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Psychoneuroendocrinology Nov 2023The neuroactive metabolite of progesterone, allopregnanolone (ALLO), has been implicated in premenstrual syndrome (PMS) physiopathology and preclinical studies suggested... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The neuroactive metabolite of progesterone, allopregnanolone (ALLO), has been implicated in premenstrual syndrome (PMS) physiopathology and preclinical studies suggested that low doses of fluoxetine increase the ALLO brain concentration.
OBJECTIVES
To assess which low dose of fluoxetine (2 mg/d, 5 mg/d or 10 mg/d), administered exclusively during the luteal phase of menstrual cycle, has a potential effect for preventing or mitigating emotional PMS symptoms.
METHODS
In this randomized, double-blind, placebo-controlled pilot study, we followed 40 women (mean age = 29.7 +/- 7.4 years) with emotional PMS, during two menstrual cycles: cycle 1, without pharmacological intervention; and cycle 2, with pharmacological intervention. Participants took capsules, on average, seven days preceding the likely date of menses. We assessed the severity of PMS symptoms in both cycles using the Daily Record of Severity of Problems scale (DRSP).
RESULTS
There was an increase in the DRSP scores during the late luteal phase of cycle 1, confirming the diagnosis of emotional PMS. Low doses of fluoxetine (5 mg/d: 33.5%; 10 mg/d: 48.4%) reduced DRSP total score in the day before menses (day-1) at cycle 2 compared with day-1 at cycle 1. Fluoxetine 10 mg/d had the most consistent decline in emotional PMS symptoms; 70% of the participants reported a reduction greater than 40% in the DRSP score.
CONCLUSIONS
Low doses of fluoxetine, which may have no or few effect on the serotonergic system, but may interfere in the progesterone metabolization, seem to have some potential to mitigate emotional PMS symptoms. While the 10 mg/d of fluoxetine had the best performance on reducing emotional PMS symptoms, the 5 mg/d dose also seems to have some effect on emotional PMS symptoms. Further larger studies will help establish the lowest effective dose of flouxetine for PMS treatment.
Topics: Female; Humans; Young Adult; Adult; Fluoxetine; Pilot Projects; Progesterone; Premenstrual Syndrome; Menstrual Cycle; Pregnanolone; Double-Blind Method
PubMed: 37572412
DOI: 10.1016/j.psyneuen.2023.106360 -
The Journal of Clinical Endocrinology... Dec 2023Adrenal venous sampling (AVS) is considered the gold standard for differentiating unilateral and bilateral forms of primary aldosteronism. Currently, almost all AVS...
CONTEXT
Adrenal venous sampling (AVS) is considered the gold standard for differentiating unilateral and bilateral forms of primary aldosteronism. Currently, almost all AVS procedures are performed via femoral vein access.
OBJECTIVE
The aim of this study was to evaluate the success rate and safety of AVS via an antecubital approach.
METHODS
In a retrospective multicenter study involving 7 Chinese medical centers, patients with primary aldosteronism who underwent AVS via an antecubital approach between January 2012 and December 2018 were analyzed. Successful sampling was determined by a selectivity index (cortisol in the adrenal vein/cortisol in inferior vena cava) greater than 2.
RESULTS
A total of 1226 participants (mean age, 47.1 years; 57.9% male) were included. The puncture site was right and left antecubital vein in 1211 (98.8%), and 15 (1.2%) patients. The access of 6 patients (0.5%) was changed to right femoral vein due to the failure of antecubital vein cannulation or anatomic variation of adrenal vein. The success rate of bilateral, right, and left sampling was 91.5%, 94.9%, and 95.1%, respectively. The success rate of bilateral, right, and left sampling increased from 82.9%, 87.1%, and 88.6% during the initial 70 cases (total of initial 10 cases at each center) to 92.0% (P = .012), 95.3% (P = .008), and 95.5% (P = .018) with subsequent cases. Adrenal vein rupture occurred in 5 patients (0.41%), with no sequelae.
CONCLUSION
This multicenter study demonstrates that AVS via an antecubital approach is safe and feasible, with a high rate of successful sampling, which may be an alternative to the femoral vein access method.
