Irregular Menses: A Signal for Cardiovascular Disease and Diabetes

Compared with women with regular menstrual cycles, women with irregular menses are 20% more likely to develop cardiovascular disease and 17% more likely to develop type 2 diabetes over 20 years.

There is a lack of consideration of the link between menstrual disorders and metabolic conditions. Researchers, led by Sylvia Kiconco MSc, at the Monash University School of Public Health and Preventive Medicine in Victoria, Australia, found that this lack of consideration limits the screening and preventative measures in women transitioning through menopause. Due to the link between PCOS or early menopause with adverse cardio-metabolic outcomes, such as diabetes, hypertension, heart disease, and stroke, researchers aimed to explore the relationship between menstrual irregularity among women in their forties and long-term cardio-metabolic outcomes.

The study population came from the Australian Longitudinal Study on Women’s Health (ALSWH) database spanning 20 years, over eight surveys. The eight data surveys were collected in 1996, 1998, 2001, 2004, 2007, 2010, 2013, and 2016. Women in the 1946 to 1951 birth cohort aged 45 – 50 years at the first survey. Eligible study participants (n = 13,543) were chosen based on whether they had responded to questions related to the diagnosis of diabetes, heart disease, and menstrual regularity in their first survey. This group was then split into women who reported regular and irregular menstrual cycles and were assessed at each following survey to determine the number of women who did or did not develop the outcomes. (surveys 2 to 8).

Participants who reported irregular cycles ‘often’ were placed in the irregular menstrual cycle cohort. Those who reported irregular cycles ‘never,’ ‘rarely,’ or ‘sometimes’ were placed in the regular menstrual cycle cohort. And those missing a response to their menstrual regularity were excluded. The primary outcome focused on diabetes and heart disease (MI and angina). Participants who responded ‘yes’ to having had diabetes or heart disease at survey one were excluded from the analysis. At surveys 1 and 2, participants were questioned if they had received a diagnosis of these outcomes within the last two years or more than two years ago. And if they answered ‘yes’ to receiving the diagnosis within the last two years, they were considered to have had the outcome after the first survey. If they answered ‘yes’ to receiving the diagnosis more than two years ago, they were considered to have the outcomes at or before the time of the survey.

At surveys 3 through 8, participants were again questioned if they received a diagnosis of these outcomes within the last three years. Again, those who responded ‘yes’ were classified as having had the outcomes, and those who responded ‘no’ were classified as not having the outcomes. 

Of the 13,543 participants analyzed, 12,135 reported regular and 1408 irregular menstrual cycles. Those with irregular menses had a 17% (HR = 1.17; 95% CI, 1 – 1.38) higher risk for developing type 2 diabetes, and a 20% (HR = 1.2; 95% CI, 1.01 – 1.43) higher risk for developing cardiovascular disease. The time to event for diabetes and cardiovascular disease was significantly shorter in women who reported irregular menstrual cycles than those who reported regular menstrual cycles.

The only significant modifier between incident diabetes and menstrual regularity was hormone replacement therapy. Participants who had not used hormone replacement therapy and had irregular menstrual cycles were 30% more likely to develop diabetes (HR: 1.30, 95% CI: 1.09 – 1.55). However, the risk for diabetes was not significantly modified by hormone replacement therapy.

Researchers mentioned several explanations for their observed findings. First, menstrual irregularity is at the basis of PCOS, which causes insulin resistance, increasing the risk of developing type 2 diabetes and cardiovascular risk. The physiological changes are linked to gonadal steroid levels, insulin resistance, alterations in body fat, and increased hypertension and hyperlipidemia, which are risk factors for long-term adverse cardio-metabolic outcomes.

Secondly, participants with premature and early menopause have impaired vascular function due to loss of estrogen and a higher risk of non-fatal CVD than those who experience menopause at age 50 – 11 years.

Researchers concluded that menstrual irregularity is correlated with a long-term cardio-metabolic disease but can be modulated by hormone use. And that screening for diabetes and heart disease in women in their 40s who experience common conditions associated with irregular menstrual cycles such as polycystic ovary syndrome and early menopause. 

Practice Pearls:

• Women with irregular menstrual cycles are 20% more likely to develop cardiovascular disease and 17% more likely to develop type 2 diabetes mellitus over 20 years.
• It is essential to screen for cardiovascular disease and diabetes in women with irregular menstrual cycles in their 40s.
• Hormone replacement therapy in women with irregular menstrual cycles may decrease their risk of developing cardiovascular disease and diabetes.

 

Reference for “Irregular menses: a signal for cardiovascular disease and diabetes”:

Kiconco, Sylvia, et al. “Menstrual Cycle Regularity as a Predictor for Heart Disease and Diabetes: Findings from a Large Population‐Based Longitudinal Cohort Study.” Wiley Online Library, John Wiley & Sons, Ltd, 24 Nov. 2021, https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.14640?saml_referrer.

 

Azeezat Rasaki, PharmD. Candidate, Florida A&M University, College of Pharmacy