Effects of Drospirenone–Ethinylestradiol and/or Metformin on CD4+CD28null T Lymphocytes Frequency in Women With Hyperinsulinemia Having Polycystic Ovary Syndrome: A Randomized Clinical Trial

Moro, Francesca; Morciano, Andrea; Tropea, Anna; Sagnella, Francesca; Palla, Carola; Scarinci, Elisa; Ciardulli, Andrea; Martínez, Daniela; Familiari, Alessandra; Liuzzo, Giovanna; Tritarelli, Alessandra; Cosentino, Nicola; Niccoli, Giampaolo; Crea, Filippo; Lanzone, Antonio; Apa, Rosanna

doi:10.1177/1933719113488444

Cited by 21 publications

(14 citation statements)

References 64 publications

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“…IL-17 and IFN-γ levels were higher in patients with poor glucoregulation at baseline (defined as a glycated hemoglobin >7%); nonetheless, a 12-week treatment with metformin could reduce IL-17 in diabetic patients. Finally, in patients with polycystic ovary syndrome (PCOS), the administration of metformin combined with drospirenone/ethinylestradiol has been shown to reduce the frequency of CD4 + CD28 null T cells ( 51 ), a subset of CD4 + Th1 cells lacking the co-stimulatory receptor CD28 thought to be involved in autoimmune diseases such as RA ( 52 ).…”

Section: Effects Of Metformin On Immune Cells Involved In Autoimmune mentioning

confidence: 99%

Metformin and Autoimmunity: A “New Deal” of an Old Drug

et al. 2018

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Metformin (dimethyl biguanide) is a synthetic derivative of guanidine, isolated from the extracts of Galega officinalis, a plant with a prominent antidiabetic effect. Since its discovery more than 50 years ago, metformin represents a worldwide milestone in treatment of patients with type 2 diabetes (T2D). Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice, provided the basis for defining metformin as a potential antiaging molecule. Moreover, emerging in vivo and in vitro evidence support the novel hypothesis that metformin can exhibit immune-modulatory features. Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases, such as the T helper 17/regulatory T cell balance, germinal centers formation, autoantibodies production, macrophage polarization, cytokine synthesis, neutrophil extracellular traps release, and bone or extracellular matrix remodeling. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin and, from another standpoint, may open the way to assess whether metformin can be a candidate molecule for clinical trials involving patients with immune-mediated diseases. In this article, we will review the available preclinical and clinical evidence regarding the effect of metformin on individual cells of the immune system, with emphasis on immunological mechanisms related to the development and maintenance of autoimmunity and its potential relevance in treatment of autoimmune diseases.

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Section: Effects Of Metformin On Immune Cells Involved In Autoimmune mentioning

confidence: 99%

Metformin and Autoimmunity: A “New Deal” of an Old Drug

et al. 2018

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“…To this regard, the effects of different therapeutic regimens on CD4 + CD28 − T cell frequencies have been investigated in patients with hyperinsulinemic polycystic ovary syndrome, in which increased frequencies of this subset have also been observed (but an association with CMV has not been investigated). Treatment with drospirenone–ethinylestradiol and metformin resulted in a significant reduction of frequencies of CD4 + CD28 − T cells ( 88 ). Moreover, it has been demonstrated in organ transplant recipients that treatment with polyclonal anti-thymocyte globulin preferentially triggers apoptosis in CD4 + CD28 − compared to CD4 + CD28 + T cells ( 89 ).…”

Section: Could Cd4 + Cd28 − T Cmentioning

confidence: 99%

Expansions of Cytotoxic CD4+CD28− T Cells Drive Excess Cardiovascular Mortality in Rheumatoid Arthritis and Other Chronic Inflammatory Conditions and Are Triggered by CMV Infection