Topics: Humans; Male; Middle Aged; Female; Hyperaldosteronism; Hydrocortisone; Adrenal Glands; Vena Cava, Inferior; Retrospective Studies; Femoral Vein; Aldosterone
PubMed: 37466201
DOI: 10.1210/clinem/dgad433 -
BMC Veterinary Research Sep 2023Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its...
BACKGROUND
Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its assessment might be challenging because of the effect of individual factors. In a recent study, intact female dogs showed the highest value of urinary aldosterone-to-creatinine ratio (UAldo:C) compared to other sex categories. In humans and rodents, an influence of progesterone has been reported by several studies. To our knowledge, the relationship between aldosterone and progesterone has not yet been investigated in dogs. The aim of this prospective study was to investigate this relationship in sexually intact Chihuahua females, measuring both hormones twice in the same bitch, that is in anoestrus when progesterone concentrations are baseline and in dioestrus when they are high.
RESULTS
The study population consisted of 14 sexually intact Chihuahua bitches. Serum progesterone (34.06 (21.17-44.90) vs. 0.19 [0.13-0.38] ng/ml; P < 0.001) and urinary aldosterone (9886.98 ± 5735.22 vs. 5005.72 ± 2127.73 pg/ml; P = 0.01) were significantly higher in dioestrus compared to anoestrous. Urinary aldosterone-to-creatinine ratio was higher in dioestrus compared to anoestrus (4.16 [3.17-6.80] vs. 3.39 ± 1.64 µg/g), but it did not reach the statistical significance (P = 0.056). Serum progesterone showed a moderate positive correlation with urinary aldosterone (ρ = 0.638, P < 0.001) and UAldo:C (ρ = 0.516, P = 0.005).
CONCLUSIONS
The results of the present study suggest the existence of a progesterone-aldosterone relationship in canine species, indicating that sex and phase of reproductive cycle should be taken into account when interpreting aldosterone concentrations. Further studies are needed to confirm these results on a larger canine population and to identify the underlying mechanisms in this species.
Topics: Humans; Animals; Dogs; Female; Aldosterone; Progesterone; Creatinine; Prospective Studies; Diuretics; Anti-Arrhythmia Agents; Cardiotonic Agents
PubMed: 37670293
DOI: 10.1186/s12917-023-03704-2 -
Pediatric Research Aug 2023Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune...
BACKGROUND
Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited.
METHODS
Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1β, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145).
RESULTS
Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1β (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample.
CONCLUSIONS
Our results indicate that these biological response systems may react differently to different forms of early-life adversity.
IMPACT
Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1β, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.
Topics: Humans; Child; Hydrocortisone; Cortisone; Tumor Necrosis Factor-alpha; Stress, Psychological; Saliva; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Dehydroepiandrosterone
PubMed: 36650307
DOI: 10.1038/s41390-022-02415-y -
Psychoneuroendocrinology Nov 2023Childhood adversity increases the risk of developing psychosis, but the biological mechanisms involved are unknown. Disaggregating early adverse experiences into core... (Review)
Review
Childhood adversity increases the risk of developing psychosis, but the biological mechanisms involved are unknown. Disaggregating early adverse experiences into core dimensions of deprivation and threat may help to elucidate these mechanisms. We therefore systematically searched the literature investigating associations between deprivation and threat, and neural, immune and stress hormone systems in individuals on the psychosis spectrum. Our search yielded 74 articles, from which we extracted and synthesized relevant findings. While study designs were heterogeneous and findings inconsistent, some trends emerged. In psychosis, deprivation tended to correlate with lower global cortical volume, and some evidence supported threat-related variation in prefrontal cortex morphology. Greater threat exposure was also associated with higher C-reactive protein, and higher and lower cortisol measures. When examined, associations in controls were less evident. Overall, findings indicate that deprivation and threat may associate with partially distinct biological mechanisms in the psychosis spectrum, and that associations may be stronger than in controls. Dimensional approaches may help disentangle the biological correlates of childhood adversity in psychosis, but more studies are needed.
