March 22, 2019
2 min read

Delayed menarche heightens overt nephropathy risk in type 1 diabetes

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Overt nephropathy is more likely to develop in women with type 1 diabetes who are older at age of menarche compared with those who are younger, according to findings published in Diabetic Medicine.

“A major question of concern in type 1 diabetes is the association of age at menarche with glycemic control; however, studies evaluating the impact of glycemic control on the age at menarche in young women with type 1 diabetes have provided conflicting results,” Tina Costacou, PhD, associate professor of epidemiology at the University of Pittsburgh Graduate School of Public Health, and colleagues wrote. “Another question relates to the possibility that delayed menarche in type 1 diabetes reflects risk of vascular complication development later in life, a hypothesis which has not been extensively studied.”

To test whether age at menarche affected microvascular complications related to type 1 diabetes, Costacou and colleagues conducted cross-sectional and prospective analysis of 25 years of follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study. Participants were recruited after being diagnosed with type 1 diabetes at the Children’s Hospital of Pittsburgh between 1950 and 1980. In Costacou and colleagues’ analysis, data from 315 women from the study (mean age, 27.3 years; mean age at diabetes onset, 8.7 years) were included.

During the 25 years of follow-up, participants completed biennial surveys and were clinically examined biennially for 10 years with additional examinations at age 18 and 25 years. Age at menarche was self-reported by participants while assessments for overt nephropathy, proliferative retinopathy and distal symmetric polyneuropathy were carried out at each visit. In addition, measurements of HbA1c, HDL cholesterol, total cholesterol and triglycerides were taken while medical history and demographics were ascertained via surveys.

The researchers found that 13% of the women in the cohort had delayed menarche, which was defined as onset beyond age 15 years, while age 13 years was established as the median age at menarche. Menarche occured at least 1 year or more after type 1 diabetes onset in 77.8% of the study population.

Women with delayed age of menarche were 3.19 times more likely to develop overt nephropathy (OR = 3.19; 95% CI, 1.33-7.64) compared with those with normal age at menarche, which was defined as happening from age 11.5 to 15 years. Similar significant associations were not found for proliferative retinopathy or confirmed polyneuropathy.


Multivariable Cox proportional hazards regression revealed a risk in confirmed polyneuropathy with each increase in age at menarche (OR = 1.14; 95% CI, 0.89-1.47), but no significant association was found in overt nephropathy or proliferative retinopathy.

Lastly, the researchers conducted multivariable left-censored models and found an association between each increase in age at menarche and the risk for overt nephropathy (OR = 1.16; 95% CI, 1.03-1.3). In addition, women with delayed age at menarche were 2.3 times more likely to develop overt nephropathy (OR = 2.3; 95% CI, 1.4-3.79) than those with normal age at menarche.

“The present study extends the evidence suggesting that age at menarche may play an important role in the presence and development of microvascular complications in women with long-standing, childhood-onset type 1 diabetes,” the researchers wrote. “Should further studies confirm that age of menarche in women with a diagnosis of type 1 diabetes plays a role in subsequent microvascular complication risk, women with a delayed onset of menses could be targeted for early screening and timely interventions to prevent the development of advanced microvascular disease.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.