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Insufficient nutrition during fetal development may lead to early menopause

5 December 2018

Study demonstrates association between prenatal exposure to famine and early reproductive ageing

Previous studies have demonstrated that fetal malnutrition can lead to adult chronic disorders such as type 2 diabetes and coronary artery disease. A new study out of China now suggests that it also can lead to early menopause and premature ovarian failure. 

Infants are especially sensitive to changes in their environment while still in the womb, during their earliest stages of development. It has already been documented that the development of the hypothalamic-pituitary-gonadal axis during the fetal stage plays a critical role in adulthood reproductive health. Natural menopause is a milestone of ovarian aging that results in the end of a woman's reproductive years.

Although several studies have investigated the association between famine exposure in early life and risk of various metabolic diseases in adulthood, the association with reproductive aging was not evaluated. This new study involving nearly 2,900 Chinese women specifically sought to address the effect of early life exposure to famine on age at menopause.

The study concluded that prenatal famine was associated with a higher risk of early menopause (age younger than 45 years), as well as a higher risk of premature ovarian failure. Although study participants were born during China's infamous famine occurring between 1956 and 1964, the study provides valuable insights into the benefits of proper nutrition during early life stages for women of any culture.

Study results appear in the article "Early life exposure to famine and reproductive aging among Chinese women."

"The findings that natural menopause occurs earlier after prenatal famine exposure suggests that food deprivation during early fetal life affects how long the future ovaries function," says Dr. JoAnn Pinkerton, NAMS executive director. "For those women, if they are not taking estrogen therapy until the average age of menopause, their early menopause could be associated with increased risk of heart disease, osteoporosis, depression, and memory changes and changes in vaginal and sexual health."


Objective: To assess the effect of early life exposure to famine, as endured during 1959 to 1961 in China, on reproductive aging in adult women.

Methods: Between 2011 and 2012, 2,868 women born around the Chinese famine period (1956-1964) were enrolled in this study from three communities in China. Age at natural menopause was obtained retrospectively from a structured questionnaire. The associations of early life famine exposure with reproductive aging during adulthood were estimated, with adjustment of socioeconomic status, lifestyle factors, and body mass index.

Results: Women exposed to prenatal famine had a higher risk of early menopause (ie, natural menopause <45 years, odds ratio: 1.59, 95% confidence interval [CI]: 1.07, 2.36), and a nonsignificant trend of higher risk of premature ovarian failure (ie, natural menopause <40 y, odds ratio: 1.94, 95% CI: 0.93, 4.00), compared to unexposed women. Exposure to famine during childhood was not significantly associated with reproductive aging. In a secondary analysis focusing on the fetal exposure, prenatal famine exposure was associated with a higher risk of premature ovarian failure (odds ratio: 2.07, 95% CI: 1.08, 3.87), and a nonsignificant trend of higher risk of early menopause (odds ratio: 1.37, 95% CI: 0.98, 1.91), compared to those unexposed to prenatal famine.

Conclusions: Our study showed that fetal exposure to famine was associated with an increased risk of early menopause. Such findings provided evidence in favor of the thrifty phenotype theory in reproductive aging and helped better understand the etiology of early menopause.


 Wang N, Huang Y, Wen J, Su Q, Huang Y, Cai L, Lin W, Zong L, Huang H, Qian X, Zhu F, Sun H, Yao J, Tang K, Chen L, Liang J, Li L, Lin L, Lu J, Bi Y, Wang W, Zheng Y, Chen G1. Early life exposure to famine and reproductive aging among Chinese women. Menopause. 2018 Dec 3. doi: 10.1097/GME.0000000000001259. [Epub ahead of print] 

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