Abstract Introduction Hyperlipidemia contributes to vasculogenic erectile dysfunction (ED) by reducing endothelial nitric oxide bioavailability. Although atorvastatin has been reported to improve ED, the upstream mechanism by which it restores endothelial nitric oxide synthase (eNOS) activity remains unclear. This study aimed to evaluate the therapeutic effect of atorvastatin in hyperlipidemia-induced erectile dysfunction (HLED) and to determine whether protein kinase A (PKA)-associated phosphorylation of eNOS at Ser633 contributes to this effect. Methods Hyperlipidemia-induced erectile dysfunction was induced in rats by a high-fat diet. Animals received low- or high-dose atorvastatin, with tadalafil as a positive control. Erectile function, serum lipid profiles, oxidative stress, penile fibrosis, and cavernosal eNOS signaling were assessed. In parallel, oxidized low-density lipoprotein (ox-LDL)-injured rat corpus cavernosum endothelial cells (RCECs) were treated with atorvastatin in the presence or absence of the PKA inhibitor H89. Results Atorvastatin improved dyslipidemia, reduced systemic oxidative stress, attenuated penile fibrosis, and partially restored erectile function in HLED rats. Hyperlipidemia-induced erectile dysfunction was associated with decreased eNOS phosphorylation at Ser1177 and Ser633 and increased phosphorylation at Thr495. Atorvastatin enhanced PKA activation and eNOS Ser633 phosphorylation while reducing inhibitory Thr495 phosphorylation in penile tissue. In ox-LDL-treated RCECs, atorvastatin reduced intracellular lipid and ROS accumulation and improved endothelial function, accompanied by increased PKA Thr197 and eNOS Ser633 phosphorylation. These effects were largely blunted by H89. Discussion These findings suggest that atorvastatin ameliorates HLED by restoring endothelial function through a PKA-associated increase in eNOS Ser633 phosphorylation. This upstream endothelial mechanism may complement the action of phosphodiesterase type 5 inhibitors and provide additional benefit for hyperlipidemia-associated vasculogenic ED. The combined in vivo and in vitro design supports mechanistic relevance, although pathway inference relies partly on pharmacological inhibition with H89 and limited time-point analyses. Collectively, our results identify PKA-associated eNOS Ser633 activation as an important mechanism underlying the endothelial-protective effect of atorvastatin in HLED.
Abstract Introduction Erectile dysfunction (ED) is a prevalent male health condition that substantially correlates with impaired sexual function and reduced overall quality of life. Non-restorative sleep (NRS), a prevalent subjective sleep disturbance, has recently been identified as an under-recognized factor linked to ED. Nonetheless, the psychological factors involved in the association between NRS and ED remain poorly clarified. Rumination and psychological resilience are two promising psychological variables that may participate in this correlational pathway yet have not been empirically examined in the NRS-ED context. The present study aimed to explore the potential indirect correlational link between NRS and ED through rumination, and further evaluate whether resilience moderates this associative pathway. Methods Between February 2024 October 2025, we conducted a cross-sectional study of 880 men with ED recruited from the Andrology Clinic of the First Affiliated Hospital of Anhui Medical University. Participants completed the NRS Scale (lower scores indicate more severe NRS), Ruminative Responses Scale, 10-item Connor–Davidson Resilience Scale, and the 5-item International Index of Erectile Function (IIEF-5). Pearson correlations, bootstrapped mediation, and moderated mediation models with covariate adjustment, and latent profile analysis (LPA) in Mplus were performed to identify rumination subgroups and compare erectile function across profiles. Results Non-restorative sleep severity was significantly associated with worse ED and elevated rumination (all P < .001). Rumination partially mediated the association between NRS and ED. Exploratory LPA identified 3 statistical patterns representing sample heterogeneity in rumination severity (low 28.86%, moderate 43.18%, high 27.96%), rather than clinically distinct phenotypes. Higher rumination severity corresponded to significantly poorer erectile function (high vs. low severity IIEF-5 scores: 8.92 ± 3.84 vs. 14.95 ± 5.03). Resilience significantly moderated this pathway, acting as a buffer that attenuated both the effect of NRS on rumination and the subsequent impact of rumination on ED. Conclusion Our findings demonstrate that NRS is linked to ED via a ruminative associational pattern, and this association varies across levels of resilience. These findings suggest that integrated therapeutic strategies targeting these cognitive-emotional factors could facilitate more personalized clinical management for patients.
Abstract Introduction Bartholin gland disease impairs sexual function, yet most studies focus on surgical technique rather than the broader sexual health burden, and none has systematically examined sexual distress or genital self-image in this population. We aimed to characterize the sexual health burden of Bartholin gland disease across four domains: pain (Visual Analogue Scale [VAS]), sexual function (Female Sexual Function Index [FSFI]), sexual distress (Female Sexual Distress Scale-Revised [FSDS-R]), and genital self-image (Female Genital Self-Image Scale [FGSIS]), at two time points (before and after treatment) and to compare findings against matched healthy controls. Methods This prospective cohort study enrolled 25 women diagnosed with a Bartholin gland cyst or abscess (patient group) and 25 age-matched healthy controls at a single training and research hospital. Patients were evaluated twice: at presentation before any treatment (T1) and after symptom resolution (T2). Controls were assessed once. Outcome measures were the VAS (applied to patients only), FSFI (cut-off <26.55), FSDS-R (cut-off ≥11), and FGSIS. Sample size was calculated a priori (d = 0.80, α = 0.05, power = 80%; G*Power 3.1). Results and Discussion Groups were comparable for age (36.1 ± 6.6 vs. 34.2 ± 7.6 years, P = .472), body mass index (BMI), and parity. At T1, 48.0% of patients had clinically significant sexual dysfunction (FSFI <26.55) and 16.0% met the distress threshold (FSDS-R ≥ 11). All four scales improved significantly from T1 to T2 (P < .001 for each). By T2, FSFI (31.72 ± 3.34 vs. 31.11 ± 1.87, P = .187), FSDS-R (1.44 ± 1.69 vs. 0.56 ± 0.65, P = .068), and FGSIS (24.40 ± 2.33 vs. 23.20 ± 1.94, P = .066) no longer differed from controls. Notably, FGSIS was already similar between patients and controls at T1 (22.92 ± 3.28 vs. 23.20 ± 1.94, P = .784). VAS pain scores fell from 5.96 ± 2.64 to 1.04 ± 0.20 (effect size dz = 1.906). T1 FSFI scores did not differ by pathology type (cyst vs. abscess, P = .479) or surgical procedure (P = .866). Strong correlations were observed between FSFI and FSDS-R (r = −0.829, P < .001) and between VAS and FSDS-R (r = +0.561, P = .004). Bartholin gland disease carries a measurable sexual health burden that substantially resolves after treatment. Genital self-image appears to remain intact even during active disease. Systematic screening with FSFI and FSDS-R should be integrated into routine management; surgical decision-making should account for the higher dyspareunia risk associated with marsupialization.
