Skip to main content
Top
Published in: International Urology and Nephrology 7/2015

01-07-2015 | Urology - Original Paper

Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats

Authors: Xian-Jin Wang, Tian-Yuan Xu, Lei-Lei Xia, Shan Zhong, Xiao-Hua Zhang, Zhao-Wei Zhu, Dong-Rui Chen, Yue Liu, Yong Fan, Chen Xu, Min-Guang Zhang, Zhou-Jun Shen

Published in: International Urology and Nephrology | Issue 7/2015

Login to get access

Abstract

Objective

The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1–Bcl-2 interaction, were investigated.

Methods

Male Sprague–Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson’s trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum.

Results

Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-β1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration.

Conclusions

Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1–Bcl-2 interaction.
Literature
1.
go back to reference Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A et al (2014) A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol 65:99–112PubMedCrossRef Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A et al (2014) A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol 65:99–112PubMedCrossRef
2.
go back to reference Traish AM (2014) Adverse health effects of testosterone deficiency (TD) in men. Steroids 88:106–116PubMedCrossRef Traish AM (2014) Adverse health effects of testosterone deficiency (TD) in men. Steroids 88:106–116PubMedCrossRef
3.
go back to reference Chua RG, Calenda G, Zhang X, Siragusa J, Tong Y, Tar M et al (2009) Testosterone regulates erectile function and Vcsa1 expression in the corpora of rats. Mol Cell Endocrinol 303:67–73PubMedCentralPubMedCrossRef Chua RG, Calenda G, Zhang X, Siragusa J, Tong Y, Tar M et al (2009) Testosterone regulates erectile function and Vcsa1 expression in the corpora of rats. Mol Cell Endocrinol 303:67–73PubMedCentralPubMedCrossRef
4.
go back to reference Zhang XH, Melman A, Disanto ME (2011) Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone? J Sex Med 8:1865–1879PubMedCrossRef Zhang XH, Melman A, Disanto ME (2011) Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone? J Sex Med 8:1865–1879PubMedCrossRef
5.
go back to reference Palese MA, Crone JK, Burnett AL (2003) A castrated mouse model of erectile dysfunction. J Androl 24:699–703PubMed Palese MA, Crone JK, Burnett AL (2003) A castrated mouse model of erectile dysfunction. J Androl 24:699–703PubMed
6.
go back to reference Mills TM, Stopper VS, Wiedmeier VT (1994) Effects of castration and androgen replacement on the hemodynamics of penile erection in the rat. Biol Reprod 51:234–238PubMedCrossRef Mills TM, Stopper VS, Wiedmeier VT (1994) Effects of castration and androgen replacement on the hemodynamics of penile erection in the rat. Biol Reprod 51:234–238PubMedCrossRef
8.
go back to reference Gordy C, He YW (2012) The crosstalk between autophagy and apoptosis: where does this lead? Protein Cell 3:17–27PubMedCrossRef Gordy C, He YW (2012) The crosstalk between autophagy and apoptosis: where does this lead? Protein Cell 3:17–27PubMedCrossRef
9.
go back to reference Lian J, Karnak D, Xu L (2010) The Bcl-2-Beclin 1 interaction in (−)-gossypol-induced autophagy versus apoptosis in prostate cancer cells. Autophagy 6:1201–1203PubMedCentralPubMedCrossRef Lian J, Karnak D, Xu L (2010) The Bcl-2-Beclin 1 interaction in (−)-gossypol-induced autophagy versus apoptosis in prostate cancer cells. Autophagy 6:1201–1203PubMedCentralPubMedCrossRef
10.
go back to reference Nguyen HG, Yang JC, Kung HJ, Shi XB, Tilki D, Lara PN Jr et al (2014) Targeting autophagy overcomes Enzalutamide resistance in castration-resistant prostate cancer cells and improves therapeutic response in a xenograft model. Oncogene 33:4521–4530PubMedCentralPubMedCrossRef Nguyen HG, Yang JC, Kung HJ, Shi XB, Tilki D, Lara PN Jr et al (2014) Targeting autophagy overcomes Enzalutamide resistance in castration-resistant prostate cancer cells and improves therapeutic response in a xenograft model. Oncogene 33:4521–4530PubMedCentralPubMedCrossRef
11.
go back to reference Boutin B, Tajeddine N, Vandersmissen P, Zanou N, Van Schoor M, Mondin L et al (2013) Androgen deprivation and androgen receptor competition by bicalutamide induce autophagy of hormone-resistant prostate cancer cells and confer resistance to apoptosis. Prostate 73:1090–1102PubMedCrossRef Boutin B, Tajeddine N, Vandersmissen P, Zanou N, Van Schoor M, Mondin L et al (2013) Androgen deprivation and androgen receptor competition by bicalutamide induce autophagy of hormone-resistant prostate cancer cells and confer resistance to apoptosis. Prostate 73:1090–1102PubMedCrossRef