et al. 2017

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A large proportion of cardiovascular (CV) pathology results from immune-mediated damage, including systemic inflammation and cellular proliferation, which cause a narrowing of the blood vessels. Expansions of cytotoxic CD4+ T cells characterized by loss of CD28 (“CD4+CD28− T cells” or “CD4+CD28null cells”) are closely associated with cardiovascular disease (CVD), in particular coronary artery damage. Direct involvement of these cells in damaging the vasculature has been demonstrated repeatedly. Moreover, CD4+CD28− T cells are significantly increased in rheumatoid arthritis (RA) and other autoimmune conditions. It is striking that expansions of this subset beyond 1–2% occur exclusively in CMV-infected people. CMV infection itself is known to increase the severity of autoimmune diseases, in particular RA and has also been linked to increased vascular pathology. A review of the recent literature on immunological changes in CVD, RA, and CMV infection provides strong evidence that expansions of cytotoxic CD4+CD28− T cells in RA and other chronic inflammatory conditions are limited to CMV-infected patients and driven by CMV infection. They are likely to be responsible for the excess CV mortality observed in these situations. The CD4+CD28− phenotype convincingly links CMV infection to CV mortality based on a direct cellular-pathological mechanism rather than epidemiological association.

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“…In PCOS patients with no reproductive requirements, the long-term use of COCs have shown to increase the risk of venous thrombosis. However, none of the study patients reported venous thromboembolism (VTE) but milder ADRs that included breast tenderness/swelling along with headache and dizziness as reported elsewhere [32]. The degree of cycle control was also effective with majority of women having normal menstruation at follow up ( Table 2).…”

Section: Discussionmentioning

confidence: 83%

Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study

Zhang

Zeng

et al. 2020

BMC Women's Health

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Background: To investigate the effectiveness and safety of 3 mg drospirenone and 20 μg ethinyl estradiol tablet (3 mg DRSP/20 μg EE) in the treatment of polycystic ovary syndrome (PCOS). Methods: This single center, prospective observational study was conducted in 140 patients with PCOS. They were prescribed 3 mg DRSP/20 μg EE in a 24/4/ regimen for 3 months. Patients were instructed to take oral DRSP/EE tablets (once daily) on the 2nd day of menstruation, for 28 consecutive days for 1 cycle. After 3 months of treatment, anthropometric assessments along with variations in sex hormones related index, glucolipid metabolic index, changes in bilateral ovarian volume, as well as adverse effect of the combination were evaluated. Results: When compared to baseline, body mass index (BMI, 22.07 ± 4.09 vs. 21.35 ± 3.22, p < 0.001) and waist hip ratio (WHR, 0.86 ± 0.07 vs. 0.854 ± 0.06, p = 0.026) decreased significantly after treatment. Sex-hormones such as luteinizing hormone (LH) (10.88 vs. 5.81 U/L), testosterone (T) (1.85 vs. 1.51 nmol/L) and free androgen index (FAI) (5.37 vs. 1.50) decreased significantly after treatment (p < 0.001). Follicular stimulating hormone (FSH) increased significantly at 3 months as compared to before treatment (5.13 vs. 5.42 U/L, p = 0.009). Plasma insulin (11.03 vs. 11.10 pmol/L), fasting (4.97 vs. 4.93 mmol/L) and 2 h-blood glucose levels (7.18 vs. 7.04 mmol/L) did not change when compared to baseline. Plasma triglycerides (TG, 1.32 vs. 1.65 mmol/L) significantly increased 3 months after treatment when compared to before treatment (p < 0.001). However, high density lipoprotein-cholesterol (HDL-C) levels increased significantly after treatment (1.41 vs. 1.57 mmol/L, p < 0.001). It was seen that, when compared to baseline, bilateral ovarian volume (left and right) was significantly lower after treatment (p < 0.05). It was seen that 81 patients reported no adverse reactions. Of the common discomforts reported, breast swelling and pain, gastrointestinal disorder and dizziness and headache were most frequent. Conclusions: Treatment of PCOS patients with3 mg DRSP/20 μg EE has shown beneficial hormonal and lipid profile along with considerable safety profile.

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Effects of Drospirenone–Ethinylestradiol and/or Metformin on CD4+CD28null T Lymphocytes Frequency in Women With Hyperinsulinemia Having Polycystic Ovary Syndrome: A Randomized Clinical Trial

Abstract: In women with hyperinsulinemic PCOS, combined therapy with DRSP/EE and metformin may reduce cardiovascular risk.

Cited by 21 publications

References 64 publications

Metformin and Autoimmunity: A “New Deal” of an Old Drug

Metformin and Autoimmunity: A “New Deal” of an Old Drug

Expansions of Cytotoxic CD4+CD28− T Cells Drive Excess Cardiovascular Mortality in Rheumatoid Arthritis and Other Chronic Inflammatory Conditions and Are Triggered by CMV Infection

Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study

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