Table of Contents  
LETTER TO THE EDITOR
Year : 2018  |  Volume : 20  |  Issue : 6  |  Page : 634-636

Worsening of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in patients with prostate cancer after androgen deprivation therapy


1 Department of Urology, Toho University Sakura Medical Center, Sakura-shi, Chiba 285-8741, Japan
2 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA

Date of Submission09-Dec-2017
Date of Acceptance19-Mar-2018
Date of Web Publication01-Jun-2018

Correspondence Address:
Dr. Takanobu Utsumi
Department of Urology, Toho University Sakura Medical Center, Sakura-shi, Chiba 285-8741, Japan; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aja.aja_33_18

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How to cite this article:
Oka R, Utsumi T, Endo T, Yano M, Kamijima S, Kamiya N, Suzuki H. Worsening of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in patients with prostate cancer after androgen deprivation therapy. Asian J Androl 2018;20:634-6

How to cite this URL:
Oka R, Utsumi T, Endo T, Yano M, Kamijima S, Kamiya N, Suzuki H. Worsening of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in patients with prostate cancer after androgen deprivation therapy. Asian J Androl [serial online] 2018 [cited 2020 Dec 5];20:634-6. Available from: https://www.ajandrology.com/text.asp?2018/20/6/634/233682 - DOI: 10.4103/aja.aja_33_18



Dear Editor,

Prostate cancer (PCa) is the most frequently diagnosed male cancer in Western countries, and the number of PCa patients is also rapidly increasing in Japan.[1],[2] Simultaneously, androgen deprivation therapy (ADT) has also been increasingly used in PCa patients in recent years.[3],[4],[5] However, the long-term use of ADT is associated with a variety of pivotal adverse events, including diabetes, anemia, osteoporosis, serum lipid profile changes, and cardiovascular disease (CVD).[1],[2] Higher low-density lipoprotein cholesterol (LDL-C) and/or lower high-density lipoprotein cholesterol (HDL-C) are well-established risk factors for CVD, and control of their levels has been an important goal in the treatment and prevention of CVD.[6],[7] Recently, another alternative parameter, the LDL-C to HDL-C (L/H) ratio, has been reported to be strongly associated with CVD and is thought to be a better predictor of future CVD than LDL-C alone. Closely monitoring serum lipid profile, including the L/H ratio changes affected by ADT, is a key to preventing CVD in PCa patients. Moreover, we previously suggested that a higher L/H ratio might have an impact on the development of arterial stiffness after ADT administration.[7] Although some cutoff points of the L/H ratio have been reported in clinical use, it has been suggested that thrombosis can occur when the L/H ratio increases to around 2.5 or more in East Asian populations.[6] The aim of the present study was to investigate the changes in serum lipid profile and to identify the clinical factors associated with an increased L/H ratio in PCa patients who received ADT.

This was a retrospective study approved by the institutional review board of Toho University Sakura Medical Center (No. 2012-008). All patients enrolled in the study gave their written informed consent. One hundred patients with pathologically confirmed PCa scheduled to receive ADT for more than 6 months between March 2012 and August 2015 were analyzed. Patients and the statistical analysis methods are minutely described in the Supplementary Materials and Methods [Additional file 3]. Briefly, the patients were divided into three groups for assessment: (I) receiving medical treatment for dyslipidemia (n = 29); (II) baseline L/H ratio of 2.5 or more without medical treatment for dyslipidemia (n = 22); and (III) baseline L/H ratio of <2.5 without medical treatment for dyslipidemia (n = 49). Group III patients were also assessed using uni- and multivariate analyses to determine the associations between an increased L/H ratio and baseline variables.

Supplementary Table 1 [Additional file 1] shows the baseline characteristics of the patients in this study. [Figure 1] shows the changes in serum lipid profiles and testosterone at baseline and after 3 and 6 months of follow-up in all enrolled patients. ADT significantly lowered testosterone levels. After 3 months of follow-up, total cholesterol (TC, P<0.001), HDL-C (P=0.010), and LDL-C (P=0.007) were significantly increased, while triglycerides and L/H ratio did not show significant changes in all patients. Supplementary Table 2 [Additional file 2] shows the results of patients in each group. TC, HDL-C, and LDL-C increased significantly after 6 months of ADT administration in each group of patients. The L/H ratio (mean±s.d.) increased significantly from 1.8±0.5 to 1.9±0.6 (P = 0.004) in Group III patients, while it did not change significantly in Group I and II patients. The L/H ratio increased to 2.5 or more in 7 of the 49 patients in Group III after 6 months of follow-up. The clinical predictors associated with an increased L/H ratio of 2.5 or more on uni- and multivariate analyses are summarized in [Table 1]. Multivariate analysis revealed that HDL-C was an independent predictor of an increased L/H ratio of 2.5 or more after 6 months of follow-up (odds ratio: 1.13, P = 0.013).
Figure 1: Changes in serum lipid profile and testosterone at baseline and after 3 and 6 months of follow-up in prostate cancer patients after ADT; (a) TC, (b) HDL-C, (c) LDL-C, (d) L/H, (e) triglycerides, and (f) testosterone. *P < 0.05. TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; L/H: ratio of LDL-C to HDL-C; ADT: androgen deprivation therapy.

