Influence of androgen deprivation therapy on physical performance and muscle strength in prostate cancer patients — a systematic review

Abstract

The aim of this study was to assess the impact of androgen deprivation therapy (ADT) on muscle strength and physical performance in prostate cancer (PC) patients.

The systematic search was carried out across four databases: PubMed, Embase, Web of Science, and Scopus. Out of 5239 studies, 6 were included, where the standardized functional tests assessing functional mobility were used. The protocol was registered on PROSPERO. Data indicated that the grip strength decreases most rapidly at the beginning of ADT therapy and does not return to its initial values. The gait speed decreases with the duration of ADT and indicates that the patients are at increased risk of adverse outcomes. According to the Short Physical Performance Battery and the time Up and Go test results PC patients present good performance and good mobility. Changes in muscle strength and physical performance in PC patients undergoing ADT are visible and need attention of professionals to prevent further body composition changes.

Introduction

Prostate cancer (PC) is the most prevalent type of cancer in men after the age of 60 and is responsible for one third of cancer-related deaths among men in the European Union [1]. Due to the increasing average lifespan of men in developed countries, the population of PC patients is expected to grow, leading to a greater demand for professional medical care for those affected by the disease. The primary method of treating PC, regardless of the presence of metastases, is androgen deprivation therapy (ADT) that slows down the progression of the neoplasm by decreasing the level of testosterone and dihydrotestosterone which can often make PC shrink or grow slower for a period of time [2, 3]. However, this therapy causes numerous undesirable side effects, including changes in body composition such as increase in body fat mass (FM) and decrease in lean body mass (LBM) [4]. Reduction in LBM is associated with decrease of muscle strength, that further leads to the lack of energy and loss of agility, worsened physical condition and other subfactors of quality of life (QoL) [5]. Finally, the reduced LBM increases the risk of falls, which can lead to injuries and, subsequently, complications that may result in increased mortality [6]. To prevent the negative effects of ADT treatment, specifically the reduction of LBM, it is crucial to focus on body composition changes, including sarcopenia development.

There are a variety of tests/methods tailored to the patient’s functional capabilities [7]. Handgrip strength test is a simple and effective tool for general muscle strength assessment, while the chair rise test evaluates lower limb muscle strength and endurance, directly correlating with daily functionality, frailty and fall risk. Gait speed serves as an indicator of overall physical strength and agility, whereas the Short Physical Performance Battery (SPPB) determines body balance, muscle strength and physical endurance. Regular conduction of given tests ensures the early detection of declining physical performance, allowing for quick implementation of preventive measures in order to prevent further deterioration of muscle condition and, as a result, maintain a relatively good QoL for patients [6]. Literature supports addition of physical activity during ADT as an effective form of prevention of muscle strength loss [8].

In this systematic review, we aimed to assess the impact of ADT on muscle strength and in relation to the physical performance in PC patients undergoing the treatment.

Materials and methods

Search strategies

The search was carried out across four databases: PubMed, Embase, Web of Science, and Scopus. The protocol was registered on PROSPERO and is currently available at the following link: https://www.crd.york.ac.uk/PROSPERO/view/CRD420250655254. The search strategy involved the use of MeSH terms, Emtree terms, and specific keywords, which were tailored to each database. No filters were applied. Search strategy was included in the Supplementary File — Tab. S1.

Study selection

Studies on men suffering from prostate adenocarcinoma confirmed by histopathology, qualified for ADT treatment based on the guidelines, i.e. the European Society of Urology (EAU) and the European Society for Medical Oncology (ESMO), were included. No restrictions regarding age of patients or ADT implementation was done. Any additional intervention for example: exercise, supplements intake or nutritional therapy was an exclusion criterium. The data on the muscle strength or physical performance was collected at the baseline and in follow-up (if available). The following methods/tests for performance and mobility in the included studies were used: the handgrip, the gait speed, the SPPB and the Time Up and Go Test (TUG). The SPPB consists of three components: a balance test, a timed walk, and a chair stand test. Each component of the SPPB is scored, and the scores are combined to create a total SPPB score, ranging from 0 to 12, where higher scores indicate better physical performance. TUG is performance-based measure of lower extremity function, mobility and fall risk that can be completed, for example, by healthy individuals aged 60–80 years in 10 seconds or less. The authors of the reviewed articles were contacted via e-mail when necessary. The results of the search are displayed in a flow diagram (Fig. 1), following the PRISMA guidelines [9].

Figure 1.

