Menstrual cycle patterns tied to T2D risk

Long, irregular menstrual cycles across the reproductive life span is associated with a greater risk of developing type 2 diabetes (T2D) in women, particularly among those who are overweight or obese, physically inactive, and had poor eating habits, a prospective study has shown.

Given the complications associated with T2D, it is critical to identify patient groups with greater susceptibility to develop targeted preventive strategies, the researchers stressed. “[Our] 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 [T2D risk] among women with menstrual cycle dysfunction.”

The study comprised 75,546 premenopausal women (mean age 37.9 years) from the US Nurses’ Health Study II. Evaluations were based on self-reported menstrual cycle length and regularity at age 14–17, 18–22, and 29–46 years. Cycle regularity was reported as very regular (within 3–4 days of expected period), regular (within 5–7 days of expected period), usually irregular, always irregular, or no period. [JAMA Netw Open 2020;3:e2027928]

During 1,639,485 person-years of follow-up, 7.4 percent of participants (n=5,608) were documented to have incident T2D.

After adjusting for time-varying BMI and lifestyle risk factors, women who reported having ‘always irregular’ cycles or ‘no period’ were more likely to develop T2D than those who had ‘very regular’ cycles (adjusted hazard ratios [adjHRs], 1.32, 1.41, and 1.66 for ages 14–17, 18–22, and 29–46 years, respectively; p<0.001 for all).

Women reporting a usual cycle length of ≥40 days or too irregular to estimate were also more likely to develop T2D vs those reporting a usual cycle length of 26–31 days (adjHRs, 1.37 and 1.50 for ages 18–22 and 29–46 years, respectively; p<0.001 for both).

“[These findings suggest that] women who experienced irregular or long menstrual cycles in adolescence and throughout adulthood were more likely to develop T2D than women without menstrual cycle dysfunction,” the researchers explained.

The interactions between irregular cycles and T2D risk were stronger in women aged 29–46 years with overweight or obesity (p<0.001 for additive interaction), had a low-quality diet (p=0.03 for additive interaction), and low levels of physical activity (p<0.001 for additive interaction). A similar trend was observed in the interactions between cycle length and T2D risk (p<0.001, p=0.004, and p<0.001 for additive interaction, respectively).

“[As such,] weight management strategies [are] particularly important for women presenting with cycle dysfunction … [The] significant additive interaction of unhealthy menstrual cycle patterns and physical inactivity and low-quality diet with [T2D risk also highlights] the importance of maintaining an overall healthy lifestyle in preventing T2D,” said the researchers.

Cross-classification from ages 18–22 to 29–46 years revealed that T2D risk was strongest among women who had ‘usually irregular’ or ‘always irregular’ cycles (adjHR, 1.55) and those whose cycle length changed from <32 days to ≥32 days (adjHR, 1.62).

“A disrupted hormonal environment is suspected to play a critical role in the association between menstrual cycle dysfunction and [T2D risk],” said the researchers. “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 [T2D risk],” they elaborated.

Despite the long follow-up and large sample size, the homogeneous ethnic/racial and educational background may limit generalizability of the results. Diminished recall accuracy for earlier age ranges may have also factored in despite having data at different age ranges, as the greater T2D risk was particularly observed among women who reported long or irregular cycles later in life.

“[Nonetheless, our findings] highlight the need for women’s healthcare professionals to consider menstrual cycle characteristics across the reproductive life span as an independent sign when evaluating metabolic risk of their patients and point to potential lifestyle interventions to prevent the development of T2D in women with menstrual cycle dysfunction,” they concluded.