Clinical Research

A sample of linked articles demonstrating sex differences in clinical research, the need to include women in research, and the need to stratify analyses by sex. Thousands of other articles exist which demonstrate sex and gender differences.

TOOLS — PubMed search tool
BIAS — General articles about bias in clinical research
CLINICAL TRIALS — How to think about and integrate knowledge of sex and gender differences into clinical research
DEVICES — Sex differences in medical device research
SPECIALTY AREAS, ORGANS, ORGAN SYSTEMS, CONDITIONS, AND SPECIAL POPULATIONS:

Research showing sex and gender differences across many health domains and for many health problems

Cardiology
Dermatology
Endocrinology
Gastroenterology
Gynecology
Immunology
Men’s health
Musculoskeletal
Neurology
Nutrition
Pain
Psychology/psychiatry
Pulmonology
Special populations

Tools

PubMed Search Tool

The Sex and Gender Specific Health website’s resources page contains a PubMed search tool to find articles showing sex and gender differences for health conditions. Basic and advanced PubMed tools are available, as well as instructions for use. Click on Literature Search & Database Resources.

Bias

General articles about bias in clinical research

Exclusion of Women From Clinical Research: Myth or Reality?

May 2008
Exclusion of women from clinical research: myth or reality?.  Rogers, W. A., Ballantyne, A. J., & Australian Gender Equity in Health Research Group.  Assessment of inclusion of men and women in Australian clinical research.

Women are missing in trials of drugs and vaccines for HIV

February 1, 2016
A systematic review of the inclusion (or exclusion) of women in HIV research: from clinical studies of antiretrovirals and vaccines to cure strategies. Curno, M. J., Rossi, S., Hodges-Mameletzis, I., Johnston, R., Price, M. A., & Heidari, S.  Women represented a median of 19.2% participants in ARV studies (387), 38.1% in VAX studies (53), and 11.1% in CURE studies (104). Although women comprise nearly half of people living with HIV, they continue to be under-represented in clinical studies.

Clinical Trials

How to think about and integrate knowledge of sex and gender differences into clinical research

SWHR Clinical Trials Information

The Society for Women’s Health Research (SWHR) provides resources for researchers about research in women’s health and sex and gender based health.

Dialogues on Diversifying Clinical Trials

September 22 – 23, 2011
Successful Strategies for Engaging Women and Minorities in Clinical Trials. By the Society for Women’s Health Research and the US Food and Drug Administration Office on Women’s Health.

Evaluation of Gender Differences in Clinical Investigations

July 22, 1993
On July 22, 1993, the FDA published the Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs, in the Federal Register [58 FR 39406]. The guideline was developed amidst growing concerns that the drug development process did not provide adequate information about the effects of drugs or biological products in women and a general consensus that women should be allowed to determine for themselves the appropriateness of participating in early clinical trials.

Progress of Sex, Race, and Ethnicity in Clinical Trials

March 15, 2011
Inclusion, analysis, and reporting of sex and race/ethnicity in clinical trials: have we made progress? Geller, S. E., Koch, A., Pellettieri, B., & Carnes, M. The National Institutes of Health (NIH) Revitalization Act of 1993 requires that NIH-funded clinical trials include women and minorities as participants; other federal agencies have adopted similar guidelines. The objective of this study is to determine the current level of compliance with these guidelines for the inclusion, analysis, and reporting of sex and race/ethnicity in federally funded randomized controlled trials (RCTs) and to compare the current level of compliance with that from 2004, which was reported previously.

Sex Differences in Scientific Research

2008
BOOK REVIEW of Sex Differences: Summarizing More Than a Century of Scientific Research. By Lee Ellis, Scott Hershberger, Evelyn Field, Scott Wersinger, Sergio Pellis, David Geary, Craig Palmer, Katherine Hoyenga, Amir Hetsroni, and Kazmer Karadi. P. The book includes a massive compendium of citations for reported sex differences. Overall, the book will be a valuable reference resource for researchers in a variety of disciplines.

Sex Differences and Individual Differences in Science

June 9, 2003
Understanding the biology of sex and gender differences: using subgroup analysis and statistical design to detect sex differences in clinical trials. Keitt, S. K., Wagner, C. R., Tong, C., & Marts, S. A.  In July 2001, the Society for Women’s Health Research convened a workshop to address strategies for conducting subgroup analyses to detect sex differences. Workshop participants concluded that understanding sex differences will enable medical researchers to design healthcare interventions for both men and women more effectively and that one can plan for and conduct sex analysis without compromising the quality of the study or making the study prohibitively expensive.

