| 1. |
- Eberhard, Jakob, et al.
(author)
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Risk factors for post-treatment hypogonadism in testicular cancer patients.
- 2008
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In: European Journal of Endocrinology. - 1479-683X. ; 158:4, s. 561-570
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined. METHODS: Blood was collected from 143 TGCC patients (after orchidectomy, prior to further therapy (T0) and 6, 12, 24, 36 and 60 months (T6, T12, T24, T36 and T60) after therapy). Biological hypogonadism (BH) was defined as: serum testosterone below 10 nmol/l and/or LH >10 IU/l; odds ratios (ORs) for BH with BH at T0, age, stage of disease, testicular characteristics, and androgen receptor polymorphism as predictors were calculated as well as the OR for developing BH post-treatment (one to two cycles of adjuvant chemotherapy (ACT) versus three to four cycles of higher dose chemotherapy (HCT) versus adjuvant radiotherapy (RT)). RESULTS: HCT increased the OR for BH at T6 (OR 22, 95% confidence interval (CI) 4.4-118) and T12 (OR 5.8, 95% CI 1.5-22). RT increased the OR at T6 (OR 10, 95% CI 2.1-47) and at T12 (OR 3.9, 95% CI 1.1-14). Microlithiasis predicted BH at T0 (OR 11, 95% CI 1.2-112), T12 (OR 3.9, 95% CI 1.1-13), T24 (OR 3.0, 95% CI 1.0-8.8), T36 (OR 5.4, 95% CI 1.7-17) and T60 (OR 4.4, 95% CI 1.2-16). BH at T0 was a risk for BH at T6 (OR 53, 95% CI 19-145), T12 (OR 125, 95% CI 37-430), T24 (OR 88, 95% CI 26-300) and T36 (OR 121, 95% CI 32-460). CONCLUSIONS: It is clinically relevant that BH at T0 and testicular microlithiasis were predictive factors for post-treatment BH. HCT and RT gave temporary BH.
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| 2. |
- Eberhard, Jakob, et al.
(author)
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Emotional disorders in testicular cancer survivors in relation to hypogonadism, androgen receptor polymorphism and treatment modality.
- 2010
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 122, s. 260-266
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Journal article (peer-reviewed)abstract
- PURPOSE: It has been documented that testicular germ cell cancer (TGCC) patients may be at increased risk of developing emotional distress (EMD). Hence, the aim of the present study was to investigate whether EMD is related to the presence of hypogonadism, androgen receptor (AR) polymorphism and/or treatment intensity. PATIENTS AND METHODS: Three to five years after treatment, testosterone and luteinizing hormone (LH) levels were measured in 165 TGCC patients. These patients also completed a questionnaire concerning mental health. EMD was measured by the Hospital Anxiety and Depression Scale (HADS). The androgen receptor (AR) gene has two polymorphic regions in exon I; glutamine encoding CAG and glycine encoding GGN repeats. Association between emotional disorders and AR polymorphisms as well as type of treatment was assessed. RESULTS: Neither anxiety (OR 1.0; 95% CI 0.40-2.4) nor depression (OR 1.1; 95% CI 0.20-6.4) were overrepresented in biochemically hypogonadal TGCC patients and no association between AR polymorphisms and EMD was found. Patients treated with >/=5 cycles of cisplatinum based chemotherapy due to refractory or relapsed disease were more prone to experiencing symptoms of anxiety (p=0.006), but not depression (p=0.38). CONCLUSIONS: Biochemical hypogonadism and AR polymorphism do not seem to be risk factors for EMD in TGCC patients. Patients with refractory or relapsed disease receiving >/=5 cycles of cisplatinum based chemotherapy may, to a higher degree than patients receiving less intense therapy, suffer from anxiety.
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| 3. |
- Eberhard, Jakob, et al.
(author)
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Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated for testicular germ cell cancer: a longitudinal study.
- 2004
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 19:6, s. 1418-1425
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Journal article (peer-reviewed)abstract
- Abstract in Undetermined BACKGROUND: Testicular cancer (TC) patients have a high survival rate, and the question of post-therapy recovery of sperm production and its dependence on genetic predisposition is of major interest. METHODS: Ejaculates were obtained from 112 TC patients at one or more of the following time points: post-orchidectomy, or 6, 12, 24, 36 and 60 months post-therapy. The lengths of the androgen receptor (AR) function modulating CAG and GGN repeats in leukocyte DNA were also analysed. RESULTS: No significant decrease in sperm concentration was seen in men who received 1-2 cycles of adjuvant chemotherapy (ACT). Radiotherapy (RT) or more than two cycles of chemotherapy (HCT) caused an initial decline in sperm concentration, which returned to pre-treatment levels 2-5 years after therapy. In the HCT group, sperm concentration 12-24 months post-treatment (T(12-24)) was inversely correlated with CAG length (rho = -0.72, P = 0.03). The type of treatment, but not the concentration at T(0), was an independent predictor of sperm concentration at T(6) (P < 0.0005) and T(12-24) (P = 0.004). CONCLUSION: ACT did not induce a significant decline in sperm concentration. After HCT and RT, a significant reduction of sperm concentration was observed, recovering to pre-treatment levels 2-5 years post-treatment. In HCT-treated patients, the AR CAG length influenced the recovery of spermatogenesis.
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| 4. |
- Eberhard, Jakob, et al.
(author)
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Sexual Function in Men Treated for Testicular Cancer.
- 2009
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In: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 6, s. 1979-1989
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Journal article (peer-reviewed)abstract
- ABSTRACT Introduction. Testicular germ cell cancer (TGCC) patients may be at risk of developing sexual dysfunction after treatment. Aim. The aim of this study was to assess the prevalence of sexual dysfunctions in TGCC patients 3 to 5 years after treatment, and relate findings to biochemical hypogonadism, treatment intensity, and the expected prevalence in the Swedish male population. Methods. A questionnaire study on 129 consecutive TGCC patients 3 to 5 years post-treatment was performed. Comparators were an age-matched nationally representative group of men (N = 916) included in a study on sexual life in Sweden. Main Outcome Measures. Sexual functions (including erectile dysfunctional distress), time since last intercourse, sexual satisfaction, and experience of sexological treatment seeking were assessed using the same questions used in the epidemiological study on sexual life in Sweden. The findings in TGCC patients were correlated to biochemical signs of hypogonadism and type of oncological treatment: Surveillance, adjuvant chemotherapy, adjuvant radiotherapy, or standard doses of chemotherapy. Results. A higher proportion of TGCC patients than comparators were likely to report low sexual desire (odds ratio [OR] 6.7 [95% confidence interval {CI} 2.1-21]) as well as erectile dysfunction (OR 3.8 [95% CI 1.4-10]). No significant differences were observed regarding erectile dysfunctional distress, change of desire over time, interest in sex, premature or delayed ejaculation, time since last intercourse, need for or receiving sexual advice, or sexual satisfaction. Hypogonadism did not predict erectile dysfunction (OR 1.1 [95% CI 0.26-4.5]) or low sexual desire (OR 1.2 [95% CI 0.11-14]). Treatment modality had no obvious impact on sexual function. Conclusion. Men treated for testicular cancer had higher risk of having low sexual desire and erectile dysfunction 3 to 5 years after completion of therapy than comparators. These sexual dysfunctions were not significantly associated with treatment intensity or hypogonadism. Eberhard J, Ståhl O, Cohn-Cedermark G, Cavallin-Ståhl E, Giwercman Y, Rylander L, Eberhard-Gran M, Kvist U, Fugl-Meyer KS, and Giwercman A. Sexual function in men treated for testicular cancer. J Sex Med **;**:**-**.
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| 5. |
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| 6. |
- Isaksson, Sigrid, et al.
(author)
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Inhibin B concentration is predictive for long-term azoospermia in men treated for testicular cancer.
- 2014
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In: Andrology. - : Wiley. - 2047-2927 .- 2047-2919. ; 2:2, s. 252-258
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Journal article (peer-reviewed)abstract
- Azoospermia is a serious potential side effect following treatment for testicular cancer (TC). Our purpose was to examine possible predictors of long-term azoospermia in TC survivors. Ejaculates and blood samples were obtained from 217 patients at post-orchidectomy but before further treatment (T0 ) and/or at one or more of the time points 6, 12, 24, 36-60 months after treatment (T6 , T12 , T24 , T36-60 ). All patients delivered ejaculates at T36-60 , of which 117 also had confirmed presence of spermatozoa in the ejaculate at T0 , enabling longitudinal analyses. Types of therapy, cryptorchidism and Inhibin B before and after treatment were evaluated in relation to risk of azoospermia at T36 . Inhibin B levels at T6 , T12 and T24 were predictors of azoospermia at T36 with cut-off levels at 49.7, 55.9 and 97.8 ng/L respectively (sensitivity 100%, specificity 57-78%). The frequency of azoospermia in all patients at T36-60 was 7.8% (95% CI 4.9-12%). As compared to surveillance patients, only those receiving >4 cycles of chemotherapy or ≥4 cycles of chemotherapy + radiotherapy (RT) had increased risk of long-term azoospermia (63% vs. 4.4% in the surveillance group; p = 0.0018). In conclusion, all patients with sperm production at post-orchidectomy but before further treatment and Inhibin B >56 ng/L 12 months after treatment had sperm production 3 years post-treatment. Eight per cent of TC survivors had azoospermia 3-5 years post-treatment, with highest risk in those receiving >4 cycles of chemotherapy or ≥4 cycles of chemotherapy in combination with RT.
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| 7. |
- Krege, Susanne, et al.
(author)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part I
- 2008
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In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 478-496
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Research review (peer-reviewed)abstract
- Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 8. |
- Krege, Susanne, et al.
(author)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II
- 2008
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In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 497-513
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Research review (peer-reviewed)abstract
- Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. in addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 9. |
- Leandersson Bogefors, Karolina, et al.
(author)
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Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of spermatogenesis following testicular germ cell cancer treatment
- 2017
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In: Asian Journal of Andrology. - 1008-682X .- 1745-7262. ; 19:5, s. 538-542
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Journal article (peer-reviewed)abstract
- Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients (n = 130) delivered ejaculates at the following time points: postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy (T0, T6, T12, T24, T36, and T60). The CAG lengths were categorized into three groups, <22 CAG, 22-23 CAG, and >23 CAG, and the GGN tracts were also categorized into three groups, <23 GGN, 23 GGN, and >23 GGN. At T12, men with 22-23 CAG presented with a statistically significantly (P = 0.045) lower sperm concentration than those with other CAG numbers (8.4 × 10 6 ml-1 vs 16 × 10 6 ml-1 ; 95% CI: 1.01-2.65). This association was robust to omitting adjustment for treatment type and sperm concentration at T0 (P = 0.021; 3.7 × 10 6 ml-1 vs 10 × 10 6 ml-1 ; 95% CI: 1.13-4.90). The same trends were observed for total sperm number. The least active AR variant seems to be associated with a more rapid recovery of spermatogenesis. This finding adds to our understanding of the biology of postcancer therapy recovery of fertility in males and has clinical implications.
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| 10. |
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