Promising Drug Candidates for the Treatment of Polycystic Ovary Syndrome (PCOS) as Alternatives to the Classical Medication Metformin Original paper
Researched by:
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Divine Aleru
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Divine Aleru
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Divine Aleru
Researched by:
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Divine Aleru
ID
Divine Aleru
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study focused on identifying new drug candidates for the treatment of Polycystic Ovary Syndrome (PCOS), with an emphasis on evaluating the effects of various compounds on PCOS pathophysiology. The study investigated the use of Irosustat (STX64), STX140, and compound 1G as potential alternatives to metformin in managing symptoms related to hormonal imbalance, metabolic dysfunction, and oxidative stress commonly seen in PCOS.
Who was studied?
The study utilized female Wistar rats to investigate the therapeutic effects of these drug candidates. PCOS was induced in the rats by administering letrozole (1 mg/kg/day) for 35 days, with the onset of abnormal estrous cycles confirming the induction of the condition. Rats were then divided into treatment groups, with one group receiving metformin (500 mg/kg/day) as a reference drug, while the others received STX64, STX140, or 1G for 30 days. The effects were analyzed through biochemical measurements, oxidative stress markers, and histological studies.
What were the most important findings?
The study found that the drug candidates Irosustat, STX140, and compound 1G all demonstrated promising effects on PCOS-related features. Treatment with these compounds resulted in significant improvements in various biochemical parameters, including lipid profiles, blood glucose levels, and hormone levels (testosterone, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol). These treatments also showed beneficial effects on oxidative stress and inflammation pathways, with improvements in Akt, mTOR, and AMPK-α signaling pathways. Histological studies revealed a reduction in the weight of ovaries and the disappearance of fluid-filled cysts in the treatment groups, suggesting potential for reversing ovarian morphology associated with PCOS. The drug candidates also demonstrated less adverse effect on metabolic parameters compared to untreated PCOS rats, thus highlighting their therapeutic potential as alternatives to metformin.
From a microbiome perspective, these improvements could be linked to the modulation of gut microbiota and reduced systemic inflammation. For example, Irosustat and STX140, by regulating androgen levels and improving metabolic health, may impact the gut’s microbial balance, favoring beneficial bacteria that support metabolic functions and reduce inflammation. Additionally, these compounds’ effects on oxidative stress markers could influence the gut-brain axis, which is crucial in the pathophysiology of PCOS.
What are the greatest implications of this study?
The greatest implication of this study lies in the identification of promising drug candidates, particularly Irosustat, STX140, and compound 1G, as potential treatments for PCOS, especially for patients who do not tolerate metformin. These drug candidates work by targeting oxidative stress, inflammatory pathways, and hormonal imbalances, which are central to PCOS pathophysiology. The findings suggest that these drugs could offer a more comprehensive treatment approach compared to current options, potentially improving not only the metabolic and hormonal aspects of PCOS but also the quality of life for affected women. The study also opens the door for further exploration into the use of these compounds in human trials, highlighting the need for personalized treatment options for women with PCOS
Polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age, characterized by irregular menstrual cycles, hyperandrogenism, and insulin resistance. It is often associated with metabolic dysfunctions and inflammation, leading to fertility issues and increased risk of type 2 diabetes and cardiovascular disease.