Changes in bone mineral density and body composition during initial and long‐term gonadotropin‐releasing hormone agonist treatment for prostate carcinoma

Lee, Hang; McGovern, Katelyn; Finkelstein, Joel S.; Smith, Matthew R.

doi:10.1002/cncr.21381

Cited by 137 publications

(100 citation statements)

References 57 publications

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“…Sixteen longitudinal studies were included in the systematic review, 14 cohort studies [7,16,[18][19][20][21][22][23][24][25][26][27][28][29] and two RCTs [17,30]. Both RCTs were the continuation phase of a randomized design comparing the efficacy of two types of hormone therapy (LHRH analogue vs. anti-androgen).…”

Section: Study Characteristicsmentioning

confidence: 99%

The effect of androgen deprivation therapy on body composition in men with prostate cancer: Systematic review and meta-analysis

et al. 2010

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General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Abstract Introduction The use of androgen deprivation therapy (ADT) in the treatment of prostate cancer is associated with changes in body composition including increased fat and decreased lean mass. Limited information exists regarding the rate and extent of these changes. This systematic review was conducted to determine the effects of ADT on body composition in prostate cancer patients. Methods Literature searches were conducted on MEDLINE, EMBASE and Web of Science for studies until January 2009. Only longitudinal studies that examined ADT and body composition in prostate cancer patients were included. Data were extracted on body weight, BMI, percentage of fat mass and lean body mass. Results Sixteen studies (14 cohorts and 2 RCTs) met the inclusion criteria. Pooled data, calculated according to a random effects model, showed that ADT increased % body fat by on average 7.7% (95% CI 4.3, 11.2, from seven studies, P<0.0001) and decreased % lean body mass by on average −2.8% (95% CI −3.6, −2.0, from six studies, P<0.0001) but for both there was marked heterogeneity between studies (I2=99% I2=73%, respectively). Similarly, body weight (2.1%, P<0.0001 from nine studies) and BMI (2.2%, P< 0.0001, from eight studies) increased significantly. More extensive changes were seen with longer duration of treatment. Conclusions Substantial increases in fat and declines in lean mass were observed in prostate cancer patients treated with ADT. Lifestyle changes or suitable interventions to minimize the effect of ADT on body composition need to be investigated. Implications for cancer survivors Prostate cancer survivors should be made aware of the side effect of treatment on body composition and further work is required to determine what interventions can minimize the impact of ADT on body composition and therefore what evidence based advice they should be provided with. In general, though recommendation of a healthy diet and moderate exercise is reasonable.

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Section: Study Characteristicsmentioning

confidence: 99%

The effect of androgen deprivation therapy on body composition in men with prostate cancer: Systematic review and meta-analysis

et al. 2010

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“…The prevalence of metabolic syndrome in the recent deprivation group was 26%, whereas the chronic deprivation group presented a prevalence of 48%. Therefore, in our population, there is an increase in the prevalence of metabolic syndrome in patients submitted to androgen deprivation 22,23 .…”

Section: Metabolic Syndrome Secondary To the Hormonal Deprivationmentioning

confidence: 88%

Riscos cardiovasculares do bloqueio androgênico

Ribeiro

Câmara²,

Segre³

et al. 2010

Arq. Bras. Cardiol.

