Tag Archive for: hormone therapy

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. 

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.

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!