Tag Archive for: estrogen

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 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.