Abstract
Objective: To evaluate the association between visceral adiposity index (VAI) - a novel indicator for the assessment of visceral adipose tissue and prostate enlargement in non diabetic patients.
Material and methods: Four hundred patients who were admitted to the Urology clinic between January and December 2014 with complaints of BPH(benign prostatic hyperplasia )/LUTS(male lower urinary tract symptoms)were enrolled in this cross-sectional study. Patients were divided into two groups according to their prostate volume and international prostate symptom score (IPSS) value. They were compared in terms of age, body mass index (BMI), VAI, prostate volume, PSA, post micturional residual volume (PMRV), uroflowmetry Q max value, triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and fasting blood sugar (FBS).
Results: Although univariate analyses reveal that age, BMI, waist circumference (WC), FBS, TG, HDL-C level and TG/HDL ratio were correlated with prostate volume, only age [1.125 OR (1.088–1.164), p = .00001], BMI [1.119 OR (1.040–1.204), p = .003], TG [1.043 OR (1.016–1.071), p = .002], HDL-C [0.923 OR (0.860–0.990), p = .025] and VAI [1.194 OR (1.110–1.305), p = .011] were statistically significant in multivariate analysis. A positive correlation was found between VAI value and prostate volume in the Spearman correlation test (r = 0.29, p = .00001). The calculated area under the curve (AUC) for prostate volumes of 30, 40 and 50 ml were 0.680 (0.621–0.738), 0.625 (0.570–0.681) and 0.590 (0.528–0.652), respectively.
Conclusion: Our study revealed a positive correlation between VAI and prostate volume. Our results are needed to be tested with well-designed randomized prospective cohort studies.
Introduction
Benign prostate hyperplasia (BPH) and accompanying lower urinary tract symptoms is one of the most common disease in aging men which results in severe and frequent low urinary symptoms reducing the quality of life [Citation1]. Although evidence suggest important associations between prostate enlargement and multiple systems including the changes in the fields of nerve, endocrine, immune or local factors, the exact mechanism has not yet been provided [Citation2,Citation3].
The association between prostate enlargement and metabolic derangements and its possible implications in clinical settings are of great interest. As patients with BPH are aging male population, the context of metabolic disorders comprise a broad spectrum including testosterone deficiency, suboptimal vitamin D status and chronic inflammatory changes particularly resulting from obesity and related diseases. Scientific evidence suggest potential association of metabolic disorders including inflammatory markers with benign and malignant proliferative diseases [Citation4]. In this regard it is plausible to propose a close relationship between the most frequent benign neoplasm of aging male, benign prostatic hyperplasia and those aforementioned agents. Many studies provide strong link between metabolic syndrome and prostate enlargement [Citation5–7]. Metabolic syndrome and/or its individual components are closely related to visceral adiposity which was considered to be associated with insulin resistance, diabetes mellitus, hypertension and atherosclerosis [Citation8,Citation9]. Amato et al. [Citation10] introduced a new metabolic index, visceral adiposity index (VAI), based on waist circumference, body mass index (BMI), TGs and high-density lipoprotein (HDL) cholesterol expressing visceral fat function and distribution indirectly. They found that VAI was associated with all components of metabolic syndrome and higher VAI levels were correlated with insuline sensitivity deterioration. The studies about VAI were accumulated on the potential association between VAI and cardiovascular risk factors including diabetes mellitus, metabolic syndrome and its components [Citation11,Citation12] and literature is sparse in terms of the potential association of BPH. Given that common mechanisms might be implicated in BPH pathogenesis, it is reasonable to assume that VAI might be associated with BPH/LUTS (male lower urinary tract symptoms).
Body size and composition have long been hypothesized to influence the risk of prostate hyperplasia. Although a cluster of published epidemiological data demonstrates that obesity may increase the risks of BPH and LUTS [Citation13–15] it still lacks the quantitative evidence to certify this association. Furthermore, using only anthropometric indices cannot be sufficient to evaluate the visceral adiposity and VAI is a new index combining both anthropometric and lipid parameters that reflects visceral adiposity more precisely. In light of these factors, we aimed to evaluate the association between VAI and BPH/LUTS.
To the best of our knowledge this is the first study in the literature comparing VAI scores between patients grouped according to IPSS score and prostate volume.
