Personalizing Medicine by Sex, Gender and Hormonal Status: Progress, Opportunities and Challenges

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (10 August 2022) | Viewed by 29064

Special Issue Editors


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Guest Editor
Department of Radiology, Director, Center on Gender, Hormones and Health, Stony Brook University, School of Medicine, Stony Brook, NY 11794-2565, USA

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Guest Editor
Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A8, Canada
Interests: women; schizophrenia; psychosis; clinical psychiatry; neuroscience
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Special Issue Information

Dear Colleagues,

Biological sex, gender, and gonadal hormone status have a substantial influence on the incidence, prevalence, presentation, treatment response, and outcome of diverse disorders and pathologies across all medical fields. Despite increasing recognition of the importance of these variables, demographic data collected from patients and participants in clinical trials do not routinely include information on gonadal hormone status (e.g., puberty, stage of menstrual cycle, menopause, or andropause). In this Special Issue, practitioners and investigators in diverse fields of medicine summarize their experience and outline opportunities and challenges in the use of sex, gender, and gonadal hormone status to personalize and improve the diagnosis and treatment of conditions including diabetes, breast cancer, epilepsy, schizophrenia, and brain injury.

Prof. Anat Biegon
Prof. Dr. Mary V. Seeman
Guest Editors

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Keywords

  • sex differences
  • personalized medicine
  • gonadal hormone modulation
  • brain function
  • ovarian/endometrial cancer
  • drug addiction

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Published Papers (8 papers)

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Research

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10 pages, 888 KiB  
Article
Influence of Pregnancy on the Occurrence of Lumbar Spine Pain in Polish Women: A Retrospective Study
by Aleksandra Bryndal, Sebastian Glowinski and Marian Majchrzycki
J. Pers. Med. 2022, 12(3), 357; https://doi.org/10.3390/jpm12030357 - 26 Feb 2022
Cited by 6 | Viewed by 2674
Abstract
(1) Background: Low Back Pain is a major health concern. Pregnancy-related lower back pain is a common complaint among women. The aim of this study was to determine the influence of pregnancy history on the occurrence and profile of pain in the lower [...] Read more.
(1) Background: Low Back Pain is a major health concern. Pregnancy-related lower back pain is a common complaint among women. The aim of this study was to determine the influence of pregnancy history on the occurrence and profile of pain in the lower spine. (2) Methods: The diagnosis of Lower Back Pain during pregnancy was based on the authors’ questionnaire, Visual Analogue Scale (VAS), Oswestry Disability Index and Roland Morris Disability Questionnaire. The research group consisted of 1112 women who were students or came for various reasons to the Gynecology and Obstetrics Clinical Hospital of Poznan University of Medical Sciences and completed the questionnaires. Patients were divided into two groups. The first group consisted of women who had never been pregnant (never-pregnant, n = 872 (78.4%), and the second group consisted of women who had been pregnant at least once in their lives (ever-pregnant, n = 240 (21.6%)). (3) Results: In the never-pregnant and the ever-pregnant women, respectively, the intensity of pain was 4.6 ± 1.6 and 5.0 ± 2.0 on the VAS scale, the degree of disability on the Oswestry Disability Index Questionnaire was 5.0 ± 3.9 and 5.5 ± 4.4, while the impact of pain on functioning on the Roland Morris Disability Questionnaire was 3.9 ± 3.1 and 3.9 ± 3.3. There were no significant differences (Mann-Whitney U test) between the studied groups in the parameters tested. (4) Conclusions: Pregnancy is a risk factor for back pain during pregnancy, but one year or more after pregnancy the occurrence of back pain is similar to that in women who have never been pregnant. Full article
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13 pages, 271 KiB  
Article
What Can We Learn from Sex Differences in MS?
by Patricia K. Coyle
J. Pers. Med. 2021, 11(10), 1006; https://doi.org/10.3390/jpm11101006 - 7 Oct 2021
Cited by 38 | Viewed by 4194
Abstract
Multiple sclerosis (MS) is the major acquired central nervous system disease of young adults. It is a female predominant disease. Multiple aspects of MS are influenced by sex-based differences. This has become an important area of research and study. It teaches us how [...] Read more.
Multiple sclerosis (MS) is the major acquired central nervous system disease of young adults. It is a female predominant disease. Multiple aspects of MS are influenced by sex-based differences. This has become an important area of research and study. It teaches us how the impact of sex on a disease can lead to new insights, guidelines, management, and treatments. Full article
9 pages, 244 KiB  
Article
Sex as a Prognostic Factor in Systematic Reviews: Challenges and Lessons Learned
by Elena Stallings, Alba Antequera, Jesús López-Alcalde, Miguel García-Martín, Gerard Urrútia and Javier Zamora
J. Pers. Med. 2021, 11(6), 441; https://doi.org/10.3390/jpm11060441 - 21 May 2021
Cited by 1 | Viewed by 2704
Abstract
Sex is a common baseline factor collected in studies that has the potential to be a prognostic factor (PF) in several clinical areas. In recent years, research on sex as a PF has increased; however, this influx of new studies frequently shows conflicting [...] Read more.
Sex is a common baseline factor collected in studies that has the potential to be a prognostic factor (PF) in several clinical areas. In recent years, research on sex as a PF has increased; however, this influx of new studies frequently shows conflicting results across the same treatment or disease state. Thus, systematic reviews (SRs) addressing sex as a PF may help us to better understand diseases and further personalize healthcare. We wrote this article to offer insights into the challenges we encountered when conducting SRs on sex as a PF and suggestions on how to overcome these obstacles, regardless of the clinical domain. When carrying out a PF SR with sex as the index factor, it is important to keep in mind the modifications that must be made in various SR stages, such as modifying the PF section of CHARMS-PF, adjusting certain sections of QUIPS and extracting data on the sex and gender terms used throughout the studies. In this paper, we provide an overview of the lessons learned from carrying out our reviews on sex as a PF in different disciplines and now call on researchers, funding agencies and journals to realize the importance of studying sex as a PF. Full article

