UCalgary research reveals importance of route of administration of menopausal hormone therapy

As women near menopause, they begin to experience fluctuations in estrogen levels, and following menopause, produce less estrogen and progesterone. This causes symptoms related to menopause and may increase the risk for cardiovascular diseases including heart failure, according to the American Heart Association.

In 2022, the Menopause Foundation of Canada Landmark Report showed more than 95 per cent of women experience symptoms related to menopause, such as hot flashes, cognitive changes, sexual dysfunction, sleep disturbances and mood swings. These changes can have a big impact on a person’s quality of life, work productivity, social relationships and overall health.

Dr. Shafeena Premji, MD, is a North American Menopause Society-certified menopause practitioner, a board member of the Canadian Menopause Society, and clinical assistant professor at the Cumming School of Medicine (CSM). She says menopause symptoms can last for seven years or longer.

“How individuals experience these symptoms can vary, and some resolve with time,” says Premji. “But the symptoms can be debilitating to the point that some individuals leave their jobs because they feel they can no longer manage.”

Hormone therapy — yes or no?

Menopausal hormone therapy (MHT) can alleviate some of these symptoms. Taken in the early stages of menopause, MHT may also have cardiovascular benefits, although current guidelines in Canada note that hormone therapy shouldn’t be considered as a prevention or treatment of hypertension or heart disease.

To further confuse matters, MHT use became controversial in the early 2000s when a study linked  estrogen-based therapies to breast cancer, says Premji. In fact, MHT was largely abandoned between 2002 and 2004.

The findings of this study have been challenged. In 2022, the North American Menopause Society published its 2022 hormone therapy position statement, which noted that for most healthy women under the age of 60 or who are within 10 years of menopause onset, the benefits of hormone therapy outweigh the risks.

Still, Premji says many women are still fearful about taking MHT and 40 per cent of them don’t even bring up their symptoms with their doctor. Moreover, Premji adds that treating menopause with HMT was taken out of medical school curricula, leaving many physicians in the dark about how they can help their patients.

“Women are left basically stranded and feeling alone when even their family doctors can’t help them,” says Premji.

Method of therapy is what matters

Dr. Sofia Ahmed, MD, a professor at the CSM, hopes to help solve at least one part of the puzzle when it comes to MHT. She is a leader in investigating the impact of estrogen-based hormone therapy on the cardiovascular system.

Ahmed recently co-led a study that investigated whether the route of administration of estrogen-based menopausal therapy — by mouth, patch or vaginal creams or suppositories — altered a woman’s risk of developing high blood pressure, which is linked with cardiovascular disease.

The study, recently published in Hypertension, a peer-reviewed journal of the American Heart Association, found that how estrogen-based menopausal therapy is taken matters.

“Our study found that those who ingested estrogen-based therapies in pill form were 14 per cent more likely to develop high blood pressure than those who received their estrogen through a skin patch and 19 per cent higher than those using vaginal estrogen creams or suppositories,” says Ahmed.

“Our goal was to provide individuals and their health-care team with the information they need to make a personal decision about whether and how MHT is used.”

The study, which included data collected from more than 112,000 Albertan women age 45 years and older, also found that taking a specific form of estrogen, non-oral estradiol, at the lowest dose for the shortest period resulted in the lowest levels of high blood pressure. 

Study bridges knowledge gap

University of Calgary MD, PhD candidate Cindy Kalenga, the study’s lead author, notes that previous studies have also shown that specific types of HRT have been associated with higher rates of heart disease, but researchers weren’t sure why. 

This study was meant to work toward bridging that knowledge gap.

“We know that post-menopausal women have increased risk of high blood pressure when compared to pre-menopausal women. Previous studies have shown that specific types of hormone therapy have been associated with higher rates of heart disease,” says Kalenga.

“We chose to dive deeper into factors associated with hormone therapy, such as the route of administration (oral versus non-oral) and type of estrogen, and how they may affect blood pressure.”

Ahmed says more work needs to be done investigating the impact of different forms of HRT, including those that combine estrogen and progestin, on the risk of heart and kidney diseases.

“It’s really important to have greater knowledge on safe and effective hormonal treatments during menopause,” says Ahmed. “At the end of the day, it’s an individualized decision about what is best for the person going through menopause and should include open dialogue with their physician or health-care team. We need large, randomized studies factoring in all the complexities of hormone therapy around this important transition period in the female lifecycle.”