Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer

Planas, Jacques; Celma, A.; Placer, J.; Cuadras, M.; Regis, Lucas; Gasanz, Carlos; Trilla, Enrique; Salvador, Carlos; Lorenté, David; Moróte, Juan

doi:10.1080/21681805.2016.1227876

Cited by 14 publications

(12 citation statements)

References 15 publications

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“…As expected, treatment significantly influenced free testosterone concentrations of the patients. Previous research corresponds with this finding, but in contrast to our study, most research measured serum testosterone, 16,34 but see Reference [35]. Measuring salivary testosterone offers the opportunity to detect the level of the free and bioactive testosterone.…”

Section: Discussionsupporting

confidence: 80%

The impact of long‐term androgen deprivation therapy on cognitive function and socioeconomic decision making in prostate cancer patients

et al. 2020

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Objective: Androgen deprivation therapy (ADT) enhances survival of advanced prostate cancer patients and is therefore used as a concomitant therapy. However, ADT has been reported to cause negative side effects on cognition and emotional processing. So far, research referred to the effects of short-term treatment. Since the brain may adapt to androgen deprivation, we were especially interested in the longterm effects of ADT on cognitive and socioeconomic decision making. Methods: Participants underwent a battery of tests that have been associated with testosterone. We compared the results of three matched test groups: (1) prostate cancer patients with ADT up to 20 years, (2) prostate cancer controls without treatment and (3) healthy controls. We further measured the morning testosterone content in participants' saliva. Results: Testosterone concentration was positively associated with visuospatial performance across and within the test groups. Patients with long-term ADT showed an overall decline in cognitive performance. Compared with untreated patients, ADT was also associated with a reduced intergroup bias during socioeconomic decision making, which was in line with previous observations in young men suggesting that testosterone may promote ingroup favoritism. Finally, depression scores were increased in ADT, while quality of life was negatively associated with the treatment. Conclusion: These findings conform to results made after short-term treatment. ADT promotes negative side effects on cognitive function. We also show for the first time that testosterone deprivation may affect socioeconomic decision making. Nevertheless, it should be emphasized that these effects cannot outweigh the previously described advantages of ADT in the treatment of prostate cancer.

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Section: Discussionsupporting

confidence: 80%

The impact of long‐term androgen deprivation therapy on cognitive function and socioeconomic decision making in prostate cancer patients

et al. 2020

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“…The behaviour of serum testosterone and serum LH after LH-RH agonist withdrawal has also been studied. The overall impression is that serum testosterone recovery may be slow, especially following a long administration of LH-RH agonists, while serum LH quickly increases after LH-RH withdrawal, reaching levels greater than those observed before LH-RH agonist administration [ 18 , 20 , 21 ]. Serum LH measurement has been used to analyse the switch from LHRH antagonists to LH-RH agonists; it has been noted that it remains low and stable during this manoeuvre [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…A limitation of our study was the difficulty to know the exact moment when a patient loss the effect of LH-RH agonist, especially in those patients using long-depot formulations. The behaviour of serum testosterone after LH-RH agonist withdrawal is well known trough the intermittent ADT studies [ 25 ]; however, less is known after long periods of continuous LH-RH agonist treatment [ 21 ]. Moreover, there is a lack of knowledge about the exact behaviour of serum LH after LH-RH agonist withdrawal because the actual CLIAs were not always used in the past [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients

et al. 2017

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BackgroundLuteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists.MethodsSerum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients “on LH-RH agonists”, 303 “off LH-RH agonist” in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion “no LH-RH agonist” who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on “LH-RH agonists” and 19 “off LH-RH agonists”, serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS).ResultsThe area under the curve (AUC) to distinguish patients “on versus off LH-RH agonists” was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients “on LH-RH agonists” was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients “on versus off LH-RH agonists” was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method.ConclusionsSerum LH is more accurate than serum testosterone regardless the method, to distinguish patients “on versus off LH-RH agonists”. The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.

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“…There was also no significant difference in the number of training sessions attended between the short‐term and long‐term group. Regarding testosterone levels, although testosterone recovery after cessation of treatment is dependent on duration of ADT , given the length of time since cessation of treatment in the present study, most men had recovered testosterone levels to within the normal or borderline range, and baseline testosterone was not a moderator of muscle strength or body composition. In addition, there was no change in testosterone levels over the 12‐month period.…”

Section: Discussionmentioning

confidence: 53%

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12‐month randomized controlled trial in men with prostate cancer

et al. 2017

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ObjectivesTo explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. Patients and MethodsIn a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 AE 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. ResultsTime on ADT significantly moderated the exercise effects on chair rise (b interaction = À1.3 s, 95% confidence interval [CI] À2.6 to 0.0), whole-body lean mass (b interaction = 1194 g, 95% CI 234 to 2153) and ASM mass (b interaction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (b interaction = À1107 g, 95% CI À2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time À1.5 s (95% CI À2.5 to À0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass À1377 g (95% CI À2156 to À598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (À2.0 s, 95% CI À3.0 to À1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. ConclusionsMen with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. TrialAs a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects.

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Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer

Cited by 14 publications

References 15 publications

The impact of long‐term androgen deprivation therapy on cognitive function and socioeconomic decision making in prostate cancer patients

The impact of long‐term androgen deprivation therapy on cognitive function and socioeconomic decision making in prostate cancer patients

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12‐month randomized controlled trial in men with prostate cancer

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