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Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction
Open accessAbstract
Background: Psychological stress and its two stress response systems, the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), are closely related to psychogenic erectile dysfunction (pED). However, the analyses of perceived stress and stress systems in pED patients need to be more in-depth, especially the interactions between them. Methods: Our study included 75 patients with pEDs and 75 healthy men. The International Index of Erectile Function-5 (IIEF-5) and the 10-item Perceived Stress Scale (PSS-10) were used for assessing the severity of ED and perceived stress. All participants collected saliva samples on three consecutive days at eight specific times with strict reference to the time of morning awakening for measuring cortisol parameters and wore electrocardiography for 24 h to derive heart rate variability (HRV). Results: The PSS-10 scores of pED patients were significantly higher than the control group (p<0.001). Although PSS-10 and IIEF-5 scores were negatively correlated in pED patients, there was no statistical significance between them (r=−0.049, p=0.677). Compared with the control group, the HRV parameters of pED patients were significantly increased in LF/HF ratio (p=0.014) but significantly decreased in LF, HF, and pNN50 (p<0.001). However, the two groups had no statistically significant differences in cortisol variables (all p>0.05). The interaction between sympathovagal modulation (HF, rMSSD) and cortisol awakening response (CAR AUCi) explained significantly greater variance in perceived stress than either stress system alone. Higher parasympathetic activity combined with a higher cortisol awakening response was associated with greater perceived stress. Conclusion: Our results suggested that the interrelation between ANS and HPA axis activity might enhance our comprehension of how stress affected the physical and mental health of pED patients.
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TL;DR
In 75 men with psychogenic erectile dysfunction (pED) and 75 healthy controls, pED patients reported greater perceived stress and showed autonomic imbalance (lower LF, HF, pNN50; higher LF/HF) but no significant differences in salivary cortisol measures. In pED patients, interactions between parasympathetic HRV indices (HF, rMSSD) and cortisol awakening response (CAR AUCi) explained additional variance in perceived stress beyond either system alone.
Key findings
- pED patients had significantly higher PSS-10 scores (17.44 ± 4.75 vs. 13.97 ± 6.08, p < 0.001) and lower IIEF-5 scores (8.40 ± 2.34 vs. 23.12 ± 0.97, p < 0.001); PSS-10 and IIEF-5 were negatively but not significantly correlated in pED patients (r = −0.049, p = 0.677).
- HRV differed significantly: pED patients had lower LF (median 670.00 vs. 1893.00 ms², p < 0.001), lower HF (622.00 vs. 3845.00 ms², p < 0.001), lower pNN50 (16.50 vs. 18.50 ms, p < 0.001), and higher LF/HF ratio (0.66 vs. 0.60, p = 0.014).
- No cortisol variable differed significantly between groups (all p > 0.05).
- In pED patients, HF × CAR AUCi and rMSSD × CAR AUCi interactions accounted for an additional 6.1% and 5.9% of variance in perceived stress; higher HF or rMSSD combined with higher CAR AUCi was associated with greater perceived stress (HF: k = 3.333, p = 0.009; rMSSD: k = 3.065, p = 0.009). In controls, only pNN50 was associated with perceived stress in the singular HRV model, and no significant interactions were found.
Methods
- Case-control study at a urology male clinic from March 2016 to August 2022; 75 pED patients and 75 healthy men completed the study (ages 20–49, mean 31.9 ± 7.1 years).
- Participants completed the IIEF-5 and PSS-10, collected saliva eight times per day for three consecutive weekdays for cortisol parameters, and wore 24-h electrocardiography for HRV.
- Analyses used independent-sample t-tests, Kruskal-Wallis tests, chi-square/Fisher’s exact tests, and hierarchical linear regression comparing singular HRV or cortisol models with inter-relation models including two-way interactions; simple slope analyses interpreted significant interactions.
Limitations
- The authors state that comparisons with other studies were difficult due to the lack of research on HPA axis activity and perceived stress in ED, and that their use of hierarchical regression, interaction, and simple slope analyses may have increased chances of finding meaningful associations.
- The authors state that more stress measures and additional autonomic/HPA measures (e.g., salivary alpha-amylase, pre-ejection period, cortisone, dehydroepiandrosterone) are needed, and that the cross-sectional design cannot determine causal direction.
- Evident from the text: the study was single-center, used a modest sample size, and recruited only men, which may limit generalizability; the authors also note a smaller sample size as a possible reason for not detecting subtle HPA axis changes.
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In the paper
“Compared with the control group, the HRV parameters of pED patients were significantly increased in LF/HF ratio (p=0.014) but significantly decreased in LF, HF, and pNN50 (p<0.001).”
- Also stated in: § Measurement of cortisol and HRV parameters · plain
“the LF and HF power of the pED group were significantly lower than those of the control group (both p<0.001)”
- Also stated in: § Demographic, symptomatic, and psychological characteristics · plain
“| LF (ms2), median (range) | 670.00 (121.00-6289.00) | 1893.00 (150.00-4876.00) | <0.001 |”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Abstract > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Measurement of cortisol and HRV parameters · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with the control group, the HRV parameters of pED patients were significantly increased in LF/HF ratio (p=0.014) but significantly decreased in LF, HF, and pNN50 (p<0.001).”
- Also stated in: § Measurement of cortisol and HRV parameters · plain
“the pED patients had a significantly higher LF/HF ratio than the controls (p=0.014).”
- Also stated in: § Demographic, symptomatic, and psychological characteristics · plain
“| LF/HF, median (range) | 0.66 (0.07-14.05) | 0.60 (0.03-3.47) | 0.014 |”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Abstract > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Measurement of cortisol and HRV parameters · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other parameters had no significant interactions.”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Results > Singular versus inter-relation models
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The interaction between sympathovagal modulation (HF, rMSSD) and cortisol awakening response (CAR AUCi) explained significantly greater variance in perceived stress than either stress system alone.”
- Also stated in: § Singular versus inter-relation models · plain
“Inter-relation models with the interactions of HF*CAR AUCi and rMSSD*CAR AUCi accounted for significantly greater variance in perceived stress than the singular HRV or cortisol models.”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Abstract > Results
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Singular versus inter-relation models · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In pED patients, CAR AUCi, CAR AUCg, and diurnal cortisol AUCg demonstrated significant associations with perceived stress in the models.”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Results > Singular versus inter-relation models
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Materials and methods > Participants
“history of psychogenic ED for at least six months”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Results > Demographic, symptomatic, and psychological characteristics
“the disease course lasted from three to nine months, with a median of about five months.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Results > Demographic, symptomatic, and psychological characteristics
“pNN50 (ms), median (range)”
§ Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction > Results > Demographic, symptomatic, and psychological characteristics
“pNN50, percent of R-R intervals differing more than 50 ms from each other”
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Metadata
- Authors
- Xu, J., Chen, Y., Gu, L., Liu, X., Yang, J., Li, M., Rao, K., Dong, X., Yang, S., Huang, B., Jin, L., Wang, T., Liu, J., Wang, S., & Bai, J.
- Affiliations
- Tongji Hospital (CN)
- Corresponding author
- Bai, Jian
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2023-03-03
- Volume
- 14
- Pages
- 1103621-1103621
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC10020360
- OpenAlex
- W4323045105
- Cited by
- 13
- References
- 35
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 2
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- psychogenic erectile dysfunction, hypothalamic-pituitary-adrenal axis, autonomic nervous system, perceived stress, cortisol awakening response, heart rate variability, parasympathetic activity, psychological stress
- MeSH terms
- Autonomic Nervous System, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Erectile Dysfunction, Male, Pituitary-Adrenal System
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