Flow chart describing the study selection process

Each database was searched by two independent teams and the list of articles was downloaded. With the help of the Zotero program, duplicates were filtered out, and the results were subsequently reviewed by three researchers, then double checked by other two. Only articles written in English were included. First, articles with titles unrelated to the study topic were excluded from the review. At this stage, articles were selected for abstract review. Conference abstracts, reviews, and study protocols were excluded. The next step involved qualifying articles for full-text review through assessment of abstracts’ suitability. Additionally, articles from earlier stages that raised doubts were included in this poll. Finally, studies eligible for inclusion were listed and assessed by authors independently. All disagreements were resolved by mutual discussion.

Risk of bias

The risk of bias was assessed in all included articles using the Newcastle-Ottawa scale. For cross-sectional studies, a custom 10-point modification of the scale was used. The cut-off point was 6 points.

Results

The systematic review included 6 papers (cohort study, cross-sectional, case-control) published between 2007 and 2024 (Tab. 1). Based on the measure, analyzed papers were divided into three groups (single assessment, during ADT, at baseline and at the follow-up assessment at baseline during ADT and follow-up and single assessment during ADT). Study populations ranged from 11 to 1448 individuals who came from the USA [11–13], Australia [10, 14] or Turkey [15]. The control population consisted either of either healthy individuals [13–15] or oncological patients [10–14]. Only the study by Leong et al. [12] specified the specific agent used for ADT. In general, the studied patients can be characterized as older men with several comorbidities [10, 12, 13], with mean body mass index (BMI) suggested overweigh development. Only two studies assessed LBM [10,13]. The Self-reported Charlson Score for description of the diseases occurrence was used by Gonzalez et al. [11] (Supplementary File — Tab. S2). The Gleason score in ADT patients indicated an advanced stage of PC. In two studies [10, 15], the presence of cancer metastases was one of the exclusion criteria, while in others, such patients were included in the study group [11, 12, 14]. Similarly, only a portion of the patients underwent chemotherapy, radiotherapy, or prostatectomy [11, 12, 14]. This fact showed the studies heterogeneity. The measurement of PSA levels and total testosterone was described in only 3 research papers. The duration and type of ADT varied between 3 months [13], and 39.7 months [13]. In one of the studies [13], two research groups were included, subjected respectively to Short-term ADT (therapy duration of less than 6 months) and Long-term ADT (therapy duration of more than 6 months) (Supplementary File — Tab. S3). The patients mobility was assessed using dedicated tests. In most studies, muscle strength was measured using a dynamometer [10–12, 14, 15], while other researchers used the Gait Speed [13, 14], SPPB [10, 13] and TUG [12] (Tab. 2). Data indicated that the grip strength decreases most rapidly at the beginning of ADT therapy and does not return to its initial values. The gait speed decreases with the duration of ADT and indicates that the patients are at increased risk of adverse outcomes. According to the SPPB and the TUG test results, PC patients present good performance and good mobility.

Table 1.

Description of included studies (n = 6)

Analysed parameter	Assessment at the baseline and at the follow-up		Assessment at the baseline, during adt and at the follow-up	Single assessment during the ADT
Study	Cheung et al. [10]	Gonzalez et al. [11]	Leong et al. [12]	Clay et al. [13]	Owen et al. [14]	Soyupek et al. [15]
Year	2016	2016	2024	2007	2019	2008
Country	Australia	USA	USA	USA	Australia	Türkiye
Study design	Case-control study	Longitudinal study	Prospective cohort study	Cross-sectional study	Cross-sectional study	Case-control study
Study population	n = 34	Baseline n = 62 Follow-up: n = 37/262	Gonadotropin-releasing hormone agonist: n = 1448 Degarelix: n = 175 Bicalutamide: n = 824 Dutasteride: n = 32 Abiraterone: n = 60 Enzalutamide: n = 24 Apalutamide: n = 23 Darolutamide: n = 19 Cyproterone: n = 3 Estrogen: n = 2 Investigational hormonal therapies: n = 5	Short-term: ADT1: n = 13 Long-term: ADT2: n = 42	n = 70	n = 20
Control population	PC no ADT: baseline n = 29	PC no ADT: (prostatectomy) n = 86 Follow-up: n = 72/67	No ADT n = 2236	Healthy: n = 20 PC no ADT: n = 25	PC no ADT: n = 52 Healthy: n = 70	Healthy: n = 20
Newcastle Ottawa scale*	7	8	8	6	7	6

ADT — androgen deprivation therapy; PC — prostate cancer; Short-term ADT — therapy duration of less than 6 months; Long-term ADT — therapy duration of more than 6 months

Table 2.

