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Effects of dutasteride on sex hormones and cerebrospinal steroids in patients treated for benign prostatic hyperplasia

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Abstract

Purpose

Neuroactive steroids may have a role in regulating sexual function. This case-control study assessed whether dutasteride, a 5α-reductase inhibitor used for treatment of patients with benign prostate hyperplasia (BPH), impacts on the levels of neuroactive steroids, leading to erectile dysfunction (ED) and/or hypoactive sexual desire (HSD).

Methods

Forty patients with BPH and moderate-to-severe lower urinary tract symptoms (LUTS), pre-scheduled for prostate transurethral resection or open prostatectomy were enrolled. Twenty of these patients with prostate volume ≤40 mL were treated with α-blockers (Group A) and the remaining 20, with prostate volume >40 mL, with dutasteride plus α-blockers (Group B) for at least 6 months before surgery. Serum sex steroids and gonadotropin levels were measured the day before surgery, and the neuroactive steroid levels were assessed in the cerebrospinal fluid (CSF) collected during spinal anesthesia, at the day of surgery.

Results

Before surgery, the International Index of Erectile Function 5-item score was higher in Group A that Group B (18.8 ± 4.8 vs. 15.1 ± 5.4, p < 0.01). Group A showed lower total testosterone (TT) (4.5 vs.6.4 ng/ml, p < 0.01) and 17β-estradiol (E2) (24.3 vs.30.7 pg/ml, p < 0.05) serum levels than Group B. CSF levels of TT (1446.6 vs. 19.9 pg/ml, p < 0.05) and dihydrotestosterone (7.9 vs. 1.4 pg/ml, p < 0.05) were higher and CSF E2 levels were lower (26.0 vs.36.0 pg/ml, p < 0.01) in Group A than Group B.

Conclusions

A decrease of neuroactive steroids in the CSF of patients treated with dutasteride occurs. This may be one of the mechanisms by which dutasteride may cause ED and HSD.

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References

  1. K.B. Egan,, The epidemiology of benign prostatic hyperplasia associated with lower urinary tract symptoms: prevalence and incident rates. Urol. Clin. North. Am. 43, 289–297 (2016).

    Article  Google Scholar 

  2. M. Stöhrer, B. Blok, D. Castro-Diaz, E. Chartier-Kastler, G. Del Popolo, G. Kramer et al. EAU guidelines on neurogenic lower urinary tract dysfunction. Eur. Urol. 2009. https://doi.org/10.1016/j.eururo.2009.04.028

  3. C.G. Roehrborn, BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int. 101, 17–21 (2008)

    Article  Google Scholar 

  4. V. Favilla, G.I. Russo, S. Privitera, T. Castelli, R. Giardina, A.E. Calogero, R.A. Condorelli, S. La Vignera, S. Cimino, G. Morgia, Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis. Aging Male 19, 175–181 (2016)

    Article  CAS  Google Scholar 

  5. R.C. Melcangi, D. Caruso, F. Abbiati, S. Giatti, D. Calabrese, F. Piazza et al. Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J. Sex. Med 10, 2598–2603 (2013)

    Article  CAS  Google Scholar 

  6. L. Liu, S. Zhao, F. Li, E. Li, R. Kang, L. Luo et al. Effect of 5α-reductase inhibitors on sexual function: a meta-analysis and systematic review of randomized controlled trials. J. Sex. Med. 13, 1297–1310 (2016)

    Article  Google Scholar 

  7. G. Corona, G. Tirabassi, D. Santi, E. Maseroli, M. Gacci, M. Dicuio et al. Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis. Andrology 5, 671–678 (2017)

    Article  CAS  Google Scholar 

  8. L. Drake, M. Hordinsky, V. Fiedler, J. Swinehart, W.P. Unger, P.C. Cotterill et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J. Am. Acad. Dermatol. 41, 550–554 (1999)

    CAS  PubMed  Google Scholar 

  9. R.V. Clark, D.J. Hermann, G.R. Cunningham, T.H. Wilson, B.B. Morrill, S. Hobbs, Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J. Clin. Endocrinol. Metab. 89, 2179–2184 (2004)

    Article  CAS  Google Scholar 

  10. D. Thiboutot, G. Harris, V. Iles, G. Cimis, K. Gilliland, S. Hagari, Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin. J. Invest. Dermatol. 105, 209–214 (1995)

    Article  CAS  Google Scholar 

  11. A. Catalano, G. Martino, F. Bellone, M. Papalia, C. Lasco, G. Basile, A. Sardella, G. Nicocia, N. Morabito, A. Lasco, Neuropsychological assessment in elderly men with benign prostatic hyperplasia treated with dutasteride. Clin. Drug. Investig. 39(1), 97–102 (2019)

    Article  Google Scholar 

  12. H. Wessells, J. Roy, J. Bannow, J. Grayhack, A.M. Matsumoto, L. Tenover et al. Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia. Urology 61, 579–584 (2003)

    Article  Google Scholar 

  13. C.G. Roehrborn, P. Boyle, J.C. Nickel, K. Hoefner, G. Andriole, Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 60(3), 434–441 (2002)

    Article  Google Scholar 

  14. R. Bruskewitz, C.J. Girman, J. Fowler, O.F. Rigby, M. Sullivan, R.B. Bracken, H.A. Fusilier, D. Kozlowski, S.D. Kantor, E.L. Johnson, D.Z. Wang, Waldstreicher J for the PLESS Study Group Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. Urology 54(4), 670–678 (1999)

    Article  CAS  Google Scholar 

  15. N. Mondaini, P. Gontero, G. Giubilei, G. Lombardi, T. Cai, A. Gavazzi et al. Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon? J. Sex. Med. 4, 1708–1712 (2007)

    Article  Google Scholar 

  16. J. Imperato-McGinley, Benign prostatic hyperplasia: dihydrotestosterone and 5 alpha-reductase inhibition therapy. Prog. Clin. Biol. Res. 386, 197–203 (1994)

    CAS  PubMed  Google Scholar 

  17. S. Gur, P.J. Kadowitz, W.J. Hellstrom, Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin. Drug Saf. 12, 81–90 (2013)

    Article  CAS  Google Scholar 

  18. S. Giatti, B. Foglio, S. Romano, M. Pesaresi, G. Panzica, L.M. Garcia-Segura et al. Effects of subchronic finasteride treatment and withdrawal on neuroactive steroid levels and their receptors in the male rat brain. Neuroendocrinology 103, 746–757 (2016). 2016

    Article  CAS  Google Scholar 

  19. V. Favilla, S. Cimino, P. Alessio, G. Li Volti, G.I. Russo, F. Trovato, G. Morgia, Neuroactive steroid levels in cerebrospinal fluid of patients treated with dutasteride: a case-control study. Eur. Urol. Suppl. 18, e252 (2019)

    Article  Google Scholar 

  20. G.C. Panzica, J. Balthazart, C.A. Frye, L.M. Garcia-Segura, A.E. Herbison, A.G. Mensah-Nyagan et al. Milestones on steroids and the nervous system: 10 years of basic and translational research. J. Neuroendocrinol. 24, 1–15 (2012)

    Article  CAS  Google Scholar 

  21. C.F. Zorumski, S.M. Paul, Y. Izumi, D.F. Covey, S. Mennerick, Neurosteroids, stress and depression: potential therapeutic opportunities. Neurosci. Biobehav. Rev. 37, 109–122 (2013)

    Article  CAS  Google Scholar 

  22. R. Steven, King emerging roles for neurosteroids in sexual behavior and function. J. Androl. 29, 524–533 (2008)

    Article  Google Scholar 

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Authors and Affiliations

  1. Section of Urology, Department of Human and Pediatric Pathology Gaetano Barresi, University of Messina, Messina, Italy

    Vincenzo Favilla

  2. Department of Clinical and Experimental Medicine, University of Catania, 95123, Catania, Italy

    Rossella Cannarella, Sandro La Vignera, Rosita A. Condorelli & Aldo E. Calogero

  3. Department of Surgery, Urology Section, University of Catania, 95123, Catania, Italy

    Federica Trovato, Enrico Grimaldi & Sebastiano Cimino

  4. Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy

    Giovanni Li Volti & Alfio Distefano

  5. Department of Anaesthesia and Intensive Care, University of Catania, 95123, Catania, Italy

    Giuseppa La Camera

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  1. Vincenzo Favilla
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Correspondence to Rossella Cannarella.

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Favilla, V., Cannarella, R., Trovato, F. et al. Effects of dutasteride on sex hormones and cerebrospinal steroids in patients treated for benign prostatic hyperplasia. Endocrine 73, 712–718 (2021). https://doi.org/10.1007/s12020-021-02675-4

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  • DOI: https://doi.org/10.1007/s12020-021-02675-4

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