12.
go back to reference Lunardi A, Ala U, Epping MT, Salmena L, Clohessy JG, Webster KA et al (2013) A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet 45:747–755PubMedCentralPubMedCrossRef Lunardi A, Ala U, Epping MT, Salmena L, Clohessy JG, Webster KA et al (2013) A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet 45:747–755PubMedCentralPubMedCrossRef
14.
go back to reference Zhang MG, Wang XJ, Shen ZJ, Gao PJ (2013) Long-term oral administration of 5α-reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats. Urology 82(3):743.e9–743.e15 Zhang MG, Wang XJ, Shen ZJ, Gao PJ (2013) Long-term oral administration of 5α-reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats. Urology 82(3):743.e9–743.e15
16.
go back to reference Zhang MG, Shen ZJ, Zhang CM, Wu W, Gao PJ, Chen SW et al (2011) Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats. BJU Int 108:440–446PubMedCrossRef Zhang MG, Shen ZJ, Zhang CM, Wu W, Gao PJ, Chen SW et al (2011) Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats. BJU Int 108:440–446PubMedCrossRef
17.
go back to reference Zhang MG, Wu W, Zhang CM, Wang XJ, Gao PJ, Lu YL et al (2012) Effects of oral finasteride on erectile function in a rat model. J Sex Med 9:1328–1336PubMedCrossRef Zhang MG, Wu W, Zhang CM, Wang XJ, Gao PJ, Lu YL et al (2012) Effects of oral finasteride on erectile function in a rat model. J Sex Med 9:1328–1336PubMedCrossRef
18.
go back to reference Mulhall JP, Verma N, Deveci S, Tal R, Kobylarz K, Muller A (2014) Sildenafil citrate improves erectile function after castration in a rat model. BJU Int 113:656–661PubMedCrossRef Mulhall JP, Verma N, Deveci S, Tal R, Kobylarz K, Muller A (2014) Sildenafil citrate improves erectile function after castration in a rat model. BJU Int 113:656–661PubMedCrossRef
19.
go back to reference Cho MC, Park K, Kim SW, Paick JS (2015) Restoration of erectile function by suppression of corporal apoptosis, fibrosis and corporal veno-occlusive dysfunction with Rho-kinase inhibitors in a rat model of cavernous nerve injury. J Urol 193:1716–1723PubMedCrossRef Cho MC, Park K, Kim SW, Paick JS (2015) Restoration of erectile function by suppression of corporal apoptosis, fibrosis and corporal veno-occlusive dysfunction with Rho-kinase inhibitors in a rat model of cavernous nerve injury. J Urol 193:1716–1723PubMedCrossRef
20.
go back to reference Han DH, Lee JH, Kim H, Ko MK, Chae MR, Kim HK et al (2012) Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells. BJU Int 109:1404–1413PubMedCrossRef Han DH, Lee JH, Kim H, Ko MK, Chae MR, Kim HK et al (2012) Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells. BJU Int 109:1404–1413PubMedCrossRef
21.
go back to reference Sung HH, Choo SH, Han DH, Chae MR, Kang SJ, Park CS et al (2015) Effect of the novel BK channel opener LDD175 on the modulation of corporal smooth muscle tone. J Sex Med 12:29–38PubMedCrossRef Sung HH, Choo SH, Han DH, Chae MR, Kang SJ, Park CS et al (2015) Effect of the novel BK channel opener LDD175 on the modulation of corporal smooth muscle tone. J Sex Med 12:29–38PubMedCrossRef
22.
go back to reference Kim JJ, Han DH, Lim SH, Kim TH, Chae MR, Chung KJ et al (2011) Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells. Asian J Androl 13:742–746PubMedCentralPubMedCrossRef Kim JJ, Han DH, Lim SH, Kim TH, Chae MR, Chung KJ et al (2011) Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells. Asian J Androl 13:742–746PubMedCentralPubMedCrossRef
23.
go back to reference Muguruma H, Kawanishi Y, Sugiyama H, Kagawa J, Tanimoto S, Yamanaka M et al (2008) Effect of aldosterone on isolated human penile corpus cavernosum tissue. BJU Int 102:500–503PubMedCrossRef Muguruma H, Kawanishi Y, Sugiyama H, Kagawa J, Tanimoto S, Yamanaka M et al (2008) Effect of aldosterone on isolated human penile corpus cavernosum tissue. BJU Int 102:500–503PubMedCrossRef
24.
go back to reference Waldkirch E, Uckert S, Schultheiss D, Geismar U, Bruns C, Scheller F et al (2008) Non-genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue. BJU Int 101:71–75PubMed Waldkirch E, Uckert S, Schultheiss D, Geismar U, Bruns C, Scheller F et al (2008) Non-genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue. BJU Int 101:71–75PubMed