Methods
Patients selection
Four hundred patients who were admitted to the Urology outpatient clinic between January and December 2014 with lower urinary tract symptoms due to BPH were enrolled in this cross-sectional study. Institutional review board approval from Okmeydani Training and Research Hospital Ethics Committee was obtained before the start of the research with the reference number of 48670771-514.10. All participants signed an informed consent before being enrolled in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Exclusion criterias
Patients with the suspicion of prostate cancer because of high PSA (>4 ng/dl) and abnormal digital rectal examination received an ultrasonography guided transrectal biopsy. If prostate cancer was detected they were excluded from the study. Patients with acute or chronic prostatitis, urethral stricture, neurogenic bladder, or previous lower urinary tract surgery were also excluded from the study. Since PSA levels would change, patients taking 5-α reductase inhibitors for benign prostate hyperplasia were also excluded from the study. The participants with the diagnosis of diabetes were also excluded from the study.
Interventions
Detailed medical history and physical examination were performed for all patients. The weight and height of participants were measured and BMI was calculated as weight in kilograms divided by height in meters square (kg/m2). Waist circumference was measured at the narrowest point and at the end of normal exhalation by using a flexible tape without compressing skin and with 0.1 mm precision.
Lower urinary tract symptoms were assessed using the international prostate symptom score (IPSS). The questionnaire based on seven questions was completed during the interview. LUTS was appropriately stratified as none/mild (0–7), moderate (8–19), or severe (20–35) and uroflow test measuring the peak urinary flow rate was also performed to appreciate the complaints of the patients objectively. Digital rectal examination was performed to establish the approximate prostate volume and patients with suspicious findings were assessed for Transrectal ultrasound guided (TRUS) guided biopsy. Prostate volume was measured according to the prostate ellipsoid formula, multiplying the largest anteroposterior (height, H), transverse (width, W) and cephalocaudal (length, L) prostate diameters by 0.524 (H × W × L × π/6) using TRUS. Post void residual volume was measured for all patients by ultrasonography. FBS, TG, total cholesterol, HDL cholesterol and PSA levels were measured from a fasting time blood draw. LDL cholesterol was calculated by means of the formula of Friedewald and colleagues. We divided the study population into two groups: mild-moderate symptoms and severe symptoms. We also divided the participants into two groups according to prostate volume: Prostate volume <40 ml and Prostate volume >40 ml. We compared the anthropometric characteristics (height, weight and waist circumference), age, body mass index (BMI), biological parameters (LDL-C, total cholesterol level, TGs, HDL-C, blood glucose level and VAI) and BPH/LUTS measurements (prostate volume, IPSS, post void residual volume, Q max value, PSA level) between the two groups.
VAI was calculated for males from the formula as used in the previous study by Zou et al. [Citation7].
VAI: WC/[39.68 + (1.88 × BMI)] × TG/1.02 × 1.31/HDL
where WC: waist circumference; BMI: body mass index; TG: tryglycerideand HDL: high-density lipoprotein
Statistical analysis
Sample size was estimated to detect a VAI value difference of 0.50 between prostate volume groups. The selection of a VAI value difference of 0.50 was based on a pilot study conducted in 30 patients (none of the data from the pilot study were included in the analysis). The standard effect size was set at 0.41 with 80% effect (1-β) and 5% standard error (α) margin. According to this calculation, n = 95 cases for each group were found sufficient.
The participants were divided into two groups according to prostate volume (prostate volume greater than 40 ml or not) and symptom score (patients with mild or moderate symptoms and those with severe symptoms). The normality test was performed using Kolmogorov-Smirnov test. Mann Whitney U test was performed comparing continuous variables between the two groups. Chi square test was performed for categorical variables. Univariate and multivariate logistic regression analyses were performed to identify the potential confounders affecting prostate volume. Hosmer and Lemeshow test was performed to determine the eligibility of logistic regression analysis. Spearman correlation test was performed between prostate volume and VAI value. Receiver operating characteristic (ROC) curves were plotted with sensitivity (true-positive fraction) on the y-axis and 1-specificity (false-positive fraction) on the x-axis. ROC curve was plotted for VAI value to predict prostate volume.
All analyzes were performed using SPSS ver. 20 (SPSS Inc., Chicago, IL ). All demographic values were presented as means with standard deviations. All tests for statistical significance were 2-tailed and p < 0.5 was deemed significant.
Results
A total of 400 participants were eligible based on exclusion/inclusion criteria. Among them, 186 (46.5%) had mild-moderate symptom score, while 214 (53.5%) had severe symptom score. Patients with severe symptoms have been found to have statistically higher BMI and FBS, but lipid profile measurements were not statistically different. Mean value of VAI in patients with mild-moderate symptoms was 4.07 ± 1.92, while that was 4.12 ± 1.93 in patients with severe symptoms and no statistically significant difference was observed. Patients with severe symptoms have larger prostate volume (54.78 ± 27.52 and 42.91 ± 17.43 respectively, p = .0001). The patients, whose clinical and demographic features were stratified by symptom score are presented in .
Table 1. Clinical and demographic features of the patients stratified by symptom score.
Compared with the lower prostate volume group, patients with larger prostate volume were more likely to have higher age (67.26 ± 7.97 vs. 62.14 ± 7.69; p = .0001), BMI (27.39 ± 3.67 vs. 25.79 ± 3.46; p = .0001), FBS (91.13 ± 10.50 vs. 87.09 ± 12.70; p = .0001), WC (99.88 ± 12.52 vs. 95.13 ± 9.80; p = .0001), TG (116.66 ± 46.93 vs. 101.49 ± 32.54; p = 0.0001) and VAI (4.48 ± 2.04 vs. 3.71 ± 1.73; p = .0001) ratio. summarizes the main characteristics of the patients stratified by prostate volume.
Table 2. Clinical and demographic features of the patients stratified by prostate volume.
Table 3. Univariate and multivariate analysis of the factors effective on prostate volume.
Univariate and multivariate logistic regression analyzes were conducted to determine the potential confounders for prostate volume. Hosmer and Lomeshow test was performed and we found that the binary logistic regression model was eligible (p = .082). Although univariate analyzes revealed that age, BMI, WC, FBS, TG, HDL-C level and VAI were correlated with prostate volume, only age [1.125 OR (1.088–1.164), p = .00001], BMI [1.119, OR (1.040–1.204), p = .003], TG [1.043 OR (1.016–1.071), p = .002], HDL-C [0.923 OR (0.860–0.990), p = .025] and VAI [1.194 OR (1.110–1.305), p = .011] were statistically significant in multivariate analysis. The details are demonstrated in .
demonstrates the ROC curve for VAI to predict prostate volume. The calculated area under the curve (AUC) with confidence intervals (CI) for prostate volumes of 30, 40 and 50 ml were 0.680 (0.621–0.738), 0.625 (0.570–0.681) and 0.590 (0.528–0.652), respectively. A positive correlation was found between VAI value and prostate volume in the Spearman correlation test (r = 0.29, p = .00001). demonstrates the dot graph of this association.
Figure 1. ROC curves of VAI levels for prostate volume cutoff level of (A) 30, (B) 40 and (C) 50 ml, respectively.
Figure 2. The doth graph of the association between VAI and prostate volume.
Discussion
The purpose of our study was to examine the association between VAI and prostate enlargement. Our cross-sectional study demonstrated a positive correlation between VAI and prostate volume.
Many indices were identified for evaluating adipose tissue. Of these, the leading index is BMI and many studies have demonstrated a positive correlation between prostate size, LUTS and BMI. However, BMI has some handicaps such as combining adipose and non-adipose body components, thus other indices such as waist-to-hip ratio were introduced. Seim et al. [Citation16] demonstrated that elevated waist-to-hip ratio and BMI were associated with increased LUTS.
Kristal et al. [Citation17], examined risk factors for BPH in 5667 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) and found that each 0.05 increase in waist-to-hip ratio was associated with a 10% increased risk of BPH. A case-control study by Dahle et al. [Citation18] also demonstrated that men with higher waist-to-hip ratios were more likely to undergo BPH surgery. WC, which is used to determine central obesity, was also associated with LUTS [Citation19–21]. Lee et al. [Citation19] demonstrated that WC was associated with MetS components as well as larger prostate size and worsened voiding function and suggested WC as an easy diagnostic tool to elucidate the presence of occult voiding dysfunction. These studies clearly provide a link between BPH/LUTS and obesity, but some potential issues should be taken into account while interpreting these data. It is unclear whether WC or BMI or waist-to-hip ratio constitutes the best anthropometric parameter for correlating voiding dysfunction with central obesity. Furthermore, these are only measurement tools indirectly suggestive of general body composition or central obesity and their accuracy can easily be affected by ethnical and racial changes.
