Early or Late Menopause Ups Risk for Type 2 Diabetes

Marcia Frellick

July 27, 2016

Women who had their final menstrual period before age 45 or after 55 have a higher risk of developing type 2 diabetes (hazard ratio [HR], 1.04 and HR, 1.08, respectively, compared with those who had their final period between ages 46 and 55), new study results indicate.

The findings were published online July 27 in Menopause.

Erin S LeBlanc, MD, MPH, with Kaiser Permanente Center for Health Research, Portland, Oregon, and colleagues examined 124,379 women in the Women's Health Initiative (WHI), a multicenter study launched in 1991 by the National Institutes of Health that looked at preventing disease in postmenopausal women.

Dr LeBlanc and colleagues also found that in related age-adjusted models, women with the shortest reproductive periods (less than 30 years) had a 37% greater risk of developing type 2 diabetes than those with reproductive periods of 36 to 40 years. Likewise, women with the longest reproductive span (more than 45 years) had a 23% higher risk than women with medium-length reproductive years.

Dr LeBlanc told Medscape Medical News the study suggests that lifetime estrogen exposure may play a role in whether a woman develops type 2 diabetes or not and that there may be a "sweet spot" where optimal estrogen exposure meets lowest risk for type 2 diabetes.

The research team had hypothesized that because endogenous estrogen has been known to have protective effects against developing diabetes, cardiovascular disease, and osteoporosis, those with shorter reproductive years would have less protection from diabetes.

Estrogen helps to preserve insulin secretion and stabilize glucose levels. Low estrogen negatively affects body-fat distribution and fat accumulation, important factors in type 2 diabetes risk.

The surprise was that the data showed those with the longest reproductive years also had a higher risk for type 2 diabetes. "I don't have a good biological explanation for that," Dr LeBlanc said.

Results Can Help Target Lifestyle Changes

Of course, there's little women can do about age of menopause, given its strong genetic component, but those in the higher-risk groups can consider lifestyle changes, and clinicians, armed with this new information, can better counsel patients in the higher-risk groups.

"I don't want women thinking this is something terrible and they're doomed to get diabetes" if they are in the higher-risk groups, Dr LeBlanc said.

"The point of our study is to give women who have early menopause or late menopause another motivator for adopting a healthy lifestyle, because we know that a healthy lifestyle can substantially reduce a woman's risk of developing diabetes."

For clinicians, this is another factor to add to the conversation on why it's important to maintain a healthy weight, eat a balanced and nutritious diet, and increase exercise levels, she noted.

The authors add that previous work on this topic has had small sample sizes and lacked rigorous, prospective ascertainment of type 2 diabetes.

Strengths of this study include its large size, ability to more clearly characterize participants' reproductive history, long follow-up, and prospective ascertainment of diabetes.

Other Factors Not Linked to Risk

The researchers examined several other factors, including number of previous pregnancies, age at first birth, whether menopause was surgical or natural, body mass index, and hormone therapy after menopause. But none of these factors had a statistically significant link to risk of developing type 2 diabetes.

Age at which periods started and irregular periods were also not statistically significant in risk for diabetes.

Study limitations included that women were asked to recall their age at start of menstruation, which could have resulted in measurement error. And because medically diagnosed diabetes was not available for all WHI women, the researchers relied on participants' reports of diabetes.

"[H]owever, self-reports of 'treated diabetes' in WHI have been shown to be sufficiently accurate to allow use in epidemiologic studies such as this one," they write.

The findings by Dr LeBlanc, et al, are aligned with those of a previous European study (Diabetes Care. 2013;36:1012-1019).

"In that nested, prospective case-cohort study of more than 8000 postmenopausal women followed for 11 years, there was a 6% increased risk of type 2 diabetes per standard deviation of lower reproductive lifespan in years," the authors write.

But it still remains unknown how endogenous estrogen affects type 2 diabetes risk. Exploring that could lead to answers on how a woman could decrease diabetes risk as she ages, Dr LeBlanc and colleagues observe.

Further research could also test whether targeting women in these identified higher-risk groups could bring down the incidence of diabetes, Dr LeBlanc concluded.

The WHI program is funded by the National Institutes of Health. Dr LeBlanc's institute has received research funding from Amgen, AstraZeneca, Bristol Meyers Squibb, and Merck for unrelated projects. The coauthors had no relevant financial relationships.

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Menopause. Published online July 27, 2016. Available here.

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