| 41. |
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| 42. |
- Giwercman, Aleksander, et al.
(författare)
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Novel protein markers of androgen activity in humans : proteomic study of plasma from young chemically castrated men
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. Results: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (<8 nmol/l) vs normal (>12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. Funding: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program.
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| 43. |
- Giwercman, Aleksander, et al.
(författare)
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Testicular cancer and molecular genetics.
- 2005
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Ingår i: Andrologia. - : Hindawi Limited. - 0303-4569 .- 1439-0272. ; 37:6, s. 224-225
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Tidskriftsartikel (refereegranskat)
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| 44. |
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| 45. |
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| 46. |
- Giwercman, Yvonne, et al.
(författare)
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The 5alpha-Reductase Type II A49T and V89L High-Activity Allelic Variants are More Common in Men with Prostate Cancer Compared with the General Population.
- 2005
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 48:Jul 20, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare men with prostate disease with those from the general population regarding polymorphisms in the androgen receptor gene and in the 5 alpha-reductase II (SRD5A2) gene. Materials and methods: The SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n = 89), benign prostate hyperplasia (n = 45) and healthy military conscripts (n = 223). Results: The SRD5A2 high-activity allele variants A49T AT and V89L LL were more frequent in CaP-patients compared to general population, p = 0.026 and p = 0.05, respectively. CaP progression was, however, independent of SRD5A2 variants. In contrary, men with GGN < 23 had a higher risk of dying from the disease than their counterparts with longer repeats. Conclusions: Men with CaP were more often genetically predisposed to a higher enzymatic activity in the turn over from T to DHT compared to the general population. In our population, androgen receptor genotype affected CaP outcome.
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| 47. |
- Isaksson, Sigrid, et al.
(författare)
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Inhibin B concentration is predictive for long-term azoospermia in men treated for testicular cancer.
- 2014
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Ingår i: Andrology. - : Wiley. - 2047-2927 .- 2047-2919. ; 2:2, s. 252-258
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Tidskriftsartikel (refereegranskat)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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| 48. |
- Kvist, Linus, et al.
(författare)
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Exposure to persistent organic pollutants and sperm sex chromosome ratio in men from the Faroe Islands.
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 73, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- People in the Arctic as well as fishermen on the polluted Swedish east coast are highly exposed to persistent organic pollutants (POPs). These compounds have been shown to affect the sperm Y:X chromosome ratio. In present study, the aim was to investigate whether polychlorinated biphenyl (PCB) congeners and 1,1,-dichloro-2,2,-bis(p-chlorophenyl)ethane (p,p'-DDE) influence sperm sex chromosome ratio in Faroese men, and whether these men differ regarding Y:X ratio compared to Greenland Inuit and Swedish fishermen. The study population (n=449) consisted of young men from the general population (n=276) as well as proven fertile men (n=173). The Y:X ratio was assessed by fluorescent in situ hybridization. Serum concentrations of POPs were measured using gas chromatography. Associations between POP concentrations and Y:X ratio were calculated using linear and non-linear regression models as well as trend analysis and pairwise comparison of exposure data categorized into quartiles. The selected POPs were associated with Y:X ratio in fertile Faroese men, but not in the total population; p,p'-DDE (95% CI for B=-0.005 to -0.001, p=0.005) and ΣPCB (95% CI for B=-0.005 to -0.001, p=0.012). Since p,p'-DDE and ΣPCB correlated significantly (r=0.927, p<0.001), the results involving the exposure variables can be regarded as a single finding. The Y:X ratio for the total Faroese population was 0.500±0.018, which was statistically significantly lower than in both Inuit and Swedish fishermen (0.512 for both). In conclusion, Faroese men presented with lower Y:X ratio than Greenland Inuit and Swedish fishermen. Although no direct health effects are expected due to the lower Faroese Y:X ratio, it could be indicative of adverse effects on the reproductive system.
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| 49. |
- Kvist, Linus, et al.
(författare)
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Serum levels of perfluorinated compounds and sperm Y:X chromosome ratio in two European populations and in Inuit from Greenland.
- 2012
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238.
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated whether perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), which exhibit reproductive toxicity in experimental animals, affect sperm sex chromosome ratio. The Y:X ratio was determined by fluorescence in situ hybridization. Serum concentrations of PFOA and PFOS were measured in 607 men from Greenland, Poland and Ukraine using liquid chromatography-tandem mass spectrometry. Data was analyzed by linear and nonlinear regression. We observed no associations between PFOA and Y:X ratio (p=0.845 in a linear model, p=0.296 in a nonlinear model). A positive nonlinear association between PFOS and Y:X ratio was observed (p=0.016), with no association in a linear model (p=0.118). Analyzing the populations separately, a negative trend between categorized PFOS exposure and Y:X ratio was observed for the Inuit (B=-0.002, p=0.044). In conclusion, there was a negative trend between Y:X ratio and PFOS in the Inuit, while there was no association between PFOA and the Y:X ratio in adult men.
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| 50. |
- Leandersson Bogefors, Karolina, et al.
(författare)
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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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Ingår i: Asian Journal of Andrology. - 1008-682X .- 1745-7262. ; 19:5, s. 538-542
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Tidskriftsartikel (refereegranskat)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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