Irregular Menstrual Cycles Associated With Increased Risk of T2D

In a cohort study of nurses, irregular and long menstrual cycles throughout life were associated with a greater risk of type 2 diabetes (T2D). Results, published in JAMA Network Open, showed a stronger association existed between T2D and irregular menstrual cycles in women with obesity, who were overweight, had a low-quality diet, or had low levels of physical activity.

“These findings suggest that menstrual cycle characteristics may serve as an early sign of the long-term risk of developing T2D and that lifestyle interventions may be a useful strategy to reduce the risk of T2D among women with menstrual cycle dysfunction,” researchers wrote.

By 2045, it is estimated diabetes will affect nearly 700 million adults worldwide and a total of 11.1% of the world’s female population. Currently, nearly 20% of women experience irregular and long menstrual cycles, and several studies have shown that menstrual cycle dysfunction is associated with insulin resistance.

Although insulin resistance is a key feature early in the pathogenesis of T2D, evidence linking T2D with long or irregular menstrual cycles is lacking. To better understand the association between the 2 conditions, investigators analyzed data collected from the Nurses’ Health Study II.

The ongoing prospective cohort study began in 1989 and initially enrolled 116,429 American female nurses between the ages of 25 and 42 years. At each follow-up cycle, more than 90% of participants completed postal or electronic questionnaires.

In the 1989 questionnaire, women retrospectively reported menstrual cycle characteristics during high school and between ages 18 and 22 years. Participants were followed up with again in 1993 and “after exclusions, 75,546 premenopausal women were followed up from 1993 to June 30, 2017.”

Mean (SD) participant (n = 75,546) age was 37.9 (4.6) years at baseline. Compared with women who reported very regular menstrual cycles, those with irregular cycles or no period exhibited “a higher mean body mass index (BMI) (28.1 [7.8] vs 24.9 [5.3]) and mean total caloric intake (1825.5 [567.0] vs 1798.5 [543.4] kcal/d), as well as lower mean alcohol consumption (2.6 [6.5] vs 3.2 [6.1] g/d) and lower mean AHEI-2010 diet score (46.9 [10.8] vs 48.2 [10.8]),” researchers found.

During the 1,639,485 person-years of follow-up, 5608 (7.4%) of participants documented new cases of T2D.

Adjusted analyses revealed:

• Women reporting always having irregular menstrual cycles in the age ranges of 14 to 17 years, 18 to 22 years, and 29 to 46 years were 32% (95% CI, 22%-44%), 41% (95% CI, 23%-62%), and 66% (95% CI, 49%-84%), respectively, more likely to develop T2D than those reporting very regular cycles (within 3-4 days of expected period) in the same age range.
• Women reporting a usual cycle length of 40 days or more in the age ranges of 18 to 22 years and 29 to 46 years were 37% (95% CI, 19%-57%) and 50% (95% CI, 36%-65%), respectively, more likely to develop T2D during follow-up compared with women reporting a usual cycle length of 26 to 31 days in the same age ranges.
• Women reporting always irregular cycles or no period were more likely than women who reported very regular cycles to be current smokers (302 of 2542 [11.9%] vs 4333 of 41,698 [10.3%]) and have a family history of diabetes (484 of 2542 [19.1%] vs 6599 of 41,698 [15.6%]).
• Relative excess risk of T2D due to the interaction between irregular and long menstrual cycles and the overall unhealthy lifestyle score was 0.73 (95% CI, 0.57-0.89) and 0.68 (95% CI, 0.54-0.83), respectively.
• An additive interaction of menstrual cycle dysfunction and overweight and obesity, physical inactivity, and low-quality diet with risk of T2D.

Overall risk of developing T2D was greatest “among women who maintained irregular cycles across the reproductive life span and those whose cycle length changed from less than 32 days to 32 days or more,” authors wrote.

Disrupted hormonal environments are thought to play an important role in the relationship between menstrual cycle dysfunction and T2D risk. “Irregular and long menstrual cycles are strong indicators of hyperinsulinemia, which can synergize with pituitary gonadotropins to stimulate androgen production in ovarian theca cells, further exacerbating insulin resistance and increasing the risk of type 2 diabetes,” researchers explained.

Menstrual cycle disorders are also associated with dysregulated inflammatory processes which could be involved in T2D development.

The current analysis found an association between irregular menstrual cycle and T2D development across the body mass index (BMI) spectrum. However, the additive interaction between cycle characteristics and BMI “suggests that the adverse hormonal and inflammatory risk profile observed among women with long or irregular cycles is further exacerbated by overweight and obesity, making weight management strategies particularly important for women presenting with cycle dysfunction.”

Study participants did have a relatively homogenous racial/ethnic and educational background, which may limit the generalizability of findings and marks a limitation to the trial.

Reference

Wang Y, Shan Z, Arvizu M, et al. Associations of menstrual cycle characteristics across the reproductive life span and lifestyle factors with risk of type 2 diabetes. JAMA Netw Open. Published online December 21, 2020. doi:10.1001/jamanetworkopen.2020.27928