ABSTRACT
Diabetes mellitus (DM) and premenstrual syndrome (PMS) are global health challenges. Both disorders are often linked to a range of physical and psychological symptoms that significantly impact the quality of life of many women. Yet, the exact relation between DM and PMS is not clear, and the management of both conditions poses a considerable challenge. In this review, we aimed to investigate the interplay between DM, anti-diabetic drugs, and the different theories and symptoms of PMS. Female sex hormones are implicated in the pathophysiology of PMS and can also impair blood glucose control. In addition, patients with diabetes face a higher susceptibility to anxiety and depression disorders, with a significant number of patients experiencing symptoms such as fatigue and difficulty concentrating, which are reported in patients with PMS as well. Complications related to diabetic medications, such as hypoglycemia (with sulfonylurea) and fluid retention (with thiazolidinediones) may also mediate PMS-like symptoms. DM can, in addition, disturb the normal gut microbiota (GM), with a consequent loss of beneficial GM metabolites that guard against PMS, particularly the short-chain fatty acids and serotonin. Among the several available anti-diabetic drugs, those (1) with an anti-inflammatory potential, (2) that can preserve the beneficial GM, and (3) possessing a lower risk for hypoglycemia, might have a favorable outcome in PMS women. Yet, well-designed clinical trials are needed to investigate the anti-diabetic drug(s) of choice for patients with diabetes and PMS.
ABSTRACT
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology. METHOD: We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging. CONCLUSION: Metformin and sotatercept appear as promising therapeutic drugs for PAH. CLINICAL TRIALS REGISTRATION: This work was registered in PROSPERO (CDR42022340658).
