Felice Gersh - Academia.edu (original) (raw)

Papers by Felice Gersh

Global advances in health and medicine, 2013

Endocrinology & metabolic syndrome, Dec 14, 2015

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that ... more Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

Mayo Clinic Proceedings, Jul 1, 2020

Clemens KK, Tangri N. A safety comparison of metformin versus sulfonylurea initiation in patients... more Clemens KK, Tangri N. A safety comparison of metformin versus sulfonylurea initiation in patients with type 2 diabetes and chronic kidney disease: a retrospective cohort study.

Endocrinology & metabolic syndrome, Dec 14, 2015

Mayo Clinic Proceedings, Jul 1, 2023

Heart, May 22, 2020

Patient and public involvement Patients and/ or the public were not involved in the design, or co... more Patient and public involvement Patients and/ or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not required. Provenance and peer review Commissioned; internally peer reviewed.

Endocrinology & metabolic syndrome, Jan 4, 2018

Endocrinology & metabolic syndrome, Feb 2, 2017

MOJ women's health, Aug 3, 2016

A high fat, high simple sugar diet impacts the gut microbiota, causing dysbiosis, gut barrier dis... more A high fat, high simple sugar diet impacts the gut microbiota, causing dysbiosis, gut barrier disruption, endotoxemia, and local gut and systemic inflammation. As the normal tight junctions between the cells comprising the single layer protective barrier are compromised, "leaky gut" syndrome develops, permitting the passage of lipopolysaccharides (LPS) from the overgrowth of pathological Gram negative bacteria to cross the gut barrier. Inflammatory cytokines, systemic inflammation, insulin resistance, increased levels of IGF 1 and testosterone, and anovulation-all the classic symptoms of PCOS, occur. The hypothesis published by Professor Tremellen, proposing that the standard Western diet induces and exacerbates PCOS, was confirmed in January 2016 by Dr. Zhu. His published research conclusively showed that women with PCOS, across the entire weight spectrum, have higher systemic levels of LPS compared with matched women without PCOS.

Mayo Clinic Proceedings, Dec 1, 2021

Estradiol (E2) plays an underrecognized role in modulating body-wide systems, including important... more Estradiol (E2) plays an underrecognized role in modulating body-wide systems, including important interactions with the renin-angiotensin-aldosterone system (RAAS). The RAAS is an immunomodulating system that is critical for maintaining homeostasis across multiple organ systems. The diverse interactions between E2 and the RAAS help maintain cardiometabolic homeostasis, including successful physiologic responses to trauma and infectious pathogens. Estradiol deficiency (ie, menopause) results in impaired responses and increased susceptibility to infectious pathogens. Both immune and cardiometabolic function decline with reduced E2 production, in part because the RAAS becomes dysregulated by E2 deficiency, leaving RAAS predominantly in its proinflammatory state and predisposing to systemic low-grade inflammation. Estradiol deficiency and RAAS dysregulation contribute to impaired immune responses and increased incidence of cardiac hypertrophy, hypertension, atherosclerotic cardiovascular disease, arrhythmias, and heart failure. The RAAS consists of dual, counterbalancing pathways-proinflammatory and anti-inflammatory. Estradiol is a signaling agent that plays a major role in determining which RAAS pathway predominates. The proinflammatory pathway is activated early in response to infection or trauma, followed by up-regulation of the anti-inflammatory pathway, to resolve inflammation and to restore homeostasis. Estradiol influences activation of the "switch" to restore the anti-inflammatory state. The dysregulated RAAS is a primary target of current cardiovascular therapeutics focused on blocking portions of its proinflammatory pathway. However, RAAS-modifying pharmaceuticals often provide imperfect solutions to these physiologic disruptions and underscore the need for improved approaches to menopausal medicine. Estradiol therapy and optimal lifestyle practices combined with RAAS-modifying pharmaceuticals may be an ideal strategy to optimize postmenopausal health.

