Women who were underweight in early or mid-adulthood had a higher risk for early menopause, an analysis of data from the Nurses’ Health Study found.
Women who were underweight at age 18 had more than 50% higher risk for early menopause, compared with those of normal weight (odds ratio 1.54; 95% CI 1.24-1.90), and women who were underweight at 35 had nearly 60% higher risk (OR 1.59; 95% CI 1.21-2.09), reported Kathleen Szegda, PhD, of the University of Massachusetts in Amherst, and colleagues.
Repeatedly gaining and losing weight was also linked with higher risk. Women who were underweight at 18 and gained and lost 20 pounds three or more times by age 30 had more than double the odds of early menopause (OR 2.40; 95% CI 1.08-5.33), Szegda’s group said online in the journal Human Reproduction.
Women who were underweight at the time they enrolled in the study were 30% more likely to experience early menopause (OR 1.30; 95% CI 1.08-1.57). However, women who were overweight at enrollment were 30% less likely (OR 0.70; 95% CI 0.58-0.84), the study found.
Up to 10% of women experience early menopause, the study authors noted. “Early menopause has been associated with a higher risk of cardiovascular disease and other health conditions such as cognitive decline, osteoporosis, and premature mortality,” Szegda told MedPage Today in an email. “In addition, early menopause has implications for family planning. Physicians may want to consider discussing these findings with underweight premenopausal female patients.”
Szegda and colleagues prospectively analyzed data on 78,759 women who indicated they were premenopausal when they enrolled in the Nurses’ Health Study 2 in 1989. These women reported their weight at age 18, and their current height and weight, at enrollment. Their mean age at enrollment was 34.8 years.
Participants completed questionnaires every two years to update their health information. At approximately 22 years of follow-up, 2,804 participants reported early menopause, defined as natural menopause occurring before age 45. The study authors used multivariable logistic regression analysis to explore the relationship between early menopause and various measures of adiposity, including body-mass index (BMI), at age 18, age 35, and at baseline. They defined underweight as a BMI of less than 18.5 and overweight as a BMI of 25 or higher.
The researchers found similar results when they examined the relationship between waist-to-hip ratio and early menopause. For example, women with ratios of 0.85 to <0.90 had significantly lower risk compared to women with ratios less than 0.75 (OR 0.70; 95% CI 0.55-0.90).
Several possible mechanisms may link underweight and early menopause, the study authors said. Previous research demonstrated that low body weight increases risk for functional hypothalamic amenorrhea (FHA), which results from dysregulation of the hypothalamic-pituitary-gonadotropin (HPG) axis, leading to anovulation, hypoestrogenism, and increased infertility risk. “While reproductive factors associated with fewer ovulatory cycles (e.g., greater parity, oral contraceptive use) have generally been associated with later menopausal age, it is possible that anovulation caused by HPG axis disruption is differentially associated with rate of reproductive aging,” they said.
Research has also shown that FHA commonly leads to increased activation of the hypothalamic-pituitary-adrenal axis, leading to elevated levels of corticotrophin releasing hormone, aderenocorticotrophin, and cortisol “It is possible that chronic elevation of these stress related hormones may increase early menopause risk, as some studies have found earlier age of menopause among women experiencing elevated stress levels,” Szegda and colleagues suggested.
It is also possible the relationship is based simply on body size, the study authors said. “Adult body size may be correlated with size at birth and consequently size of the ovarian pool, which is determined prenatally. A smaller ovarian pool would potentially result in an earlier age of menopause. Additional studies should examine relationships between birth weight, early life adiposity, and menopause timing.”
The study did not distinguish between women with anorexia nervosa, which is associated with amenorrhea and hormone imbalances, and women who were simply constitutionally thin, the authors noted. In addition, the study cohort was primarily white, so the study had limited power to assess whether the associations between body weight and early menopause varied by race or ethnicity, they said.
“In summary, our findings suggest that both overall and abdominal adiposity are non-linearly associated with risk of early natural menopause,” Szegda and colleagues said. “Women who were underweight in early or mid-adulthood, especially those who reported severe weight cycling, had higher risk for early menopause compared to lean-normal weight women. Additional prospective research is needed to understand how low adiposity may physiologically impact the timing of menopause.”
The study was funded by the National Institutes of Health.
No study authors reported relevant relationships with industry.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner