Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies

Abstract

Summary:We studied 24 male patients aged 26-62 years (median 41) prospectively presenting over a 5 year period with clinical features of hypogonadism and erectile dysfunction (ED), who had been treated with autologous or allogeneic bone marrow/stem cell transplant for a variety of haematological malignancies and had received either high-dose chemotherapy or high-dose chemotherapy combined with total body irradiation (TBI). Ten healthy adult controls (aged 35-50 years) were also studied. Erectile dysfunction (ED) was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume including orchidometry, FSH, LH and testosterone measurements. Libido and ejaculatory function were also recorded. Patients had severe hypogonadism as evidenced by low mean testicular volume (7.0 ؎ 2.4 ml vs 20 ؎ 2.0 ml; P Ͻ 0.001), elevated gonadotrophins (FSH = 18.54 ؎ 7.61 vs 5 IU/l (P Ͻ 0.001); LH = 8.02 ؎ 2.89 vs 3.9 IU/l (P Ͻ 0.001)) and low normal mean testosterone levels (16.4 nmol/l ؎ 9.1 vs 22.4 nmol/l (P Ͻ 0.5)). Cavernosal arterial insufficiency was found in 11/14 of TBI-treated and in 3/10 HDC-treated patients, indicative of vasculogenic damage to corpora cavernosal vessels. Patients were given a therapeutic trial with testosterone replacement therapy (TRT). Those who had diminished libido had a marked improvement in their symptoms but the effect of TRT on ED was equivocal. In conclusion, this is the first report to show vasculogenic insufficiency in patients with haematological malignancies treated by BMT. Although hypogonadism can account for diminished libido, arteriogenic insufficiency is likely to be an important factor accounting for ED in these patients, especially those treated by TBI. We recommend a comprehensive assessment including endocrine profile and colour flow Doppler study in formulating the best management plan in recipients of high-dose therapy presenting after transplant with ED. Keywords: high-dose chemotherapy; bone marrow transplantation; cavernosal arteriogenic insufficiency; erectile dysfunctionThe long-term survival of recipients of high-dose chemotherapy (HDC) with or without total body irradiation (TBI) for haematological and non-haematological malignancies has risen dramatically in the last decade, yet little is known about the quality of life of the long-term survivors. Gonadal dysfunction is the most common long-term side-effect in the high-dose therapy and bone marrow transplantation (BMT) setting and is associated with significant morbidity. We 1 and others have shown germ cell damage 2 as well as Leydig cell insufficiency (low basal and HCG-stimulated testosterone levels) in such patients. 3 We have also shown that high-dose chemo-radiotherapy causes acute functional castration in patients with haematological malignancies within 72 h of TBI and there is a 50% loss of testicular volume. Subsequently patients may present with premature andropause. 1 Sexual dysfunction is a commonly recognised presentation in patients with ...

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. HRT is not contraindicated in cancer patients, including SCT recipients.…”

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

“…A peak systolic velocity (PSV) of Ͻ30 cm/s was defined as an index of vascular insufficiency. 6 Response to the intracavernosal injection was graded 0-III as above.…”

“…This was undertaken according to our previously published protocol. 6 Testicular volume was assessed clinically by using Prader's orchidometer and confirmed by testicular ultrasound. In the event of discrepancy, the ultrasonic measurement was used.…”

“…ED was graded using previously published criteria as follows: severe erectile dysfunction with no evidence of erection was scored as grade 0, tumescence without rigidity as grade I, partial erection inadequate for a successful penetration as grade II, and full rigidity as grade III. 6 Libido and ejaculation were defined according to Master's and Johnson's criteria. 3 …”

“…5 All five of the patients that we studied had subnormal penile Doppler blood flow rates as well as Leydig cell insufficiency. Subsequently, we reported 6 cavernosal arterial insufficiency in recipients of marrow/stem cell transplant following high-dose chemotherapy without TBI.…”