Clinical Infectious Diseases, Sep 23, 2020

mapped to predicted immune epitopes [5]. Taken together, our analysis suggests that asymptomatic ... more mapped to predicted immune epitopes [5]. Taken together, our analysis suggests that asymptomatic reinfection may be a potentially underreported entity. Genetically distinct SARS-CoV-2 rules out persistent viral shedding or reactivation. Both individuals had a higher viral load during reinfection, highlighting the need for continuous surveillance. It is noteworthy that a genetic variant 22882T>G (S: N440K) found during reinfection in I2 possibly confers resistance to neutralizing antibodies [6]. To the best of our knowledge, this is one of the earliest reports of genetically characterized reinfection from India. Notes Acknowledgments. The authors thank Krishna Latha Thammineni, Ravi Kumar Chaudhary, and Abhinav Jain for assistance in data collection and Anjali Bajaj for assistance in preparing the manuscript. The authors also acknowledge Mercy Rophina, Afra Shamnath, and Mohit Mangla for the compilation of functionally relevant variants used in this analysis. Financial support.

Heart, Feb 22, 2021

Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many ... more Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many conditions, including cardiovascular (CV) disease (CVD) prevention. The adverse results from the Women’s Health Initiative (WHI) ended the widespread prescriptive use of HT for nearly 20 years. The WHI findings have been broadly and unfairly applied to all hormone formulations, including modern treatments using human-identical hormones. Although CV health is indisputably linked to oestrogen status, HT involving any combination of hormones currently is not recommended for primary or secondary prevention of CVD. In the wake of more positive results from recent studies and re-evaluation of the WHI, HT has re-emerged as an issue for specialists in CVD to discuss with their patients. Rigorous scientific analysis is needed to explain the paradox of cardioprotection conferred by endogenous ovarian hormones with apparent cardiotoxicity inflicted by HT. This review will cover the origins of HT, hormone terminology and function, and key studies that contribute to our current understanding. Based on evolving evidence, if HT is to be used, we propose it be initiated immediately after cessation of ovarian hormone production and dosed as transdermal oestradiol combined with cyclic dosing of human-identical progesterone (P4).

Progress in Cardiovascular Diseases, May 1, 2020

Australian & New Zealand Journal of Obstetrics & Gynaecology, Aug 17, 2021

BackgroundThere has been increasing awareness that polycystic ovary syndrome (PCOS) phenotypes ma... more BackgroundThere has been increasing awareness that polycystic ovary syndrome (PCOS) phenotypes may represent a mismatch between ancient genetically programmed metabolic and reproductive survival mechanisms and modern lifestyle practices. In‐utero developmental programming of metabolic and endocrine pathways may play an important role in activating gene variants that predispose the offspring to develop PCOS when exposed to specific postnatal conditions. Postnatal exposure to lifestyle factors such as poor‐quality diet and endocrine disrupting chemicals may modulate epigenetically programmed pathways that result in the observed pathophysiological changes and clinical features seen in women with PCOS.AimTo review the developmental origins and transgenerational transmission of PCOS and the impact of lifestyle, androgens and endocrine disrupting chemicals on fetal epigenetic programming.Materials and MethodsThe literature was reviewed using Google, Google Scholar, Medline and PubMed databases. The results are presented as a narrative review.ResultsHuman observational and animal experimental data support the hypothesis that PCOS is an inherited condition that arises as a result of developmental programming of normal gene variants. It is likely that these genes can be amplified by in‐utero androgen exposure and activated by a range of postnatal lifestyle and environmental factors. Endocrine disrupting chemicals have the potential to influence developmental programming of PCOS susceptibility genes.ConclusionsThe current evidence suggests that developmental epigenetic programming following exposure to an adverse maternal metabolic and endocrine environment contributes to the pathogenesis of PCOS. Lifestyle interventions, as recommended by the International Guidelines, have the potential to reduce both symptoms and transgenerational transmission of PCOS.

Mayo Clinic proceedings, 2018

There is an ongoing debate in the medical community regarding the effects of testosterone on card... more There is an ongoing debate in the medical community regarding the effects of testosterone on cardiovascular (CV) health. For decades, there has been conflicting evidence regarding the association of endogenous testosterone levels and CV disease (CVD) events that has resulted in much debate and confusion among health care providers and patients alike. Testosterone therapy has become increasingly widespread, and after the emergence of studies that reported increased CVD events in patients receiving testosterone therapy, the US Food and Drug Administration (FDA) released a warning statement about testosterone and its potential risk regarding CV health. Some of these studies were later found to be critically flawed, and some experts, including the American Association of Clinical Endocrinologists and an expert panel regarding testosterone deficiency and its treatment, reported that some of the FDA statements regarding testosterone therapy were lacking scientific evidence. This article s...

