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Objectives
We reviewed testosterone changes for patients who were treated with radiation therapy (RT) alone on NRG oncology RTOG 9408.
Methods and materials
Patients (T1b-T2b, prostate-specific antigen <20 ng/mL) were randomized between RT alone and RT plus 4 months of androgen ablation. Serum testosterone (ST) levels were investigated at enrollme...
Citations
... Studies showed that after abdominal radiotherapy for rectal cancer, sexual dysfunction and a reduction in sexual activity and desire are very common in men and women [10,11]. Recent studies have shown that radiotherapy can decrease serum testosterone levels in patients with prostate cancer [12]. In the animal model, 24 h after exposure of mice to 1-4 Gy γ radiation, increasing apoptosis in the germline cells was observed. ...
Objectives
The present study aims to investigate the effects of resistance training on sex hormones and sperm parameters in male rats under X-ray.
Methods
In this experimental study, 24 Sprague Dawley rats (200–250 g) were randomly assigned into four groups: healthy control, irradiated control, healthy training and irradiated training. Irradiation was induced at a dose of 4 Gy on the whole body. The resistance training protocol was performed for 10 weeks. Finally, blood serum was used to assess FSH, LH and testosterone and sperm quality. Data were analyzed using ANOVA and Tukey’s post hoc test.
Results
The results showed that radiation significantly reduced serum levels of LH (p=0.42), FSH (p=0.001) and testosterone (p=0.28) between radiation control and healthy control groups. Also, no significant difference was observed between serum levels of LH (p=0.135) and testosterone (p=0.419) in radiation resistance training and the healthy control groups. In addition, significant differences were observed between radiation resistance training and radiation control groups in sperm parameters such as sperm count (p=0.02) and progressively motile sperm (p=0.031).
Conclusions
It seems that short-term resistance training can improve sperm parameters, including sperm count and sperm motility through increasing serum levels testosterone and LH in male rat under X-ray.
... Previous studies on external-beam radiation therapy (EBRT) have evaluated changes in serum testosterone levels in patients receiving EBRT for prostate cancer [1][2][3][4][5][6][7][8][9] and other pelvic malignancies. 10,11 The NRG, a newly developed clinical trials network group consisting of the coordinated efforts of National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group recently reported on the RTOG 9408 and found that a total dose of 68.4 Gy to the prostate was only associated with a median decrease in testosterone of 13.5% at 3 months after treatment. ...
... 10,11 The NRG, a newly developed clinical trials network group consisting of the coordinated efforts of National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group recently reported on the RTOG 9408 and found that a total dose of 68.4 Gy to the prostate was only associated with a median decrease in testosterone of 13.5% at 3 months after treatment. 7 The majority of previous studies have also shown that the patients only experienced transient decrease of serum testosterone levels after EBRT. 2,[4][5][6]8 Further, low-dose scattered radiation to testicular Leydig cells is believed to be the most likely explanation for this phenomenon. ...
... However, data were either from a database of past clinical trials, and thus testosterone follow-up was not unified, 7,8 or acquired from a limited number of patients. 3,5,6 Moreover, one study has reported that scattered testicular radiation does not play a significant role in the reduction of serum testosterone level. 2 These limitations and inconsistencies raise a concern regarding a long-term impact of radiation on testosterone levels. ...
Purpose:
Concern about a long-term effect of the delivery of intensity modulated radiation therapy (IMRT) for prostate cancer on serum testosterone levels remains unelucidated. We evaluated how IMRT for localized prostate cancer affects serum testosterone levels during a follow-up period of up to 10 years.
Methods and materials:
We retrospectively evaluated data from 182 patients with localized prostate cancer who underwent definitive IMRT alone between 2007 and 2014. Serum total testosterone (TT) levels were measured by blood draws between 6 AM and 11 AM before treatment and at every posttreatment follow-up for 10 years. Pretreatment values and each posttreatment testosterone value were compared using a Wilcoxon signed rank test. The data set was stratified into 4 groups based on the pretreatment testosterone (pre-TT) values using quartiles.