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Table 1: Uni- and multivariate analyses of the clinical variables at baseline for new-onset of low-density lipoprotein/high-density lipoprotein cholesterol ratio ≥2.5 after androgen deprivation therapy

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LDL-C levels increased significantly in this study, even in patients who took lipid-lowering drugs, while HDL-C levels also increased significantly [Supplementary Table 2]. In our study, enrolled patients did not have new-onset CVD within 6 months of follow-up. Although the duration of follow-up might have been too short to investigate new-onset CVD after ADT, increased HDL-C levels might have offset the cardiovascular risk caused by increased LDL-C levels. The L/H ratio is considered to be a clinically useful marker of cardiovascular events, and an increased L/H ratio is associated with an increased risk of cardiovascular events; in particular, baseline L/H ratios above 2.5 are associated with an increased risk of cardiovascular events.[8] In this study, the L/H ratio showed a significant increase in Group III. This study is the first to show that there exist a group of patients who have a higher risk of a worsening L/H ratio within the initial 6-month follow-up period after ADT despite having favorable baseline serum lipid profiles. Moreover, this study is the first to suggest that HDL-C is an independent predictor of an increased L/H ratio of 2.5 or more after 6 months of follow-up. Although these relationships still remain controversial, hypercholesterolemia is reported to be associated with a shorter time to castration-resistant PCa (CRPC) after ADT and survival after treatment for CRPC.[9],[10] From the viewpoint of not only cardiovascular risk but also cancer management, it seems to be very important to aggressively manage dyslipidemia with the use of statins after initiation of ADT in patients with PCa.

Clinicians should pay attention not only to patients receiving medical treatment for dyslipidemia or with an L/H ratio of 2.5 or more but also to patients with an L/H ratio of <2.5. This study shows that patients with a baseline L/H ratio of <2.5 have a risk of worsening L/H ratio, although they seem to be “good lipid metabolism patients.” Clinicians can identify and manage PCa patients with a greater risk of worsening serum lipid profiles after ADT more effectively.


  Author Contributions Top


RO recruited patients, conducted this project, drafted the manuscript, and performed the statistical analyses; TU recruited patients, planned this project, performed the statistical analyses, and proofread the manuscript; TE, MY, and SK recruited patients and proofread the manuscript; NK recruited patients, proofread the manuscript, and participated in this project design and coordination; HS recruited patients, proofread the manuscript, participated in this project design and coordination, and obtained the grant for this project. All authors read and approved the final manuscript.


  Competing Interests Top


Hiroyoshi Suzuki received an honorarium, fees for promotional materials, and research funding from Takeda, Astellas, Janssen, AstraZeneca, Sanofi, and Nippon Kayaku.


  Acknowledgment Top


This work was supported by JSPS KAKENHI (Grant-in-Aid for Scientific Research (C), Grant Number 16K11030 to Hiroyoshi Suzuki).

Supplementary information is linked to the online version of the paper on the Asian Journal of Andrology website.



 
  References Top

1.
Suzuki H, Kamiya N, Imamoto T, Kawamura K, Yano M, et al. Current topics and perspectives relating to hormone therapy for prostate cancer. Int J Clin Oncol 2008; 13: 401–10.  Back to cited text no. 1
    
2.
Imamoto T, Suzuki H, Utsumi T, Endo T, Takano M, et al. Association between serum sex hormone levels and prostate cancer: effect of prostate cancer on serum testosterone levels. Future Oncol 2009; 5: 1005–13.  Back to cited text no. 2
    
3.
Hou WH, Huang CY, Wang CC, Lan KH, Chen CH, et al. Impact of androgen-deprivation therapy on the outcome of dose-escalation prostate cancer radiotherapy without electice pelvic irradiation. Asian J Androl 2017; 19: 596–601.  Back to cited text no. 3
    
4.
Kao LT, Lin HC, Chung SD, Huang CY. No increased risk of dementia in patients receiving androgen deprivation therapy for prostate cancer: a 5-year follow-up study. Asian J Androl 2017; 19: 414–7.  Back to cited text no. 4
    
5.
Wang Y, Dai B, Ye DW. Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients. Asian J Andorl 2017; 19: 178–83.  Back to cited text no. 5
    
6.
Chen QJ, Lai HM, Chen BD, Li XM, Zhai H, et al. Appropriate LDL-C-to-HDL-C ratio cutoffs for categorization of cardiovascular disease risk factors among Uygur adults in Xinjiang, China. Int J Environ Res Public Health 2016; 13: 235.  Back to cited text no. 6
    
7.
Oka R, Utsumi T, Endo T, Yano M, Kamijima S, et al. Effect of androgen deprivation therapy on arterial stiffness and serum lipid profile changes in patients with prostate cancer: a prospective study of initial 6-month follow-up. Int J Clin Oncol 2016; 21: 389–96.  Back to cited text no. 7
    
8.
Kameda S, Sakata T, Kokubo Y, Mitsuguro M, Okamoto A, et al. Association of platelet aggregation with lipid levels in the Japanese population: the Suita study. J Atheroscler Thromb 2011; 18: 560–7.  Back to cited text no. 8
    
9.
Jeon JC, Park J, Park S, Moon KH, Cheon SH, et al. Hypercholesterolemia is associated with a shorter time to castration-resistant prostate cancer in patients who have undergone androgen deprivation therapy. World J Mens Health 2016; 34: 28–33.  Back to cited text no. 9
    
10.
Di Lorenzo G, Sonpavde G, Pond G, Lucarelli G, Rossetti S, et al. Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol Focus 2017. pii: S2405-4569 (17) 30083-4.  Back to cited text no. 10
    


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