Blog 2: What Do We Know About Menopause and Hormone Therapy?

Women's Health Blog
5 min readOct 27, 2023

Authors: Romina Garcia de leon, PhD Student, University of Toronto, Alana Brown, PhD Student, University of Toronto, Echo 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!

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Women's Health Blog

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