Although we did not find significant differences between the patients grouped according to IPPS score, a positive correlation was found between prostate volume and VAI. This might result from the fact that although BPH and LUTS are closely related conditions, LUTS is a relatively recent term defining a cluster of symptoms arising from prostate and bladder disorders. Although we excluded conditions other than BPH that might cause LUTS, they are not completely overlapping terms. Furthermore, we should also take into account that the participants in our study were only divided into two groups in terms of LUTS severity as mild-moderate and severe and we did not assess the irritative and obstructive symptoms separately. These considerations might have altered the results.
Previous studies [Citation22–25] have shown that prostate volume was higher in obese patients. We excluded the participants with diabetes since diabetes is also another risk factor for larger prostate volume. There are many reports suggesting a causal relationship between high insulin levels and the development of BPH and hypothesizing increased sympathetic nerve activity in men with BPH [Citation26,Citation27]. Higher VAI means basically higher waist circumference, which is a well-known risk factor for insulin resistance. This is a condition resulting in higher IGF-1 levels, which is a proliferative factor for prostate growth. Our study revealed that patients with higher VAI scores have larger prostate size indicating that VAI was associated with static components of BPH/LUTS.
MetS, which is a cluster of potential cardiovascular risk factors including dyslipidemia, type 2 DM or hyperinsulinemia, hypertension and central obesity, is a growing health problem worldwide and obese patients constitute the main part of this syndrome. Patients with higher VAI scores were found to have larger BMI and WC. Obesity enhances many risk factors like hypertension and diabetes and it results in hyperinsulinemia. There has also been evidence for a positive correlation between obesity and inflammation. This is another link between higher VAI scores and larger prostate volume. It is reasonable to propose that inflammation resulting from many systematical changes emerging from obesity may result in prostate enlargement, which ultimately causes LUTS. In light of these explanations, the components of VAI may be interpreted as the metabolic assessment of the patients. When considering that the patients with BPH/LUTS who are over 50 years strong correlation has been found between BPH/LUTS and MetS. Life style modifications would be beneficial to decrease the cardiovascular risk as well as lower urinary tract symptoms. Although two groups stratified by symptom score did not reveal statistically significant differences in terms of VAI score, we should take into account that participants enrolled in our study all had the complaints of BPH/LUTS. Thus we should interpret these results with this in mind. Maybe comparing the patients with no complaints of BPH/LUTS and those with BPH/LUTS would result in more reliable and precise conclusions.
We have identified the ROC curve for VAI to prostate volume and AUC was calculated. Although the result of this association was statistically significant, the area under the curve was not very large for all prostate volumes (30, 40 and 50 ml) and it was not plausible to provide different VAI cutoff values. However, we may conclude from these curves that VAI is more indicative for prostate volume of 30 ml compared to others (40 and 50 ml).
Considering demographic characteristics of the participants included in our study, hypogonadism and related disorders should not be overlooked in the population. Testosterone deficiency syndrome is a biochemical and clinical entity associated with aging and characterized by a deficiency in serum testosterone level that may affect multiple organ systems and lead to significant deterioration in the quality of life. Many studies indicate a close relationship between hypogonadism and metabolic disorders [Citation28,Citation29]. Several inflammatory cytokines such as TNF-α, IL-6 and IL-1β released from particularly visceral adipose tissue disrupt the hypothalamic-pituitary-testicular axis which ultimately result in decreased testosterone production [Citation30]. Men with lower testosterone level are likely to have increased fat mass and deteriorated metabolism indicators such as diabetes mellitus, dyslipidemia, hypertension and ultimately worsened BPH/LUTS parameters. Several studies demonstrated that androgen replacement therapy improves obesity, metabolic syndrome and BPH/LUTS parameters [Citation31–34]. Beside sex hormones, as an integral part of the general health, we should also pay attention to vitamin D status of the aging male patients. Scientific evidence suggest conflicting results on the association between vitamin D and prostate enlargement but hypogonadal men are more likely to have low vitamin D levels [Citation35,Citation36]. From this point of view, although we did not evaluate hormonal profile of the patients, we may postulate that those with higher VAI are at increased risk for hypogonadism symptoms and related metabolic disorders.
