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Improving Quality of Life for Patients with Male Cancers
By Kyla Trkulja
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Male cancers, specifically prostate and testicular cancer, pose a serious threat to men’s health–both physically and psychologically. While the outcomes of these cancers are more favourable relative to others,1 patients and survivors face a variety of challenges including mental health struggles and lessened quality of life.2
Dr. Robert Hamilton, a surgeon-investigator at the Princess Margaret Cancer Centre, is working to improve the quality of life for these men through both his clinical practice and research. His training included a medical degree (MD) and Urology Residency from University of Toronto, a Master’s Degree from University of North Carolina at Chapel Hill, and a Research Fellowship at Duke University. “I knew I wanted to have my career be more than just sitting in the office seeing the next patient and doing the next surgery,” he said, describing the curiosity that led him to pursue research. “When you’re the one asking the research questions, you quickly realize that you can affect more than just that one patient that’s in front of you.”
Dr. Hamilton came to Princess Margaret Cancer Centre in 2012 after completing his Oncology Fellowship in New York City. “I was always interested in cancer, the biology, as well as the psychological or psychosocial functional aspects of what the cancer did to people,” Dr. Hamilton explained. His interest in urology stemmed both from the favourable outcomes, which allows him to positively affect the patients, and from the deep personal interactions with patients due to the intrinsic nature of urological organs. “It’s incredibly rewarding that you can help [patients] in [the psychological] domain as well as conquer the cancer biology.”
Dr. Hamilton has seized the unique opportunity to improve the quality of life of cancer patients and survivors both in and out of the clinic. He is currently the only physician in Canada to utilize minimally invasive robotic surgery for testicular cancer, which decreases the length of hospital stay compared to traditional surgery.3 The nerve-sparing small incisions promote a quicker recovery time and cause fewer post-operative complications, making this an innovative technique to improve the quality of life of testicular cancer patients and survivors.
To tackle the mental health challenges of survivorship, Dr. Hamilton teamed up with Dr. Anika Petrella who was completing her PhD in health behaviour under the supervision of Drs. Catherine Sabiston and Andrew Matthew. Dr. Petrella started ‘The Ball’s in Your Court’ program in collaboration with the University of Toronto after noticing that the mental health burden on young men diagnosed with testicular cancer was a huge challenge. “These [15 to 35-yearold] men who get told they have testes cancer go from thinking they’re going to live forever to wondering if there’s a chance they could die relatively soon. It’s a fundamental uppercut to the ego, and that has profound implications.” In fact, Dr. Hamilton described this mental shock and denial as the biggest challenge impacting these patients.
The unique life experiences and young age of the population meant that these patients could not be effectively integrated into existing survivorship programs. Thanks to Dr. Petrella’s research, a physician- and counsellor-led program was created to engage testicular cancer survivors with physical and group wellness sessions outside of the hospital, allowing them to make meaningful connections, and become more resilient. “You don’t think of yourself as a patient when you’re there,” Dr. Hamilton said.
Dr. Hamilton’s translational research covers topics ranging from basic science to population health sciences. In prostate cancer, he focuses on chemoprevention, with an emphasis on statin medications to
DR. ROBERT HAMILTON
MD, MPH, FRCSC; Clinician-Investigator at Princess Margaret Cancer Centre; University of Toronto Department of Surgery & Division of Urology
Photo Credit: Dr. Robert Hamilton
lower cholesterol and improve outcomes after diagnosis. For testicular cancer, his main focus is on survivorship and identifying biomarkers associated with cancer susceptibility and patient prognosis.
Before the COVID-19 pandemic, Dr. Hamilton was one of the leaders in utilizing virtual care for his patients to improve their quality of life. In-person follow-up appointments usually require patients taking time off of work and travelling long distances for a brief appointment telling them that everything is normal. In Dr. Hamilton’s model, after an initial meeting with early-stage cancer patients to discuss diagnosis, staging, and expectations, the remainder of the patient’s visits were virtual unless there was something of concern. Importantly, the virtual care was asynchronous, allowing patients to view their results or ask questions at any time. Dr. Hamilton was also able to interpret test results and answer questions. The ultimate goal was to enhance the quality of life for patients, as well as their adherence to follow-up appointments. The phase one trial for this virtual care system showed promising results. Patient compliance and quality of life improved while clinic burden was reduced. Princess Margaret Cancer Centre was also able to expand its services to more patients in remote areas across Ontario. Even with virtual care becoming more popular as a result of COVID-19, Dr. Hamilton’s asynchronous and patientcentered approach remains unique, and he hopes that his methods will be used to shape the future of virtual healthcare. him to make a tremendous impact on male cancer patients and survivors. Balancing it all can be a challenge but being able to positively affect people’s lives both in and out of the clinic is described by Dr. Hamilton as an honour and a privilege. “That’s the excitement of it, which I love. I wouldn’t do anything else.”
References
1. Filippou, P., Ferguson, J. E., 3rd, & Nielsen, M. E. (2016). Epidemiology of Prostate and Testicular Cancer. Seminars in interventional radiology, 33(3), 182–185. https://doi.org/10.1055/s-0036-1586146 2. Schepisi, G., De Padova, S., De Lisi, D., et al. (2019). Psychosocial
Issues in Long-Term Survivors of Testicular Cancer. Frontiers in endocrinology, 10, 113. https://doi.org/10.3389/fendo.2019.00113 3. Ray, S., Pierorazio, P. M., & Allaf, M. E. (2020). Primary and post-chemotherapy robotic retroperitoneal lymph node dissection for testicular cancer: a review. Translational andrology and urology, 9(2), 949–958. https://doi.org/10.21037/tau.2020.02.09
Dr. Mary Seeman offers possible answers.
By S. Hussain Ather
A Disease Marked by Difference
Men develop schizophrenia earlier than women, usually by up to three to five years.1,2 Men are also more likely to show harmful symptoms and decreased social functioning, while women respond more rapidly to treatment. However, the reason for these differences is not clear. Researchers have searched for explanations for decades. They have raised potential answers from environmental, psychological, and neurobiological contexts, but the answers are far from straight-forward. Dr. Mary Seeman, Professor Emerita in the Department of Psychiatry at the University of Toronto has dedicated her career to exploring gender differences and disparities in psychiatric diseases. With over 12,000 citations, Dr. Seeman has made significant contributions to her field. In this interview, she sheds light on the complexities of gender and schizophrenia.
Lost in Causes and Conjecture
Schizophrenia affects 20 million people worldwide.3 The disease is characterized by delusions and hallucinations, paranoia, and difficulty concentrating that change the brain’s wiring to alter the way we perceive the world. This creates fundamental changes, not only in the way the nervous system reacts to the world around it, but in how patients with schizophrenia develop and construct their own identities. The disease results from a combination of interactions between genetic, psychosocial, and environmental factors. This means the search for the cause of the disparity between men and women depends on this complicated mix of factors.
Dr. Seeman noted many possible reasons why men develop schizophrenia earlier than women. These can occur at any time during the life course, even as early as in utero with complications during pregnancy or delivery. Dr. Seeman noted, “all neurodevelopmental illnesses really are far more common in boys.” Early exposure to physical trauma could also expose boys to more neurobiological stressors that could cause the disease. Alongside this, in childhood, males tend to show greater communication problems than females, with a higher prevalence of speech disorders and slower language acquisition. These can contribute to difficulties with emotional expression associated with schizophrenia.4,5
The hormone hypothesis is another explanation for sex disparities in schizophrenia. Low levels of testosterone in men have been associated with more severe symptoms of the disease. While female schizophrenia patients often have more severe symptoms in the low estrogen phase of their menstrual cycle.1
The gender disparities in schizophrenia may also stem from psychosocial causes. Adherence to traditional normative beliefs of male behaviour and masculinity, notably emotional repression and selfreliance, could be a contributing factor.6 These norms and beliefs discourage men from seeking help and treatment for mental illnesses.
There are also important neurobiological components. Schizophrenia patients have deficits in intracortical myelin (ICM), myelin found in the gray matter of the cortex in the brain.7 Rates of myelination also differ between genders, with women showing a higher rate of increase in fiber density in associative white matter regions of the brain as they age.8 These regions consist of myelinated axons, responsible for communication between regions. The brains of patients with schizophrenia tend to have abnormalities in their white matter tracts.9 Dr. Seeman noted, these deficits could also be contributing to the gender differences.
DR. MARY SEEMAN
Photo Credit: Kenneth Chou
Finally, Dr. Seeman noted that the discrepancy between men and women could also hinge on issues of sampling, confounding variables, and the individuals studied. “There are many parts of the world where this conclusion may not apply.” In some countries, such as Croatia, no gender difference was observed.1⁰,11 Age of onset for the disease has been observed to be the same in others, and, for families with a history of schizophrenia, the difference in age of onset is typically eliminated, Dr. Seeman noted.
On ways to move forward
Dr. Seeman and other researchers have presented various answers to the question of why there exists a difference in expression and disease progress in men and women diagnosed with schizophrenia. The links between these answers and the disparity itself can be explored more thoroughly. It is still unclear how exactly these causes play out in the grand scheme of schizophrenia. Exploring the underlying etiology and pathophysiology of the disease through interdisciplinary research in psychiatry, epidemiology, and similar fields, could shed light on this relationship. References
1. Li R, Ma X, Wang G, et al. Why sex differences in schizophrenia?. J
Transl Neurosci. 2016 Sep;1(1):37. 2. Leung MD DA, Chue MRC Psych DP. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand. 2000
Jan;101(401):3-8. 3. James SL, Abate D, Abate KH, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.
Lancet. 2018 Nov 10;392(10159):1789-858. 4. Seeman MV. Care gaps in schizophrenia: male/female differences.
The University of British Columbia: This Changed My Practice. 2013 Mar 18. 5. Seeman MV. Does gender influence outcome in schizophrenia?.
Psychiatr Q. 2019 Mar;90(1):173-84. 6. Lanzenberger R, Kranz GS, Savic I. Sex Differences in Neurology and Psychiatry, 1st edition. Elsevier; 2020. 7. Tishler TA, Bartzokis G, Lu PH, et al. Abnormal trajectory of intracortical myelination in schizophrenia implicates white matter in disease pathophysiology and the therapeutic mechanism of action of antipsychotics. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 May 1;3(5):454-62. 8. Schmithorst VJ, Holland SK, Dardzinski BJ. Developmental differences in white matter architecture between boys and girls. Hum
Brain Mapp. 2008 Jun;29(6):696-710. 9. Fields RD. White matter in learning, cognition and psychiatric disorders. Trends Neurosci. 2008 Jul 1;31(7):361-70. 10. Folnegović Z, Folnegović-Šmalc V. Schizophrenia in Croatia: age of onset differences between males and females. Schizophrenia research. 1994 Dec 1;14(1):83-91. 11. Jablensky A, Cole SW. Is the earlier age at onset of schizophrenia in males a confounded finding?: Results from a cross-cultural investigation. The British Journal of Psychiatry. 1997 Mar;170(3):234-40.
Is autism an “extreme male brain” condition?
A conversation about sex and gender variability in autism with Dr. Meng-Chuan Lai
By Iciar Iturmendi Sabater
Autism diagnoses are three to four times more common in men than women. Women are diagnosed with autism later than men. A growing number of concerns have been raised over ascertainment bias in autism. Does the male to female ratio in autism diagnosis truly range from 4:1 to 3:1? Or is it possible that a particular research focus on male samples has led to autism definitions solely drawn from the observation of autistic male characteristics?1
Dr. Meng-Chuan Lai’s scientific work lies at the center of this debate. Dr. Lai is an associate professor at the University of Toronto’s Institute of Medical Science (IMS), and a psychiatrist and O’Brien Scholar at the Centre for Addiction and Mental Health and the Hospital for Sick Children. As a Clinician-Scientist, he studies sex and gender variability in individuals with neurodevelopmental conditions, especially autism.
A theory that may be associated with this ascertainment bias in autistic* women and explain sex and gender differences in prevalence rates is the “extreme male brain” hypothesis, proposed twenty years ago. It was derived from the observation that in the general population and at the group level, women are on-average better at understanding the world through a social or empathizing lens, whereas men are on-average better at grasping meaning from a more technical lens. Yet among the autistic population, autistic women match their male counterparts’ higher systemizing abilities compared to their empathizing abilities. Thus, the extreme male brain hypothesis states that autistic women may show a shift towards ‘male’ profiles in these specific cognitive and behavioural characteristics.2
Dr. Lai calls for careful interpretation of this hypothesis, “the extreme male brain hypothesis, when misunderstood and mistaken as a fact, has led to the stereotype that autistic women should look like autistic men. As a consequence, lots of autistic women who do not show characteristics close to stereotypical autistic men would be perceived as not autistic. This negative impact was not intended based on my understanding of the hypothesis.” For Dr. Lai, the hypothesis was formulated from a cognitive and behavioural lens and confined in the domains of “empathising” and “systemising,” but it does not necessarily extrapolate onto the origins and neurobiological mechanisms underlying autistic cognition and behaviour.
There are three main reasons why it is important to go beyond the extreme male brain hypothesis of autism and study of sex and gender influences in autism, which Dr. Lai refers to as the “ABCs”: A for Aetiology (origin), B for Biological heterogeneity, and C for Clinical practice and care. At each level, research on sex and gender variability may reveal new information about the nature of autism.3 Before diving into this explanation, Dr. Lai emphasizes that “future autism research should differentiate sex and gender, and account for diverse gender identities.”
First, studying sex and gender influences may point towards different sex- and gender related origins of autism. Population studies suggest that multiple genetic factors contribute to the development of autism, and that the genetic load required for autism to manifest is higher for female than male individuals. Beyond genetics, it is possible that male-specific factors make boys more prone to developing autism. For example, higher levels of prenatal sex steroid hormones relate to heightened autistic-like traits or autism diagnosis likelihood later in life.3 This link between sex-hormones and autistic characteristics could reinforce the idea that autism is indeed an extreme male brain condition. However, new research challenges the extreme male brain hypothesis by considering how biology and social factors relate to sex and gender differences in autism.3
The idea of heterogeneity posits that the biological and developmental factors that lead to autism vary from one individual to another. That is, the different developmental pathways lead to autism and the adaptation of autistic individuals, like many roads lead to Rome. While many research efforts currently aim to unveil the sex and gender neurobiology that may differentially underlie autistic
DR. MENG-CHUAN LAI, MD, PhD
Staff Psychiatrist, Clinician Scientist and O’Brien Scholar at the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health, Hospital for Sick Children, and University of Toronto. Associate Professor in the Department of Psychiatry, and Graduate Faculty at the Institute of Medical Science and Department of Psychology, University of Toronto. Honorary Visiting Fellow at the Department of Psychiatry, University of Cambridge. Adjunct Attending Psychiatrist and Assistant Professor of Psychiatry at the National Taiwan University Photo Credit: CAMH
characteristics, Dr. Lai pioneers research on social phenomena that may influence the manifestation of autistic features. Part of his work focuses on understanding so-called camouflaging behaviours used to manage the impression one causes on others with the aim to pass as ‘normal’. Dr. Lai’s research suggests that autistic women are more likely to camouflage their autistic characteristics (social and communication differences, restricted interests, and repetitive behaviours) than autistic men. This observation has led to the hypothesis that recognizing autism may be easier and come earlier in boys and men since girls and women invest greater efforts in going unnoticed as autistic.5 This would mean that autism is not necessarily more common in boys and men, but rather that it is harder to acknowledge in girls and women. Future research is required to clarify how these differences in camouflaging are driven by biological, cultural, and developmental factors.
As a psychiatrist, Dr. Lai became interested in understanding how differently people process and cope in social situations throughout his general psychiatric training early in his career. This takes us to the last level of importance in understanding sex and gender differences in autism: clinical practice and care. “My research ideas are not necessarily pre-defined, but more posthoc: they come after learning from clinical encounters and lived experiences shared by many autistic people,” Dr. Lai shares. In recent years, the autistic community has emphasized the need to make research in autism participatory. Autistic individuals should be included in the design, implementation, and interpretation of findings. Dr. Lai suggests that “it is not just about learning directly from autistic individuals, but also from their caregivers.” In this way, Dr. Lai’s work at the IMS reconciles understanding sex and gender variability in autism from an aetiological, biological, and clinical practice lens. To achieve this, he highlights the importance of interdisciplinary collaboration and participatory research, “true collaboration should involve a commitment and discussion from the earliest stages when studies are being conceptualised and designed, rather than just receiving input on the interpretation of findings later on.”
The interdisciplinary and collaborative products of Dr. Lai’s research on sex and gender influences in autism may help gain a better understanding of this condition in the years to come.
* Identity-first language has been used throughout this article to fit evidence available on the language preferences of the autistic community.6
References
1. Mo K, Sadoway T, Bonato S, Ameis SH, Anagnostou E, Lerch JP, et al. Sex/gender differences in the human autistic brains: A systematic review of 20 years of neuroimaging research. NeuroImage Clin. 2021; 32:102811. 2. Baron-Cohen S. The extreme male brain theory of autism. Trends
Cogn Sci. 2002;6(6):248–54. 3. Lai MC, Lombardo M V., Auyeung B, Chakrabarti B, Baron-Cohen
S. Sex/Gender Differences and Autism: Setting the Scene for Future
Research. J Am Acad Child Adolesc Psychiatry. 2015;54(1):11–24. 4. Lai M-C, Lombardo M V, Ruigrok AN, Chakrabarti B, Auyeung B,
Szatmari P, et al. Quantifying and exploring camouflaging in men and women with autism. Autism . 2017; 21(6):690-702. 5. Kenny L, Hattersley C, Molins B, Buckley C, Povey C, Pellicano E.
Which terms should be used to describe autism? Perspectives from the UK autism community. Autism 2016; 20(4): 442-62.