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increasing in the last years, a fact attributed mainly to the routine measurement of the prostate-specific antigen (PSA) in males aged 45 years and older. This type of cancer presents the highest correlation with age and it is believed, in the USA, that one in every six men will be diagnosed with prostate cancer in his lifetime 3 . In spite of the high incidence, the mortality rates are relatively low, with a projected number of deaths of little more than 27,000 in the USA in the year 2007, corresponding to 9% of the total number of cancer-related deaths. Approximately 86% of the diagnoses are attained when the disease is still localized and the disease-free five-year survival rate is close to 100% 4 . Prostate cancer treatment: attention to androgen deprivationRegarding the treatment, prostate cancer presents several therapeutic possibilities, such as radiotherapy/brachytherapy, prostatectomy, androgen deprivation therapy and even an expectant conduct in special situations, depending on the clinical stage of the disease, tumor aggressiveness assessment, the presence of comorbidities and the patient's life expectancy. Androgen deprivation therapy was first used by Huggins and Hodges in 19415 . Its effect is based on the fact that the prostatic neoplastic cells present a large number of androgen receptors on their surface and that their growth depends on the stimulation of these receptors. In brief, we can affirm that testosterone is the main circulating androgen and most of it is produced by Leydig cells in the testes, after central stimulation by the gonadotropin-releasing hormone (GnRH) and the luteinizing hormone (LH), which are secreted by the hypothalamus and the pituitary, respectively. After entering the prostate, testosterone is converted by 5α-reductase into dihydrotestosterone and binds to a cytoplasmic receptor, forming a complex that modulates the nuclear transcription and consequently, all cell activity 6 . The figure below illustrates this hormonal axis and the specific mediations used to block it (Figure 1).The androgen deprivation can be attained through GnRH agonists, steroidal and nonsteroidal antiandrogens, estrogens or bilateral orchiectomy. This review will cover only GnRH agonists and orchiectomy, the modalities considered to be the most efficient ones. GnRH agonists such as leuprolide and goserelin result in a central deprivation of testosterone secretion by suppressing the physiological pulsatility of GnRH secretion, with a consequent negative regulation of the pituitary receptors and lower LH secretion. These are long-acting medications administered by depot-injections. The orchiectomy is another form to inhibit androgen activity AbstractProstate adenocarcinoma is the most common cancer type in the male sex after skin cancer. Among the several types of treatment for prostate cancer, the androgen deprivation therapy has been highly recommended in patients with metastatic or locally advanced disease, which probably results in increased survival. However, the androgen deprivation is the cau...

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“…Notably, high rates of bone loss were observed despite concurrent administration of supplemental calcium and vitamin D and careful exclusion of secondary causes of osteoporosis [26,28]. Bone mineral density appears to decline steadily during long-term treatment [29,30].…”

Section: Changes In Bone Mineral Density During Androgen Deprivation mentioning

confidence: 99%

“…The similarity of results between these prospective 3-month and 12-month studies suggests that body composition changes are an early adverse effect and may be clinically important even with short-term therapy. Analyses of prospective changes in body composition during initial and long-term GnRH agonist treatment also suggests that fat mass increases and lean body mass decreases mostly during initial GnRH agonist therapy [30].…”

Section: Treatment-related Changes In Body Compositionmentioning

confidence: 99%

Androgen deprivation therapy for prostate cancer: new concepts and concerns

Smith

2007

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

148

129

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Purpose of review-The aim of this review is to summarize new concepts and concerns regarding treatment-related osteoporosis, diabetes, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer.Recent findings-Gonadotropin-releasing hormone agonists increase bone turnover, decrease bone mineral density, and increase fracture risk. Bisphosphonates, selective and estrogen receptor modulators significantly increase bone mineral density during androgen deprivation therapy. Ongoing randomized controlled trials will assess efficacy of denosumab, toremifene, and zoledronic acid to prevent fractures in this setting. Gonadotropin-releasing hormone agonists also increase fat mass, decrease insulin sensitivity, and increase serum lipoproteins. In contrast to the classical metabolic syndrome, however, the phenotype of men during androgen deprivation therapy is characterized by increased high-density lipoprotein cholesterol and preferential accumulation of subcutaneous fat. Gonadotropin-releasing hormone agonists are associated with greater risk of incident diabetes and cardiovascular disease in men with prostate cancer.Summary-Androgen therapy increases risk of fractures, diabetes mellitus, and cardiovascular disease in men with prostate cancer. Current and planned studies will evaluate strategies to prevent these treatment-related adverse effects.

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Changes in bone mineral density and body composition during initial and long‐term gonadotropin‐releasing hormone agonist treatment for prostate carcinoma

Cited by 137 publications

References 57 publications

The effect of androgen deprivation therapy on body composition in men with prostate cancer: Systematic review and meta-analysis

The effect of androgen deprivation therapy on body composition in men with prostate cancer: Systematic review and meta-analysis

Riscos cardiovasculares do bloqueio androgênico

Androgen deprivation therapy for prostate cancer: new concepts and concerns

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