Expanding the Frontiers of Women’s Health Research

June 16, 2003
Expanding the frontiers of women’s health research—US style. Pinn, V. W.  Sex analyses in studies can have clinical implications. Research on women’s health and sex and gender factors is providing the data with which to better arm the physician for possible variations in approaches, drug dosages, or diagnostic practices for not only women but also men. This new knowledge is creating new challenges to ensure that future physicians possess a full understanding of how to better provide gender-appropriate healthcare.

Devices

Sex differences in medical device research

Evaluating Sex Differences in Medical Device Clinical Trials

March 21, 2012
Evaluating sex differences in medical device clinical trials: time for action.  Dhruva, S. S., & Redberg, R. F.  The safety and effectiveness of medical treatments can differ in men and women for many reasons related to different epidemiologic characteristics, physiology, and body size. In general, women have higher bleeding rates and procedural morbidity and mortality than men, which means that their risk/benefit ratios for many implanted medical devices can differ from men. Therefore, sex-specific safety and effectiveness data are necessary for informed patient decision making.

Enrollment and Monitoring of Women in Post Approval Studies for Medical Devices Mandated by the FDA

March 2014
Enrollment and monitoring of women in post-approval studies for medical devices mandated by the Food and Drug Administration. Pinnow, E., Herz, N., Loyo-Berrios, N., & Tarver, M.  FDA implemented new procedures to ensure participation by sex is evaluated in PAS reviews.

Evaluation of Sex-Specific Data in Medical Device Clinical Studies: Guidance for Industry and FDA Staff

August 22, 2014
This document provides guidance on the study and evaluation of sex-specific data in medical device clinical studies. The purpose of this guidance is to outline the FDA’s expectations regarding sex-specific patient enrollment, data analysis, and reporting of study information. The primary intent is to improve the quality and consistency of available data regarding the performance of medical devices in both sexes by encouraging appropriate enrollment by sex in clinical studies of devices, and that data from such studies is appropriately analyzed by sex. This information can be of benefit to patients and their medical providers, as well as clinical researchers and others.

Specialty Areas, Organs, Organ Systems, Conditions, and Special Populations

Categories include: cardiology, dermatology, endocrinology, gastroenterology, gynecology, immunology, men’s health, musculoskeletal, neurology, nutrition, pain, psychology/psychiatry, pulmonology, special populations Research showing sex and gender differences across many health domains and for many health problems

Cardiology

Pivotal WISE Study Delineates Sex Differences in Ischemic Cardiac Disease

February 2006
Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. Shaw, L. J., Merz, C. N. B., Pepine, C. J., Reis, S. E., Bittner, V., Kelsey, S. F., … & Rogers, W. J. The 2006 WISE Study (Women’s Ischemia Syndrome Evaluation), sponsored by the NHLBI, is arguably one of the most significant, pivotal studies which opened our eyes to sex differences in ischemic cardiac disease, which is commonly MI with Non Obstructive Coronary Arteries (MINOCA) in women.  It pleads for education of clinicians on sex differences in not only symptoms (more likely to be fatigue, nausea, and jaw pain), but also in risk markers (high-sensitivity CRP), cardiac testing results (stress echocardiography), SPECT cardiac imaging (single-photon emission computed tomographic imaging),  and treatment programs.

Prevalence of Midlife Cardiovascular Diseases Based on Gender

October 26, 2009
Sex-specific trends in midlife coronary heart disease risk and prevalence. Towfighi, A., Zheng, L., & Ovbiagele, B.  This study aimed to determine sex-specific midlife prevalence of myocardial infarction (MI) and risk of future coronary heart disease. Over the past 2 decades, MI prevalence has increased among midlife women, while declining among similarly aged men. Also, although the risk of future hard cardiovascular events remains higher in midlife men compared with midlife women, the gap has narrowed in recent years. Greater emphasis on vascular risk factor control in midlife women might help mitigate this worrisome trend.

Sex Differences in Heart Failure

March 2014
The Israel Nationwide Heart Failure Survey: Sex Differences in Early and Late Mortality for Hospitalized Heart Failure Patients Klempfner R, Koifman E, Goldenberg I, Hamdan A, Tofler GH, Kopel E ABSTRACT Background: Current data on the influence of gender on the prognosis of heart failure (HF) are conflicting, possibly due to usage of different endpoints […]

Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men

January 18, 2006
Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. Berger, J. S., Roncaglioni, M. C., Avanzini, F., Pangrazzi, I., Tognoni, G., & Brown, D. L.  For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.

Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men Update

March 17, 2009
Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the US Preventive Services Task Force. Wolff, T., Miller, T., & Ko, S. Aspirin reduces the risk for myocardial infarction in men and strokes in women. Aspirin use increases the risk for serious bleeding events.

Sex differences with transcatheter aortic valve implantation for severe aortic stenosis

February 7, 2012
Sex-related differences in clinical presentation and outcome of transcatheter aortic valve implantation for severe aortic stenosisHayashida, K., Morice, M. C., Chevalier, B., Hovasse, T., Romano, M., Garot, P., … & Lefèvre, T. (2012).  Female sex is associated with better baseline clinical characteristics and improved survival, and is identified as a predictor of midterm survival after TAVI Women undergoing transcatheter aortic valve implantation (TAVI) are generally healthier than their male counterparts and have better survival after the procedure, a single-center study showed. Although there was no difference in 30-day survival, a greater percentage of the women were alive at one year (76% versus 65%).

Sex differences in Myocardial Hypertrophy after Aortic Valve Replacement

September 14, 2010
Regression of myocardial hypertrophy after aortic valve replacement: faster in women? Petrov, G., Regitz-Zagrosek, V., Lehmkuhl, E., Krabatsch, T., Dunkel, A., Dandel, M., … & Hampl, H.  In patients with aortic stenosis, pressure overload induces cardiac hypertrophy and fibrosis. Female sex and estrogens influence cardiac remodeling and fibrosis in animal models and in men. Women adapt to pressure overload differently from men. Less fibrosis before surgery may enable faster regression after surgery.

Sex Differences in Stroke Risk with Atrial Fibrillation

May 9, 2012
Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation   Meytal Avgil Tsadok, PhD; Cynthia A. Jackevicius, PharmD, MSc; Elham Rahme, PhD; Karin H. Humphries, DSc; Hassan Behlouli, PhD; Louise Pilote, MD, MPH, PhD  Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.

Sex Differences in Pharmacokinetics and Pharmacodynamics of Anti-Hypertensive Drugs

November 17, 2011
Sex-related differences in pharmacokinetics and pharmacodynamics of anti-hypertensive drugs. Ueno, K., & Sato, H. Sex-specific differences in pharmacokinetics and pharmacodynamics have been reported to have important clinical consequences. In this review, some representative sex-specific differences in absorption and transporters (that is, P-glycoprotein (P-gp)), metabolic processes (that is, those that involve cytochrome P450 (CYP)), clearance (Cl) processes (for example, renal excretion or other pharmacokinetic parameters) and involvement of sex hormones (that is, estrogen and testosterone) in the regulation of some metabolic enzymes are introduced for each of the following categories of anti-hypertensive drugs: calcium-channel blockers, angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors, diuretic agents, and β-adrenergic-receptor blockers (β-blockers). In many cases, female sex is a risk factor for adverse effects or attenuated clinical responses because of lower Cl, smaller distribution volumes, higher activity of some metabolic enzymes (especially hepatic CYP3A4), or presence of sex hormones.

Unintended Benefits of Statins and Sex Differences in Risks

Sex comparison of diagnostic accuracy of CTA for CAD

July/August 2012
Sex comparison of diagnostic accuracy of 64-multidetector row coronary computed tomographic angiography: results from the multicenter ACCURACY trial.  Tsang, J. C., Min, J. K., Lin, F. Y., Shaw, L. J., & Budoff, M. J. Background     The diagnosis of coronary artery disease (CAD) in women remains a challenge, given their lower prevalence of obstructive disease and the suboptimal performance of traditional noninvasive tests (exercise electrocardiography and stress myocardial perfusion imaging). Coronary computed tomographic angiography (CTA) is a validated method for detection and exclusion of obstructive coronary artery stenosis. Coronary CTA found comparable diagnostic accuracy for women in comparison with men for the detection of obstructive coronary stenosis at both thresholds of 50% and 70%.

Sex Differences in PreAdmisssion of STEMI

October 2012
Article in Press Abstract Analysis of Sex Differences in Preadmission Management of ST-Segment Elevation (STEMI) Myocardial Infarction. Greenberg, M. R., Miller, A. C., MacKenzie, R. S., Richardson, D. M., Ahnert, A. M., Sclafani, M. J., … & Burmeister, D. B. No significant gender differences were apparent in the STEMI patients analyzed, whether the MI Alert was initiated in the ED or prehospital initiated. Initiating prehospital-based alerts significantly decreased the time to the cath lab.

