Tag Archive for: hormones

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 Even though those findings have been withdrawn, that statement caused a lot of damage.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.

Understanding Sex Difference in Addiction: The Road to Tailored Treatments

Authors: Tanisse Epp, PhD Student, Carleton University, MSc Neuroscience, University of British Columbia | Editors: Romina Garcia de leon, Shayda Swann (Blog Coordinators) 

Published: Dec 1, 2023

For a long time, society believed that alcohol and drug use was primarily a problem for men. As a result, research has mostly focused on studying addiction in men. But in recent years, there has been more attention to women and how they use drugs and alcohol. As the number of women using drugs and alcohol keeps increasing, closing the gap between men and women has become extremely important. Recently, there has been a promising rise in research looking at sex differences within addiction research. This research has highlighted significant differences in how addiction develops and progresses differently in men and women. These differences have important implications for treatment and relapse risk.

Consumption Patterns 

Despite men having higher rates of substance use disorders than women, women are more vulnerable to many aspects of the disorder. For example, women have a shorter time period from initial drug use to meeting the criteria for substance use disorder and seeking treatment compared to men. This phenomenon is called the ‘telescoping effect.’ It means that women tend to develop problematic substance use issues in fewer years compared to men. This effect has been reported across multiple drug classes, including cocaine, methamphetamine, alcohol, opioids, tobacco, and cannabis, and non-pharmacological addictions, such as gambling

Pre-clinical research has proposed a potential mechanism underlying this sex difference in the nucleus accumbens (the dopamine centre involved in addiction) and the dorsal striatum (the action-oriented center driving the physical action of taking substances). For instance, when exposed to drugs, female rats show a smaller response in the nucleus accumbens at first, but they have a quicker and stronger reaction in the dorsal striatum, driving an escalation in drug use. Additionally, gonadal hormones have been proposed to be involved. Research, both in clinical and pre-clinical settings, has demonstrated that estradiol, a female hormone, can lead to an increased ‘high’ from smoking cocaine and a stronger drive to obtain cocaine. This suggests that estradiol may play a role in the quicker progression from casual to chronic cocaine use in females compared to males. 

Craving

While the telescoping effect plays a significant role in the early stages of addiction, craving becomes a crucial factor in sustaining addiction and raising the risk of relapse after quitting. Exploring potential sex differences in craving will contribute to a greater understanding of how we can support both men and women during abstinence to decrease the risk of relapse. Current research on the sex differences within craving is mixed. Some studies have found no significant differences in craving between men and women for cocaine or alcohol use disorder. In contrast, for opioid use disorder, women have greater craving scores than men. These mixed findings may be related to the involvement of sex hormones in the changes in spine density in neurons and how this impacts craving. Changes to neuronal spine density (how neurons connect in the brain) in the nucleus accumbens are thought to promote craving over time. Sex hormones impact spine density, where testosterone decreases and estradiol increases spine density. The interactions between sex hormones, types of substances used, and their impact on neuronal connections likely contribute to variations in craving.

Psychosocial Factors 

Psychosocial factors are known to impact the onset of addiction, such as stressful life events and childhood trauma. One study found that greater severity of childhood emotional trauma, sexual trauma, and overall childhood trauma was associated with higher cocaine use and an increased risk of relapse in women with cocaine use disorder, and this association was not found in men. This association is not limited to childhood trauma, but previous research has shown that women have a greater daily use of cocaine following stress-induced relapse compared to men. Both stress and trauma-related findings are theorized to be related to hypoactivation observed in the ventromedial prefrontal cortex (vmPFC; a key brain region contributing to reward and decision-making) in women. The dysregulation of the vmPFC is suggested to increase relapse and drug-seeking behaviour in women as it creates a more significant obstacle in self-regulation and control over emotionally regulated behaviours.

Implications and Treatment

While acknowledging the neural and behavioural sex differences in addiction has gained research interest, sex has not been well-considered in the development of treatment options for addiction. While some specific targets, such as noradrenergic, cholinergic, antidepressants, and GABA, have been examined in addiction research, there is a lack of focus on how sex differences affect these areas. Only noradrenergic targets consistently show that women tend to have better outcomes with tobacco and cocaine addiction. However, other treatment strategies, like withdrawal treatment or reinforcement blocking, do not have apparent sex-specific effects. Sex considerations should influence addiction medication and treatment development, given that women often experience more stress-related vulnerability, quicker addiction onset, and severe withdrawal symptoms, making research into these areas essential for sex-informed treatments.

