Medical Bulletin 22/ June/ 2024

According to a study published in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, women who have their ovaries removed before menopause, particularly before the age of 40, have reduced white matter integrity in multiple regions of the brain later in life.

Premenopausal bilateral oophorectomy (PBO) causes abrupt endocrine dysfunction (e.g., loss of estrogen, progesterone, testosterone, and an increase in gonadotropins). Studies suggest that females with PBO are at an increased risk of cognitive impairment and dementia.

Long-term ovarian hormone deprivation in rats is associated with reduced white matter integrity. Among humans, females have lower white matter fractional anisotropy compared to males across multiple brain regions, potentially reflecting differences in sex hormone exposure.

For the study, the research team examined data from the Mayo Clinic Study of Aging to identify women over the age of 50 with available diffusion tensor imaging, a magnetic resonance imaging (MRI) technique that measures white matter in the brain. The cohort was comprised of:

1.22 participants who had premenopausal bilateral oophorectomy (PBO) before age 40

2.43 participants who had PBO between the ages of 40 and 45

3.39 participants who had PBO between the ages of 46 and 49

4.907 participants who did not have PBO before the age of 50.

The results showed that females who had premenopausal bilateral oophorectomy before the age of 40 had significantly reduced white matter integrity in multiple regions of the brain. There were also trends in some brain regions such that women who had PBO between the ages of 40-44 or 45-49 years also had reduced white matter integrity.

“Having both ovaries removed results in an abrupt decrease in both estrogen and testosterone in women. Therefore, one possible explanation for our results is the loss of both estrogen and testosterone. While these findings are important for women to consider before having premenopausal bilateral oophorectomy for non-cancerous conditions, we need a larger and more diverse cohort of women to validate these results,” said Michelle Mielke, the study’s corresponding author.

Reference: Michelle M. Mielke, Ryan D. Frank, Luke R. Christenson, Robert I. Reid, Julie A. Fields, Zhenya E. Knyazhanskaya, Firat Kara, Prashanthi Vemuri, Walter A. Rocca, Kejal Kantarci; Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life; Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association; https://doi.org/10.1002/alz.13852

A team of researchers from McMaster University has revealed a new, simple clinical test to detect Calcium Release Deficiency Syndrome (CRDS), a life-threatening genetic arrhythmia that causes dangerously fast heartbeats and can lead to severe complications such as sudden cardiac arrest and death.

The findings were published in the journal JAMA.

While 3,50,000 to 4,50,000 cardiac arrests occur annually around the globe, many of these cases remain unexplained. One of the potential underlying causes is Calcium Release Deficiency Syndrome (CRDS), a rare genetic heart condition that standard clinical tests often fail to detect.

CRDS affects the heart's ability to manage calcium release, which is crucial for proper cardiac function. Due to its rarity and the subtlety of its symptoms, CRDS frequently goes undiagnosed, leading to sudden cardiac arrests that are labelled as unexplained.

The case-controlled study, co-led by Jason Roberts and Wayne Chen involved 68 study participants from 10 centres in seven countries. The participants were from four categories of heart conditions, including Calcium Release Deficiency Syndrome (CRDS) patients and unexplained cardiac arrest (UCA) survivors.

The researchers revealed that the new diagnostic method, performed using an electrocardiogram, monitors for changes in ECG after a brief period of a fast heartbeat and a pause, which can occur naturally or be induced by artificially pacing the heart.

"CRDS has been linked to many tragic incidents and heartbreaking stories affecting families. There have been numerous cases where patients experienced fainting episodes, but their tests showed no issues, which led doctors to believe the fainting was not due to a dangerous heart condition. A portion of these individuals, often young and otherwise healthy, subsequently suffered sudden cardiac arrests, and some did not survive. This novel and simple diagnostic method, which can be performed using an electrocardiogram in a broad range of clinical settings, is hopefully an important step towards improving our evaluation of initially unexplained cardiac arrest (UCA),” said the authors.

The team anticipates that this simple pacing test will be incorporated into the routine diagnostic tests for initially unexplained cardiac arrest, providing hope for better outcomes and prevention of future tragedies.

Reference: Ni M, Dadon Z, Ormerod JOM, et al. A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome. JAMA. Published online June 20, 2024. doi:10.1001/jama.2024.8599

According to a new brain imaging study led by researchers at Weill Cornell Medicine, the transition to menopause is marked by a progressively higher density of estrogen receptors (ER) on brain cells, a measure that remains elevated in women up to their mid-sixties.

The findings were published in the journal Scientific Reports.

A central feature of menopause is the decline in the body’s production of estrogen. This leads to various bodily changes including the cessation of menstruation, but also to neuropsychiatric effects such as “brain fog,” depression and anxiety.

In the study, the researchers scanned the brains of 54 healthy women aged 40-65 using PET with a tracer that binds to ERs. These receptors are found in multiple areas of the brain, especially in women, and mediate the many cognitive and behavioural effects of the female sex hormone estradiol, the most potent form of estrogen.

Scans comparing women at different menopausal stages revealed progressively higher ER density in several estrogen-regulated brain networks in the postmenopausal and perimenopausal groups compared to premenopausal controls.

Researchers interpreted this as a compensatory response to lowering levels of available estrogen— as estrogen levels drop during the menopause transition, the cells express additional receptors to sop up as much estrogen as possible.

The analyses also found that high ER density in some of these regions was associated not only with menopause status but also with patients’ reports of menopause-related cognitive and mood symptoms.

The results suggested that this technique may be a valuable tool for studying the brain effects of menopause and estrogen therapy.

“Using this method, we were able, for the first time, to measure ER activity in the brain, and to identify potential predictors of some of these common symptoms of menopause,” said study lead author Dr Lisa Mosconi.

The researchers further plan to use ER-PET imaging to study the long-term consequences of estrogen level changes in the brain—including persistently low levels after menopause, and rising levels with estrogen therapy.]

Reference: Mosconi, L., Nerattini, M., Matthews, D.C. et al. In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology. Sci Rep 14, 12680 (2024). https://doi.org/10.1038/s41598-024-62820-7