Results:
The median absolute or relative changes in TT levels from pretreatment were -0.42 ng/mL or -12.0% at 3 months after radiation therapy (P < .0001). Subsequently, TT levels gradually recovered to nearly the pretreatment levels 24 to 36 months after IMRT. When analyzed according to the pre-TT quartile, median TT levels initially decreased at the 3- to 12-month period in all the quartiles; however, median TT levels increased from the 18-month period in the first and second quartile groups, whereas they were maintained at less than the pretreatment levels in the third and the fourth quartile groups throughout the entire decade after radiation therapy. The proportion of patients with hypogonadal status, defined as TT levels <3.00 ng/mL, did not increase over time.
Conclusions:
A transient and modest decrease of TT levels after IMRT spontaneously recovered to the pretreatment levels at the 24- to 36-month period except in patients in the higher quartile of pre-TT. This might have been partly owing to a variable sensitivity of individual testicular function to scattered radiation. Patients with lower pre-TT did not demonstrate a progressive overall rate of hypogonadism until 10 years after radiation therapy.
... Adverse effects of such radiation on spermatogenesis are mediated through the testes and exhibit further detrimental consequences on androgen production [124,161]. Nicholas et al. [162] exposed their patients to photon-based radiotherapy (RT) and reported de-creased serum testosterone levels. Another study on the exposure of patients with low prostate cancer risk to 76 Gy intensity-modulated radiotherapy (IMRT) for 36 months showed a decline in their testosterone levels [163]. ...
Hypogonadism is an endocrine disorder characterized by inadequate serum testosterone production by the Leydig cells of the testis. It is triggered by alterations in the hypothalamic–pituitary–gonadal axis. Erectile dysfunction (ED) is another common disorder in men that involves an alteration in erectile response–organic, relational, or psychological. The incidence of hypogonadism and ED is common in men aged over 40 years. Hypogonadism (including late-onset hypogonadism) and ED may be linked to several environmental factors-induced oxidative stresses. The factors mainly include exposure to pesticides, radiation, air pollution, heavy metals and other endocrine-disrupting chemicals. These environmental risk factors may induce oxidative stress and lead to hormonal dysfunctions. To better understand the subject, the study used many keywords, including “hypogonadism”, “late-onset hypogonadism”, “testosterone”, “erectile dysfunction”, “reactive oxygen species”, “oxidative stress”, and “environmental pollution” in major online databases, such as SCOPUS and PUBMED to extract relevant scientific information. Based on these parameters, this review summarizes a comprehensive insight into the important environmental issues that may have a direct or indirect association with hypogonadism and ED in men. The study concludes that environmental factors-induced oxidative stress may cause infertility in men. The hypothesis and outcomes were reviewed critically, and the mechanistic approaches are applied through oxidant-sensitive pathways. This study also provides reccomendations on future therapeutic interventions and protective measures against such adverse environmental factors-induced hypogonadism and ED.
... Testicular atrophy and variation of the male sex hormones and quality of sexual life following prostate radiotherapy have also been observed [14]. On the other hand, testosterone suppression was not observed after PT, and this may have been due to lower scatter radiation doses delivered to testicular Leydig cells [15,16]. Yoon et al. [17] reported that secondary doses during prostate PT were ∼10 −4 Sv Gy -1 at 50 cm from the beam isocenter and were an order of magnitude lower than during conventional IMRT. ...
... Testosterone deficiency causes late-onset hypogonadism and promotes obesity, insulin resistance, metabolic syndrome and type 2 diabetes mellitus [29,30]. Based on the present results and previous findings [15,16], PT for prostate cancer is considered to be beneficial because it does not decrease serum testosterone and does not appear to have an impact on these metabolic diseases and symptoms. If the possibility of metabolic syndrome is reduced and muscle strength is maintained, the urinary and bowel QOL may also be maintained [31]. ...