 

*This blog was posted in honour of Substance Use Awarenss Week

Behind the Science: The Bidirectional Relationship of Behaviour and Stress

Authors: Romina Garcia de leon and Shayda Swann, Women’s Health Blog Coordinators | Interviewee: Dr. Annie Duchesne, Ph.D., University of Northern British Columbia

Published: Nov 17th, 2023

Can you give us a brief explanation of your research? 

I’m particularly interested in understanding how variations in hormones influence or regulate our behaviour, but also how our behaviour may regulate our hormonal processes. 

Over the years, I’ve been interested in understanding how contexts such as stressful situations might be influencing ovarian hormones (estrogens and progesterone). There’s a lot of interplay between the stress and endocrine systems. They often tend to regulate the same or similar affective and cognitive processes, but they’re often studied independently. I have a lot of interest in understanding the two systems together, and I’ve developed various approaches. 

The first approach involves measuring hormone levels and exposing people to different tasks. The second approach is to use observational studies where we take advantage of already accessible databases to try to answer these questions. These studies allow us to add a bit more complexity, given the larger sample sizes.

Studying this interplay is also relevant when we’re interested in questions of sex and gender. The sociocultural constructions of sex-related traits is a central dimension of gender. These constructions inform the way in which people are expected to behave in general and with respect to sex-related traits and situations. And often, our gendered constructions transform sex-related phenomena into specific sources of stress. So I do believe there’s a lot of relevance in studying the handover between stress and the gonadal system, particularly when interested in understanding the ramifications of sex and gender. 

How did you get into the field of women’s health? 

My undergraduate degree was in molecular biology. From these studies, the question that remained was how do people adapt to their environments. My first foray into this question was through conducting research on materno-fetal physiology within Dr. Julie Lafond’s laboratory. Specifically, understanding the metabolic physiology of the placenta. At that time Dr. Lafond’s laboratory was interested in how maternal variation in lipidic and toxicological profiles could influence fetal development through placental physiology. This research experience allowed me to realize the central role that the endocrine system plays in communicating what’s going on in the environment and adaptively relaying this information to all other physiological systems so that the organism is best prepared for a variety of upcoming situations. 

During my Master’s degree, I channelled my interest in endocrinology, development and adaptation to investigate the development of the biobehavioural stress processes. Fascinated by Michael Meaney’s research – which transformed our neurobiological understanding of the interplay between the environment, maternal behaviour and the development of the hormonal stress response, I went to work with Dr. Ron Sullivan who was one of the few researchers who looked at the sex difference in the role that maternal behaviour could have in the development of the stress responses. There, I discovered that variation in the environment can differently impact male and female rats, but also realized how we systematically excluded female animals from most behavioural neuroscience research. I continued to research the interplay between stress and sex-related variables during my PhD which I conducted in humans under the supervision of Dr. Jens Pruessner where I studied the interplay between stress and the menstrual cycle on affective processes. Finally, during my postdoctoral research, I continued to investigate neurobehavioural underpinnings of reproductive phenomena by investigating the cognitive correlates of menopause-related endocrine changes in Dr. Gillian Einstein’s lab. Findings from this project support that the type of menopause, in particular whether you have had a spontaneous or surgical menopause moderates the neurocognitive correlates related to menopause.

Could you highlight some of your most important findings or highlights from your research?

One central idea is that the relationship between hormones and behaviour is context-contingent. For instance, during my PhD, I demonstrated that the relationship between cortisol levels and participants’ reported levels of stress changed completely depending on which menstrual cycle they were in. These are crucial findings! Once you have recognized that how hormones can influence brain and behaviour is contingent on context, the second important question is what are the contextual dimensions that are relevant?  

What has been an increasingly important field of investigation in behavioural neuroendocrinology, particularly about women’s health, is the use of feminist theory and feminist research to articulate and operationalize aspects of women’s experiences as relevant contextual dimensions, to then investigate how that particular context may moderate the interplay between hormones, brain and behaviour.  

