U of S research points to potential menopause treatment

The possibility of treating and preventing the unwanted symptoms of menopause before they appear is now closer than ever because of Heidi Vanden Brink’s graduate research.

"We know there are profound changes in estrogen production during the transition into menopause," said Vanden Brink, who recently completed her Master's of Health Science in Department of Obstetrics, Gynecology and Reproductive Sciences, College of Medicine. "These changes in hormone production that come with age are associated with unwanted symptoms and health risks, but no one had looked at where these profound changes are coming from."

Previous research at the U of S—including that of Vanden Brink's supervisor Angela Baerwald, assistant professor in the College of Medicine—discovered that ovarian follicle development occurs in a wave-like pattern two to three times during a menstrual cycle in women of reproductive age. The growth of follicles—fluid-filled ovarian sacs that contain an egg—can be monitored using ultrasonography and can be either major or minor waves, Vanden Brink explained.

A major follicle wave develops during the follicular phase of the menstrual cycle, approximately the two-week interval following menses. From this major wave, one follicle becomes dominant among all the others, produces estrogen and results in ovulation at mid-cycle. Following ovulation, during what is known as the luteal phase, minor or major follicle waves may develop. Major waves occur in approximately 30 per cent of young women in the luteal phase, however the dominant follicles do not ovulate, they simply regress. In minor follicle waves, all ovarian follicles grow and then regress without the development of a dominant follicle, she explained.

The next question that needed to be answered was what happens as women get older and the number of eggs and follicles remaining in the ovaries declines, do these patterns of follicular wave development persist? "We wanted to characterize ovarian function during the transition to menopause which happens at around 45 years of age."

To find the answer, Baerwald, Vanden Brink and Donna Chizen, associate professor in the College of Medicine, and collaborators from the University of Sydney and Prince Henry's Institute of Medical Research conducted a study. The team used ultrasound technology to monitor follicle development and took blood samples to determine hormone concentrations in women. This was done to compare the follicular development patterns of women aged 18-35, those in peak reproductive life, with women aged 45-55, the typical age for the transition to menopause.

What interested Vanden Brink was what she discovered in the 45-55 year-old group. "In women in that group, some had normal follicular patterns. However, we found unique major growth patterns in the luteal phase in six of 17 women in the 45-55 year age group."

In these six women, Vanden Brink continued, the dominant follicles of the luteal phase major waves grew to be twice the size compared to the dominant follicle in younger women and they persisted for twice as long. Further yet, four of these six women had sharp increases in estrogen production that exceeded the normal range.

In one case, a woman in the 45-55 year old age group had a major wave that ovulated in the early follicular phase around the time of menses. "Knowing that ovulation can occur at unexpected times during a woman's menstrual cycle in her late reproductive life has important contraceptive implications," Vanden Brink said.

More importantly what this also means, she continued, "is that we were able to identify the origin of the previously reported atypical estrogen production as women age. Typically with the transition to menopause, treatment is based on symptoms, like hot flashes, fatigue and depression. Now we can start to look at treatment strategies and preventative measures based on physiology, ideally before the unwanted symptoms of the transition occur."

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