Low bone mineral density is associated with hypogonadism and cranial irradiation in male childhood cancer survivors.

We investigated if bone mineral density was related to testosterone deficiency and/or previous cancer treatment in men who were childhood cancer survivors. Men with untreated testosterone deficiency or previous treatment with cranial irradiation were at increased risk of impaired bone health. Prevention of osteoporosis should be considered in their follow-up. INTRODUCTION: Childhood cancer survivors (CCS) are at increased risk of hypogonadism. Reduced bone mineral density (BMD) has been reported in CCS but it is unclear whether this is due to hypogonadism or a direct effect of cancer therapy. This study investigated BMD in CCS, and association with hypogonadism, previous treatment and cancer type. METHODS: Investigation of 125 CCS (median age 33.7 at inclusion; 9.6 at diagnosis) and 125 age-matched population controls. Serum testosterone and luteinizing hormone were assayed and BMD at total hip and lumbar spine L1-L4 measured. The mean difference in BMD (g/cm2; 95% CI) between CCS and controls was analysed. Odds ratios (OR; 95% CI) for low BMD were also calculated. RESULTS: Overall, BMD in the CCS cohort did not significantly differ from controls. However, compared with eugonadal CCS, the CCS with untreated hypogonadism had lower BMD at the hip (mean difference - 0.139 (- 0.210; - 0.067); p < 0.001) and spine (- 0.102 (- 0.174; - 0.030); p = 0.006). They also had a higher risk of low hip BMD (OR 4.1 (1.3; 14); p = 0.018). CCS treated with cranial irradiation also had lower BMD (hip - 0.076 (- 0.133; - 0.019); p = 0.009; spine - 0.071 (- 0.124; - 0.018); p = 0.009) compared with controls. The latter associations remained statistically significant after adjustment for hypogonadism. CONCLUSIONS: CCS with hypogonadism or previously treated with cranial irradiation are at increased risk of impaired bone health. Prevention of osteoporosis should be considered as an important part in future follow-up of these men.

High risk of hypogonadism in young male cancer survivors.

OBJECTIVE: Cancer and its treatment in childhood and young adulthood can cause hypogonadism, leading to increased risk of long-term morbidity and mortality. The aim of this study was to evaluate the risk of presenting with biochemical signs of hypogonadism in testicular cancer survivors (TCS) and male childhood cancer survivors (CCS) in relation to the type of treatment given. DESIGN: Case-control study. PATIENTS: Ninety-two TCS, 125 CCS (mean age 40 and median age 34 years, respectively; mean follow-up time 9.2 and 24 years, respectively) and a corresponding number of age-matched controls. MEASUREMENTS: Fasting morning blood samples were analysed for total testosterone (TT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The odds ratios (OR) for hypogonadism, defined as primary, secondary, compensated or ongoing androgen replacement, were calculated for TCS and CCS and for subgroups defined by diagnosis and treatment. RESULTS: Hypogonadism was found in 26% of CCS and 36% of TCS, respectively (OR: 2.1, P = .025 and OR = 2.3, P = .021). Among CCS, the OR was further increased in those given testicular irradiation (OR = 28, P = .004). Radiotherapy other than cranial or testicular irradiation plus chemotherapy, or cranial irradiation without chemotherapy, associated also with increased ORs (OR = 3.7, P = .013, and OR = 4.4, P = .038, respectively). Among TCS, those receiving >4 cycles of cisplatin-based chemotherapy had OR = 17, P = .015. CONCLUSIONS: Biochemical signs of testosterone deficiency are recognized as markers of decreased life expectancy. Thus, the risk of hypogonadism in TCS and CCS should be recognized and emphasizes the need of long-term follow-up for these men.

High prevalence of androgen deficiency and abnormal lipid profile in infertile men with non-obstructive azoospermia.

In men with non-obstructive azoospermia (NOA), the risk of hypogonadism is often overlooked. Testicular sperm extraction (TESE) may increase this risk. The objective of this study was to elucidate the prevalence of hypogonadism in NOA-patients, the impact of TESE on hormone balance and the association between testosterone deficiency and dyslipidaemia. Men with NOA who had undergone TESE during the period 2004-2009 were eligible. Hypogonadism was defined as total testosterone <10 nmol/L and/or LH >10 IU/L and/or ongoing androgen replacement therapy. Sixty-five consecutive men who had undergone TESE owing to NOA and from whom post-TESE serum testosterone levels measured before 1100 h were available. Furthermore, 141 fertile men served as controls. Serum concentrations of testosterone, LH and lipids were assessed. Odds ratios (OR) for biochemical hypogonadism were calculated. Pre- and post-TESE hormone levels were compared. Lipid profile was related to testosterone levels. Hypogonadism was found in 47% (95% CI, 0.36, 0.59) of the NOA-men. As compared with fertile controls, the OR for hypogonadism post-TESE was 17 (95% CI 6.6-45). Serum LH (p = 0.03), but not testosterone (p = 0.43), differed significantly pre- and post-TESE. Compared with eugonadal NOA-men, the OR for having deviations in lipid profile was 3.3 (95% CI 1.3-8.8) for the hypogonadal NOA-men. NOA-men are at very high risk of androgen deficiency, which even in young subjects is associated with dyslipidaemia. Medical management of these men should therefore include endocrinological evaluation and follow-up after completion of infertility treatment.

