Abstract / Summary
Background. The involutional and hormonal shifts characterizing the postmenopausal period in women operate as a permissive physiological background for the accelerated development of metabolic and neurological complications. When coupled with carbohydrate metabolism disorders, particularly type 2 diabetes mellitus (T2DM), the degenerative cascade targeting the autonomic nervous system is exacerbated. The urogenital and cardiovascular forms of autonomic neuropathy represent underdiagnosed yet profoundly disabling complications. Lower urinary tract dysfunction (LUTD) in this cohort seriously induces social maladaptation, anxiety, and introversion, ultimately leading to a precipitous decline in the patients' overall quality of life. Objectives. To comprehensively evaluate the clinical and physiological features of autonomic nervous system disorders (both cardiac and urogenital) in postmenopausal women presenting with various degrees of carbohydrate metabolism disorders (T2DM and Impaired Glucose Tolerance — IGT), and to assess the therapeutic efficacy and safety of selective M-cholinoblocker trospium chloride in managing secondary lower urinary tract dysfunction. Materials and Methods. A prospective clinical study enrolled 45 postmenopausal women who were stratified into three distinct functional cohorts: Group 1 comprised patients with established T2DM (n=20, median disease duration 6.0 [3.5–8.5] years), Group 2 consisted of individuals with impaired glucose tolerance (IGT, n=15), and Group 3 served as a healthy normoglycemic comparison control (n=10). Within the metabolic groups, distinct subgroups were isolated based on the presence (Subgroup A) or absence (Subgroup B) of micturition disorders. Twenty-eight patients from subgroups 1A and 2A underwent a 4-week therapeutic intervention with trospium chloride administered at 30 mg/day as an adjunct to standard background therapy. Autonomic regulation was quantified using comprehensive heart rate variability (HRV) spectral analysis and a battery of standardized cardiovascular autonomic reflex tests (deep controlled breathing, Valsalva maneuver, and orthostatic testing). Urodynamic parameters were tracked via bladder ultrasound and automated uroflowmetry nomograms. Results. Comprehensive neurophysiological mapping demonstrated that autonomic denervation processes are initiated early at the pre-diabetic stage (IGT), with mixed (sympathovagal) involvement dominating the cohort. Analysis of initial vegetative tone (IVT) revealed a stark parasympathetic shift in Group 1 (61% of cases), whereas sympathetic predominance was observed in Groups 2 and 3 (52% and 50% respectively); notably, the state of physiological eutonia was completely absent in the T2DM group. Spectral analysis of HRV demonstrated a profound reduction in total spectral power (TP) across all metabolic groups, driven by a collapse in high-frequency (HF) and low-frequency (LF) modulations alongside a relative expansion of very low-frequency (VLF) waves, signifying a shift from reflex-autonomic to lower metabolic-humoral regulation. Strong negative correlations were confirmed between glycated hemoglobin (HbA1c) and vital spectral parameters: TP (R=-0.27, p=0.00), VLF (R=-0.30, p=0.00), and LF (R=-0.25, p=0.01). Furthermore, triglyceride (TG) levels negatively correlated with TP (R=-0.34, p=0.00), outlining the combined role of hyperglycemia and dyslipidemia in neuropathy progression. Urodynamic evaluations identified severe detrusor-sphincter instability and residual urine retention solely in the T2DM cohort, which correlated positively with HbA1c (R=0.28, p=0.041), TG (R=0.43, p=0.00), and the vegetative stress index (SI) (R=0.39, p=0.03). Following 4 weeks of trospium chloride therapy, the daily frequency of voiding significantly normalized from 12 to 9 episodes in subgroup 1A (p<0.05) and from 12 to 8 episodes in subgroup 2A (p<0.05). Urgent urges were drastically reduced from 6 to 1 episode/day, and the minimum voided volume increased significantly (p<0.05) without altering central cardiovascular spectral parameters, proving high organ selectivity. Conclusion. Functional lower urinary tract dysfunction in postmenopausal women with metabolic syndromes does not merely represent a localized urogenital failure but serves as a sensitive clinical marker for widespread, asymptomatic mixed cardiac autonomic neuropathy. Targeted pharmacological correction using trospium chloride at a dose of 30 mg/day achieves stable symptomatic resolution, actively reverses social maladaptation, and serves as an essential component of the multidisciplinary pathogenetic management of diabetic autonomic neuropathy.