Assessment of muscle strength measurements and physical performance in prostate cancer patients

Analyzed parameter	Assessment at the baseline and at the follow-up		Assessment at the baseline, during DT and at the follow-up	Single assessment during the ADT
Study	Cheung et al. [10]	Gonzalez et al. [11]	Leong et al. [12]	Clay et al. [13]	Owen et al. [14]	Soyupek et al. [15]
Grip strength methodology (dynamometer)	Performance: three trials for each arm Result: the best attempt	Performance: two trials for a dominant hand Result: the mean value	Performance: three trials for each arm, averaged	N/A	Position: seating, forearm resting on the chair, elbow bend at 90° Performance: three trials, each hand, alternating between hands Result: the best attempt	According to American Society of Hand Therapists Performance: three trials for dominant hand Result: the mean score 30–second periods between trials for both hands
Grip strength baseline study group	Dominant: 41.5 kg median, IQR 36.0–44.0 Non-dominant: 39.0 median, IQR 33.0–44.0	16.59 kg mean	Mean ± SD: 34.0 kg (33.4–34.5)	N/A	37.9 ± 6.5 kg	27.94 ± 5.82 kg
Grip strength follow-up study group	Dominant: 6 months, 36.0 kg median, IQR 32.0–42.0 12 months, 38.0 kg median, IQR 31.0–43.0 Non–dominant: 6 months, 32.0 kg median, IQR 24.0–40.0 12 months, 34.0 kg median, IQR 27.5–41.0	6 months: 16.15 kg mean 12 months: 15.71 kg mean	Mean ± SD: 24.7 kg (23.8–25.7)	N/A	N/A	N/A
Grip strength baseline control group	Dominant: 40.0 kg median, IQR 34.0–45.0 Non-dominant: 38.0 kg median, IQR 30.0–44.0	17.03 kg mean	Mean ± SD: 38.1 kg (37.6–38.7)	N/A	PC no ADT: Mean ± SD: 41.7 ± 6.7 kg Healthy: Mean ± SD: 43.3 ± 8.0 kg	Healthy: Mean ± SD: 39.17 ± 4.87 kg
Grip strength follow-up control group	Dominant: 6 months, 41.0 kg median, IQR 34.0–46.0 12 months, 43.0 kg median, IQR 37.0–48.0 Non-dominant: 6 months, 38.0 kg median, IQR 31.0–45.5 12 months, 42.0 kg median, IQR 32.5–44.0	6 months: 17.18 kg mean 12 months: 17.42 kg mean	Median (IQR): 31.3 kg (30.6–31.9)	N/A	N/A	N/A
TUG baseline study group	N/A	N/A	Mean ± SD: 10.2 s (10.1–10.3)	N/A	N/A	N/A
TUG follow-up study group	N/A	N/A	Mean ± SD: 10.1 s (9.9–10.4)	N/A	N/A	N/A
TUG baseline control group	N/A	N/A	Mean ± SD: 8.6 s (8.4–8.8)	N/A	N/A	N/A
TUG follow–up control group	N/A	N/A	Mean ± SD: 8.4 s (8.2–8.7)	N/A	N/A	N/A
Gait speed baseline study group	N/A	N/A	N/A	Short–term ADT1: Mean ± SD: 1.04 ± 0.25 m/s IQR 0.89–1.20 Long–term ADT2: Mean ± SD: 0.99 ± 0.21 m/s IQR 0.93–1.06	Mean ± SD: 1.43 (0.2) m/s	N/A
Gait speed follow-up study group	N/A	N/A	N/A	N/A	N/A	N/A
Gait speed baseline control group	N/A	N/A	N/A	PC no ADT: Mean ± SD: 1.06 ± 0.13 m/s IQR 1.01–1.12 Healthy: Mean ± SD: 1.17 ± 0.26 m/s IQR 1.04–1.29	PC no ADT: Mean ± SD: 1.48 ± 0.19 m/s Healthy: Mean ± SD: 1.50 ± 0.22 m/s	N/A
Gait speed follow-up control group	N/A	N/A	N/A	N/A	N/A	N/A
SPPB baseline study group	12 median, IQR 12–12	N/A	N/A	Short–term ADT1: Mean ± SD: 10.4 ± 1.7 IQR 9.4–11.4 Long–term ADT2: Mean ± SD: 9.6 ± 1.7 IQR 9.1–10.1	N/A	N/A
SPPB follow-up study group	6 months: 12 median, IQR 11–12 12 months: 12 median, IQR 11–12	N/A	N/A	N/A	N/A	N/A
SPPB baseline control group	12 median, IQR 11–12	N/A	N/A	PC no ADT: Mean ± SD: 10.4 ± 0.9 IQR 10.1–10.8 Healthy: Mean ± SD: 10.3 ± 0.9 IQR 9.9–10.7	N/A	N/A
SPPB follow-up control group	6 months: 12 median, IQR 12 12 months: 12 median, IQR 12	N/A	N/A	N/A	N/A	N/A