Topics: Humans; Psychotic Disorders; Prefrontal Cortex; Hydrocortisone; Adult Survivors of Child Abuse
PubMed: 37651860
DOI: 10.1016/j.psyneuen.2023.106371 -
International Journal of Molecular... Dec 2023C11-oxy C and C11-oxy C steroids have been identified as novel steroids but their function remains unclear. This study aimed to investigate the pre-receptor regulation...
C11-oxy C and C11-oxy C steroids have been identified as novel steroids but their function remains unclear. This study aimed to investigate the pre-receptor regulation of C11-oxy steroids by 11β-hydroxysteroid dehydrogenase (11βHSD) interconversion and potential agonist and antagonist activity associated with the androgen (AR) and progesterone receptors (PRA and PRB). Steroid conversions were investigated in transiently transfected HEK293 cells expressing 11βHSD1 and 11βHSD2, while CV1 cells were utilised for agonist and antagonist assays. The conversion of C11-hydroxy steroids to C11-oxo steroids by 11βHSD2 occurred more readily than the reverse reaction catalysed by 11βHSD1, while the interconversion of C11-oxy C steroids was more efficient than C11-oxy C steroids. Furthermore, 11-ketodihydrotestosterone (11KDHT), 11-ketotestosterone (11KT) and 11β-hydroxydihydrotestosterone (11OHDHT) were AR agonists, while only progestogens, 11β-hydroxyprogesterone (11βOHP4), 11β-hydroxydihydroprogesterone (11βOHDHP4), 11α-hydroxyprogesterone (11αOHP4), 11α-hydroxydihydroprogesterone (11αOHDHP4), 11-ketoprogesterone (11KP4), 5α-pregnan-17α-diol-3,11,20-trione (11KPdione) and 21-deoxycortisone (21dE) exhibited antagonist activity. C11-hydroxy C steroids, 11βOHP4, 11βOHDHP4 and 11αOHP4 exhibited PRA and PRB agonistic activity, while only C11-oxo steroids, 11KP4 and 11-ketoandrostanediol (11K3αdiol) demonstrated PRB agonism. While no steroids antagonised the PRA, 11OHA4, 11β-hydroxytestosterone (11OHT), 11KT and 11KDHT exhibited PRB antagonism. The regulatory role of 11βHSD isozymes impacting receptor activation is clear-C11-oxo androgens exhibit AR agonist activity; only C11-hydroxy progestogens exhibit PRA and PRB agonist activity. Regulation by the downstream metabolites of active C11-oxy steroids at the receptor level is apparent-C11-hydroxy and C11-oxo metabolites antagonize the AR and PRB, progestogens the former, androgens the latter. The findings highlight the intricate interplay between receptors and active as well as "inactive" C11-oxy steroids, suggesting novel regulatory tiers.
Topics: Humans; Progesterone; Receptors, Progesterone; Androgens; Progestins; HEK293 Cells; Steroids; Receptors, Steroid; 11-beta-Hydroxysteroid Dehydrogenases
PubMed: 38203272
DOI: 10.3390/ijms25010101 -
Minerva Medica Apr 2024Allergic rhinitis (AR) and nonallergic rhinitis are prevalent diseases. In western countries, type 2 inflammation usually characterizes these medical conditions and... (Review)
Review
Allergic rhinitis (AR) and nonallergic rhinitis are prevalent diseases. In western countries, type 2 inflammation usually characterizes these medical conditions and mainly sustains nasal obstruction. Budesonide aqueous nasal spray (BANS) is an intranasal corticosteroid (INCS) that has been available since the early 1980s. BANS is indicated for treating allergic rhinitis, nonallergic rhinitis, and nasal polyps (both as treatment and prevention after surgery). Consolidated evidence confirms its efficacy in treating seasonal and perennial AR, and nonallergic rhinitis. In addition, BANS is safe with negligible local and systemic side effects. Recent guidelines for patients with AR recommend using INCS as the first line in many situations. In particular, patients may assess the perception of symptoms' severity using the Visual Analog Scale. A score ≥5/10 means uncontrolled symptoms and requires adequate treatment. BANS could appropriately be used in patients with uncontrolled symptoms and/or moderate/severe nasal obstruction. In conclusion, BANS represents a valuable option in managing patients with type 2 inflammation of the nose.