28.
go back to reference Bhasin S, Enzlin P, Coviello A, Basson R (2007) Sexual dysfunction in men and women with endocrine disorders. Lancet 369:597–611PubMedCrossRef Bhasin S, Enzlin P, Coviello A, Basson R (2007) Sexual dysfunction in men and women with endocrine disorders. Lancet 369:597–611PubMedCrossRef
29.
go back to reference Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F et al (2004) Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 291:2978–2984PubMedCrossRef Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F et al (2004) Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 291:2978–2984PubMedCrossRef
30.
go back to reference Morrison D, Aitchison M, Connelly DT, Mair FS (2011) Sexual dysfunction in cardiovascular disease. BMJ 343:d4437PubMedCrossRef Morrison D, Aitchison M, Connelly DT, Mair FS (2011) Sexual dysfunction in cardiovascular disease. BMJ 343:d4437PubMedCrossRef
31.
go back to reference Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA (2005) Erectile dysfunction and subsequent cardiovascular disease. JAMA 294:2996–3002PubMedCrossRef Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA (2005) Erectile dysfunction and subsequent cardiovascular disease. JAMA 294:2996–3002PubMedCrossRef
32.
go back to reference Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K et al (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445–544PubMedCentralPubMedCrossRef Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K et al (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445–544PubMedCentralPubMedCrossRef
33.
go back to reference Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752PubMedCrossRef Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752PubMedCrossRef
34.
go back to reference Hotta Y, Shiota A, Kataoka T, Motonari M, Maeda Y, Morita M et al (2014) Oral l-citrulline supplementation improves erectile function and penile structure in castrated rats. Int J Urol 21:608–612PubMedCrossRef Hotta Y, Shiota A, Kataoka T, Motonari M, Maeda Y, Morita M et al (2014) Oral l-citrulline supplementation improves erectile function and penile structure in castrated rats. Int J Urol 21:608–612PubMedCrossRef
35.
go back to reference Penson DF, Ng C, Cai L, Rajfer J, Gonzalez-Cadavid NF (1996) Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol Reprod 55:567–574PubMedCrossRef Penson DF, Ng C, Cai L, Rajfer J, Gonzalez-Cadavid NF (1996) Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol Reprod 55:567–574PubMedCrossRef
36.
go back to reference Shen ZJ, Zhou XL, Lu YL, Chen ZD (2003) Effect of androgen deprivation on penile ultrastructure. Asian J Androl 5:33–36PubMed Shen ZJ, Zhou XL, Lu YL, Chen ZD (2003) Effect of androgen deprivation on penile ultrastructure. Asian J Androl 5:33–36PubMed
37.
go back to reference Traish AM, Guay AT (2006) Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 3:382–407PubMedCrossRef Traish AM, Guay AT (2006) Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 3:382–407PubMedCrossRef
38.
go back to reference Kataoka T, Hotta Y, Maeda Y, Kimura K (2014) Assessment of androgen replacement therapy for erectile function in rats with type 2 diabetes mellitus by examining nitric oxide-related and inflammatory factors. J Sex Med 11:920–929PubMedCrossRef Kataoka T, Hotta Y, Maeda Y, Kimura K (2014) Assessment of androgen replacement therapy for erectile function in rats with type 2 diabetes mellitus by examining nitric oxide-related and inflammatory factors. J Sex Med 11:920–929PubMedCrossRef
39.
go back to reference Aversa A, Bruzziches R, Francomano D, Natali M, Lenzi A (2009) Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine? Ther Adv Urol 1:179–197PubMedCentralPubMedCrossRef Aversa A, Bruzziches R, Francomano D, Natali M, Lenzi A (2009) Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine? Ther Adv Urol 1:179–197PubMedCentralPubMedCrossRef
40.
go back to reference Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I (1999) Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140:1861–1868PubMed Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I (1999) Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140:1861–1868PubMed
41.
go back to reference Mostafa T, Rashed LA, Kotb K (2010) Testosterone and chronic sildenafil/tadalafil anti-apoptotic role in aged diabetic rats. Int J Impot Res 22:255–261PubMedCrossRef Mostafa T, Rashed LA, Kotb K (2010) Testosterone and chronic sildenafil/tadalafil anti-apoptotic role in aged diabetic rats. Int J Impot Res 22:255–261PubMedCrossRef
