Reproductive Period Shorter in Women With Type 1 Diabetes

Women with type 1 diabetes appear to have a shorter reproductive period of around 2.5 years compared to those without diabetes, new research suggests.

The study is the first to examine the age of both starting periods (menarche) and menopause in women with type 1 diabetes.

But the researchers also found that the reproductive period is only shortened for those diagnosed with type 1 diabetes before starting their periods.

“It’s important for women with type 1 diabetes to know that if they want to have a family they could prioritize childbearing to a bit earlier…Two years can be a big deal to a woman,” senior author Tina Costacou, PhD, told Medscape Medical News in an interview.

The findings are also important with regard to cardiovascular risk factor management and bone health, as menopause increases the risks for cardiovascular disease, stroke, and osteoporosis, she noted.

Earlier Menarche, Earlier Menopause in Women With Type 1 Diabetes  

The findings, from the Epidemiology of Diabetes Complications (EDC) trial and the Study of Women’s Health Across the Nation (SWAN), were published online in Menopause by Yan Yi, MPH, of the University of Pittsburgh, Pennsylvania, and colleagues.

The EDC cohort included women diagnosed with type 1 diabetes at the Children’s Hospital of Pittsburgh during 1950-1980 when they were younger than 17 years old. Women without diabetes were from the Pittsburgh site of SWAN, a multisite, longitudinal epidemiologic study of the menopausal transition launched in 1996-1997.

Women in the EDC were significantly younger than the SWAN group (42.8 vs 46.0 years) and much less likely to be Black, given that SWAN recruited minority populations by design (3.8% vs 32.6%).  

Compared to 178 women without diabetes in SWAN, the reproductive period in 105 women with type 1 diabetes in EDC was approximately 2.5 years shorter after adjustment for confounders, due to both later menarche and earlier natural menopause.

Those with type 1 diabetes began menses an average of 0.6 years later compared with the SWAN group, at age 13.2 vs 12.6 years (P = .003).

However, this delay was not seen in those diagnosed with type 1 diabetes after reaching menarche (12.2 years; P = .20).

At the time of the last available follow-up, the mean age of women with type 1 diabetes was 58.7 years compared to 64.0 years among those without diabetes (P < .0001). Women with diabetes were also significantly less likely to have ever used oral contraceptives (63.5% vs 77.5%) or to have ever been pregnant (72.4% vs 91.0%).

After adjustment for confounders, the delay in age of menarche was 0.5 years (P = .002). The difference in age at natural menopause after adjustments was 2.0 years (P < .0001).

Overall, type 1 diabetes was associated with 2.5 fewer reproductive years (P < .0001).

When the women were stratified by menarche onset before or after diagnosis of type 1 diabetes, the difference was only significant for the former group.

Age at menarche (P = .14), age at natural menopause (P = .08), and length of reproductive period (P = .29) did not differ significantly from those without diabetes for the women with type 1 diabetes diagnosed after menarche.

Mechanisms Unclear

The authors say the mechanisms aren’t yet clear but suggest the combined endogenous insulin deficiency, hyperglycemia, and exogenous hyperinsulinemia that occur in type 1 diabetes might disrupt hypothalamic-pituitary-ovarian axis function. Insulin receptors are widely distributed in the central nervous system and ovaries, they note.

“When insulin is produced by the pancreas, a large proportion goes to the liver…The body controls how much insulin goes into tissues. In type 1 diabetes, the body can’t do that. When injected, insulin floods everything. Maybe that’s related to ovarian aging,” Costacou hypothesized.

Another hypothesis relates to hyperglycemia and oxidative stress, which may also result in ovarian aging. Thus, she said, “The solution may be a more normal way of administering insulin.”

Yi and colleagues have conducted a subsequent analysis of factors associated with reproductive period length in the type 1 diabetes group, including A1c and insulin dose. Those findings are expected to be published later this year.

EDC and SWAN were funded by the National Institutes of Health. Yi and Costacou have reported no relevant financial relationships.

Menopause. Published online March 1, 2021. Abstract

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