Tag Archive for: menopause

Let’s (meno)pause and reflect on cardiovascular disease in females

Authors: Nabilah Gulamhusein, BSc, PhD Candidate, Libin Cardiovascular Institute

Cumming School of Medicine, University of Calgary | Editors: Romina Garcia de leon, Janielle Richards  (Blog Coordinators) Expert reviewer: Alexandra Lukey 

Published: Friday October 18th, 2024 

Cardiovascular disease is an umbrella term used to describe a variety of conditions that affect the heart and blood vessels such as heart attack, coronary heart disease and stroke. Globally, cardiovascular disease is a leading cause of death among women, and elevated blood pressure or hypertension is one of the most common modifiable risk factors for cardiovascular mortality. Recognizing the importance of blood pressure control, the World Health Organization has set a global target of a 25% relative reduction in uncontrolled hypertension by 2025. Within Canada, the number of people living with hypertension has remained relatively steady between 2007 and 2017, however, the rates of awareness, treatment and control have worsened in women. Hence, there is an urgent need to identify factors across a female’s lifespan that may contribute to hypertension.

 Menopause is a natural part of the ageing process and is marked by the cessation of menses for 12 consecutive months. The average age of menopause in Canada is 51 years. Menopause can be associated with a variety of symptoms including genitourinary symptoms, hot flashes, sleep disturbances and cognitive changes. Up to 75% of individuals will face debilitating vasomotor symptoms, such as night sweats and hot flashes, and can severely impact an individual’s quality of life; the average length for such symptoms is 7 years. According to the North American Menopause Society Position Statement, the first line of treatment for vasomotor symptoms is menopausal hormone therapy, for people without contraindications. Menopausal hormone therapy often consists of estrogen and progestins, which may be used individually or together to help treat symptoms of menopause. 

Although it is estimated that by the year 2025, there will be more than a billion menopausal individuals on the planet, surprisingly little is known about menopausal hormone therapy and its relation to cardiovascular disease. Historically, menopausal hormone therapy was prescribed to women with the intent of providing cardiovascular protection, as seen in the Nurses’ Health Study. However, there has been a paradigm shift as a more recent randomized controlled trial showed no difference in coronary heart disease between people taking menopausal hormone therapy and those taking placebo. The discrepant findings continue to be debated in the literature and a variety of possible factors for the conflicting findings have come to light. For example, the timing at which menopausal hormone therapy is initiated, the dosage, route of administration and formulation may all play an important role in contributing to different study findings, though further research is required.

A part of my doctoral thesis aims to address this research gap. Previous studies have shown that individuals using transdermal estrogen have a significant decrease in blood pressure when compared to those taking a placebo. To further complement this observation, oral use of estrogen has been shown to be associated with higher systolic and diastolic blood pressures, and greater risk of hypertension. Despite these findings, studies have been limited in sample size and a mechanism for this has not yet been identified. Therefore, my research program aims to examine the relationship between the route of menopausal hormone therapy administration and blood pressure while elucidating a mechanism as to how this may occur. 

 Overall, this study will help us advance our knowledge about cardiovascular health in females, inform clinicians about optimal delivery for menopausal hormone therapy, and ultimately help empower females to make decisions about their own health and what is right for them. 

 

 

Behind the Science: Decoding Menopausal Hormone Therapy

Interviewee: Dr. Laura Gravelsins, Postdoctoral researcher, University of Toronto, Centre for Addiction and Mental Health |Authors/Editors: Romina Garcia de leon, Janielle Richards (Blog Co-coordinators)

Published: October 11th, 2024

Can you tell us a little bit about your research?

There’s a large body of literature to suggest that menopausal hormone therapy (MHT) may benefit brain aging in females and reduce their dementia risk. However, not all females show memory benefits when taking MHT. The main goal of my research is to understand why there’s such a varied cognitive response to MHT. MHT comes in many forms, for example, it varies in dosage, formulation, route of administration, and timing of initiation. These many forms of MHT are usually not accounted for in research. By accounting for the various forms of MHT, as well as other biological and lifestyle factors, we aim to clarify why some, but not all, females show memory benefits when taking MHT. Our goal is to move toward personalized or precision medicine, and identify effective formulations of MHT that will support healthy brain aging in all females. 

What led you to do this work? 

I think where it really started is in my undergraduate studies. I was taking a physiology course which was very content heavy. We reached the unit on female reproductive physiology and I remember it was skimmed over quickly.  We were encouraged to refer to the textbook for more detail, rather than having the topic prioritized in lectures. This experience made me realize that women’s health isn’t given the attention it deserves. Fortunately, around the same time, I stumbled upon a research article by Dr. Emily Jacobs that explored the interactions between the menstrual cycle and dopamine levels, and how these interactions affect working memory. This was the first article I encountered that combined a female-specific factor with neuroscience. It opened my eyes to the endless possibilities within this area of research, and made me realize that female-specific health factors are actually something that can make your research more interesting, rather than be a complicating or nuisance variable.  I think I was very lucky to have had this realization at this stage in my research journey. This motivated me to focus on women’s health research during my undergraduate studies, then my graduate work, and that’s how I ended up here today.

Are there any findings that you can share with us? 

My PhD research focused on females with surgically induced menopause, specifically those with risk-reducing bilateral salpingo-oophorectomy (BSO) because they carry a genetic mutation that puts them at a higher risk for breast and ovarian cancers. Unfortunately, early ovarian cancer detection techniques are poor, so the best preventative option for these individuals is to get their ovaries removed when they’re quite young. BSO is recommended as early as 40 years old, several years before spontaneous/natural menopause. 

There is substantial research indicating the importance of ovarian hormones for brain health in later life. Previous studies, including work from Dr. Walter Rocca’s lab, have shown that females with bilateral oophorectomy may be at greater risk for dementia without MHT. In our research, we recruited midlife women, averaging in their mid-40s, to assess changes in memory, sleep patterns, and brain function, while also evaluating the effects of estradiol-based MHT. Overall, we found that estradiol-based MHT benefitted working memory, sleep, and hippocampal volume, but was not fully protective. When plotting individual data points, we observed that for some individuals estradiol-based MHT works really well. For others, it’s not as effective. 

What’s next for you and your research?

My background has been primarily in quantitative research, so looking at performance metrics from neuropsychological tests and memory assessments, and quantifying brain volumes and hormone levels to understand individuals. I’m hoping to incorporate more qualitative components into my research next. Adopting a mixed-methods approach, which combines both quantitative and qualitative data, would allow me to explore how individuals perceive their memory changes and can provide rich insights that numbers alone may not capture. Even if someone does not score low on a quantitative measure, their subjective experience is really valuable. I hope to incorporate this qualitative perspective into my future work. 

Women’s Health Interrupted Podcast: Season 2 Recap

Authors: Edidiong Daniel, BSc. Environmental Toxicology | WHRC Social Media Committee Member | Editor: Romina Garcia de leon Reviewer: Bonnie Lee

Published: July 19th, 2024

We’ve come to the end of Season 2 of the Women’s Health Interrupted Podcast! – a podcast that centers on women’s health across these four themes: general health and wellness, brain health, socio-cultural determinants of health as well as politics, policy, and advocacy. The second season of the Women’s Health Interrupted Podcast was hosted by UBC’s Masters of Journalism students, Chhavi Mehra and Sarah Williscraft, and featured guests across various institutions and fields. All episodes are available on any major podcast streaming platform. If you haven’t tuned in yet, here’s a quick recap!

Season 2 kicked off with Dr. Lori Brotto, a professor in the UBC Department of Gynecology, a registered psychologist in Vancouver, and Executive Director of the Women’s Health Research Institute of BC, discussing Cultivating Female Sexual Desire through Mindfulness. Dr. Brotto shared the role of mindfulness and environmental influence in cultivating female sexual desires and discussed the orgasm gap and contributing factors, while also debunking some myths surrounding female sexuality.

Next, we had Dr. Najah Adreak, a clinical researcher and an advocate for cardiovascular health and treatment, especially for underserved women patients, for episode two: Why are Women’s Cardiovascular Concerns Often Downplayed? Dr. Adreak discussed why women’s cardiovascular health is often downplayed and also shed light on the knowledge gaps in women’s cardiovascular health, the differences between male and female hearts, how hormonal changes and social determinants of health can affect women’s heart health long-term, and the role of physicians in filling the knowledge gaps in female cardiovascular health.

In the third episode: All You Need to Know about Gynecological Cancer, co-hosts of the Gynecologic Oncology Sharing Hub (GOSH) podcast Nicole Keay and Stephanie Lam told us everything we should know about gynecological cancer, explaining how gynecological cancer differs from other forms of cancer and the importance of researching these cancers as separate entities. Nicole and Stephanie also shared new research tools for gynecological cancer such as the Opportunistic Salpingectomy for prevention strategy and the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) for endometrial cancer diagnosis.

Dr. Lindsay Larios, assistant professor at the University of Manitoba’s Faculty of Social Work, joined us to discuss Abortion Rights with Precarious Immigration Status, highlighting the challenges in accessing abortion and general reproductive care as immigrants in Canada. Dr. Larios explained how access to reproductive care for pregnant immigrants differs based on class, race, ethnicity, and other socioeconomic factors, the difference between private and public health insurance for immigrants, the importance of including reproductive rights and justice framework in Canada’s immigration system, and reforms and repairs that need to happen.

For episode 5: Housing and Health Barriers Faced by 2SLGBTQ+ Youth, Dr. Alex Abramovich, an Independent Scientist with the Institute of Mental Health Policy Research at The Centre for Addiction and Mental Health, took us through the current state of housing access for 2SLGBTQ+ Youths in Canada. Dr. Abramovich laid out some factors that impact access to housing for 2SLGBTQ+ youths in Canada and shared some useful resources for 2SLGBTQ+ youths experiencing homelessness. 

PhD student, Amanda Namchuk, and recent B.Sc. in Biology graduate, Tallinn Splinter, came on the podcast to discuss the Exclusion of Women from health Research: Then and Now. Amanda and Tallinn helped differentiate between sex and gender and addressed the need for sex and gender-based research using the difference in the breakdown of Tylenol in men and women, among others, as a clear case study. They also explained how the exclusion of women in research impacts historically underserved communities and the role of big institutions like the Canadian Institutes of Health Research (CIHR) and journals in ensuring sex and gender are properly incorporated in scientific research.

Featuring Dr. Ann-Marie de Lange from the University of Oxford, and Dr. Claudia Barth, biologist and cofounder of the Women’s NeuroNetwork, we went deep into the brain for episodes 7 and 8. Dr. Ann-Marie de Lange discussed some common misconceptions about how pregnancy affects the brain, highlighted some changes that happen to the brain during pregnancy and after birth, and shared what women can do to improve their brain health for episode 7: Mommy Brain: It’s Not Just in Your Head. In episode 8: How Does Menopause Affect the Brain, Dr. Barth shed light on some hormonal changes that happen to the brain during menopause, menopausal symptoms, the impact of menopause on mental health and neurological disorders, and the need to educate women and men on menopause.

Dr. Debra Anderson, Dean of the Faculty of Health at the University of Technology Sydney, explained how lifestyle factors and health behaviors such as smoking, exercise, and nutrition can impact quality of life in the ninth episode: This is How You Can Improve Your Quality of Life. Dr. Anderson also stressed the importance of looking at women as a whole and also shared a shocking revelation on how big a role calcium plays in reducing premenstrual syndrome (PMS).

For episode ten: Domperidone for Low Milk Supply: Is it Safe? we were joined by Dr. Janet Currie, a social worker and the founder and director of Focus Consultants, and Dr. Suzanne Hetzel Campbell, a professor at UBC School of Nursing, to discuss the use of domperidone, a drug approved to treat stomach problems in Canada, in treating low milk supply in breastfeeding mothers. Dr. Currie and Dr. Campbell mentioned some factors that have contributed to the dramatic increase in domperidone use, safety concerns, and what Health Canada can do to better regulate the safe and effective use of off-label drugs like domperidone.

Finally, we had Kirann Mann, a first-year obstetrics and gynecology resident at McMaster University, for our eleventh episode on Breaking the Stigma Around Pelvic Floor Dysfunction. Kirann explained the pelvic floor, what it does, and the importance of maintaining pelvic floor health, and listed some symptoms of a weak pelvic floor and stressors in one’s life that impact pelvic floor health. Kirann also explained how socioeconomic factors like socioeconomic status, education level, and racial and ethnic background can create disparities in gaps and knowledge, and shed light on how the pelvic floor awareness campaign builds community surrounding pelvic floor health.

What an incredible journey Season 2 took us on. The Cluster is so grateful to all the wonderful experts that took the time to sit down with us and discuss these timely women’s health topics with us. We hope you were able to learn a new thing or two from all the different disciplines and perspectives featured throughout Season 2. All episodes and corresponding resources can be found on our website. We hope you join us for Season 3. Stay tuned!

 

 

Navigating Menopause: Could Better Support Reduce Depression Risk?

Author: Pia Lustig, Psychology student and intern at FemiLab, Lausanne University Hospital, Switzerland | Editor: Romina Garcia de leon (blog coordinator)

Published: May 24th, 2024

There is a wide range of factors that contribue to depression during menopause;  including genetic markers, previous depression history, and menopause symptoms. However, If we look beyond biology, could there be other reasons why women across the world experience menopause so differently? And how much of a factor does society, and the narratives around menopause affect lived experience of this transition?

The natural menopause transition normally starts around mid-forties and continues for 5-10 years. As the body prepares for the “post-fertility” phase, a woman can experience a spectrum of symptoms, including hot flashes and night sweats, insomnia, weight gain, and vaginal dryness. However, there are certain social factors that are also at play. As is the case in many cultures, women are more likely to be caretakers of elderly parents, the primary caretaker of children and household duties. Moreover, women carry out more than 2.5 times more unpaid care work and household duties than men. Balancing the many responsibilities between home, work, and relationships may lead to burn out. When menopause is added to the equation, this becomes further excacerbated. Suddenly, physiological changes come into play. Vasomotor symptoms such as sleeplessness combined with hormonal fluctuations might make everyday life feel like an emotional rollercoaster. Moreover, symptoms like vaginal dryness, hair growth in unwanted places and excessive weight which may lead to feelings of shame and insecurities.

Research shows that women´s self-perception influences overall moods during the menopause transition. If their perception of the transition is more positive, women are less likely to develop depression. The kind of messages women receive from their immediate circle – family and friends –are pivotal in shaping their perceptions and reducing the risk of depression. Can they openly discuss their experiences around menopause, and do they receive the support they need? Equally important is the workplace environment. Are they understanding and accommodating of the possible symptoms women may be facing during working hours?  How is the media representing women in midlife? Are women represented in a way that emphasizes their worth beyond youth, or are they overlooked and deemed less relevant, less attractive? Is menopause even talked about publicly, or does it remain a topic shrouded in silence and shame?

The messages from the environment are closely linked to the broader culture that shapes women’s experiences, including societal attitudes toward women’s health. Globally, the risk of depression is twice as high for women as for men, research shows that women in Western societies experience higher rates of depression during the menopause transition. Furthermore, when looking at self-reported menopausal symptoms, some groups of women in Asia and Latin America hardly report symptoms at all. To understand why women´s experiences are so different, we may need to focus on society´s perceptions about women during this time in their lives, and to what extent the external environment is providing support. In some cultures, status is elevated passing the childbearing years. For example, for Taiwanese women menopause is viewed in a positive and holistic light. If societal perceptions influence menopausal symptoms and depression risk – this is an important avenue to focus on.

Can we support women going through the menopause transition better as a society and as loved ones? Viewing menopause-related risk for depression from a broader perspective could help us better understand how to best support women in these transitional stages. We might discover that support networks and positive messages from the environment may be part of the key that solves the puzzle.

 

 

 

2024 Women’s Health Research Symposium: Advancing Women’s Health Through Menopause Research

Author: Shayda Swann | Editors: Romina Garcia de leon (Blog Co-coordinator) and Katherine Moore (Director of Operations)

Published: April 4, 2024

On International Women’s Day (March 8th 2024), the Women’s Health Research Institute hosted the 9th annual Women’s Health Research Symposium, titled Midlife Women’s Health Research: Unpacking the Science of the Menopause Journey and its Health Impacts. In this blog, we’ll be highlighting the work shared by the keynote speaker, Dr. Susan Reed (MD, MPH). 

Why menopause matters

Perhaps the most obvious reason why menopause matters is because half of the world’s population will experience it. This ubiquitous experience brings bothersome symptoms that can reduce women’s quality of life, lead to work absences, and reduce overall productivity. Despite this, only a fraction of health funding goes towards menopause research. For instance, of the ~9,000 grants funded by the Canadian Institutes of Health Research from 2009-2020, only 5.9% evaluated female specific outcomes, let alone menopause-focused work. We encourage readers to review our three-part menopause series where we cover many of these topics in depth (Part 1, Part 2, and Part 3). 

Reviewing landmark studies in menopause research

The Study of Women’s Health Across the Nation (SWAN) began in 1994 and was a US-based cohort of 3,000 women aged 42-52. They identified that “menopause transition symptoms”, such as menstrual irregularity and vasomotor symptoms (i.e., hot flushes and night sweats) peaked between ages 46-56 and that most people experience menopausal symptoms for up to 10 years. They also reported that symptoms were typically most bothersome in the two years before and after the final menstrual period. Additionally, the SWAN study identified important predictors of vasomotor symptoms, such as adiposity (body fat), having less than a college education, stress, depression, and anxiety. The SWAN study also reported key findings around sleep, mood, cognition, cardiovascular disease, metabolic health, bone health, and sexual health. For instance, they found that low libido was associated with vasomotor symptoms and that bone loss is most rapid in the year preceding the final menstrual period.  

Another study, called MsFLASH, further advanced our understanding of this important phase in women’s lives, with a focus on alleviating menopause symptoms. First, they found that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrin reuptake inhibitors (SNRIs) have a modest benefit of reducing vasomotor symptoms in women who cannot or prefer not to take hormonal therapies. Unfortunately, exercise, omega-3s, and yoga were not found to be beneficial therapies. Similarly, they found that neither vaginal estrogen nor vaginal moisturizer decreased the number of moderate-to-severe vulvovaginal discomfort episodes compared to placebo. 

What do we know about treating menopause?

From the studies cited above and others, Dr. Reed shared the current evidence for menopause treatment options. This is a very brief overview and we encourage all women to discuss specific treatment approaches with a trusted health care provider. First, menopause hormone therapy can be initiated in most women with symptoms between ages 50-59 who are 1) low risk for cardiovascular disease, breast cancer, or venothromboembolism (blood clots) or 2) moderate risk based on informed decision-making. Treatments should be initiated within 10 years of the final menstrual period or before age 60. 

Knowledge translation

Dr. Reed also shared several useful patient-centred resources to help women navigate the menopause transition. For instance, the Menopause Priority Setting Partnership has a survey where women can share their priorities for future menopause research projects. The MsFLASH study also developed a fantastic website which includes a primer on menopause, an overview of treatment options, and a tool to build a personalized “menoplan”. 

Thanks to the organizers of the Women’s Health Research Symposium for another excellent meeting and for prioritizing mid-life women’s health! 

Brain Health in Pregnancy, Menopause, and Beyond – Is There a Link with Alzheimer’s disease?

Interviewee: Alesia V. Prakapenka, Assistant Professor, Biomedical Sciences, College of Graduate Studies, Midwestern University  Authors/Editors: Romina Garcia de leon, Shayda Swann (Blog Co-coordinators)

Published: January 5, 2024

 

Could you tell us more about the work you do in women’s health?

 

In my lab, we use animal models to understand how hormones impact brain and behavioral health within females and we take on a lifespan approach. We recently were awarded a grant from the Alzheimer’s Association to investigate the relationship between pregnancy, age, and menopause on healthy aging and Alzheimer’s disease progression in female rodent models. We’re very excited to get that work started. Primary outcomes include both short-term and long-term memory measures, as well as evaluation of memory types that engage different brain regions, including hippocampus, frontal cortex, and striatum. We’re also interested in anxiety-like and depressive-like behaviors as these are modulated by hormones and are associated with Alzheimer’s disease. 

 

How did you become involved in this field?

 

I’m fascinated by how learning, memory, and the brain works in general. When I was in high school, I took a psychology class and one of the units was on the brain. That sparked my interest, and I really wanted to learn more about what we know and what we don’t know about the brain. As an undergraduate, I got involved in research in a lab that used animal models to study learning and memory, and one interesting aspect of it was that the lab only worked with male animals. That got me thinking and looking more into the research on how learning and memory works in males versus females. To me, it seemed like there was a gap in understanding female learning, memory, and brain functions compared to males. So, for graduate school, I pursued research that focused specifically on female learning and memory with my co-mentors, Drs. Heather Bimonte-Nelson and Rachael Sirianni. Specifically, I worked on developing strategies to target the delivery of hormones, such as estrogens, to the brain to optimize their cognitive effects in females. My graduate research led to many more questions than answers regarding hormones and female health, which I am excited to continue to research. 

 

What does a typical day in your field look like? 

 

If we’re working with the animals, the timelines are planned out months in advance. With this new project looking at pregnancy and Alzheimer’s disease, for example, we have a schedule set for 2-3 years because we are working with animals throughout their lifespan. Some days, we’re administering treatments, checking in on the health of animals, or testing behavior and memory tasks. And then other days we’re getting to work with the tissue – process it, tag it with antibodies, and then visualize it. And then other days we’re on a computer looking at lots and lots of spreadsheets, analyzing the data and putting it together to understand and share what we find.

 

Are there any interesting findings from your work that you’d like to highlight?

 

My lab is in its second year, so our data collection is currently very fresh and ongoing. For example, as we establish our behavior tasks and protocols in the lab, we are finding that dose-dependent effects of 17beta-estradiol on spontaneous alternation behaviors are modulated by specific task parameters in female rats. And although we do not yet have findings from our lab for our recently funded work, I’d love to highlight valuable findings from other labs’ in the field that informed and sparked this research direction. There are multiple findings, for example, showing that pregnancy is neuroprotective and beneficial for female brain health. There’s also some evidence to suggest that pregnancy can be associated with increased Alzheimer’s disease risk. So, we aim to investigate factors, such as age and menopause type, that may help explain the disparate effects of pregnancy on healthy aging and Alzheimer’s disease pathogenesis.

 

What impact do you hope to see with your work?

 

The impact I hope to see with my work is rooted in student mentorship. Majority of students that I work with are either on a pre-healthcare career path or in their first or second year of medical or dental school. My approach is to mentor students, most of whom will be future healthcare professionals and inevitably working with the female population, to appreciate the complexity of female health and embrace it. I hope to help them understand the research on female health, critically analyze it, and appreciate it so that when they are forming that medical plan for an individual, they can be comfortable addressing female-specific health aspects.

 

Look out for Dr. Prakapenka’s upcoming work funded by the Alzheimer’s Association, through the Sex and Gender in Alzheimer’s Award, titled ‘Alzheimer’s disease pathogenesis in mothers: a role for age and menopause’.

Menopause Hormone Therapy from a Consumer’s Point-of-View

Authors: Amanda Thebe, Fitness and Nutrition Coach Editors: Romina Garcia de leon, Shayda Swann

Published: December 29, 2023

Women don’t have much agency when it comes to menopause, and that has to change. Historically, menopause has either been demonized or swept under the rug as something women should soldier on with. And this has done women a huge disservice. It has led to a massive knowledge gap that means women aren’t getting access to the help they need, either because they don’t know what is happening to them or where to turn.

We aren’t taught about menopause in school, it is hardly ever discussed in the workplace (thankfully, that is changing), and when it comes to advocating for ourselves within the medical community, women are more likely to have incorrect treatments or be completely dismissed by their GP. Why? Well, we know doctors receive very little medical training unless they opt into take it. And the result of this leaves women floundering.

Women are unfortunately at the receiving end of the WHI Study 2002, which boldly told the world that menopause hormone therapy (MHT) causes breast cancer. Even though those findings have been withdrawn, that statement caused a lot of damage. Doctors became hesitant to prescribe MHT, and that hesitancy still exists today despite the menopause societies recommending MHT as a safe treatment option for some menopause symptoms. And the people that suffer the most because of this are women with symptoms who are desperately looking for help.

Going to the doctors to advocate for yourself during menopause can be a minefield. If women simply don’t know that they’re in perimenopause, they may just present with one or two symptoms and be treated for those symptoms without the doctor looking at the full picture. Alternatively, women might go to the doctor asking for help with what they know to be perimenopause, only to be turned away empty-handed or with a referral to a specialist because the doctor feels hesitant or uninformed about providing help. This type of negative experience leaves a lasting mark on a woman, who typically has to build up quite a lot of courage to ask for the help she needs. According to the American Association of Retired Persons (AARP), 80% of medical residents in the United States did not feel competent to discuss or treat women in menopause! 

We need to help women know that MHT should be an option open for discussion so that they can see if they can be a candidate for the treatment of their symptoms. The MQ6 is a great tool that doctors can use to screen midlife women for menopause and find appropriate treatments. Many women who start taking MHT really feel the benefit and start to see improvements in their symptoms and, therefore, in their quality of life.

On the flip side of this, there is a pervasive message, especially on social media and within menopause online communities, from women who take MHT successfully to treat their menopause symptoms,  and from some “celebrity doctors” that MHT is a panacea. This can lead to many women feeling excluded from the conversation because the truth is not every woman can or should take it. MHT is a powerful drug that doesn’t suit all women, especially those with contraindications. We all have a duty to make sure that the information we share about MHT and non-hormonal alternatives stay within the medical consensus statements. 

These same platforms often talk about (peri)menopause as a disease or deficiency that must be treated with hormones and the bizarre idea that we weren’t meant to live past menopause in the past. This type of disinformation is very harmful during a vulnerable time of a woman’s life. It is essential to empower women during this time with accurate knowledge, so that they know that if they are suffering, there is help available to them, and they do not have to suffer. But that this is a life transition (for most women) which is meant to happen and that we can and do thrive in postmenopause.

From a personal perspective, I was relieved to be offered MHT by a very progressive doctor, only to have a very negative experience with it. Many years later, when I learned I had a sensitivity to hormones, it all made sense. During those 5 years, I often would flounder into deep depression or struggle with chronic cluster migraines every time I tried MHT. And I know I am not alone. Thankfully for people like me, or for others who can never take MHT,  other pharmaceuticals do exist, and women should be given this information.

In an ideal world, if a woman is one of the 75% with moderate symptoms or 25% with life-altering symptoms, and they go to their doctor for help, they should be heard. They should have an assessment to make sure they are in perimenopause and then be offered the most appropriate treatment for them – which may or may not include MHT. Ultimately, menopause is a shared experience amongst all women, but we must be treated on an individual basis for our unique circumstances.

Behind the Science: Pregnancy and Multiple Sclerosis – What’s The Link?

Interviewees: Pia Campagna, Postdoctoral Fellow, Monash University, Melbourne, Australia Authors/Editors: Romina Garcia de leon, Shayda Swann (Blog Co-coordinators)

Published: December 15th, 2023

When there are clear sex differences in disease prevalence, researchers must question the underlying factors. Women with Multiple Sclerosis (MS) outnumber men 4 to 1. What is being done to understand this statistic? How can we look into female-specific factors to disentangle these questions? 

For this month’s Behind the Science, we interviewed Pia Campagna who provided some insight into these questions.  

 

Can you tell us about your research? 

Our lab studies Multiple Sclerosis (MS) and other neuro-immunological conditions. Much of my work focuses on incorporating women’s health into MS research by looking at pregnancy and menopause. MS affects 2 million people globally, roughly 75% of which are women. Previous work from our group has shown the clinical effect of pregnancy, where a pregnancy before disease onset delays the onset of MS symptoms by 3.4 years. After onset, the effect of pregnancy is more controversial, but work from our group has shown a protective effect of pregnancy on long-term disability accumulation.In my postdoc, I’m seeking to understand the biological mechanisms underpinning these clinical effects via a national multi-site prospective study.

 

Why did you want to get involved in women’s health? 

I started research in MS due to the demographic of those affected – women. Because of this, it’s an interesting population to study in light of all of the female-specific experiences that interact with this disease. For example, it’s a disease that’s primarily diagnosed in a woman’s reproductive years (20-40 years old) so there are interactions with pregnancy, and due to the chronic nature, women are living with MS during perimenopause and menopause too.

I started my Ph.D., focused on genomics, prognostic modelling and machine learning in MS. It just so happened that other people in our group were doing this fascinating work on pregnancy. I had the opportunity to delve into the epigenetic impacts of pregnancy in women with MS, which sparked my interest in women’s health route MS. I did love the bioinformatic aspects of my Ph.D. work and hope to incorporate that down the line when we have the data available. 

 

Is there anything interesting that you’ve learned from your research findings?

When we compared the whole blood DNA methylation profiles of women with MS who had not given birth, we identified differences in methylation patterns at genes enriched in neurogenesis and axon guidance pathways. After noticing these signals, we hypothesized that the hormonal changes from pregnancy created long-term effects that drive changes to the clinical course of MS.  Now, we are collecting blood from women with and without MS before, during and after pregnancy, so eventually we’ll be able to look at DNA methylation in these different stages, as well as a range of other -omic profiles. 

What impact do you hope to see with this work in the long term?

Not only is the prevalence of MS increasing worldwide but so is the female-to-male ratio. I hope that research focuses more on the female-specific aspects of the disease, which is still very understudied. Although there’s strong evidence that pregnancy is beneficial before onset, and some evidence of a beneficial long-term effect, , it’s surprising to me that we still don’t know how or why. Detangling this will not only be beneficial to women but also more individualized therapeutic targets benefit men as well. Another frontier in MS research that I would like to see more of is the impact of menopause. For example, we still don’t know if the disease gets worse after menopause, how estrogen loss interacts with disease-modifying therapies, or whether they’re as effective. Understanding the clinical aspects of menopause and subsequently, the biological aspects of menopause is an important route to take moving forward.

Where can people learn more about your work?

Menopause Series Part 3: What Do We Know About Menopause and Hormone Therapy?

Authors: Romina Garcia de leon, PhD Student, University of Toronto, Alana Brown, PhD Student, University of Toronto, Jingmin Zhang, BSc, Human Biology, University of Toronto, Krembil Research Institute, | Editors: Shayda Swann

Published: October 27th, 2023

*Regarding terminology: “HT” is usually used when discussing spontaneous menopause, while “HRT” is usually used when discussing early oophorectomy (surgical menopause), with the idea being that there is a hormone that needs “replacing” after oophorectomy (but this isn’t the case for spontaneous menopause)*

As we learned in Blog 1, “What You Missed Learning About Menopause” – we can now appreciate that menopause is neither a single stage nor a symptom. Strikingly, most women go into menopause with little to no prior knowledge of what that will look like for them. As mentioned, menopause has a long list of symptoms that oftentimes go untreated. Yet, although there are viable treatments, there is often some confusion about which treatment is best for individuals seeking relief from their symptoms. 

Across various menopause types, in addition to visible symptoms, there are ‘invisible’ physiological changes that happen in the brain (less discussed because of brain health stigma) and body with the decrease in levels of estrogens, progesterone and follicle-stimulating hormone (FSH). As covered in Blog 2, “All About Reproductive Hormones” estrogens and progesterone have many actions that contribute to menopausal symptoms and disease risk. For example, reproductive hormones exert their effects on immune, vascular, and cardiovascular systems. Moreover, menopause can be associated with increased risk of some health conditions, such as osteoporosis, cardiovascular disease, and vulva, vagina, and urinary tract issues (more broadly genitourinary syndrome), emphasizing the importance of monitoring women’s health during midlife. Reproductive hormones also influence neuroplasticity, potentially resulting in cognitive changes. For example, many women report increased “brain fog” throughout menopause. Additionally, the early and abrupt loss of reproductive hormones, such as 17β-estradiol (E2–a type of estrogen), associated with oophorectomy (surgical removal of the ovaries) is related to increased dementia risk. Do treatments address these risks?

Common treatment options include:

  1. Hormone therapy (HT) (targets hot flashes and sleep disturbances—also known as vasomotor symptoms—and other symptoms as well…read more to find out)
  2. Vaginal estrogen (to relieve vaginal dryness and urinary symptoms)
  3. Low-dose antidepressants (to help with depressive symptoms), 
  4. Medications to prevent or treat osteoporosis

HT appears to be the most effective treatment for menopause symptoms. For individuals navigating the physiological transitions associated with menopause, HT offers a multifaceted approach to symptom management. HT not only alleviates discomfort associated with hot flashes and sleep disturbances but also has a pivotal role in mitigating bone loss, thus serving as a preventive measure against osteoporosis. Moreover, research indicates that women under 60, or those within a decade of starting menopause without a history of cardiovascular disease, may experience a decreased risk of coronary heart disease with hormone therapy.

It’s worth noting that the implications of HT on mental health and cognitive function are complex. While some studies suggest that hormone therapy may ameliorate depressive symptoms during spontaneous (“natural”)  menopause, perimenopausal and early postmenopausal stages, caution is advised for those considering initiation before the age of 50 due to potential mood destabilization. Notably, this may be different for women with oophorectomy. Additionally, the timing of HT introduction holds significance in relation to cognitive outcomes: early initiation appears to be protective against dementia, whereas late initiation and extended duration of treatment may elevate the risk. This is also seen in rodent studies, finding that hormone replacement therapy (HRT) in rats who have had an oophorectomy is beneficial for reducing Aβ plaques (associated with Alzheimer’s), but not when given at a later time point. This suggests that the timing and duration of HRT should be carefully considered in women’s personalized treatment strategies. This is also true for women taking HT for spontaneous menopause. 

Although HT is a highly effective treatment for symptoms of menopause, research on its effects remains nuanced. Some studies have led practitioners and patients to fear HT due to associations with breast and endometrial cancer risks. However, known risks (as well as benefits) of HT are specifically dependent on the individual receiving HT, their medical history (e.g., genetics, cancer history, and pregnancy history), whether the formulation contains testosterone, estradiol, and/or progesterone, dose, route of administration, age, and type of menopause. 

Generally, the known benefits outweigh the risks, especially when given the appropriate formulation… 

For instance, estrogens have been related to increased hippocampal volume and improved cognition in cis-and transgender women. However, these effects can be time- and dose-dependent. In rodent studies, for example, a low dose of estradiol was seen as beneficial, but a high dose was detrimental to cognition. In humans, estradiol appears to be beneficial for hippocampal volume and spatial memory, but only for a limited period of time and with estradiol alone. Regardless of the complexities of taking estradiol, reducing “brain fog” for some can drastically improve quality of life. These and multiple other studies showing the benefit of HT for cognition are promising for those considering treatment for these symptoms. 

What about the non-estradiol-alone options? 

There can be several types of formulations (such as estradiol alone, estradiol with multiple types of estrogens (conjugated equine estrogen or CEE), and estrogen(s) with progesterone). The type of formulation matters greatly in HT, and the benefits seen in estradiol alone are not the same for other types of HT. For example, Premarin, a common brand containing multiple estrogen formulations (CEE), was a big reason for the bad press that HT received for years. The bad press (hear more about this controversy through our WHRC Seminar series talk with Carol Tavris) followed after the Women’s Health Initiative (WHI) released a study claiming that HT increased breast cancer risk, stroke, pulmonary embolism, and dementia. However, this study only used Premarin and not estradiol alone. Since then, studies have found additional negative effects of Premarin, as it’s been shown to impair cognition and neuroplasticity in rodents and decrease hippocampal volume in human studies.

So what does this all mean? 

In short, the answer to whether HT addresses menopause symptoms depends on many factors. It simply should not be a one-size-fits-all treatment. Instead, medical practitioners should move towards an individualized approach to hormone therapy, and women (both cis and transgender people) should take their individual health histories into consideration when thinking about HT. Moreover, as outlined briefly here, much research has shown that many HT options are safe and effective for symptom management and should be discussed with one’s medical practitioner for more information. Lastly, further research should investigate HT use in trans women and men to further expand our understanding of its effects. 

Although our Menopause blog series ends here– stay tuned for more on menopause and hormone therapy soon!

 

Menopause Series Part 2: All About Reproductive Hormones

Authors: Katrine Yare, PhD, Medical & Cognitive Research Unit (MCRU), Austin Health, Melbourne, Australia | Editors:  Romina Garcia de leon and Shayda Swann

Published: October 20th, 2023

*Throughout this series, we want to acknowledge that not all women will experience menopause, and not all folks who experience menopause identify as women. We understand that different terminology will suit different folks. We hope this information is helpful to folks of diverse genders and identities*

I’m a mum, a researcher, and I study the effects of the primary reproductive hormones, 17-beta oestradiol (also called E2) and cyclical progesterone (P4) on sporadic Alzheimer’s disease (AD) in women.

Before I progress, Alzheimer’s disease (also called AD) is more prevalent in women, with two-thirds of those exhibiting symptoms of AD being post-menopausal women. My research focuses on an earlier phase of the disease, called the preclinical AD stage (before a person develops symptoms). This can develop years earlier.

A little background on women’s hormones

Understanding our bodies and how our hormones work can empower us as women to make informed choices when discussing our menopausal concerns with our health professionals. Knowledge really is power.

There are three primary estrogens in women:

  1. 17-beta-oestradiol (E2) also called oestradiol or estradiol. It is the most potent estrogen and works together with a cyclical hormone, progesterone (P4), during the reproductive phase of women’s lives.
     
  2. Oestrone (E1) also called estrone. This is the menopausal hormone, which is much less potent than E2.
     
  3. Oestriol (E3) also called estriol. E3 is a pregnancy estrogen and is the lowest potency estrogen. It works together with P4 (and other hormones), to protect the developing baby and to maintain pregnancy.

For this blog, I will concentrate on the hormones E2 and cyclical P4, which are essential in maintaining health during the reproductive phase of women’s lives.

The actions of the primary reproductive hormones, E2 and cyclical P4, are not confined to reproductive functions such as the menstrual cycle and pregnancy but play a significant beneficial role in many bodily systems (e.g., central nervous system, cardiovascular system, gastrointestinal tract, urogenital system, muscles, bone, skin, etc.), as well as modulating numerous metabolic processes and neurotransmitters.

When the levels of these hormones fluctuate during perimenopause and drop markedly during menopause, this will impact a multitude of physiological, cellular, and metabolic processes that are modulated by these hormones. As a result, most women will be impacted by this change. Some women will choose hormone therapy (HT) to alleviate symptoms, some women choose to ride through menopause without treatment, and there are also a rare few who won’t experience any overt symptoms. With respect to the latter, even though these women don’t experience overt symptoms, they are undergoing changes on a cellular and molecular level.

As discussed in the menopause series blog 1, some symptoms women may experience due to a drop in E2 and P4 include difficulty regulating body temperature, hot flushes, night sweats, vaginal dryness, dry and itchy skin, joint pain, muscle aches and pains, digestive problems, weight gain, breast tenderness, loss of breast volume, gum changes, headaches, migraines.

E2 and P4 also modulate a number of neurotransmitters. For example, E2 is a serotonin, dopamine, and cholinergic modulator, and P4 (via its metabolites) is a potent GABA-A receptor modulator. Therefore, when the levels of these two hormones drop markedly during menopause these neurotransmitters will be impacted, and, as a consequence, most women will feel the effects. Some symptoms women may experience include anxiety, depression, restlessness, brain fog, difficulty concentrating, irritability, mood swings, dizziness, and insomnia.

Paying attention to your health and well-being as your body undergoes significant change is essential whether you choose to go on HT or not. Also, establishing a good relationship with your health professional where you can freely discuss your menopausal concerns and they can help by listening and offering options or solutions, including clearly outlining benefits and risks, is extremely important.

As a menopausal woman myself, I had a horrible time during the menopausal transition. Even though I chose HT to alleviate my symptoms, which used hormones that were molecularly the same as what our bodies produced during the reproductive phase (i.e., E2 & cyclical P4) and used a route of administration that closely approximates the way our hormones are metabolized in our bodies (this will be discussed more at length in the next blog), I am vigilant about my health.

I want you to be vigilant about your health, too.