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Issues related to female reproductive health may increase the risk of metabolic conditions later in life. Image credit: Maryna Terletska/Getty Images.
  • Metabolic health — a person’s levels of blood glucose, lipids, blood pressure and body fat — may be affected by lifestyle, either beneficially or adversely.
  • Life events may also affect a person’s risk of chronic metabolic conditions, such as type 2 diabetes and high cholesterol.
  • A review has concluded that, for females, certain characteristics of reproductive milestones — including early puberty, excess weight gain in pregnancy and severe menopause symptoms — are linked to adverse metabolic health.
  • The researchers suggest that clinicians should be aware of sex-specific risk factors when assessing a person’s metabolic health.

A person who is metabolically healthy has blood glucose, lipids, blood pressure and a body mass index (BMI) within the healthy range.

Someone who is not metabolically healthy is at risk of metabolic syndrome, a group of conditions that increase the likelihood of coronary heart disease, type 2 diabetes, stroke and other health problems. In the United States, around one in three adults have metabolic syndrome.

The National Heart, Lung and Blood Institute recommends the following to maintain metabolic health, lower the risk of heart disease and decrease the likelihood of developing type 2 diabetes:

  • choosing heart-healthy foods, such as fruit, vegetables and whole grains, and limiting saturated fat, added salt, sugars, and alcohol intake
  • aiming for a healthy weight
  • getting regular physical activity
  • managing stress and getting enough sleep
  • ceasing smoking.

However, a new review of the existing evidence has suggested that, for women, not only lifestyle, but the characteristics of their reproductive milestones may adversely impact their risk of metabolic dysfunction, which could lead to type 2 diabetes and high cholesterol.

The researchers who conducted the review suggest that screening for reproductive risk factors, such as early onset of menstruation, polycystic ovary syndrome (PCOS), weight gain in pregnancy and severity of menopause symptoms, may be an initial step to help prevent or treat these metabolic diseases.

Their findings appear in Cell Metabolism.

The researchers reviewed evidence linking the traits of reproductive milestones with metabolic health and disease, and found that reproductive factors throughout lifetime were linked to metabolic health.

These included:

  • early menarche — starting menstruation before the age of 12 was linked to abnormal blood glucose levels, high cholesterol, metabolic syndrome, and type 2 diabetes
  • irregular menstruation — compared with regular menstruation, chronic irregular menstruation was linked to a higher risk of developing type 2 diabetes
  • PCOS — the researchers found a strong relationship of PCOS with obesity and type 2 diabetes
  • pregnancy — gestational diabetes, excessive weight gain during pregnancy, and gestational lipid levels were all linked to poorer metabolic health later in life
  • lactation — longer lactation was linked to better metabolic health, and a lower risk of type 2 diabetes and metabolic syndrome
  • menopause — severe menopause symptoms and early menopause were linked to higher type 2 diabetes risk, but the researchers found evidence that postmenopausal estrogen therapy could decrease that risk.

Although looking at what might cause these links was outside the scope of this research, most of these risk factors are linked to increased insulin resistance, leading to effects on metabolic health.

Dr. G. Thomas Ruiz, board-certified OB/GYN and lead OB/GYN at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, not involved in the current research agreed that this could be a factor:

“Above average weight gain in pregnancy, PCOS and gestational diabetes are all risk factors for adult-onset diabetes and all conditions are associated with insulin insensitivity. I am not sure how early menarche comes into play.”

In their review, the researchers suggest that “[t]he majority of shared risk factors fall into one of three categories, genetics, hormonal fluctuations and resulting physiology, or adiposity.”

Adiposity, or excess body fat, is linked to metabolic syndrome, and it is also linked to many of the reproductive factors investigated in this study, so could be one of the underlying causes.

However, lead author Dr. Amy R. Nichols, Research Fellow at the Harvard Pilgrim Health Care Institute and the Harvard T.H. Chan School of Public Health, told Medical News Today:

“There is strong evidence that a link exists between reproductive risk factors and metabolic disease. To the extent that we can tell from the current evidence, the relationship between these adverse reproductive outcomes with metabolic health later in life is not explained by traditional risk factors, such as excess adiposity, diet, or physical inactivity.”

The researchers do not claim that traits of reproductive milestones cause metabolic disorders, but conclude that there are links. There may be other underlying factors linking them.

“Often when someone says other factors, they are unknown, or nothing has been specifically identified. Is insulin insensitivity likely the base cause? Likely, but what predisposes to this disorder is unknown,” noted Dr. Ruiz.

”We do know it starts a spiral that leads to obesity, which creates more insulin resistance, which leads to anovulatory cycle, which lowers sex hormone binding globulin, which leads to increased free testosterone, etc,” he explained.

Although this study cannot show a causal relationship, acknowledging that these reproductive milestones may be risk factors is a step towards a better understanding of the development of metabolic dysfunction. However, the authors say further research is needed to understand these complex relationships.

Dr. Nichols told MNT: “Reproductive milestones should be considered risk factors for poorer metabolic health in later life. In addition, other factors likely impact the trajectory of cardiometabolic health. Although individuals can’t change their medical history, there are proactive actions that could potentially mitigate the adverse outcomes associated with adverse reproductive characteristics.”

She continued: “For example, lifestyle factors including diet, physical activity, and medication management may improve outcomes even in people who are at high-risk for metabolic disease because of their reproductive histories. We are currently examining whether diet may modify the effect of certain reproductive risk factors on metabolic health and hope to conduct more of this research in the future.”

She advised that clinicians should be aware of these sex-specific risk factors for metabolic disorders, adding that “[c]linicians should evaluate patients for the history or presence of known reproductive risk factors in addition to assessing traditional risk factors (e.g., smoking, diet, physical activity).“

“Screening patients for adverse reproductive characteristics would inform how medical personnel treat patients – with the potential for improved long-term outcomes,” advised Dr. Nichols.

But even for those with reproductive risk factors, metabolic diseases are not inevitable. A healthy diet and lifestyle, following the recommendations above, can help mitigate the risk and reduce the likelihood of developing conditions such as type 2 diabetes and high cholesterol in later life.