Support Care Cancer (2014) 22:1699–1704 DOI 10.1007/s00520-014-2195-2
REVIEW ARTICLE
A systematic review of opioid effects on the hypogonadal axis of cancer patients Kerry McWilliams & Claribel Simmons & Barry J. Laird & Marie T. Fallon
Received: 6 November 2013 / Accepted: 2 March 2014 / Published online: 15 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Opioids are the mainstay of analgesic therapy in patients with cancer-related pain. While many of the side effects of opioids are well documented, the effect on the hypogonadal axis is less well understood. The aim of this systematic review is to examine the relationship between opioid therapy and hypogonadism in patients with cancer. Methods An electronic search of the following databases was undertaken: MEDLINE, Embase and CINAHL from 1974 to August 2013. To be eligible for inclusion, studies had to meet the following criteria: adult patients (>18 years) with cancer taking any opioid by any route for any duration, gonadal function measured and the relationship between opioid use and gonadal function examined. All potentially eligible papers were reviewed independently and data extracted using a pro forma. Results Four studies met the inclusion criteria. Due to the heterogeneous nature of the studies, it was not possible to amalgamate the results. Three studies suggested a relationship between opioid use and hypogonadism in patients with cancer. These studies also suggested this relationship to be dose dependent. There was evidence to suggest that hypogonadism was symptomatic and associated with reduced survival. One study showed no link between opioids and hypogonadism. Conclusions Studies conducted have suggested an association between opioids and hypogonadism in patients with
K. McWilliams (*) : C. Simmons : B. J. Laird : M. T. Fallon Edinburgh Cancer Research UK Centre, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK e-mail: [email protected] K. McWilliams : C. Simmons : B. J. Laird Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK B. J. Laird : M. T. Fallon Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
cancer. This warrants further investigation. A longitudinal study examining the impact of opioids on the hypogonadal axis would be of interest. Keywords Hypogonadism . Opioids . Cancer . Endocrine
Introduction Ninety per cent of patients with cancer will experience cancer-related pain [1]. Opioids are the foundation of cancer pain control, and the World Health Organization (WHO) analgesic ladder advocates their use for the management of cancer pain [2]. Although opioids are given with the aim of analgesia, they have many well-recognised side effects including nausea, vomiting, constipation, urinary retention, dry mouth, hallucinations, myoclonus and sedation [3]. These side effects are common and require early recognition and treatment. Recently, attention has focused on adverse effects of opioids that have been less well recognised, including hypogonadism. Work to date has demonstrated hypogonadism in patients taking opioids for non-malignant pain, with low levels of luteinising hormone (LH), oestradiol, free testosterone (fT) and total testosterone (TT) [4]. The spectrum of symptoms associated with hypogonadism is similar to common cancer symptoms. These include decreased energy, lack of motivation, depressed mood, poor concentration and memory and diminished physical performance [5]. The aim of this systematic review is to examine the relationship between opioid therapy and hypogonadism in patients with cancer.
Methods Ethical approval was not required for this systematic review. An electronic search of the following databases was undertaken:
1700
MEDLINE, Embase and CINAHL (1974 to August 2013). Search terms included ‘neoplasm’, ‘cancer’, ‘opioids’, ‘endocrine’, ‘hormone’ and ‘hypogonads’. The search was limited to articles published in English and in humans. To be eligible for inclusion, studies had to meet the following criteria: adult patients (>18 years) with cancer taking any opioid by any route for any duration, gonadal function measured and the relationship between opioid use and gonadal function examined. Titles and abstracts were screened independently by two researchers and the full text of articles deemed suitable obtained. Additional articles were identified through hand searching of references. Subsequently, full-text articles were assessed for eligibility and data were extracted independently by two researchers using a pro forma. Any disagreement in selection was discussed between the researchers. The date of the last literature search was on 20 August 2013.