IQR — interquartile range; SD — standard deviation; ADT — androgen deprivation therapy; PC — prostate cancer; TUG — Timed Up and Go; SPPB — Short Physical Performance Battery; Short-term ADT — therapy duration of less than 6 months; Long-term ADT — therapy duration of more than 6 months

Discussion

The presented data indicated the changes in muscle strength, mobility and physical performance in PC patients during the ADT treatment. Both, the grip strength and the gait speed decrease the duration the oncological therapy, although the good performance and mobility among patients were described by the SPPB and the TUG test. There is a need to assess oncological patients with respect to body composition and daily function with standardized tests.

The ADT gives a significant side effects. In clinical setting, the measure of BMI is used to monitor the patients nutritional status, which unfortunately is weakly correlated with changes in the skeletal muscle index [16]. Loss of muscle mass in ADT patients is often accompanied by an increase in fat mass, which give the possibility to diagnose not only the sarcopenia itself but also the sarcopenic obesity [17]. The concentration of testosterone is positively associated with muscle mass, which in patients undergoing ADT translates into its decline [18]. Cheung et al. [10] reported a decrease in muscle strength only after the first 6 months of treatment, while measurements conducted in the 12^th month suggested an improvement. However, the obtained measurements did not reach the baseline values. In the study by Leong et al. [12] patients receiving ADT showed a significantly greater decrease in muscle contraction strength compared to patients who did not undergo ADT. In the remaining papers ADT was inextricably associated with decrease in grip strength [10–12, 14, 15]. It is worth to mention that, depending on the analyzed study, patients enrolled into the control group were either PC patients treated with other forms of therapy or healthy individuals [15]. Interestingly, Gonzalez et al. [11] indicated a trend of increased grip strength, which was probably related to the fact that clinical patients included into the control group underwent prostatectomy without pharmacological treatment. Nonetheless, muscle strength gains in the control group remained lower in comparison to its decline in the study group. Studies have shown that it is evident within the studied PC population that LBM is associated with muscle strength [19, 20]. The loss of muscle mass leads to proportional declines in muscle strength, particularly in older individuals [19, 21–23]. In the study by Araujo et al. [19] it was observed that age-related loss of strength is greater than the loss of muscle mass, suggesting that the decline in muscle strength is influenced not only by the reduction in muscle mass but also by the age-related deterioration in muscle quality. The patient groups analyzed in the selected studies were also characterized by reduced muscle strength. The included studies focused on older men with PC undergoing ADT, with a median age ranging from 67.6 to 74.4 years. The observed decline in muscle strength in the test results could be attributed to the previously mentioned association with ADT. Of course, the study population consisted of older patients who were inherently at risk of age-related declines in muscle strength. Most importantly, the included studies used different methods to evaluate muscle strength and performance. Nevertheless, each of them showed a similar trend — worsening of outcomes compared to original results in patients undergoing ADT [10–15]. In both clinical practice and scientific research, standardized tests are commonly employed for measuring muscle strength [21, 22], as was the case in the analyzed studies with regards to grip strength [10–12, 14, 15], gait speed [13, 14], SPPB [10, 13], and TUG [12]. Studies showed that although the lower limbs are more critical than the upper limbs for gait and physical function, grip strength is widely used in studies and is well correlated with the most significant outcomes [22]. Isometrically measured grip strength shows a strong relationship with lower limb muscle strength, knee extension torque, and calf muscle cross-sectional area [6]. Therefore, grip strength testing is a sufficient, reliable, and simple measure of muscle strength, additionally linked to leg strength [6, 22]. Based on current knowledge, there is no specific indication as to which tests are the best and most accurate. Thus, the choice of tests is solely based on the researcher’s personal preferences with respect to assessed population [21, 22].