For example, the menstrual cycle is best characterized as a biosocial phenomenon. Seminal work by feminist scholars has demonstrated how sociocultural attributions about women’s bodies inform how menstruating people feel and behave when menstruating, for example, feeling pressured to conceal one’s menstruation. By understanding women’s endocrine phenomenon as biosocial, relevant, yet often overlooked, contextual dimensions can be incorporated into our understanding of the neuroendocrine underpinnings of reproductive phenomena such as the menstrual cycle.    

Such an approach allows for the necessary resolution to advance bio-behavioural understandings of women’s health that avoids biological essentialist biases and prevents the belief that women are determined by their sex-related biology.

What impact do you hope to see with your work 10 years from now?

I hope I continue to complexify and nuance my understanding and investigation on behavioural neuroendocrinology, stress and reproductive phenomena. I wish that my ideas allow for a more refined and inclusive perspective. We all come to our object of study from a specific perspective or standpoint and therefore carry biases. I hope that more researchers within women’s health and behavioural neuroendocrinology (including myself here!) continue to critically engage and self-reflect on their own biases as well as the ones carried by their fields of research. 

I hope that approaching reproductive phenomena as biosocially entangled becomes more of the norm than the exception in biobehavioural research particularly concerning sex and gender. More generally, I hope that culture is no longer pinpointed against nature but rather that an organism’s biology, culture and environment are embraced as constitutive, dynamic and interdependent. 

Lastly, I hope for a continued diversification of the research in behavioural neuroendocrinology and women’s health. This includes but is not restricted to, who is conducting the research, the geographical locations from where the research is being conducted, the participants being included in the research, and the questions, methods and epistemologies used to advance understanding. 

If you’re interested in joining the NeuroGenderings Book Club, check it out here

Check out more of Dr. Duchense’s work here and here

If you’re interested in more about the processes and impact of racism and whiteness within the Canadian academic context, check out this collective.

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.

Menopause Series Part 1: What You Missed Learning About Menopause

Authors: Shayda Swann, MD/PhD Candidate, University of British Columbia, Department of Medicine, Shannon Mahony, BSc, Human Biology, University of Toronto, Krembil Research Institute | Editors: Romina Garcia de leon (Blog Coordinator) 

Published: October 6, 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*

What comes to mind when you hear “menopause”? Hot flashes? Night sweats? Irritability? Are these symptoms normal? And what age should you expect to experience them? Do you just have to live with this discomfort? In this 3-part deep dive into menopause, we hope to dive into the information we’ve learned from our fellow experts to ensure this is a time in your life where you can navigate (and maybe even celebrate) this unique phase of life! 

But first, let’s talk about what menopause actually is.Spontaneous menopause (often referred to as “natural” menopause) occurs when the ovaries gradually release lower levels of the reproductive hormones estradiol and progesterone. However, this process is not linear and hormone levels can fluctuate dramatically during this time (Figure 1). This transition phase is called perimenopause and typically occurs between ages 40-50. Because of the rapid and dynamic fluctuations in hormone levels, symptoms may be most severe during this time. Perimenopause typically lasts for 2-10 years and during this time women may have irregular periods, with shorter or longer cycles than usual. 

Figure 1. Stages of Menopause Image credit: hertilityhealth.com

When periods have stopped for at least one year (not due to pregnancy/breastfeeding, hormonal contraceptive / other medication use, or other underlying medical conditions), a woman is considered to be in spontaneous menopause. The average age of menopause in Canada is 51 and typically occurs between ages 45-55. If your periods stop before age 45, it’s worthwhile speaking with your doctor to determine if you are experiencing early menopause or if you have another underlying health condition.  In early menopause, individuals reach menopause before age 45 and progress through similar stages and hormone fluctuations as individuals in natural menopause. Premature menopause typically happens even earlier (before age 40) and diverges significantly from the typical menopause stages in that hormones fluctuate more erratically and some women may have return of menses. This type of menopause is the result of Primary Ovarian Insufficiency (POI), a condition where the ovaries stop working normally. It is believed that both premature and early menopause may be due to a variety of genetic and lifestyle factors. 

It’s also important to mention that menopause can be induced by the removal of both ovaries, known as a bilateral oophorectomy, which is also referred to as surgical menopause. This results in abrupt changes in circulating hormone levels within 24 hours. These surgeries can be to treat ovarian conditions such as endometriosis and/or for the treatment and/or prevention of cancer. Women that experience this type of menopause tend to report more severe and abrupt menopause symptoms compared to women that are spontaneously menopausal.

