replacement alone, 21 initial combination therapy (not monotherapy) in patients with ED and hypogonadism after renal or bone marrow transplant, and in patients on hemodialysis not responding to erythropoietin and/or testosterone; 20,26,31 moreover, initial combination therapy benefited patients with severe hypogonadism, testosterone <200 ng/dL (<6.9 nmol/L) and ED.…”

“…These articles included 684 patients, ranging from 8 to 173 patients in each study (Table 1). Ten studies used the International Index of Erectile Dysfunction (IIEF) as the main scoring system for baseline and follow-up assessment of treatment response, while the other 4 studies used the Androgen Deficiency in Aging Male (ADAM) questionnaire, 23 National Institute of Health (NIH) consensus criteria, 26 nocturnal penile tumescence (NPT) and penile colour duplex ultrasound 27 and one study used only nocturnal penile tumescence and rigidity monitoring. 28 We identified 5 out of 14 studies that had a prospective randomized controlled design, [16][17][18]28,29 while the remaining studies, although prospective, lacked either a control group, randomization or both.…”

Pathophysiology, evaluation and treatment of erectile dysfunction: review article

“…A disfunção dos hormônios sexuais masculinos, por si só, piora a situação de pacientes com DE, principalmente quando se leva em conta a associação com a síndrome hipogonádica do homem adulto e a doença arterial cavernosa 35 . A testosterona e seu metabólito (5 α-di-hidrotestosterona) estimulam a expressão do gene NOS (óxido nítrico sintetase), o que aumenta os níveis de NO -importante vasodilatador -no tecido erétil do corpo cavernoso [36][37][38][39][40] .…”

“…A associação de testosterona propicia além do efeito vascular da ereção peniana, um aumento da libido e da tumescência noturna em pacientes que tenham comprometimento das células de Leydig 35,39 . Entretanto, a terapia de reposição de testosterona em homens não é o tratamento de primeira linha para a DE, principalmente porque a DE depende muito pouco da redução dos efeitos deste hormônio 89,90 .…”

Treatment of gonadal damage in recipients of allogeneic or autologous transplantation for haematological malignancies

“…Male patients presenting with diminished libido and erectile dysfunction (ED) may bene- Bone Marrow Transplantation fit from combined therapy with testosterone replacement and sildenafil, 54 especially those with symptomatic Leydig cell insufficiency and cavernosal arteriogenic insufficiency. 55 Similarly, cyclical oestrogen replacement treatment (ERT) may be administered with cyclical progestogen in women with an intact uterus.…”