Patients undergoing ADT generally demonstrated significantly worse TUG test outcomes compared to those with PC not receiving the therapy [12]. A slight reduction in test completion time was observed after 12 months of therapy in both groups of PC patients: the study group (with ADT) and the control group (without ADT) [12]. The test results suggest that patients undergoing ADT may be at increased risk of falls, so a wider diagnostic protocol and assessing tools to prevent the fall risk may be worth considering [24, 25]. Another test used in the analyzed studies was the gait speed test [13, 14]. Patients receiving ADT exhibited slower gait speeds compared to both non-ADT PC patients and healthy controls, regardless of treatment duration. The longer a patient was on ADT, the worse their results tended to be [13, 14]. Another assessed test was the SPPB, with results varying across studies. Either the results [10] remained stable regardless of the ADT duration, or ADT group patients experienced a decline in performance over time [13]. Clay et al. [13] indicated that walking speed varied significantly across different ADT groups of patients, including those with short and long term ADT treatment, even after adjusting for age, Comorbidity Disease Index (CMDI), and percentage of body fat. However, it should be highlighted that age and CMDI were significantly associated with measurements of physical performance, where men on long-term ADT walked 0.18 m/s slower than control patients with no PC. These findings suggest that PC patients receiving ADT may experience mild functional limitations, although these occur only in some patients. It has been proven that chemotherapy may also contribute to loss of body muscle mass, directly leading to impaired physical function, which can be measured using the grip strength test and chair rise test [26–28]. The carcinogenesis itself and non-pharmacological therapies, such as radiotherapy, may also indirectly have a negative impact on physical fitness among patients through cancer-related fatigue [29]. Additionally, it is important to remember that the cancer itself, with respect to the therapy used, can lead to further reduction in LBM through muscle wasting, cachexia or sarcopenic obesity [30–32]. Sarcopenia is also associated with a threefold increase in the risk of falls in comparison to non-sarcopenic population, which may lead further to a significant deterioration in QoL as well as to increase in mortality among the ADT patients [33–35].

There are data suggesting that it may be possible to prevent some of the muscle mass decline in a PC population. Resistance exercise has been shown to be an effective way to counterbalance some of the adverse effects associated with ADT, such as decrease in LBM and inferior mobility among older people affected with sarcopenia [36–38]. Strength training is suspected to improve muscle fibre capillarization and increase overall size of type I and II muscle fibres among PC patients [39]. It was also shown that 16 weeks of high-load resistance exercise intervention visibly improve body muscle strength, as well as slightly increase LBM in ADT patients [40]. Implementation of integrated aerobic and resistance exercise programs for men undergoing ADT can also mitigate cancer-related fatigue and thus significantly improve the QoL of patients [41]. A systematic review by Logan et al. [42] shows that 2 to 5 sessions of football training weekly are sufficient to conserve both the LBM and bone mass density of ADT patients, although the findings concerning the LBM were inconsistent across the evaluated studies [42]. Bloom et al.[43] pointed out that there is a connection between healthy, well-balanced diet and physical performance in people affected with sarcopenia. Nevertheless, there are very little data on correlation between a nutrient-rich diet and body muscle mass or a decrease in sarcopenia morbidity [43]. Protein, vitamin D, antioxidants and Omega-3 fatty acids are suspected to play a role in sarcopenia prevention [43, 44]. The influence of magnesium or selenium supplementation etc. was examined, but a clear impact on sarcopenia has not been shown [45]. As was highlighted, a healthy lifestyle, which involves a balanced diet, sufficient protein consumption, and regular physical activity, is important for adults of all ages [46]. Education in the aspect seems to be crucial for healthy ageing and quick recovery during the treatment. This can help maintain good QoL and enhance the ability to perform daily activities. Consequently, this may contribute to better therapy outcomes and reduce the risk of complications associated with long-term hormonal treatment.

Limitations

Sample size of included studies were rather small or median, where the heterogeneity of included patients with respect to time point of measurements and clinical assessment was visible. Nevertheless, a systematic review provides the opportunity to increase the sample size of the population by the analysis of single studies taken together. Data were also interpreted with the reference to the clinical situation of the patients. Many patients suffer from additional comorbidities; differ in the stage of cancer progression and overall condition, which could influence test results. We know from clinical practice that nutritional status, QoL and daily functioning change during the treatment process, and the use of standardized tests helps in the objective assessment of the patient from single studies. Still, the use of different standardized tests make an interpretation much more complicated. Importantly, the selected patients did not use any additional therapy, such as diet therapy or exercise. This gives a real picture of a patient who cannot or is not willing to act to improve their physical condition.

Conclusions

In conclusion, the changes in muscle strength and physical performance in PC patients undergoing ADT are visible and need attention of professionals to prevent further body composition changes. Therefore, it is crucial for the patients with PC undergoing the ADT to be subjected to appropriate preventive measures and lifestyle adjustments (balanced diet, regular physical activity) to counteract the adverse effects of ADT as much as possible. Undertaking such steps will have a significant effect on patients’ QoL.