Topics: Humans; Nasal Sprays; Budesonide; Rhinitis; Administration, Intranasal; Rhinitis, Allergic
PubMed: 38414250
DOI: 10.23736/S0026-4806.24.09214-0 -
European Journal of Endocrinology Sep 2023Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the...
OBJECTIVE
Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the prevalence of frailty in patients with adrenal disorders (based on hormonal sub-type) and examine association between FI and performance-based measures of physical function.
DESIGN
Multi-centre, cross-sectional study (March 2019-August 2022).
METHODS
Adult patients with adrenal disorders (non-functioning adrenal adenomas [NFA], mild autonomous cortisol secretion [MACS], Cushing syndrome [CS], primary aldosteronism [PA]) and referent subjects without adrenal disorders completed a questionnaire encompassing 47 health variables (comorbidities, symptoms, daily living activities). FI was calculated as the average score of all variables and frailty defined as FI ≥ 0.25. Physical function was assessed with hand grip, timed up-and-go test, chair rising test, 6-minute walk test, and gait speed.
RESULTS
Compared to referent subjects (n = 89), patients with adrenal disorders (n = 520) showed increased age, sex, and body mass index-adjusted prevalence of frailty (CS [odds ratio-OR 19.2, 95% confidence interval-CI 6.7-70], MACS [OR 12.5, 95% CI 4.8-42.9], PA [OR 8.4, 95% CI 2.9-30.4], NFA [OR 4.5, 95% CI 1.7-15.9]). Prevalence of frailty was similar to referent subjects when post-dexamethasone cortisol was <28 nmol/L and was higher when post-dexamethasone cortisol was 28-50 nmol/L (OR 4.6, 95% CI 1.7-16.5). FI correlated with all measures of physical function (P < .001).
CONCLUSIONS
Whilst frailty prevalence was highest in patients with adrenocortical hormone excess, even patients with NFA demonstrated an increased prevalence compared to the referent population. Future longitudinal studies are needed to evaluate the impact of various management strategies on frailty.
Topics: Adult; Humans; Cross-Sectional Studies; Prevalence; Frailty; Hand Strength; Hydrocortisone; Prospective Studies; Adrenocortical Adenoma; Cushing Syndrome; Dexamethasone; Adenoma
PubMed: 37590964
DOI: 10.1093/ejendo/lvad113 -
Journal of Anesthesia Apr 2024Neurosteroids (NS) are a class of steroids that are synthesized within the central nervous system (CNS). Various NS can either enhance or inhibit CNS excitability and... (Review)
Review
Neurosteroids (NS) are a class of steroids that are synthesized within the central nervous system (CNS). Various NS can either enhance or inhibit CNS excitability and they play important biological roles in brain development, brain function and as mediators of mood. One class of NS, 3α-hydroxy-pregnane steroids such as allopregnanolone (AlloP) or pregnanolone (Preg), inhibits neuronal excitability; these endogenous NS and their analogues have been therapeutically applied as anti-depressants, anti-epileptics and general anesthetics. While NS have many favorable properties as anesthetics (e.g. rapid onset, rapid recovery, minimal cardiorespiratory depression, neuroprotection), they are not currently in clinical use, largely due to problems with formulation. Recent advances in understanding NS mechanisms of action and improved formulations have rekindled interest in development of NS as sedatives and anesthetics. In this review, the synthesis of NS, and their mechanism of action will be reviewed with specific emphasis on their binding sites and actions on γ-aminobutyric acid type A (GABA) receptors. The potential advantages of NS analogues as sedative and anesthetic agents will be discussed.
Topics: Anesthetics, General; Neurosteroids; Anesthetics; Pregnanolone; gamma-Aminobutyric Acid; Receptors, GABA-A
PubMed: 38252143
DOI: 10.1007/s00540-023-03291-4 -
International Journal of Gynecological... Nov 2023
Topics: Female; Humans; Endometrial Neoplasms; Medroxyprogesterone Acetate
PubMed: 37875324
DOI: 10.1136/ijgc-2023-005031