Women who give birth less than – or more than – three or four times age faster after menopause

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Having children doesn’t just make you feel like you’ve aged overnight – a new study led by Penn State researchers found that the number of times a person gives birth may also affect the body’s physical aging process.

The researchers examined several different measures that represent how a person’s body is aging and found that people who had few births — or many — seemed to have aged quicker than those who had given birth three or four times.

However, these effects were found only after a person had gone through menopause.

“Our findings suggest that pregnancy and birth may contribute to the changing and dysregulation of several different physiological systems that may affect aging once a person is post-menopause,” said Talia Shirazi, a doctoral candidate in biological anthropology at Penn State.

“This is consistent with the metabolic, immunological, and endocrinological changes that occur in the body during pregnancy and lactation, as well as the various disease risks that are associated with pregnancy and reproductive investment more generally.”

According to the researchers, pregnancy and breastfeeding use a large amount of the body’s energy and can affect many of its systems, including immune function, metabolism, and blood pressure, among others.

Additionally, people who have given birth are more likely to die from diabetes, kidney disease, and hypertension, among other conditions, than those who have not.

The researchers were curious about how the body balances these “costs of reproduction” and whether it affects how the body ages.

“We think there’s something going on, some sort of trade-off, between aging and reproduction,” Shirazi said.

“This makes sense from an evolutionary biology point of view, because if you’re spending energy in pregnancy and breastfeeding, you probably don’t have as much energy to allocate towards things like physiological maintenance and defense.”

For the study, the researchers used data on 4418 participants from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey. Data included information about reproductive health including the number of live births and whether they had gone through menopause or not.

The researchers measured biological aging in several ways based on nine biomarkers designed to assess metabolic health, kidney and liver function, anemia and red blood cell disorders, and immune function and inflammation.

“We wanted to look at measures that would help capture the age and functioning of the body’s major organ systems, instead of looking at aging at the cellular level,” said Waylon Hastings, postdoctoral researcher at Penn State.

“When we think about pregnancy, we don’t think about changes to individual cells but instead about how the immune system or metabolism changes, for example.”

The researchers found a “U‐shaped relationship” between the number of live births and accelerated biological aging.

Those reporting zero or few live births, or reporting many live births, had markers of quicker biological aging than those who reported three or four live births. This was true even when controlling for chronological age, lifestyle, and other health‐related and demographic factors.

Shirazi said that because the data was taken at one point in time, it’s not currently possible to know what caused these associations.

But she said one possible explanation for the findings — recently published in Scientific Reports — is the presence, or lack, of ovarian hormones in post-menopausal people.

“Previous research has found that generally, ovarian hormones are protective against some cellular level processes that might accelerate aging,” Shirazi said.

“So it’s possible that in pre-menopausal women the effect of hormones are buffering the potential negative effect of pregnancy and reproduction on biological age acceleration. And then perhaps when the hormones are gone, the effects can show themselves.”

Hastings said the study also suggests that additional research can be done to understand the processes that may be involved in the connection between aging and having children, as well as how these processes work over time.

“This transition into menopause, and female reproductive health in general, is very much under researched and not as well understood as it should be at this time,” Hastings said.

“So if we can see that there are these changes in aging as a function of reproduction and menopause, and we don’t have a great explanation for why, then that’s a sign we should investigate this more.”

Asher Rosinger, Ann Atherton Hertzler Early Career Professor in Global Health, and Calen Ryan, Northwestern University, also participated in this work.


A literature search was done using PubMed. Natural menopause has been defined by World Health Organization (WHO) as at least 12 consecutive months of amenorrhea not due to surgery or any other cause. The mean age at natural menopause (ANM) is 51 years in industrialized nations, while it is 48 years in poor and non-industrialized nations.[1,2,3]

Menopause is not a central event but rather a result of primary ovarian failure secondary to apoptosis or programmed cell death. This results in reduced production of estradiol, the most active form of estrogen as well as increased levels of follicle-stimulating hormone (FSH) and decreased levels of inhibin.

It is an important event in the life of women and with the increase life expectancy at birth for women they spend about more than one-third of their lives in this phase.

The ANM remains an independent risk factor for long-term morbidity[4] and mortality.

Delayed menopause has been found to be associated with:

  • Longer reproductive span and reduced overall cause mortality.
  • Increased risk of breast, endometrial, and ovarian cancers.[5]
  • Reduced risk of osteoporosis and fractures.[6]
  • Reduced risk of morbidity and mortality from cardiovascular diseases[7,8] like ischemic heart disease, myocardial infarction, and atherosclerosis.