42.
go back to reference Mostafa T, Rashed L, Kotb K, Taymour M (2012) Effect of testosterone and frequent low-dose sildenafil/tadalafil on cavernous tissue oxidative stress of aged diabetic rats. Andrologia 44:411–415PubMedCrossRef Mostafa T, Rashed L, Kotb K, Taymour M (2012) Effect of testosterone and frequent low-dose sildenafil/tadalafil on cavernous tissue oxidative stress of aged diabetic rats. Andrologia 44:411–415PubMedCrossRef
43.
go back to reference Vignozzi L, Morelli A, Filippi S, Ambrosini S, Mancina R, Luconi M et al (2007) Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes. J Sex Med 4:620–632PubMedCrossRef Vignozzi L, Morelli A, Filippi S, Ambrosini S, Mancina R, Luconi M et al (2007) Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes. J Sex Med 4:620–632PubMedCrossRef
44.
go back to reference Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S et al (2007) Differential interactions between Beclin 1 and Bcl-2 family members. Autophagy 3:561–568PubMedCrossRef Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S et al (2007) Differential interactions between Beclin 1 and Bcl-2 family members. Autophagy 3:561–568PubMedCrossRef
45.
go back to reference Wen S, Niu Y, Lee SO, Chang C (2014) Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death. Cancer Treat Rev 40:31–40PubMedCrossRef Wen S, Niu Y, Lee SO, Chang C (2014) Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death. Cancer Treat Rev 40:31–40PubMedCrossRef
46.
go back to reference Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N (2013) Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta 1833:3448–3459PubMedCrossRef Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N (2013) Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta 1833:3448–3459PubMedCrossRef
47.
go back to reference Jain MV, Paczulla AM, Klonisch T, Dimgba FN, Rao SB, Roberg K et al (2013) Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development. J Cell Mol Med 17:12–29PubMedCentralPubMedCrossRef Jain MV, Paczulla AM, Klonisch T, Dimgba FN, Rao SB, Roberg K et al (2013) Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development. J Cell Mol Med 17:12–29PubMedCentralPubMedCrossRef
48.
go back to reference Rhee H, Gunter JH, Heathcote P, Ho K, Stricker P, Corcoran NM et al (2015) Adverse effects of androgen deprivation therapy in prostate cancer and their management. BJU Int 115:3–13PubMedCrossRef Rhee H, Gunter JH, Heathcote P, Ho K, Stricker P, Corcoran NM et al (2015) Adverse effects of androgen deprivation therapy in prostate cancer and their management. BJU Int 115:3–13PubMedCrossRef
49.
go back to reference Gandaglia G, Sun M, Popa I, Schiffmann J, Abdollah F, Trinh QD et al (2014) The impact of androgen-deprivation therapy (ADT) on the risk of cardiovascular (CV) events in patients with non-metastatic prostate cancer: a population-based study. BJU Int 114:E82–E89PubMedCrossRef Gandaglia G, Sun M, Popa I, Schiffmann J, Abdollah F, Trinh QD et al (2014) The impact of androgen-deprivation therapy (ADT) on the risk of cardiovascular (CV) events in patients with non-metastatic prostate cancer: a population-based study. BJU Int 114:E82–E89PubMedCrossRef
50.
go back to reference Beebe-Dimmer JL, Freedland SJ (2013) Androgen deprivation therapy: further confirmation of known harms. BJU Int 111:690–691PubMedCrossRef Beebe-Dimmer JL, Freedland SJ (2013) Androgen deprivation therapy: further confirmation of known harms. BJU Int 111:690–691PubMedCrossRef
51.
go back to reference Ahmadi H, Daneshmand S (2013) Androgen deprivation therapy: evidence-based management of side effects. BJU Int 111:543–548PubMedCrossRef Ahmadi H, Daneshmand S (2013) Androgen deprivation therapy: evidence-based management of side effects. BJU Int 111:543–548PubMedCrossRef
Metadata
Title
Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats
Authors
Xian-Jin Wang
Tian-Yuan Xu
Lei-Lei Xia
Shan Zhong
Xiao-Hua Zhang
Zhao-Wei Zhu
Dong-Rui Chen
Yue Liu
Yong Fan
Chen Xu
Min-Guang Zhang
Zhou-Jun Shen
Publication date
01-07-2015
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 7/2015
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-015-1011-3

Other articles of this Issue 7/2015

International Urology and Nephrology 7/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine