Frequency-Dependent Effects of Repetitive Transcranial Magnetic Stimulation on Sexual Behavior Parameters in Premature Ejaculation Rodent Models

Zihang Chen; Ming Wang; Qiushi Liu; Renliang Li; Xueping Zhang; Tommaso B Jannini; Emmanuele A Jannini; Xiansheng Zhang

doi:10.1111/andr.70146

Frequency-Dependent Effects of Repetitive Transcranial Magnetic Stimulation on Sexual Behavior Parameters in Premature Ejaculation Rodent Models

Andrology. 2025 Nov 7. doi: 10.1111/andr.70146. Online ahead of print.

Authors

Zihang Chen¹, Ming Wang¹, Qiushi Liu¹, Renliang Li¹, Xueping Zhang², Tommaso B Jannini³, Emmanuele A Jannini⁴, Xiansheng Zhang¹

Affiliations

¹ Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
² Department of Urology, Weifang People's Hospital, Weifang, China.
³ Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
⁴ Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

PMID: 41204620
DOI: 10.1111/andr.70146

Abstract

Background: Premature ejaculation (PE) is one of the most prevalent sexual dysfunctions in males. Repetitive transcranial magnetic stimulation (TMS) demonstrates potential modulatory effects on ejaculatory function, however, the effects of different stimulation frequencies remain unclear.

Objectives: To investigate the effects of low-frequency and high-frequency rTMS in a rat model of rapid ejaculation and compare these outcome with dapoxetine, a standard pharmacological intervention.

Methods: Male rats exhibiting rapid ejaculation were identified based on sexual behavior parameters, then randomly allocated into four groups: 1-Hz rTMS, 10-Hz rTMS, dapoxetine control, and sham control groups. Ejaculatory behavior, hippocampal 5-hydroxytryptamine (5-HT) levels, brain-derived neurotrophic factor (BDNF) expression, and activation of the BDNF-receptor tyrosine kinase receptor B (TrkB) pathway were investigated before and after 2 weeks of treatment.

Results: Following 2 weeks of intervention, we found that all rTMS and dapoxetine groups showed significant improvements in ejaculation latency compared with controls, with the 10-Hz rTMS group showing the most substantial effect. While dapoxetine slightly outperformed 10-Hz rTMS in increasing 5-HT levels, 10-Hz rTMS induced a greater upregulation of BDNF and TrkB expression. Correlation analysis revealed that BDNF levels were positively associated with EL (r = 0.8817, p < 0.001) and negatively associated with ejaculation frequency (r = -0.8702, p < 0.001).

Conclusion: rTMS exhibited frequency-dependent therapeutic efficacy in rapid ejaculation rat models, with high-frequency protocols demonstrating superior benefits compared with low-frequency interventions. These effects are mediated through activation of the BDNF-TrkB pathway and enhanced serotonergic signaling, suggesting high-frequency rTMS as a promising non-pharmacological therapy for PE.

Keywords: brain‐derived neurotrophic factor; dapoxetine; premature ejaculation; repetitive transcranial magnetic stimulation.

Grants and funding

82371635/the National Natural Science Foundation of China