Lastly, we have spontaneous postmenopause (sometimes also called menopause). This is the time between the final menstrual period and the rest of a woman’s life. This is when estradiol and progesterone will be at their lowest. At this phase, some menopausal symptoms that are caused by hormone fluctuations, like hot flashes and night sweats, tend to subside. Other symptoms that are caused by low hormone levels, like vaginal dryness, might continue to worsen. The risk of cardiovascular disease, osteoporosis, and the genitourinary syndrome of menopause also tend to increase at this stage due to the loss of those protective hormones. 

Importantly, menopause will typically last for one-third to one-half of a woman’s life. So why don’t we know more about it? The Menopause Foundation of Canada decided to investigate this knowledge gap by surveying more than 1,000 Canadian women aged 40-60 from representative regions, educations, incomes, and ethnicities. Their results are summarized in the landmark 2022 report, The Silence and the Stigma: Menopause in Canada. Despite more than one quarter of Canadian women being perimenopausal or menopausal, they found that “menopause is overwhelmingly viewed as negative and remains shrouded in secrecy.” So let’s shed some light on this experience! 

First, the report dives into menopause symptoms that can occur with all types of menopause. You might be surprised to learn that there are more than 30 symptoms of menopause (Figure 2), and while 84% of women were aware of hot flashes and 77% about night sweats, the majority did not know that urinary tract infections, heart palpitations, body aches, headaches/migraine, anxiety, depression, memory issues, and pain during sexual intercourse were all potential symptoms of menopause. In the report, women reported experiencing an average of seven symptoms. Unfortunately, one-third of women felt that their symptoms were undertreated, despite the availability of effective treatments. 


Figure 2. Common Symptoms of Menopause Created using BioRender. Check out the

The Silence and the Stigma report also highlights the challenges women face within the medical system, in their intimate relationships, and in the workplace during menopause. More than half of respondents felt that menopause is “taboo”, and a similar proportion felt unprepared for their menopause journey, leading to feelings of isolation and loneliness. Unfortunately, only 40% of women sought treatment for their symptoms and 72% of those who did found that the medical advice was not helpful or only somewhat helpful. These experiences also impact women’s quality of life and relationships, with 41% of women reporting that menopause negatively impacted their relationship with their significant other. It also affects women’s experiences in the workplace, with three-quarters reporting that their employer was not supportive or did not know if they offered support in helping them to cope with symptoms. 

As Dr. Wendy Wolfman, MD, FRCS(C), FACOG, NCMP noted in the report, “Menopause is seen as something women must endure, like a woman’s burden. This is unacceptable.” In the next part of this series, we will go through the history of menopause hormone therapy and current research in this field. Our third blog will go more into detail about options for menopause treatments, including hormonal, non-hormonal, and lifestyle options. Stay tuned for these blogs and connect with us on social media to share your experiences of menopause, questions about treatment, or share feedback on this series! 

Behind the Science: Clearing the Fog of Midlife Ovarian Removal and Cognition

Interviewee: Alana Brown, Ph.D. Candidate, University of Toronto, Authors/Editors: Romina Garcia de leon, Shayda Swann (Blog Co-coordinators).

Published: July 14th, 2023

Could you tell us about your research?

In Dr. Gillian Einstein’s Lab of Cognitive Neuroscience, Gender, and Health, my PhD work explores the relationships between ovarian hormones (e.g., 17β-estradiol) and cognition, specifically in women with breast cancer gene mutations who opt to have bilateral salpingo-oophorectomy, which is the removal of both ovaries and fallopian tubes. This surgery usually occurs for cancer prevention purposes around 10 years prior to the typical age of spontaneous/natural menopause (~51 years). Bilateral salpingo-oophorectomy results in an abrupt and early loss of ovarian hormones. Our group in Dr. Einstein’s lab is trying to understand the cognitive impact of this hormone loss, especially given that oophorectomy is associated with an increased risk of developing Alzheimer’s disease (AD) in later life.

What drove you to study women’s health research? 

There is a dearth of research examining factors contributing to cognition among middle-aged women. The spontaneous menopause transition is a time period often defined by self-reported brain fog. So, women are specifying that their memory is changing during this period. Not only is there a gap in research to try to understand this change, but this is also a unique opportunity to answer more nuanced questions about memory in a healthy population. This research gap is even wider for women with bilateral salpingo-oophorectomy.

It is really interesting that we can ask richer questions about memory by looking at an ovarian hormone shift that affects a large number of people in the world. For example, how can the memory changes associated with ovarian hormone loss be differentiated from the memory changes associated with aging? How can we use ovarian hormone-related structural and functional brain changes to answer questions about how the brain supports memory more broadly? In the realm of neuroimaging, menopause and sex-specific factors are conflated with aging and largely overlooked and disregarded. It is very common to see neuroimaging research focusing on aging by studying groups of young adults who are 35 or younger and comparing them to groups of older adults who are 65 or older. The large gap between those age groups, representing midlife, during which menopause is typically occurring, is often ignored. There is a really small percentage of research looking at female-specific outcomes during that time.

What impact do you hope to see with this work?

I hope that this work can contribute to a larger picture of precision medicine. Given that we are studying a group of women who are at increased risk for AD, there may be implications for AD biomarkers. Female-specific AD risk factors must be studied and clarified. I hope this work can contribute to a larger body of research focused on studying people and the complexities of their lives while integrating that complexity into neuroimaging. Further, I hope we know more about the functional effects of reproductive aging and/or ovarian hormone loss in the future, above and beyond the effects of aging. This is new territory for neuroimaging. Those considering bilateral salpingo-oophorectomy deserve to be fully informed and aware of what they may experience after the surgery.

Have you seen any interesting findings yet in your research? 

We are finding that oophorectomy without 17β-estradiol  replacement therapy is associated with decreased hippocampal activation, specifically while learning/encoding during a face-name pair memory paradigm that is thought to be sensitive to AD progression. The hippocampus is a brain area critical for learning/memory and is also among the first regions affected by AD. We do not see the same pattern in individuals with oophorectomy who are taking 17β-estradiol replacement therapy. It is possible that 17β-estradiol has a role in maintaining function in the hippocampus and potential markers of AD risk could be detected in midlife. 

Where can people find more about your work?

Twitter: @4alanabrown and @EinsteinLabUofT, 

Online: https://einsteinlab.ca

LinkedIn: https://www.linkedin.com/in/alana-brown-23544a111/

Check out this recent publication by Alana and the Einstein Lab on how midlife ovarian removal affects cognition!

What I’ve Learned Living with Migraines

Author: Negin Nia, B.A. & M.J.,University of British Columbia. Editors: Romina Garcia de leon & Shayda Swann (Blog Co-coordinators).

Published: June 23, 2023

Living with migraines means every day is uncertain. When my first migraine attack happened, I experienced intense pain and went to the hospital as a precaution. The doctor said my symptoms were normal migraine signs. 

Migraines, which are described as a neurological disorder, are a common health condition, especially for women. But, it can be hard to distinguish them from a regular headache as they are easily misunderstood or dismissed. That’s why for migraine awareness month, we want to help educate others on migraines. 

Defining a migraine attack 

Migraine attacks are a moderate to severe intense pain on one side of the head. A migraine can manifest differently for each person – some have mild impairments, others may require medical attention. 

Migraines can result from a combination of genetic, environmental, and lifestyle factors which make the brain vulnerable to specific stimuli and trigger an attack. Common triggers include stress, lack of sleep, alcohol, diet, and more

Migraines are the world’s third most common ailment and the leading cause of disability in those aged 15 to 49. Migraines are more common in females than males  — one in every five females have migraines compared to one in every 15 males. 

This overrepresentation is initially seen after the onset of puberty, suggesting the role of sex hormones. There is also evidence that menstruation is a time of increased risk for migraine attacks, and a subset of people (approximately 10-20%)  report migraines exclusively during menstruation.  

Researchers suggest that fluctuations in hormones such as estrogens and progesterone have an impact. This is why for many people, migraines may lessen or worsen during pregnancy and menopause, with the use of hormonal contraceptives or hormone replacement therapy.  

The symptoms and stages

In most patients, there are four migraine stages. The first is prodrome, which is the pre-headache. Symptoms may include fatigue, yawning, insomnia, food cravings, anxiety, depression, and more. You can catch a migraine at this stage but it is often hard to distinguish it from other issues

The next stage is aura, which is associated with sensory disturbances such as loss of sight, blind spots, and flashes. It is also common to feel nauseous or sensitive to light and sound. Auras are not experienced by all –  only one-third of migraine patients experience them. Females are more likely to experience these factors compared to males. 

The third stage is the throbbing one-sided headache. Although the exact neural underpinnings remain unknown, there are some theories. The neurovascular theory explains that this pain is due to the activation of the trigeminal-nociceptive pathway and the inflammation that follows. Some work seems to link the role of serotonin in activating this pathway. Interestingly,

Raising Awareness 

There is a clear lack of public information surrounding migraines. Migraines are an invisible disability that requires more attention and care. There is also a shared feeling of shame and stigma amongst migraine patients when being downplayed for just having a “headache.” 

Given this, it is important to raise more awareness and set up proper support systems for migraine patients. By talking more about this neurological disorder, we can break stigmas and help create an environment of empathy.

Behind the Science: Sexual Pleasure in Women Living with HIV

Interviewee: Kelly Mathews, MD Student, University of British Columbia Authors/Editors: Romina Garcia de leon, Shayda Swann (Blog Co-coordinators).

Published: May 5th, 2023

Could you briefly explain what your research is about? 

I’m part of a study on healthy aging in women living with and without HIV called BCC3. It involves community members, so women living with HIV, right from the beginning. My project, in particular, is looking at sexual pleasure in women living with and without HIV, and examining if the hormone testosterone has any influence on pleasure. We also look at social variables like income, mental health, home environment, substance use, etc. to see if they have any influence on sexual health.

Why do we need more work to understand sexual pleasure in women?

HIV is not transmissible by sexual activity for people on effective antiretroviral therapy. Yet, research looking at sexual health for women living with HIV has been really pathologizing, seeing women as vectors of disease rather than sexual beings who are deserving of pleasure and satisfaction in their sex lives. 

Historically, the way we’ve studied female sexual function has been thinking that women operate in the exact same way as men do. There’s been a ton of research on the sexual response cycle in men and this has been broadly applied to women.  This doesn’t take into account how women experience pleasure and what sexual interactions are like for women. For instance, women living with HIV, have often been labeled as having sexual desire disorder, without taking into account structural factors that might be preventing them from wanting to have sex. 

I think it’s really important to emphasize these positive aspects of sexuality and the other things that give women pleasure, whether that be with a partner or on their own, and once we can figure it out then we can promote it on the frontlines to clinicians, community workers, and among community members themselves. 

Recent research suggests that a focus on pleasure can actually lead to safer sex and a reduction in chronic pain, mental health, and fatigue. So I think focusing on pleasure is really the way going forward.

Could you highlight some important findings from your research?

The biggest thing that we’ve seen so far in preliminary results is that there’s actually no difference in the prevalence of reporting ‘always’ or ‘usually’ experiencing pleasure during a sexual experience when we compare the women living with HIV and those without HIV, which was a bit of a surprise! This is something that we hope will be empowering for community members to take away from the study. We also acknowledge that it’s important to keep promoting pleasure for more people because only 60-65% of the women in our study reported ‘always’ or ‘usually’ experiencing pleasure. 

I think that this finding highlights some of the strengths of our study. We looked at pleasure not only in partnered sex, but also for women who are engaging in self-pleasure/masturbation. Not too many projects have done that in the past. I think another strength is that our control population is very similar in terms of many sociostructural factors such as housing, income, and substance use to the women living with HIV in our study. So this helps us narrow in on this pleasure piece and shows that the virus itself isn’t changing pleasure. It’s more of those social determinants of health that affect both populations.

Another important finding was that women living with HIV have lower total testosterone levels than HIV-negative women, but this was not associated with an increased or decreased odds of pleasure.

What other questions do you hope to answer next?

We’ve nearly doubled our sample size of women that we have testosterone measurements for and sexual pleasure responses. That’s going to allow us to look at a few more variables and, in particular, it’s going to allow us to do an analysis stratified by HIV status. Having spoken to some community members, a lot of people have highlighted the need for including chronic pain as well as maybe HIV medication side effects in our analysis. It would also be really interesting to look at how HIV factors like immune cell count, HIV viral load, and HIV-related stigma might impact sexual health. 

What impact do you hope to see with this work years from now? 

I think the community involvement and the design of the BCC3 study are really good and I hope that more projects will emulate that in the future and have more community members involved in every step of the project. In terms of pleasure, I really hope that there is a shift to conducting more research focusing on these positive aspects of sexuality. 
Another hope is that we can get the message out about U Equals U and reduce the stigma surrounding HIV. U Equals U, or undetectable equals untransmittable, is a saying from groundbreaking research that essentially means that there is no risk of transmitting HIV to a sexual partner if the person living with HIV is using effective HIV medication. Knowing this, my goal for the future is that more and more women living with HIV will be able to experience stigma-free sex and have the same opportunities for a satisfying sex life as someone that doesn’t have HIV.

In-vitro Fertilization and Heart Disease: Is There a Link?

Author: Elaha Niazi, University of Calgary, Libin Cardiovascular Institute, BHSc Health Sciences Editors: Romina Garcia de leon & Shayda Swann (Blog Co-coordinators)

Published: December 2nd, 2022

Note: When using the term ‘woman’ in this blog, it is to remain consistent with terms used in published literature. While ‘female’ refers to biological sex and ‘woman’ refers to gender identity, much of the medical literature currently reports findings on ‘women’ from samples of female participants. 

What comes to mind if I asked you to name a few risk factors for heart disease? Smoking? Obesity? Diabetes? What about in-vitro fertilization? 

In-vitro fertilization (IVF), a form of assisted reproductive technology, has risen in popularity since its first successful cycle in 1978. Currently responsible for approximately 2% of live births in Canada, IVF is a source of hope for families struggling with biological and/or social infertility. Biological infertility is the inability to achieve pregnancy after one year of unprotected sex and implies a sexual relationship between a male and a female, whereas social infertility applies to those who cannot conceive through intercourse due to factors related to sexual orientation.

Recent studies demonstrate that females treated with IVF may have increased cardiovascular risk compared to those who conceived naturally. The underlying mechanism of this association has not yet been determined, but it is critical to investigate to optimize patient care for females undergoing IVF treatment. But before we dig any deeper into this, we must first examine female cardiovascular disease.

Female cardiovascular disease: an overlooked and under-researched issue

Cardiovascular disease is the leading cause of death in women (shocking – I know!), yet women with cardiovascular disease remain underdiagnosed, undertreated, and undersupported. Research shows that heart attack signs are missed in more than 75% of women. Sex differences exist in mortality rates as well; after experiencing a heart attack, women have a higher chance of dying than men. 

But despite the risk of cardiovascular disease being similar between males and females, less than half of women are actually aware of their risk.

You would hope this would mean that both sexes would be equally represented in cardiovascular research, right? Unfortunately, not. Female systems and women have been historically under-represented in cardiovascular disease research, from the cellular level to animal research and human clinical trials.

Female sex- and gender-specific factors in cardiovascular health

We are now beginning to uncover that sex differences exist in the risk factors, presentation, progression and response to treatment in cardiovascular disease. An important identified contributor to these differences is sex hormones. Female sex hormones are known to directly interact with the cardiovascular system, and consequently, we see cardiovascular implications of experiences unique to females. Specifically, female sex hormones involved in menstruation, menopause, fertility and pregnancy all affect an individual’s cardiovascular risk. Furthermore, exogenous hormone administration, such as hormonal contraception or hormone replacement therapy, influences the development of cardiovascular disease and risk factors. When considering health determinants that disproportionately burden females, such as socioeconomic status and stress levels, it becomes clear that we must examine the sex and gendered factors related to female cardiovascular disease much more closely.

What happens to female sex hormones in IVF?

During IVF, female patients are treated with high doses of female sex hormones to stimulate their ovaries and promote the development of their eggs. This is called ovarian stimulation and is necessary for the subsequent steps of IVF, including egg retrieval, fertilization with sperm, and transfer of the embryo into a uterus to begin pregnancy. Many female sex hormones increase substantially during ovarian stimulation; for example, estrogen levels can increase by over 20x!  

Where does IVF fit into cardiovascular health?

Given what we already know about female sex hormones and cardiovascular disease, it is reasonable to wonder how ovarian stimulation impacts cardiovascular health. However, this has not yet been adequately studied. While we must strive to empower and expand a range of female reproductive choices, it is also important that we consider their cardiovascular implications to protect all aspects of health. To address this critical knowledge gap, I have initiated a study designed to investigate the effect of ovarian stimulation on cardiovascular risk in females treated with IVF, under the supervision of Dr. Sandi Dumanski at the University of Calgary. Healthy, pre-menopausal females planning IVF treatment will be invited to participate in this study. We will monitor changes in their hormone levels and vascular health (predictors of cardiovascular disease) as they undergo ovarian stimulation. This work will provide foundational knowledge that will play a key role in optimizing the care of females treated with IVF.

Where do we go from here?

It cannot go without saying that IVF treatment has provided hope and care for millions of families worldwide and has undergone incredible advancements in past decades — remaining a promising option for those challenged with infertility. However, the implications of this important treatment on cardiovascular health have not yet been fully elucidated. In the era of personalized medicine, and with consideration of the effects of sex and gendered factors on health, it is critical that we investigate health within female-specific contexts like IVF. I believe it is important that healthcare providers and scientists have (and use!) the tools to paint a clearer picture of unique female experiences so they can better inform the reproductive and lifestyle choices of females everywhere.

Oral Contraceptives & the Autonomic Nervous System: the Effects of the Pill on Your Body’s Autopilot System


Authors: Tania J. Pereira, PhD candidate, Women’s Cardiovascular Health lab at York University| Editors: Romina Garcia de leon, Shayda Swann  (Blog Coordinators).

Published: November 4th, 2022 

It has almost been 100 years since it was discovered that you could make an animal infertile by implanting an ovary from a pregnant animal. This discovery would be the basis for the birth control pill, although it wouldn’t be commercially available until the 1960’s. Since then, multiple variations (known as generations) have been created to reduce the side effects of birth control use – ranging from blood clotting to unwanted weight gain or acne and changes in mood. Thankfully, newer generations of birth control have been made with lower hormone levels – although some of the more minor health-related side effects persist. 

While most side effects are physically visible, what about the unseen consequences? 

Research suggests that within three months of use, birth control changes certain tissue volumes in specific regions of the brain. These regions control our emotions and how we manage emotional information. This means that birth control users could experience more negative and intense emotions. Birth control also changes the connections between different regions associated with higher cognitive function and emotional processing, meaning that birth control may alter mood by affecting how an individual regulates their emotions. 

From these changes, it is understandable how birth control might affect a user’s mood – but could other functions also be altered?

My research focuses on how birth control alters the function of your autonomic nervous system, which controls all unconscious processes, such as heart rate, blood pressure or breathing. The autonomic nervous system is a network of the brain, neurons and the body’s organs. This system is also responsible for your “fight or flight” response. 

More specifically, I am interested in how the body controls these processes in response to exercise. During exercise, key feedback about the physical movement and the metabolic environment of the exercising muscle are sent to the brain. This feedback is used to adjust your heart rate, blood pressure or breathing to support the exercise intensity.

Interestingly, birth control users have lower blood pressure responses to passive movement and handgrip exercise than non-users. Additionally, birth control users breathe more rapidly during handgrip exercise than non-users. Women generally do not increase their blood pressure during handgrip and other studies have observed that birth control rescues the blood pressure response. Both studies used similar exercises and performed the trials at similar times of their pill cycles (i.e., the birth control pill has an active dose phase ~21 days and a sugar pill or no-hormone phase ~7 days). Although, the types of birth controls used in each study were different; the first had increasing hormonal doses over the pill cycle, while the second had the same hormone dose with every pill.

While it is not clear what the effects of birth control are, both studies confirm that birth control use is altering the control of the body’s exercise response. 

There is not a lot of research on birth control, and it is made more complicated by the fact that different types of oral contraceptives can have different effects. Additionally, birth control is not the only form of hormonal contraceptive. There are implants, injections, intrauterine devices, vaginal rings, and patches. Each unique method of administration could present unique altered effects. 

My future research will aim to clarify some of these inconsistencies by more strictly controlling for phases, formulations and generations, as well as expanding the current body of knowledge on alternative hormonal contraceptives. 

Hormones are a complex and fascinating aspect of women’s health that I hope to further explore.