Since sexual function and testosterone levels after image-guided proton therapy (IGPT) have not yet been examined in detail, we prospectively evaluated changes before and after IGPT. Among patients treated with IGPT with or without combined androgen blockade (CAB) therapy between February 2013 and September 2014, patients who agreed to participate in the study and were followed up for >3 years after IGPT were evaluated. Serum testosterone levels were regularly measured together with prostate-specific antigen (PSA) levels before and after IGPT. The Erection Hardness Score (EHS) and the sexual domain summary, function subscale and bother subscale of the sexual domain in the Expanded Prostate Cancer Index Composite (EPIC) were assessed. There were 38 low-risk, 46 intermediate-risk and 43 high- or very-high-risk patients (NCCN classification). Although serum testosterone levels in low-risk patients did not decrease after IGPT, reductions were observed in the average EHS and the sexual domain summary score of the EPIC. In intermediate-, high- and very-high-risk patients, testosterone and PSA levels both increased following the termination of CAB after IGPT, and the average EHS increased. The sexual domain summary score gradually increased, but not above minimally important differences. In intermediate-risk patients, the function subscale increased from 4.4 to 14.8 (P < 0.05) 12 months after IGPT and reached a plateau after 60 months. The results of the present study would suggest the potential of IGPT, and further prospective studies to directly compare IGPT with other modalities are warranted.
... [8][9][10][11][12] Furthermore, delivery of local radiation therapy has been found to result in a transient decline in serum testosterone level in men with LPCa. 13,14 However, it remains unknown whether the sequencing of ADT with local radiation therapy has any impact on kinetics of testosterone recovery after treatment completion. Moreover, it remains unclear whether kinetics of testosterone recovery bear any association with the risk of relapse in this patient population. ...
Purpose
We performed a secondary analysis of a phase III randomized trial to determine the influence of sequencing of radiotherapy and ADT on post-treatment testosterone recovery and implications of testosterone recovery on subsequent relapse.
Methodology
Localized prostate cancer patients with Gleason score ≤7, clinical stage T1b-T3a, and prostate-specific antigen <30 ng/mL were randomized to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate radiotherapy (NHT arm) or concurrent and adjuvant ADT for 6 months starting simultaneously with radiotherapy (CAHT arm). Full testosterone recovery (FTR) was defined as recovery of testosterone to >10.5 nmol/L in patients with baseline ≥10.5 nmol/L or to baseline level in patients with baseline <10.5 nmol/L. Restricted mean survival time (RMST) since ADT initiation to supra-castrate testosterone level (>1.7 nmol/L) and FTR was compared between the arms using a truncation time point of 36 months.
Results
The adjusted difference in RMST to supra-castrate testosterone between the CAHT and NHT arm was 1.5 months (95% CI: 0.5 to 2.5, p=0.005). No difference was noted in RMST to FTR between the arms (18.7 versus 18.5 months, adjusted difference: 0.5, 95% CI: -1.4 to 2.4, p=0.61). There was no evidence of heterogeneity of treatment effect (interaction p=0.76) on risk of relapse over subgroups stratified by testosterone recovery to supra-castrate level at 15 months after start of ADT. Based on a multi-state Markov model, no independent effect of time to FTR on risk of subsequent relapse was observed (adjusted hazard ratio: 1.02, 95%CI: 0.96-1.08).
Conclusion
Patients should be counselled that after treatment with prostate radiotherapy and 6 months of ADT, it needs on average an additional 12 months for the FTR to occur. This is independent of the sequencing of ADT and radiotherapy. Furthermore, recovery of testosterone does not appear to impact the risk of subsequent relapse.
... This result is in harmony with previous investigation which revealed that Se cytoprotective effects are related to its antioxidant sparing action [43]. The serum testosterone hormone level was evaluated as an acknowledged marker for male full reproductive potential and used as an indicator for testicular injury [47]. It is a major androgenic steroid, produced from Leydig cells [5]. ...
... This study verified that radiation exposure incited testosterone level reduction. It is in a good agreement with previous studies which revealed that even low-dose scatter radiation has a harmful influence on Leydig cell function and thus testosterone level decline [1,47]. In contrast, irradiated rats treated with MSA diminished the testosterone level decline. ...
... Sertoli and Leydig cells were reported to show no histological changes at low doses of irradiation, because of their relatively radioresistant nature (Mettler 1985). In many studies, testosterone has been used to reverse deteriorating functions for therapeutic purposes, since the testosterone blood level decreases after irradiation (Zagars and Pollack 1997;Shetty et al. 2000;Nichols et al. 2017). However, testosterone treatment was not recommended in a study in rats after exposure to lowdose ionizing radiation since normal testicular functions was reported within two months after irradiation of groups independent of testosterone treatment (Demir et al. 2015). ...
Therapeutic radiation of the pelvic region has been shown to cause damage to testicular germ cells. In this study we aimed to evaluate the effects of a low therapeutic dose of 1 Gy on the induction of cellular and histological damage in early-stage testicular germ cells and the impact of this radiation on offspring sex ratio. Unirradiated and irradiated male rats were mated with unirradiated female rats. Female rats were followed and the sex of the offspring was determined. The male rats were sacrificed at the end of the second week, and the testicular germ cells were subjected to genetic analysis along with cytological and histopathological examination. Sperm DNA was amplified with primers specific to testis-specific Y-linked protein, rat actin beta and testis-specific X-linked genes. The resulting products were separated by capillary electrophoresis. Histopathological changes were investigated by light microscopy along with the TUNEL assay and immunohistochemical staining for caspase-3. There was no significant difference between the two groups for sex ratio and size of offspring. The number of sperm cells bearing X or Y chromosomes’ did not differ significantly between these two groups. However, a 1 Gy dose of radiation caused significant cytopathological and histopathological changes in the testicular tissue. In the irradiated group, edematous regions were evident. The number of caspase-3 positive cells in the germinal epithelium of the seminiferous tubules was also significantly higher in the irradiated group. Our results showed that low-dose radiation induced apoptosis and caused significant cyto- and histopathological changes in the testicular tissue. Further research is required to fully elucidate their contribution to apoptosis and if low-dose radiation may potentially lead to long-term effects in the offspring. These results may also lead us to develop a new technique using the caspase-3 staining to monitor the susceptibility to low dose radiation.
... A secondary analysis of Radiation Therapy Oncology Group 9408 found that 66.6 to 68.4 Gy in 1.8 Gy fractions was associated with a median decrease in testosterone of 9.3% at 3 months after treatment, comparable to the median decrease of 13.41% (mean, À4.49%) in the present study at the 3-to 6-month time point. 18 The largest study to date followed a cohort of 666 patients who received 52.5 to 70 Gy in 1.6 to 2.6 Gy fractions and found a median decrease of 17% at 6 months after treatment, after which testosterone recovered. 10 Oermann et al studied rates of biochemical and clinical hypogonadism in 26 patients treated at a single institution with 36.25 Gy in 5 fractions to the prostate on the CyberKnife. ...
Purpose:
The impact of higher scatter doses per fraction on testicular function and quality of life after prostate stereotactic body radiation therapy (SBRT) is poorly studied.
Methods and materials:
Six hundred thirty-six patients treated with SBRT for low- to intermediate-risk prostate cancer from 2009 to 2014 were included. Changes in testosterone and in sexual and hormonal domain scores on the Expanded Prostate Cancer Index Composite-26 (EPIC) questionnaire over a 24-month period were evaluated via a 1-sided t test. EPIC score changes were evaluated in comparison with a distribution-based minimal clinically important difference threshold, wherein changes of greater than one half or greater than one third of the standard deviation in each domain were considered as medium-sized or small-sized effects, respectively.
Results:
Median and mean percent changes in testosterone at the 3- to 6-month, 7- to 12-month, 13- to 18-month, and 19- to 24-month time periods were -13.41% and -4.49% (P = .02); -12.23% and -2.77% (P = .13); -11.20% and -0.29% (P = .47); -5.00% and + 1.20% (P = .65). When analyzed after dividing the cohort into 3 groups based on baseline testosterone values using tertiles, testosterone tended to increase in patients in the first group and decrease in patients in the third group. Overall, the decline in EPIC hormonal domain scores never exceeded the threshold for a small-sized effect, though the decline in EPIC sexual domain scores did pass this threshold at the 19- to 24-month time period (mean 10.90 point decline). This decline was not present when groups were examined individually.
Conclusions:
In this large cohort of prospectively followed patients, there was a transient decline in testosterone shortly after SBRT that normalized by 24 months posttreatment. There was no significant change in EPIC hormonal domain scores. A significant decline in EPIC sexual domain scores, consistent with a small-sized clinically detectable difference, manifested between 19 and 24 months of follow-up. These results are consistent with testosterone decline patterns and sexual function changes seen after other forms of photon-based radiation therapy.
... Among the potential side effects of EBRT, concerns have been raised over the past several decades regarding hypothesized risks of iatrogenic hypogonadism related to the incidental exposure of radiation therapy to the testicles from scattered photons or daily portal imaging [1][2][3]. However, few empirical clinical data exist to evaluate these concerns [1,2,[4][5][6][7][8][9][10][11]. ...
... A study by King et al. in 2010 raised similar concerns about iatrogenic hypogonadism, though this time highlighting the potentially unrecognized effects of daily portal imaging and/or scatter EBRT, external beam radiation therapy; LDR, low dose rate (brachytherapy); IQR, interquartile range; BMI, body mass index; IMRT, intensity modulated radiation therapy; MV, megavoltage; Tx treatment; T value, serum testosterone laboratory value dose from large fields during pelvic nodal radiotherapy, with a suggestion that doses as low as 2-4 Gy may be detrimental in older men whose Leydig cell function might be altered [3]. A more recent prospective study reported by Nichols et al. in 2017 found a 9% reduction of serum testosterone in 371 evaluated patients [11]. However, this study did not include a control arm and only followed patients for 3 months after EBRT completion, which is not adequate to allow for testosterone recovery, as implied by the time to recovery in previously published data [2,[4][5][6][7]11]. ...
... A more recent prospective study reported by Nichols et al. in 2017 found a 9% reduction of serum testosterone in 371 evaluated patients [11]. However, this study did not include a control arm and only followed patients for 3 months after EBRT completion, which is not adequate to allow for testosterone recovery, as implied by the time to recovery in previously published data [2,[4][5][6][7]11]. As with any retrospective evaluation of clinical data, there are limitations with the external validity of the findings reported herein. ...
Objective
There is a paucity of clinical data to support the hypothesis that external beam radiation therapy causes iatrogenic hypogonadism in prostate cancer patients.
Methods
All prostate cancer patients treated at a single institution with radiation therapy between 2002 and 2010 were retrospectively evaluated. Patients treated with brachytherapy alone received 0 Gy of external beam radiation therapy and served as the control group. Patients treated with combination external beam radiation therapy + brachytherapy, or external beam radiation therapy alone were categorized into groups who received 45–54 Gy or > 60 Gy of external beam radiation therapy, respectively. Serum testosterone levels were routinely measured with prostate-specific antigen tests.
Results
The median follow-up periods for 149 evaluable patients in the control group (0 Gy), the 45–54 Gy group, and > 60 Gy group were 57, 62, and 55 months, respectively (p = 0.43). Among patients who underwent external beam radiation therapy, 53% were treated with intensity-modulated radiation therapy, 65% with pelvic lymph node coverage, and 78% with 18 megavoltage photons. There were no differences in serum testosterone level declines over time between the 45–54 Gy group (p = 0.32) or the > 60 Gy group (p = 0.14) when compared to the control group (0 Gy). While body mass index was associated with baseline testosterone levels in univariate analysis (p < 0.0001), it was not associated with the rate of change following radiation therapy (p = 0.6).
Conclusion
Empirical evidence does not support the hypothesis that incidental exposure of the testicular Leydig cells from scattered photons and/or daily portal imaging affects testosterone levels.