Dermatology

Age and Gender As Independent Predictors in Melanoma

February 27, 2008
Age and gender are significant independent predictors of survival in primary cutaneous melanomaLasithiotakis, K., Leiter, U., Meier, F., Eigentler, T., Metzler, G., Moehrle, M., … & Garbe, C. Older age and male gender are associated with prognostically unfavorable primary CM. Expansion of current preventive strategies to target these subgroups is warranted. Moreover, age and gender are independent predictors of the outcome of CM patients. Females have a better prognosis than males but this difference disappears after the age of 65. Younger patients have a more favorable prognosis than older patients, a difference more pronounced in women.

Age and Gender Influences in Survival in Primary Cutaneous Melanoma

April 15, 2008
Age and gender are significant independent predictors of survival in primary cutaneous melanoma. Lasithiotakis K, Leiter U, Meier F, Eigentler T, Metzler G, Moehrle M, Breuninger H, Garbe C. Cancer. Older age and male gender are associated with prognostically unfavorable primary CM. Expansion of current preventive strategies to target these subgroups is warranted. Moreover, age and gender are independent predictors of the outcome of CM patients. Females have a better prognosis than males but this difference disappears after the age of 65. Younger patients have a more favorable prognosis than older patients, a difference more pronounced in women.

Endocrinology

Glucometabolic Disturbances and Health by Age and Gender

December 28, 2011
The association between glucometabolic disturbances, traditional cardiovascular risk factors and self-rated health by age and gender: A cross-sectional analysis within the Malmö Preventive Project.Leosdottir, M., Willenheimer, R., Persson, M., & Nilsson, P. M. (2011). Author’s observations indicate more pronounced risk factor clustering and worse self-rated health with increased glucometabolic disturbance in older women than in older men.

Gastroenterology

Sex Differences in Irritable Bowel Syndrome

July 22, 2010
Meta-analysis: do irritable bowel syndrome symptoms vary between men and women? Adeyemo, M. A., Spiegel, B. M. R., & Chang, L. In the general and IBS populations, gender differences in IBS symptoms exist, although these differences are modest. Studies suggest that female sex hormones influence the severity of IBS symptoms.

Gynecology

Nerve Block for Prevention of Hot Flashes

August 2014
Effects of stellate ganglion block on vasomotor symptoms: findings from a randomized controlled clinical trial in postmenopausal women Walega, David R. MD1; Rubin, Leah H. PhD2; Banuvar, Suzanne MPA3; Shulman, Lee P. MD3; Maki, Pauline M. PhD2,4 Abstract Objective Uncontrolled intervention studies, including studies involving breast cancer survivors, have demonstrated improvements in vasomotor symptoms […]

Effects of Menstrual Cycle on Serum Lipids

September 1, 2010
A longitudinal study of serum lipoproteins in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study. Mumford, S. L., Schisterman, E. F., Siega-Riz, A. M., Browne, R. W., Gaskins, A. J., Trevisan, M., … & Wactawski-Wende, J.  Endogenous estrogen, like exogenous estrogen, appears to have beneficial effects on the lipid profile. Because lipoprotein cholesterol levels vary across the menstrual cycle, cyclic variations in lipoprotein levels may need to be considered in the design and interpretation of studies in reproductive-age women and in the clinical management of women’s cholesterol.

HPA Axis, the Female Reproductive System, and Depression

August 1, 1998
Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Chrousos, G. P., Torpy, D. J., & Gold, P. W.  Although melancholic depression is easier to recognize, another prevalent form of major depression—atypical depression—is also more common in women than in men.  Patients feel lethargic, fatigued, and unmotivated and demonstrate hyperphagia and hypersomnia.  Several lines of evidence suggest that these symptoms are  associated with hyposecretion of CRH (3). This hyposecretion may contribute to a significant increase in the incidence of allergic and autoimmune phenomena in this form of depression and in its two homolog transient states, the postpartum blues or depression and the postcure state of patients with the Cushing syndrome.

Immunology

Autoimmune Disease through a Sex and Gender Lens

January 4, 2011
Sex differences in autoimmune diseases. Voskuhl, R. (2011). Women are more susceptible to a variety of autoimmune diseases including systemic lupus erythematosus (SLE), multiple sclerosis (MS), primary biliary cirrhosis, rheumatoid arthritis and Hashimoto’s thyroiditis. This increased susceptibility in females compared to males is also present in animal models. Being female confers a greater risk of developing these diseases than any single genetic or environmental risk factor discovered to date. Pregnancy reduces relapses in females.

Sex Differences in Autoimmune Disease

May 2012
Sex affects immunity. Pennell, L. M., Galligan, C. L., & Fish, E. N. Sex based differences in immune responses, affecting both the innate and adaptive immune responses, contribute to differences in the pathogenesis of infectious diseases in males and females, the response to viral vaccines and the prevalence of autoimmune diseases. Females have a lower burden of bacterial, viral and parasitic infections, most evident during their reproductive years. Conversely, females have a higher prevalence of a number of autoimmune diseases, including Sjogren’s syndrome, systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis (RA) and multiple sclerosis (MS). This review will focus on the differences between male and female immune responses in terms of innate and adaptive immunity, and the effects of sex hormones in SLE, MS and RA.

Role of Gender and Organ Specific Autoimmunity

May 2012
The role of gender and organ specific autoimmunity. Nussinovitch, U., & Shoenfeld, Y. Autoimmunity is influenced by multiple factors including gender and sex hormones. Sex hormones also influence innate and adaptive immune cells, number of B and T cells, antigen presentation and cytokine secretion. Herein, we review the influence of gender on organ-specific autoimmune diseases affecting the heart, blood vessels, central nervous system and gastrointestinal tract. It appears that sex hormones may have a therapeutic potential in several autoimmune conditions.

Differences in X Chromosome May Explain Sex Differences in Immunity

September 28, 2011
X-chromosome-located microRNAs in immunity: might they explain male/female differences? Pinheiro, I., Dejager, L., & Libert, C. The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females.

Sex Influences Immune Response and Treatment

September 26, 2012
Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases. Klein, SL. The intensity and prevalence of viral infections are typically higher in males, whereas disease outcome can be worse for females. Several variables should be considered when evaluating male/female differences in responses to viral infection and treatment: these include hormones, genes, and gender-specific factors related to access to, and compliance with, treatment. Knowledge that the sexes differ in their responses to viruses and to treatments for viral diseases should influence the recommended course of action differently for males and females.

Influences on the Onset of Autoimmune Hepatitis

March 7, 2009
Influence of genes, sex, age and environment on the onset of autoimmune hepatitis. Kathie Béland, Pascal Lapierre, and Fernando Alvarez.  The pathogenesis of autoimmune hepatitis (AIH) is complex. Development of this disease requires a series of events (viral infection and/or chemical exposure) in a suitable environment (genetic background of susceptibility, female sex and young age).

Autoimmunity and the Female Liver

April 2004
Autoimmunity and the female liver. McFarlane, I. G., & Heneghan, M. A.  In common with several other autoimmune diseases, there is a marked female preponderance in both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Whether this is due to gender differences relating specifically to the liver or more generally to the female constitution is unknown. Since the majority of patients present peri-menopausally and endocrinopathy is frequently associated with these conditions, it seems more likely that hormonal factors may be involved. This is clearly a potentially fruitful area for further research.

Men’s Health

BPA Affects Fertility in Males

May 2014
Urinary bisphenol A, phthalates, and couple fecundity: the Longitudinal Investigation of Fertility and the Environment (LIFE) Study. AUTHORS: Buck Louis GM, Sundaram R, Sweeney AM, Schisterman EF, Maisog J, Kannan K. Abstract OBJECTIVE: To assess the relationship between environmental chemicals and couple fecundity or time to pregnancy (TTP). DESIGN: Prospective cohort. SETTING: Communities of targeted […]

Musculoskeletal

Addressing Gaps: Sex differences in Osteoarthritis of the Knee

February 4, 2013
Addressing the gaps: sex differences in osteoarthritis of the knee. Barbara D Boyan, Laura L Tosi, Richard D Coutts, Roger M Enoka, David A Hart, Daniel P Nicolella, Karen J Berkley, Kathleen A Sluka, C Kent Kwoh, Mary I O’Connor1, Wendy M Kohrt and Eileen Resnick  Epidemiologic studies have established that there are sex differences in the incidence and severity of knee OA. Therapeutic approaches to the treatment of OA, particularly regenerative medicine strategies, have not yet taken these sex differences into consideration. The papers that follow in this series review the literature related to sex differences and OA and identify gaps in our understanding with the goal of motivating research on this important problem.