The results of our study also enable us to make some inferences regarding new therapeutic approaches for prostate enlargement. Given that visceral adiposity was found to be associated with larger prostate volume, it is plausible to promote weight loss, exercise and healthy diet within the context of standard treatments for BPH. It is clear that prospective, randomized trials evaluating appropriate treatments and life style modifications with sufficient follow-up time are needed to validate the concept of central obesity treatment on prostate enlargement.
There are some limitations to this research. Being a cross-sectional study, it prohibits ascertainment of temporal associations and necessitates further prospective studies. Cross sectional studies are affected by a variety of bias influences, thus their results are not as good as those of prospective cohort studies. Furthermore, the cross-sectional studies reflect only individual conditions and cannot permit us to form a cause and effect relationship. Secondly, we only compared the patients with the complaints of BPH/LUTS (mild-moderate/severe). The control group was not the patients with no BPH/LUTS. This could limit the interpretation of our results to general conditions. Thirdly, although VAI is a novel marker to assess the visceral adiposity far better than conventional methods, it is not as easy to apply in daily practice since it has some difficult calculations.
Our findings might have strong implications resulting from the fact that VAI includes both anthropometric and metabolic parameters, perhaps making VAI a valuable index of both fat distribution and function. Our study revealed an association between prostate enlargement and visceral adiposity index that should encourage health care professionals to recommend lifestyle changes to patients. This observation is consistent with the concept that cardiac risk factors are involved with BPH pathogenesis and raises the possibility that making lifestyle changes may possibly delay the development of BPH. These results should be tested with well-designed longitudinal studies with larger cohorts.
Conclusions
Our study revealed a positive correlation between VAI and prostate enlargement. Our results need to be tested with well-designed randomized prospective cohort studies.
Compliance with ethical standards
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Disclosure statement
No research support or funding was received in connection with this study. The authors have no significant affiliation or involvement, either direct or indirect, with any organization or entity with a direct financial interest in the subject matter or materials discussed. The authors report no conflicts of interest.
References
- Berry SJ, Coffey DS, Walsh PC, et al. The development of human benign prostatic hyperplasia with age. J Urol. 1984;132:474–479.
- Lee C, Kozlowski JM, Grayhack JT. Etiology of benign prostatic hyperplasia. Urol Clin North Am. 1995;22:237–246.
- Donnell RF. Benign prostate hyperplasia: a review of the year's progress from bench to clinic. Curr Opin Urol. 2011;21:22–26.
- Grosman H, Fabre B, Mesch V, et al. Lipoproteins, sex hormones and inflammatory markers in association with prostate cancer. Aging Male. 2010;13:87–92.
- Fu Y, Zhou Z, Yang B, et al. The relationship between the clinical progression of benign prostatic hyperplasia and metabolic syndrome: a prospective study. Urol Int. 2016;97:330–335.
- Wang JY, Fu YY, Kang DY. The association between metabolic syndrome and characteristics of benign prostatic hyperplasia: a systematic review and meta-analysis. Medicine. 2016;95:e3243.
- Zou C, Gong D, Fang N, et al. Meta-analysis of metabolic syndrome and benign prostatic hyperplasia in Chinese patients. World J Urol. 2016;34:281–289.
- Pascot A, Lemieux S, Lemieux I, et al. Age-related increase in visceral adipose tissue and body fat and the metabolic risk profile of premenopausal women. Diabetes Care. 1999;22:1471–1478.
- DeNino WF, Tchernof A, Dionne IJ, et al. Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care. 2001; 24:925–932.
- Amato MC, Giordano C, Galia M, et al. Visceral adiposity index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33:920–922.
- Lv X, Zhou W, Sun J, et al. Visceral adiposity is significantly associated with type 2 diabetes in middle-aged and elderly Chinese women: a cross-sectional study. J Diabetes. 2016; DOI: 10.1111/1753-0407.12499.