Endocrinology & metabolic syndrome, Feb 2, 2017

Endocrinology & metabolic syndrome, Dec 14, 2015

Endocrinology & metabolic syndrome, Jan 4, 2018

Global advances in health and medicine, 2013

Endocrinology & metabolic syndrome, Dec 14, 2015

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that ... more Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

Mayo Clinic Proceedings, Jul 1, 2020

Clemens KK, Tangri N. A safety comparison of metformin versus sulfonylurea initiation in patients... more Clemens KK, Tangri N. A safety comparison of metformin versus sulfonylurea initiation in patients with type 2 diabetes and chronic kidney disease: a retrospective cohort study.

Endocrinology & metabolic syndrome, Dec 14, 2015

Mayo Clinic Proceedings, Jul 1, 2023

Heart, May 22, 2020

Patient and public involvement Patients and/ or the public were not involved in the design, or co... more Patient and public involvement Patients and/ or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not required. Provenance and peer review Commissioned; internally peer reviewed.

Endocrinology & metabolic syndrome, Jan 4, 2018

Endocrinology & metabolic syndrome, Feb 2, 2017

MOJ women's health, Aug 3, 2016

A high fat, high simple sugar diet impacts the gut microbiota, causing dysbiosis, gut barrier dis... more A high fat, high simple sugar diet impacts the gut microbiota, causing dysbiosis, gut barrier disruption, endotoxemia, and local gut and systemic inflammation. As the normal tight junctions between the cells comprising the single layer protective barrier are compromised, "leaky gut" syndrome develops, permitting the passage of lipopolysaccharides (LPS) from the overgrowth of pathological Gram negative bacteria to cross the gut barrier. Inflammatory cytokines, systemic inflammation, insulin resistance, increased levels of IGF 1 and testosterone, and anovulation-all the classic symptoms of PCOS, occur. The hypothesis published by Professor Tremellen, proposing that the standard Western diet induces and exacerbates PCOS, was confirmed in January 2016 by Dr. Zhu. His published research conclusively showed that women with PCOS, across the entire weight spectrum, have higher systemic levels of LPS compared with matched women without PCOS.

Mayo Clinic Proceedings, Dec 1, 2021

Estradiol (E2) plays an underrecognized role in modulating body-wide systems, including important... more Estradiol (E2) plays an underrecognized role in modulating body-wide systems, including important interactions with the renin-angiotensin-aldosterone system (RAAS). The RAAS is an immunomodulating system that is critical for maintaining homeostasis across multiple organ systems. The diverse interactions between E2 and the RAAS help maintain cardiometabolic homeostasis, including successful physiologic responses to trauma and infectious pathogens. Estradiol deficiency (ie, menopause) results in impaired responses and increased susceptibility to infectious pathogens. Both immune and cardiometabolic function decline with reduced E2 production, in part because the RAAS becomes dysregulated by E2 deficiency, leaving RAAS predominantly in its proinflammatory state and predisposing to systemic low-grade inflammation. Estradiol deficiency and RAAS dysregulation contribute to impaired immune responses and increased incidence of cardiac hypertrophy, hypertension, atherosclerotic cardiovascular disease, arrhythmias, and heart failure. The RAAS consists of dual, counterbalancing pathways-proinflammatory and anti-inflammatory. Estradiol is a signaling agent that plays a major role in determining which RAAS pathway predominates. The proinflammatory pathway is activated early in response to infection or trauma, followed by up-regulation of the anti-inflammatory pathway, to resolve inflammation and to restore homeostasis. Estradiol influences activation of the "switch" to restore the anti-inflammatory state. The dysregulated RAAS is a primary target of current cardiovascular therapeutics focused on blocking portions of its proinflammatory pathway. However, RAAS-modifying pharmaceuticals often provide imperfect solutions to these physiologic disruptions and underscore the need for improved approaches to menopausal medicine. Estradiol therapy and optimal lifestyle practices combined with RAAS-modifying pharmaceuticals may be an ideal strategy to optimize postmenopausal health.

Clinical Infectious Diseases, Sep 23, 2020

mapped to predicted immune epitopes [5]. Taken together, our analysis suggests that asymptomatic ... more mapped to predicted immune epitopes [5]. Taken together, our analysis suggests that asymptomatic reinfection may be a potentially underreported entity. Genetically distinct SARS-CoV-2 rules out persistent viral shedding or reactivation. Both individuals had a higher viral load during reinfection, highlighting the need for continuous surveillance. It is noteworthy that a genetic variant 22882T>G (S: N440K) found during reinfection in I2 possibly confers resistance to neutralizing antibodies [6]. To the best of our knowledge, this is one of the earliest reports of genetically characterized reinfection from India. Notes Acknowledgments. The authors thank Krishna Latha Thammineni, Ravi Kumar Chaudhary, and Abhinav Jain for assistance in data collection and Anjali Bajaj for assistance in preparing the manuscript. The authors also acknowledge Mercy Rophina, Afra Shamnath, and Mohit Mangla for the compilation of functionally relevant variants used in this analysis. Financial support.