Robot-assisted nephroureterectomy for upper tract urothelial carcinoma-feasibility and complications: a single center experience.

BACKGROUND: Robot-assisted nephroureterectomy (RANU) is the primary treatment for upper tract urothelial carcinoma (UTUC) at our hospital for patients with clinical stage less than T2, and for patients with invasive tumours, but unfit for major surgery. OBJECTIVE: To assess peri-operative conditions and outcomes of RANU at our unit, and to evaluate the safety of the procedure. METHODS: The medical records of all 166 patients undergoing RANU for suspected UTUC and followed for more than three months in a large university hospital in Sweden were reviewed retrospectively. After the exclusion of twenty patients because of previous cystectomy, simultaneous surgical procedure, or other tumour types than UTUC in the pathological report, 146 patients remained for the analyses. The primary endpoint was complication rate according to Clavien-Dindo at 90 days. Secondary endpoints were perioperative bleeding, violation of oncological surgical principles, hospital stay, and re-admission within 90 days. RESULTS: The median age was 75 [(Inter Quartile Range) IQR 70-80] years and 57% of the patients had an ASA score above 2. According to Clavien-Dindo, one patient had a grade 3 complication, and no patient had a grade 4-5 complication. The median blood loss was 50 (IQR 20-100) ml and the median hospital stay was 6 (IQR 5-7) days. Twelve patients were re-admitted to the hospital within 90 days (eight with urinary tract infection/haematuria, one with hematoma, and three with other diseases). CONCLUSION: Robot-assisted nephroureterectomy is a safe procedure for patients with upper tract urothelial carcinoma, with a low risk of major surgical complications.

Symptoms of sexual dysfunction among men from infertile couples: prevalence and association with testosterone deficiency.

BACKGROUND: This case control study aimed to investigate whether symptoms of sexual dysfunction are more common in males from infertile couples than in the general population and to explore whether symptoms of sexual dysfunction are associated to hypogonadism. OBJECTIVES: Participants were 165 subfertile men in infertile heterosexual relationships, 18-50 years of age, with sperm concentrations < 15 × 106 /mL. The controls were 199 men from a population-based group, matched for age. MATERIAL AND METHODS: Logistic regression was applied in order to calculate odds ratios (ORs) for seven different symptoms of sexual dysfunction. In a multivariate model, we tested independent effects of infertility and primary as well as secondary hypogonadism. RESULTS: Statistically significant association between subfertility and symptoms of sexual dysfunction was found for lack of ability to control ejaculation (OR 2.2, 95% CI: 1.2-4.2). For hypogonadism, statistical significance was seen both in relation to low sexual interest/desire for sex (OR 2.3, 95% CI: 1.0-5.5) and for being worried about the size or shape of the penis (OR 3.6, 95% CI: 1.3-9.5). These associations remained statistically significant in males with primary but not those with secondary hypogonadism. DISCUSSION: Our study showed that men from infertile couples have an increased risk of symptoms of sexual dysfunction and this risk is linked to androgen deficiency. CONCLUSION: Assessment of reproductive hormone levels and sexual function should routinely be done in this group of males.

Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the metabolic syndrome.

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2 years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone < 10 nmol/L and/or LH > 10 IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10 mIU/L; p = 0.002) and HOMAir (mean difference: 0.792; p = 0.007) were detected. Hypogonadism group presented with increased risk (OR = 4.4; p = 0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients.

Risk of low bone mineral density in testicular germ cell cancer survivors: association with hypogonadism and treatment modality.

The cure rate of testicular cancer exceeds 95%, but testicular cancer survivors (TCS) are at increased risk of hypogonadism (HG). It has been suggested that TCS have reduced bone mineral density (BMD), but it is unclear whether this is related to HG or a direct effect of cancer therapy. The aim of this study was to evaluate whether TCS have decreased BMD, and if BMD is related to HG and/or the cancer treatment given. We investigated 91 TCS (mean age at diagnosis: 31 years; mean 9.3 years follow-up) and equal number of age matched controls (mean age at inclusion 40.3 years and 41.2 years, respectively). Total testosterone and LH were measured. BMD was determined using dual-energy X-ray absorptiometry (DXA). Low BMD (LBD) was defined as Z-score <-1. Compared to eugonadal TCS, both TCS with untreated HG (mean difference: -0.063 g/cm2 ; 95% CI: -0.122; -0.004 p = 0.037) and TCS receiving androgen replacement (mean difference -0.085 g/cm2 ; 95% CI: -0.168; -0.003; p = 0.043) presented with statistically significantly 6-8% lower hip BMD. At the spine, L1-L4, an 8% difference reached the level of statistical significance only for those with untreated HG (mean difference: -0.097 g/cm2 ; 95% CI: -0.179; -0.014; p = 0.022). TCS with untreated HG had significantly increased OR for spine L1-L4 LBD (OR = 4.1; 95% CI: 1.3; 13; p = 0.020). The associations between the treatment given and BMD were statistically non-significant, both with and without adjustment for HG. In conclusion, TCS with HG are at increased risk of impaired bone health. Prevention of osteoporosis should be considered as an important part in future follow up of these men.