Support Care Cancer (2014) 22:1699–1704
1091 records identified through database search
1056 titles rejected 35 abstracts screened and 2 identified through hand searching 24 abstracts rejected 13 full text articles assessed for eligibility 9 full text articles rejected 4 articles included
Results
Fig. 1 Literature search
The literature search process is shown in Fig. 1. A total of 1,091 titles were identified following the literature search. Thirty-five abstracts were screened independently by two researchers which resulted in 13 full-text articles being reviewed. A further two full-text articles were identified through hand searching. Following this, four articles were eligible. Eligible studies are listed and summarised in Table 1. Meta-analysis of eligible studies was not possible due to heterogeneity; therefore, a descriptive report of eligible studies is presented. The study by Skipworth et al. showed an association between opioid use and reduced LH, follicular stimulating hormone (FSH) and testosterone levels in men [6]. This pattern suggests a secondary cause of hypogonadism; reduced pituitary hormones, LH and FSH, resulted in reduced stimulation of the testes to produce testosterone. The association was dose related (TT r2 =−0.494, p
REVIEW ARTICLE
A systematic review of opioid effects on the hypogonadal axis of cancer patients Kerry McWilliams & Claribel Simmons & Barry J. Laird & Marie T. Fallon
Received: 6 November 2013 / Accepted: 2 March 2014 / Published online: 15 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Opioids are the mainstay of analgesic therapy in patients with cancer-related pain. While many of the side effects of opioids are well documented, the effect on the hypogonadal axis is less well understood. The aim of this systematic review is to examine the relationship between opioid therapy and hypogonadism in patients with cancer. Methods An electronic search of the following databases was undertaken: MEDLINE, Embase and CINAHL from 1974 to August 2013. To be eligible for inclusion, studies had to meet the following criteria: adult patients (>18 years) with cancer taking any opioid by any route for any duration, gonadal function measured and the relationship between opioid use and gonadal function examined. All potentially eligible papers were reviewed independently and data extracted using a pro forma. Results Four studies met the inclusion criteria. Due to the heterogeneous nature of the studies, it was not possible to amalgamate the results. Three studies suggested a relationship between opioid use and hypogonadism in patients with cancer. These studies also suggested this relationship to be dose dependent. There was evidence to suggest that hypogonadism was symptomatic and associated with reduced survival. One study showed no link between opioids and hypogonadism. Conclusions Studies conducted have suggested an association between opioids and hypogonadism in patients with
K. McWilliams (*) : C. Simmons : B. J. Laird : M. T. Fallon Edinburgh Cancer Research UK Centre, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK e-mail: [email protected] K. McWilliams : C. Simmons : B. J. Laird Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK B. J. Laird : M. T. Fallon Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
cancer. This warrants further investigation. A longitudinal study examining the impact of opioids on the hypogonadal axis would be of interest. Keywords Hypogonadism . Opioids . Cancer . Endocrine
Introduction Ninety per cent of patients with cancer will experience cancer-related pain [1]. Opioids are the foundation of cancer pain control, and the World Health Organization (WHO) analgesic ladder advocates their use for the management of cancer pain [2]. Although opioids are given with the aim of analgesia, they have many well-recognised side effects including nausea, vomiting, constipation, urinary retention, dry mouth, hallucinations, myoclonus and sedation [3]. These side effects are common and require early recognition and treatment. Recently, attention has focused on adverse effects of opioids that have been less well recognised, including hypogonadism. Work to date has demonstrated hypogonadism in patients taking opioids for non-malignant pain, with low levels of luteinising hormone (LH), oestradiol, free testosterone (fT) and total testosterone (TT) [4]. The spectrum of symptoms associated with hypogonadism is similar to common cancer symptoms. These include decreased energy, lack of motivation, depressed mood, poor concentration and memory and diminished physical performance [5]. The aim of this systematic review is to examine the relationship between opioid therapy and hypogonadism in patients with cancer.
Methods Ethical approval was not required for this systematic review. An electronic search of the following databases was undertaken:
1700
MEDLINE, Embase and CINAHL (1974 to August 2013). Search terms included ‘neoplasm’, ‘cancer’, ‘opioids’, ‘endocrine’, ‘hormone’ and ‘hypogonads’. The search was limited to articles published in English and in humans. To be eligible for inclusion, studies had to meet the following criteria: adult patients (>18 years) with cancer taking any opioid by any route for any duration, gonadal function measured and the relationship between opioid use and gonadal function examined. Titles and abstracts were screened independently by two researchers and the full text of articles deemed suitable obtained. Additional articles were identified through hand searching of references. Subsequently, full-text articles were assessed for eligibility and data were extracted independently by two researchers using a pro forma. Any disagreement in selection was discussed between the researchers. The date of the last literature search was on 20 August 2013.
Support Care Cancer (2014) 22:1699–1704
1091 records identified through database search
1056 titles rejected 35 abstracts screened and 2 identified through hand searching 24 abstracts rejected 13 full text articles assessed for eligibility 9 full text articles rejected 4 articles included
Results
Fig. 1 Literature search
The literature search process is shown in Fig. 1. A total of 1,091 titles were identified following the literature search. Thirty-five abstracts were screened independently by two researchers which resulted in 13 full-text articles being reviewed. A further two full-text articles were identified through hand searching. Following this, four articles were eligible. Eligible studies are listed and summarised in Table 1. Meta-analysis of eligible studies was not possible due to heterogeneity; therefore, a descriptive report of eligible studies is presented. The study by Skipworth et al. showed an association between opioid use and reduced LH, follicular stimulating hormone (FSH) and testosterone levels in men [6]. This pattern suggests a secondary cause of hypogonadism; reduced pituitary hormones, LH and FSH, resulted in reduced stimulation of the testes to produce testosterone. The association was dose related (TT r2 =−0.494, p