Heart, Feb 22, 2021

Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many ... more Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many conditions, including cardiovascular (CV) disease (CVD) prevention. The adverse results from the Women’s Health Initiative (WHI) ended the widespread prescriptive use of HT for nearly 20 years. The WHI findings have been broadly and unfairly applied to all hormone formulations, including modern treatments using human-identical hormones. Although CV health is indisputably linked to oestrogen status, HT involving any combination of hormones currently is not recommended for primary or secondary prevention of CVD. In the wake of more positive results from recent studies and re-evaluation of the WHI, HT has re-emerged as an issue for specialists in CVD to discuss with their patients. Rigorous scientific analysis is needed to explain the paradox of cardioprotection conferred by endogenous ovarian hormones with apparent cardiotoxicity inflicted by HT. This review will cover the origins of HT, hormone terminology and function, and key studies that contribute to our current understanding. Based on evolving evidence, if HT is to be used, we propose it be initiated immediately after cessation of ovarian hormone production and dosed as transdermal oestradiol combined with cyclic dosing of human-identical progesterone (P4).

Progress in Cardiovascular Diseases, May 1, 2020

Australian & New Zealand Journal of Obstetrics & Gynaecology, Aug 17, 2021

BackgroundThere has been increasing awareness that polycystic ovary syndrome (PCOS) phenotypes ma... more BackgroundThere has been increasing awareness that polycystic ovary syndrome (PCOS) phenotypes may represent a mismatch between ancient genetically programmed metabolic and reproductive survival mechanisms and modern lifestyle practices. In‐utero developmental programming of metabolic and endocrine pathways may play an important role in activating gene variants that predispose the offspring to develop PCOS when exposed to specific postnatal conditions. Postnatal exposure to lifestyle factors such as poor‐quality diet and endocrine disrupting chemicals may modulate epigenetically programmed pathways that result in the observed pathophysiological changes and clinical features seen in women with PCOS.AimTo review the developmental origins and transgenerational transmission of PCOS and the impact of lifestyle, androgens and endocrine disrupting chemicals on fetal epigenetic programming.Materials and MethodsThe literature was reviewed using Google, Google Scholar, Medline and PubMed databases. The results are presented as a narrative review.ResultsHuman observational and animal experimental data support the hypothesis that PCOS is an inherited condition that arises as a result of developmental programming of normal gene variants. It is likely that these genes can be amplified by in‐utero androgen exposure and activated by a range of postnatal lifestyle and environmental factors. Endocrine disrupting chemicals have the potential to influence developmental programming of PCOS susceptibility genes.ConclusionsThe current evidence suggests that developmental epigenetic programming following exposure to an adverse maternal metabolic and endocrine environment contributes to the pathogenesis of PCOS. Lifestyle interventions, as recommended by the International Guidelines, have the potential to reduce both symptoms and transgenerational transmission of PCOS.

Mayo Clinic proceedings, 2018

There is an ongoing debate in the medical community regarding the effects of testosterone on card... more There is an ongoing debate in the medical community regarding the effects of testosterone on cardiovascular (CV) health. For decades, there has been conflicting evidence regarding the association of endogenous testosterone levels and CV disease (CVD) events that has resulted in much debate and confusion among health care providers and patients alike. Testosterone therapy has become increasingly widespread, and after the emergence of studies that reported increased CVD events in patients receiving testosterone therapy, the US Food and Drug Administration (FDA) released a warning statement about testosterone and its potential risk regarding CV health. Some of these studies were later found to be critically flawed, and some experts, including the American Association of Clinical Endocrinologists and an expert panel regarding testosterone deficiency and its treatment, reported that some of the FDA statements regarding testosterone therapy were lacking scientific evidence. This article s...

Endocrinology & metabolic syndrome, Feb 2, 2017

Endocrinology & metabolic syndrome, Dec 14, 2015

Endocrinology & metabolic syndrome, Jan 4, 2018