Review

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20 pages, 991 KiB  
Review
Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges
by Anat Biegon, Siobhan Cohen and Dinko Franceschi
J. Pers. Med. 2022, 12(5), 725; https://doi.org/10.3390/jpm12050725 - 30 Apr 2022
Cited by 8 | Viewed by 3334
Abstract
Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in [...] Read more.
Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status. Full article
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9 pages, 263 KiB  
Review
Special Considerations in the Management of Women with Epilepsy in Reproductive Years
by Krishna Parekh, Hannah Debra Kravets and Rebecca Spiegel
J. Pers. Med. 2022, 12(1), 88; https://doi.org/10.3390/jpm12010088 - 11 Jan 2022
Cited by 4 | Viewed by 3649
Abstract
Anti-seizure medications (ASMs) fail to prevent seizure recurrence in more than 30% of patients with epilepsy. The treatment is more difficult in premenopausal women with epilepsy (WWE) because changes in plasma estrogen and progesterone concentrations during the menstrual cycle often affect seizure frequency [...] Read more.
Anti-seizure medications (ASMs) fail to prevent seizure recurrence in more than 30% of patients with epilepsy. The treatment is more difficult in premenopausal women with epilepsy (WWE) because changes in plasma estrogen and progesterone concentrations during the menstrual cycle often affect seizure frequency and intensity. Interactions between enzyme-inducin ASMs and hormonal contraceptives can lead to both a loss of seizure control and failure of contraception. Significant changes in the function of the liver and kidneys during pregnancy can accelerate metabolism and elimination of ASMs, causing breakthrough seizures. In addition, the teratogenic, cognitive, and psychological effects of ASMs on potential offspring have to be considered when choosing the best ASM regimen. Therefore, aspecialized approach is necessary for the treatment of premenopausal WWE. Full article
16 pages, 564 KiB  
Review
Stratification by Sex and Hormone Level When Contrasting Men and Women in Schizophrenia Trials Will Improve Personalized Treatment
by Mary V. Seeman and Alexandre González-Rodríguez
J. Pers. Med. 2021, 11(9), 929; https://doi.org/10.3390/jpm11090929 - 18 Sep 2021
Cited by 10 | Viewed by 3173
Abstract
Background: Sex and gender differences have been reported in the prevalence, expression, treatment response, and outcome of schizophrenia, but most reports are based on relatively small samples that have not been stratified for the impact of sex hormone levels. This literature review aims [...] Read more.
Background: Sex and gender differences have been reported in the prevalence, expression, treatment response, and outcome of schizophrenia, but most reports are based on relatively small samples that have not been stratified for the impact of sex hormone levels. This literature review aims to show how women’s hormone levels can impact the results of male/female comparisons. Methods: This is a narrative review of data from publications of the last decade. Results: Epidemiologic evidence, reports of the impact of hormones on cognition, results of sexually dimorphic responses to treatment, and male/female trajectories of illness over time all suggest that female hormone fluctuations exert major effects on male/female differences in schizophrenia. Conclusions: Information on hormonal status in women participants is rarely available in clinical studies in schizophrenia, which makes male/female comparisons largely uninterpretable. These are the current challenges. Opportunities for individualized treatment are growing, however, and will undoubtedly result in improved outcomes for both women and men in the future. Full article
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18 pages, 720 KiB  
Review
Peri- and Post-Menopausal Women with Schizophrenia and Related Disorders Are a Population with Specific Needs: A Narrative Review of Current Theories
by Alexandre González-Rodríguez, Armand Guàrdia and José Antonio Monreal
J. Pers. Med. 2021, 11(9), 849; https://doi.org/10.3390/jpm11090849 - 27 Aug 2021
Cited by 13 | Viewed by 4500
Abstract
Background: While gender differences in antipsychotic response have been recognized, the potential role of menopause in changing drug efficacy and clinical outcome in schizophrenia related disorders has been understudied. We aimed to review the relevant literature to test whether optimizing menopausal and post-menopausal [...] Read more.
Background: While gender differences in antipsychotic response have been recognized, the potential role of menopause in changing drug efficacy and clinical outcome in schizophrenia related disorders has been understudied. We aimed to review the relevant literature to test whether optimizing menopausal and post-menopausal treatment and addressing specific health needs of this stage in life will improve outcome. Methods: Non-systematic narrative review using the PubMed database (1900–July 2021) focusing on randomized controlled trial results addressing our question. Forty-nine studies met our criteria. Results: Premenopausal women show significantly better antipsychotic response than postmenopausal women. Hormone replacement therapies (HRT) should be used in postmenopausal women with schizophrenia with caution. Raloxifene, combined with antipsychotics, is effective for psychotic and cognitive symptoms in postmenopausal women with schizophrenia and related disorders. Medical comorbidities increase after menopause, but the influence of comorbidities on clinical outcomes has been poorly investigated. Preventive strategies include weighing risks and benefits of treatment, preventing medical comorbidities, and enhancing psychosocial support. Ideal treatment settings for this population warrant investigation. Conclusions: Antipsychotic dose adjustment at menopause is recommended for schizophrenia. Raloxifene may play an important role in permitting dose reduction and lessening adverse effects. Prevention of comorbidities will help to reduce the mortality rate. Full article
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Other