- Guo SX, Zhang XH, Zhang JY, et al. Visceral adiposity and anthropometric indicators as screening tools of metabolic syndrome among low income rural adults in Xinjiang. Sci Rep. 2016; DOI: 10.1038/srep36091.
- Parsons JK. Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms: new approaches to old problems. J Urol. 2007;178:395–401.
- Parsons JK, Sarma AV, McVary K, et al. Obesity and benign prostatic hyperplasia: clinical connections, emerging etiological paradigms and future directions. J Urol. 2009;182: S27–S31.
- Nandeesha H. Benign prostatic hyperplasia: dietary and metabolic risk factors. Int Urol Nephrol. 2008;40:649–656.
- Seim A, Hoyo C, Ostbye T, et al. The prevalence and correlates of urinary tract symptoms in Norwegian men: the HUNT study. BJU Int. 2005;96:88–92.
- Kristal AR, Arnold KB, Schenk JM, et al. Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. J Urol. 2007;177:1395–1400.
- Dahle SE, Chokkalingam AP, Gao YT, et al. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol. 2002;168:599–604.
- Lee RK, Chung D, Chughtai B, et al. Central obesity as measured by waist circumference is predictive of severity of lower urinary tract symptoms. BJU Int. 2012;110:540–545.
- Zucchetto A, Tavani A, Dal Maso L, et al. History of weight and obesity through life and risk of benign prostatic hyperplasia. Int J Obes. 2005;29:798–803.
- Khoo J, Piantadosi C, Worthley S, et al. Effects of a low-energy diet on sexual function and lower urinary tract symptoms in obese men. Int J Obes. 2010;34:1396–1403.
- Joseph MA, Harlow SD, Wei JT, et al. Risk factors for lower urinary tract symptoms in a population-based sample of African-American men. Am J Epidemiol. 2003;157:906–914.
- Lee S, Min HG, Choi SH, et al. Central obesity as a risk factor for prostatic hyperplasia. Obesity (Silver Spring). 2006;14:172–179.
- Sarma AV, Jaffe CA, Schottenfeld D, et al. Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and body mass index: clinical correlates of prostate volume among black men. Urology. 2002;59:362–367.
- Freedland SJ, Platz EA, Presti JC Jr, et al. Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection. J Urol. 2006;175:500–504.
- Hammarsten J, Damber JE, Karlsson M, et al. Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 2009;12:160–165.
- Nandeesha H, Koner BC, Dorairajan LN, et al. Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia. Clin Chim Acta. 2006;370:89–93.
- Ding EL, Song Y, Malik VS, et al. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295:1288–1299.
- Aktas BK, Gokkaya CS, Bulut S, et al. Impact of metabolic syndrome on erectile dysfunction and lower urinary tract symptoms in benign prostatic hyperplasia patients. Aging Male. 2011;14:48–52.
- Ebrahimi F, Christ-Crain M. Metabolic syndrome and hypogonadism-two peas in a pod. Swiss Med Wkly. 2016;21:w14283.
- Canguven O, Talib RA, El Ansari W, et al. Testosterone therapy has positive effects on anthropometric measures, metabolic syndrome components (obesity, lipid profile, Diabetes Mellitus control), blood indices, liver enzymes and prostate health indicators in elderly hypogonadal men. Andrologia. 2017; DOI: 10.1111/and.12768.
- Yassin A, Nettleship JE, Talib RA, et al. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters. Aging Male. 2016;19:64–69.
- Yassin DJ, Doros G, Hammerer PG, et al. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J Sex Med. 2014;11:1567–1576.
- Shigehara K, Sugimoto K, Konaka H, et al. Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study. Aging Male. 2011;14:53–58.
- Canguven O, Talib RA, El Ansari W, et al. Vitamin D treatment improves levels of sexual hormones, metabolic parameters and erectile function in middle-aged vitamin D deficient men. Aging Male. 2017;20:9–16.
- Park SG, Yeo JK, Cho DY, et al. Impact of metabolic status on the association of serum vitamin D with hypogonadism and lower urinary tract symptoms/benign prostatic hyperplasia. Aging Male. 2017;17:1–5.