Assessing Sex Differences in Hip Replacement

March 25, 2013
Sex and Risk of Hip Implant FailureAssessing Total Hip Arthroplasty Outcomes in the United States. Women Show Greater Rate of Failure after Total Hip Arthroplasty  Maria C. S. Inacio, MS; Christopher F. Ake, PhD; Elizabeth W. Paxton, MA; Monti Khatod, MD; Cunlin Wang, MD, PhD; Thomas P. Gross, MD, MPH; Ronald G. Kaczmarek, MD, PhD; Danica Marinac-Dabic, MD, PhD; Art Sedrakyan, MD, PhD.  After considering patient-, surgery-, surgeon-, volume-, and implant-specific risk factors, women had a 29% higher risk of implant failure than men after THA in this community-based sample.

Sports Injuries in Women

January 1, 2008
Sports injuries in women: sex-and gender-based differences in etiology and prevention. Templeton, K. J., Hame, S. L., Hannafin, J. A., Griffin, L. Y., Tosi, L. L., & Shields, N. N. It is important to review some of the areas of sex- and gender-based differences in sports injuries for which there is significant research, such as osteoporosis, the female athlete triad, and anterior cruciate ligament injuries. It is also necessary to examine those areas in which more information is needed, such as injuries to the shoulder, foot, and ankle.

Mortality in Elderly Patients After Hip Fractures

January 20, 2011
Early and late mortality in elderly patients after hip fracture: a cohort study using administrative health databases in the Lazio region, Italy.Castronuovo, E., Pezzotti, P., Franzo, A., Di Lallo, D., & Guasticchi, G. Both clinical and organizational factors of acute care are associated with the risk of early mortality. As time passes, some of these factors tend to become less important while older age, male gender, the presence of cognitive problems and the presence of other comorbidities remain significant.

Gender Differences in Knee Osteoarthritis Pain, Function, and Activity

November 10, 2011
Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement. Tonelli, S. M., Rakel, B. A., Cooper, N. A., Angstom, W. L., & Sluka, K. A. Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.

Neurology

Sex differences in neurobiology of drug addiction

September 2014
Sex differences in the neurobiology of drug addiction. Authors: Bobzean SA, DeNobrega AK, Perrotti LI. Abstract Epidemiological data demonstrate that while women report lower rates of drug use than men, the number of current drug users and abusers who are women continues to increase. Here we review the basic neurocircuitry which underlies reward and addiction; highlighting the neuroadaptive changes that occur in the mesolimbic dopamine reward and anti-reward/stress pathways. We propose that sex differences in addiction are due to sex differences in the neural systems which mediate positive and negative reinforcement and that these differences are modulated by ovarian hormones. This forms a neurobehavioral basis for the search for the molecular and cellular underpinnings that uniquely guide motivational behaviors and make women more vulnerable to developing and sustaining addiction than men.

Genetic Protein Mutation Could Explain Gender Differences in Alzheimer’s and Autism

February 3, 2015
Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer’s pathologies AUTHORS: A Malishkevich, N Amram, G Hacohen-Kleiman, I Magen, E Giladi and I Gozes ABSTRACT Activity-dependent neuroprotective protein (ADNP) is a most frequent autism spectrum disorder (ASD)-associated gene and the only protein significantly decreasing in the serum of Alzheimer’s disease (AD) patients. Is ADNP […]

Sex and Gender Differences in Alzheimer’s Disease

October 4, 2012
Alzheimer’s disease (AD) disproportionately affects women in both prevalence and severity; however, the biologic mechanisms underlying these sex differences are not fully understood. Sex differences in the brain, such as in brain anatomy, age-related declines in brain volume, and brain glucose metabolism, have been documented and may be important in understanding AD etiology. To address the evidence for sex differences in AD, the Society for Women’s Health Research (SWHR) convened an interdisciplinary roundtable of experts from academia, clinical medicine, industry, and the government to discuss the state-of-the-science in sex and gender differences in AD. Roundtable participants addressed gaps in our knowledge and identified specific sex-based research questions for future study.

Cognition in Men and Women with Autism

October 17, 2012
Cognition in males and females with autism: similarities and differences. Lai, M. C., Lombardo, M. V., Ruigrok, A. N., Chakrabarti, B., Wheelwright, S. J., Auyeung, B., … & MRC AIMS Consortium. The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC. In specific non-social cognitive domains, performance within ASC depends on sex.

Behavioral Comparison of Sex Differences in Adults with Autism Spectrum Conditions

June 13, 2011
A behavioral comparison of male and female adults with high functioning autism spectrum conditionsLai, M. C., Lombardo, M. V., Pasco, G., Ruigrok, A. N., Wheelwright, S. J., Sadek, S. A., … & MRC AIMS Consortium. On some measures, there were no differences between men and women. But adult females with ASC showed more lifetime sensory symptoms, fewer current socio-communication difficulties, and more self-reported autistic traits than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay, a pattern not seen in males.