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18 pages, 1656 KiB  
Systematic Review
Sex Differences in Patent Ductus Arteriosus Incidence and Response to Pharmacological Treatment in Preterm Infants: A Systematic Review, Meta-Analysis and Meta-Regression
by Moreyba Borges-Lujan, Gema E. Gonzalez-Luis, Tom Roosen, Maurice J. Huizing and Eduardo Villamor
J. Pers. Med. 2022, 12(7), 1143; https://doi.org/10.3390/jpm12071143 - 14 Jul 2022
Cited by 9 | Viewed by 3124
Abstract
A widely accepted concept in perinatal medicine is that boys are more susceptible than girls to complications of prematurity. However, whether this ‘male disadvantage of prematurity’ also involves persistent patent ductus arteriosus (PDA) has been scarcely investigated. Our aim was to conduct a [...] Read more.
A widely accepted concept in perinatal medicine is that boys are more susceptible than girls to complications of prematurity. However, whether this ‘male disadvantage of prematurity’ also involves persistent patent ductus arteriosus (PDA) has been scarcely investigated. Our aim was to conduct a systematic review and meta-analysis on studies addressing sex differences in the risk of developing PDA among preterm infants. We also investigated whether the response to pharmacological treatment of PDA differs between boys and girls. PubMed/Medline and Embase databases were searched. The random-effects male/female risk ratio (RR) and 95% confidence interval (CI) were calculated. We included 146 studies (357,781 infants). Meta-analysis could not demonstrate sex differences in risk of developing any PDA (37 studies, RR 1.03, 95% CI 0.97 to 1.08), hemodynamically significant PDA (81 studies, RR 1.00, 95% CI 0.97 to 1.02), or in the rate of response to pharmacological treatment (45 studies, RR 1.01, 95% CI 0.98 to 1.04). Subgroup analysis and meta-regression showed that the absence of sex differences was maintained over the years and in different geographic settings. In conclusion, both the incidence of PDA in preterm infants and the response rate to pharmacological treatment of PDA are not different between preterm boys and girls. Full article
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