Health concern’s in menopausal women is principally related to estrogen deficiency which includes sexual problems, urogenital atrophy, vasomotor symptoms, cognitive problems, cardiovascular diseases, estrogen responsive malignancy, and osteoporosis. The greatest risk associated with menopause is that of acute myocardial infarction and hypertension.

The effect is more pronounced for women with artificial menopause than with surgical menopause. The health concerns linked with the use of hormone replacement therapy (HRT)[9] and other drugs for prevention and treatment of menopausal symptoms[10] emphasizes the need to identify the modifiable risk factors and role of alternative medicine like phytoestrogens,[11] isoflavones,[12] acupuncture,[13] and yoga.[14]

ANM is influenced by various determinants[15,16,17,18] like genetic, demographic, socioeconomic, dietary, reproductive, and behavioral; of which some are modifiable like lifestyle and dietary.

Current smoking, lower education, unemployment, nulliparity being separated, divorced, widowed, vegetarian diet, and prior history of heart disease are independently associated with accelerated menopause; while parity, prior use of oral contraceptive pills, Japanese ethnicity, higher body mass index (BMI), and moderate alcohol consumption is associated with delayed ANM.

Recent studies have shown that women who carry BRCA mutation[19,20] have early onset menopause and heavy smoking compounds the risk. However, there are very few studies that evaluate the impact of dietary and lifestyle factors on the ANM.

PHYSICAL ACTIVITY

Higher BMI[21,22] at 20 years age, mid-life weight gain moderate-high, exercise participation, and enhanced leisure time physical activity[22,23,24] during adulthood and adolescence are associated with late menopause and longer reproductive span; however, severe weight loss or vigorous exercise accelerates ANM by lowering the estrogen levels. The role of moderate weight gain and physical activity with the onset of menopause has not been studied yet.

LIFESTYLE FACTORS

Behavioral or lifestyle factors like smoking,[25,26,27] alcohol consumption, and intake of coffee and tea influence ANM. Smoking and ANM have an inverse consistent relationship such that it accelerates menopause by 1.5-2 years. Polycyclic aromatic hydrocarbons present in cigarette smoke are toxic to ovarian follicles that result in decreased estrogen levels, and hence menopause.

The drug metabolism is enhanced in smokers with the result that estrogen gets more rapidly metabolized in liver and moreover smoking has an antiestrogenic effect as well. Effect of passive smoking on ANM has not been documented well.

There are studies that have documented a dose-response effect on atrophy of ovarian follicles such that heavy smokers have an earlier natural menopause as compared to light smokers. Alcohol consumption and its effect on the ANM has been evaluated in very few studies due to certain social and ethnic limitations.

Moderate alcohol[28,29,30] consumption delays ANM. Regular tea consumption also delays the ANM probably due to the antioxidant and nonsteroidal estrogenic effects of flavonoids that counteract the degenerative processes. However, there are no studies on the effect of various types of tea on age at menopause. Low level of lifelong sun[31] exposure has been found to be associated with early ANM.

DIET

The effect of nutrition on sex hormone levels and reproductive span has been extensively studied in animal models; however, large prospective studies in humans are scarce. Studies on dietary factors and ANM have conflicting[32] results; and hence, the need for further studies.

Caloric restriction particularly during early childhood decreases ANM as evidenced by famous 1944-1945 Dutch famine.[33] Dietary factors[34,35,36,37] influence ANM by virtue of their effect on serum estradiol levels. High intake of fruits and vegetables delays the onset of menopause and prolongs the reproductive lifespan because of the presence of antioxidants in fruits and vegetables that counteracts the adverse effects of reactive oxygen species on the number and quality of ovarian follicles.

Higher intake of total calories, high carbohydrate, and high protein intake are found to be associated with delayed age at menopause; however, the correlation of carbohydrate diet with ANM has conflicting results with some studies documenting inverse or no relationship.

Dietary fiber, soy products, and red meat have inconsistent results in various studies; and hence, the need for larger studies. High intake of polyunsaturated fats accelerates ANM, while total fat and saturated fat intake has no effect on menopause.

Current calcium supplementation and lifelong fish consumption influencing ANM need larger studies for confirmation. Thus; apart from genetic, reproductive, socioeconomic, and demographic factors influencing ANM there has been increasing insight and research in modifiable risk factors like diet and lifestyle, but still larger prospective studies are needed.

There is a growing need of menopausal clinics and health awareness campaigns to initiate preventive strategy specially in developing nations[38,39,40,41] like India[42] where the ANM is 2-3 years earlier than the industrialized nations.

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Funding: The National Science Foundation, National Institute on Aging, and the Natural Sciences and Engineering Research Council of Canada helped support this research.

Source: Penn State

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