Sex Impacts Memory

July 2012
Sex differences in memory of emotional images A behavioral and electrophysiological investigation Emma Glaser, Adrianna Mendreka, Martine Germaina, Nadia Lakisa, Marc E. Lavoie.  marc.lavoie@umontreal.ca ABSTRACT Current research suggests that emotional responses differ between men and women. Sex differences regarding emotional effects on memory have been recently studied through brain imaging techniques. However, the majority of […]

Sex Differences in Stroke Risk with Atrial Fibrillation

May 9, 2012
Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation   Meytal Avgil Tsadok, PhD; Cynthia A. Jackevicius, PharmD, MSc; Elham Rahme, PhD; Karin H. Humphries, DSc; Hassan Behlouli, PhD; Louise Pilote, MD, MPH, PhD  Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.

Peripheral Contributions to Sexual Differentiation of the Central Nervous System

February 3, 2012
Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system.  Swift-Gallant, A., Niel, L., & Monks, D. A. Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.

Nutrition

Sex Differences in Omega-3 Fatty Acid Supplementation

February 2012
Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation Phang, M., Sinclair, A. J., Lincz, L. F., & Garg, M. L. The physiological processing of  eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to affect platelet aggregation due to interactions with sex hormones. This distinctive sex-specific, inhibitory response suggests that men may benefit more from EPA supplementation while women are more responsive to DHA. EPA was more effective in men when compared to DHA and placebo, whereas DHA was significantly more effective than EPA and placebo in women.

Pain

Sex Differences in Pain Perception and Treatment

March 1, 2009
Sex-based differences in pain perception and treatment. Paller, C. J., Campbell, C. M., Edwards, R. R., & Dobs, A. S. Sex-based differences in pain perception and treatment. A substantial body of research indicates that women experience greater clinical pain, suffer greater pain-related distress, and show heightened sensitivity to experimentally induced pain compared with men. The factors underpinning sex differences in the experience of pain are multifactorial and complex, and include psychosocial factors and gonadal hormone levels. Women perceive more pain during the luteal phase, and estrogen antagonists provide long-term pain relief in certain situations.

Hypothalamic-Pituitary-Adrenal Axis Function and Chronic Pain Syndrome

June 15, 2010
Sex differences in hypothalamic–pituitary–adrenal axis function in patients with chronic pain syndromeTurner-Cobb, J. M., Osborn, M., da Silva, L., Keogh, E., & Jessop, D. S. CPS is associated with a degree of hypocortisolemia, particularly in male patients.

Pharmacology

Gender Differences in Drug Bioequivalence: Time to Rethink Practices

December 2, 2012
Gender Differences in Drug Bioequivalence: Time to Rethink Practices. Koren, H Nordeng and S Macleod.  Currently, bioequivalence (BE) studies are carried out exclusively in males, assuming that intrasubject variabilities are similar between the sexes. This article challenges this hypothesis on the basis of available evidence and urges that studies of BE of sufficient power be undertaken in women also for all generic drugs aimed at women.

Sex Differences in Pharmacokinetics and Pharmacodynamics of Anti-Hypertensive Drugs

November 17, 2011
Sex-related differences in pharmacokinetics and pharmacodynamics of anti-hypertensive drugs. Ueno, K., & Sato, H. Sex-specific differences in pharmacokinetics and pharmacodynamics have been reported to have important clinical consequences. In this review, some representative sex-specific differences in absorption and transporters (that is, P-glycoprotein (P-gp)), metabolic processes (that is, those that involve cytochrome P450 (CYP)), clearance (Cl) processes (for example, renal excretion or other pharmacokinetic parameters) and involvement of sex hormones (that is, estrogen and testosterone) in the regulation of some metabolic enzymes are introduced for each of the following categories of anti-hypertensive drugs: calcium-channel blockers, angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors, diuretic agents, and β-adrenergic-receptor blockers (β-blockers). In many cases, female sex is a risk factor for adverse effects or attenuated clinical responses because of lower Cl, smaller distribution volumes, higher activity of some metabolic enzymes (especially hepatic CYP3A4), or presence of sex hormones.

Psychology/Psychiatry

Estrogens of Multiple Classes and Their Role in Mental Health Disease Mechanisms

August 9, 2010
Estrogens of multiple classes and their role in mental health disease mechanisms Watson, C. S., Alyea, R. A., Cunningham, K. A., & Jeng, Y. J.  There are important differences between males and females in a number of functional responses and vulnerabilities to behavioral disorders. Signaling mechanisms, both genomic and nongenomic, operating via several different ER proteins residing in different subcellular compartments, are beginning to be found responsible for diverse actions of estrogens involved in these functions. Complex signaling cascades and receptor systems can be influenced by multiple physiological estrogens, as well as some nonphysiological (dietary, pharmaceutical) and contaminant (environmental) estrogens. Such influences could have profound effects on the functioning of the brain and nervous system.

HPA Axis, the Female Reproductive System, and Depression

August 1, 1998
Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Chrousos, G. P., Torpy, D. J., & Gold, P. W.  Although melancholic depression is easier to recognize, another prevalent form of major depression—atypical depression—is also more common in women than in men.  Patients feel lethargic, fatigued, and unmotivated and demonstrate hyperphagia and hypersomnia.  Several lines of evidence suggest that these symptoms are  associated with hyposecretion of CRH (3). This hyposecretion may contribute to a significant increase in the incidence of allergic and autoimmune phenomena in this form of depression and in its two homolog transient states, the postpartum blues or depression and the postcure state of patients with the Cushing syndrome.

Sex differences in neurobiology of drug addiction

September 2014
Sex differences in the neurobiology of drug addiction. Authors: Bobzean SA, DeNobrega AK, Perrotti LI. Abstract Epidemiological data demonstrate that while women report lower rates of drug use than men, the number of current drug users and abusers who are women continues to increase. In addition women progress through the phases of addiction differently than […]

PULMONOLOGY

Gender and Chronic Obstructive Pulmonary Disease

August 2, 2007
Gender and chronic obstructive pulmonary disease: why it matters. Han, M. K., Postma, D., Mannino, D. M., Giardino, N. D., Buist, S., Curtis, J. L., & Martinez, F. J. Gender and chronic obstructive pulmonary disease: why it matters The authors present current knowledge regarding how gender influences the epidemiology, diagnosis, and presentation of COPD in addition to physiologic and psychologic impairments and attempt to offer insight into why these differences might exist and how this may influence therapeutic management. Women may actually be at greater risk of smoking-induced lung function impairment, more severe dyspnea, and poorer health status for the same level of tobacco exposure. Nonsmokers with COPD are also more likely to be female. Men and women may be phenotypically different in their response to tobacco smoke, with men being more prone to an emphysematous phenotype and women an airway predominant phenotype.

Sex, Gender, Lung Development and Lung Disease

October 2007
It’s all about sex: gender, lung development and lung disease.  Carey, M. A., Card, J. W., Voltz, J. W., Arbes Jr, S. J., Germolec, D. R., Korach, K. S., & Zeldin, D. C. Accumulating evidence suggests that gender affects the incidence, susceptibility, and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma, and cancer.

Sex Impacts Respiratory Diseases

September 1, 2013
Sex and inflammation in respiratory diseases: a clinical viewpoint Georges J Casimir, Nicolas Lefèvre, Francis Corazza2 and Jean Duchateau Sex differences play a role in the prognosis of acute or chronic inflammatory, respiratory diseases. Learn more about the consequences of severe inflammation vary in relation to sex, depending on illness duration.

Special Populations

Current Challenges in Female Veterans’ Health

August 28, 2012
Current Challenges in Female Veterans’ Health. Eileen M. Resnick, Ph.D., Monica Mallampalli, Ph.D., and Christine L. Carter, Ph.D., M.P.H. The Society for Women’s Health Research (SWHR) convened a 1-day interdisciplinary scientific conference about women veterans’ health. The following topics were discussed: mental health (posttraumatic stress disorder [PTSD] and depression), urogenital health, musculoskeletal health, and traumatic brain injury (TBI).

Health Impacts of Stress for Women in the Military

November 27, 2010
Pregnancy and mental health among women veterans returning from Iraq and Afghanistan. Mattocks, K. M., Skanderson, M., Goulet, J. L., Brandt, C., Womack, J., Krebs, E., … & Haskell, S.  Women OEF/OIF veterans commonly experience mental health problems after military service. The burden of mental health conditions is higher among women with an identified instance of pregnancy than among those without. Because women do not receive pregnancy care at the VHA, however, little is known about ongoing concomitant prenatal and mental healthcare or about pregnancy outcomes among these women veterans


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