Consistent with our hypothesis, we found that long duration of both total and exclusive breastfeeding was associated with higher maternal ghrelin and pancreatic PYY levels at 3 years postpartum in a prospective cohort study, independent of other risk factors for metabolic disease. In contrast, we did not find that breastfeeding duration was independently associated with leptin levels, and there was no linear association of lactation with adiponectin. We further found no evidence that curtailed breastfeeding was associated with an adverse adipokine profile, suggesting that physiologic difficulties with lactation that might result in premature weaning are not themselves associated with maternal adipokine profile. This is the first study, to our knowledge, to measure the association between lactation and adipokine levels after weaning. Our results provide tentative evidence that longer lactation is associated with favorable changes in appetite regulation pathways that persist after weaning.
Our results confirm and extend earlier work relating breastfeeding to differences in maternal metabolic outcomes after weaning. In large epidemiologic studies, we and others have reported associations between longer duration of lactation and reduced risk of diabetes (1
), hypertension (8
), higher HDL cholesterol levels postweaning adjusted for preconception levels (5
), metabolic syndrome (6
), and cardiovascular disease (3
). The mechanism underlying this association is unknown. Lactation appears to mobilize adipose tissue accrued during pregnancy, and we have previously hypothesized that breastfeeding “resets” maternal metabolism after pregnancy, reducing disease risk (10
In this study, we did not find any association between lactation duration and maternal leptin levels, once we adjusted for pregravid BMI. It is likely that unadjusted associations between breastfeeding duration and leptin are confounded by maternal BMI. We also found no consistent association between lactation duration and adiponectin levels. Because leptin and adiponectin are adipocyte products, these results do not support the hypothesis that changes in adipose tissue endocrinology mediate associations between breastfeeding and maternal metabolic outcomes.
We found a modest direct association between breastfeeding duration and levels of ghrelin and PYY, two gut-secreted peptide hormones that regulate appetite through reciprocal effects on hypothalamic orexogenic and anorexigenic pathways (28
). In the fasting state, low PYY levels and high ghrelin levels stimulate hunger, whereas after feeding, PYY levels rise and ghrelin levels fall. Pardoxically, low ghrelin levels are associated with obesity, insulin resistance, hypertension, and type 2 diabetes in cross-sectional studies (13
). In a small study (n
= 18) of women at 4–5 weeks postpartum, Larson-Meyer et al. (29
) found slightly higher fasting levels of ghrelin in lactating versus nonlactating mothers (971.8 [208.9] vs. 798.8 [271.8] pg/mL), but this difference was not statistically significant. PYY did not differ between lactating and nonlactating women. Among five women in that study who exclusively breastfed, ghrelin levels did not change from baseline to 24 weeks postpartum, despite reductions in total body fat and BMI (29
). Ilcol et al. (30
) measured ghrelin concentrations during lactation in 16 women and found increases in total ghrelin from 0–3 to 4–14 days postpartum, followed by slightly lower but stable levels from 15 to 30 days postpartum. The same authors measured total ghrelin in a cross-section sample of 159 women and found stable levels from 15 to 180 days postpartum.
Rodent studies (31
) provide conflicting evidence regarding ghrelin’s role in energy balance during lactation; however, cows bred for milk production have higher plasma ghrelin levels and greater energy intake during lactation (33
). It is possible that long-term lactation and the associated negative energy balance induce changes in fasting ghrelin levels that persist after weaning, reducing the risk for metabolic disease. Alternately, women with higher baseline ghrelin levels may produce more milk, allowing them to continue breastfeeding longer. In this case, long breastfeeding durations would be a marker for reduced maternal metabolic risk.
Pancreatic PYY is an appetite-inhibiting peptide hormone secreted by the intestine in response to a meal (22
). Obese individuals secrete less PYY than normal-weight individuals, suggesting an impaired response to satiety cues. Unlike the leptin resistance that can develop with obesity, overweight individuals retain a normal appetite response to infused PYY. We found a direct association between the duration of lactation and fasting PYY levels. This difference could improve energy balance, leading to more weight loss or less weight gain among women with longer durations of lactation. In support of this speculation, we previously found that women in our cohort with ≥6 months of exclusive breastfeeding had a lower BMI and reduced pregnancy-associated weight retention at 3 years, compared with women who had never breastfed exclusively (34
When we measured the association between adipokine levels and curtailed breastfeeding, we found lower leptin and higher ghrelin levels among women who reported problems with milk supply, compared with women with curtailed breastfeeding who did not report supply problems. We acknowledge that we had only limited ability to capture biologic versus cultural or social reasons for weaning; however, our results do not support the hypothesis that difficulty with milk production is a marker for an adverse adipokine profile.
No other studies to our knowledge have measured associations between the duration of breastfeeding and ghrelin or PYY levels after weaning; however, there is tentative evidence that lactation is associated with long-term changes in other hypothalamic neuroendocrine pathways. During lactation, breastfeeding women have reduced autonomic and adrenal responses to stressors, compared with nonlactating postpartum control subjects (35
). Differences in hypothalamic-pituitary-adrenal activity may persist after weaning: Lankarani-Fard (40
) measured fasting cortisol levels among 749 postmenopausal women and reported higher levels among women with >12 months of lifetime lactation, compared with women with shorter durations of breastfeeding. Coupled with our finding of higher fasting ghrelin and PYY levels among women with longer lactation, these results suggest that lactation may have lasting effects on central neuroendocrine pathways.
Strengths of our study include its prospective assessment of maternal BMI, metabolic disease risk factors, and breastfeeding intention and duration; measurement of exclusive breastfeeding; measurement of multiple adipokines at 3 years; and our very high rate of breastfeeding initiation and continuation. We also faced several limitations, including the relatively small number of participants with fasting blood samples, which may have limited our power to detect subtle differences among duration categories. To maximize our power, we therefore modeled associations of adipokines with continuous as well as categorical measures of lactation duration.
Our study’s cross-sectional design also limits interpretation of results. Without prepregnancy measures of metabolic markers, we cannot determine whether lactation causes favorable changes in peptide hormone levels or whether more favorable profiles predispose to successful breastfeeding. Moreover, levels of measured adipokines are correlated, and our findings for PYY and ghrelin likely reflect interdependent mechanisms. In a cross-sectional, observational study such as ours, we cannot determine the causal direction of associations among adipokines. Nevertheless, our study is the first, to our knowledge, to measure adipokines after weaning, and our results provide evidence to support future, longitudinal studies. We also had limited information on hormonal contraception use at the time of the 3-year visit. However, adjustment for contraception among those for whom data were available did not alter our results, reducing the likelihood that more complete information would change our results. We also did not measure fat mass at the time of blood sample collection. Finally, false-positives are a concern, because we measured four different adipokines and performed multiple tests of association. However, our measures reflect specific hypotheses regarding pathways that are not independent, so statistical correction for multiple outcomes would be overly conservative.
In conclusion, in a prospective study of maternal and infant health, we found that longer duration of breastfeeding was associated with higher maternal levels of ghrelin and PYY at 3 years postpartum. These two gut peptides regulate appetite and are associated with reduced risk of metabolic disease. Our findings provide tentative evidence that changes in hypothalamic appetite regulation may mediate associations between longer lactation and reduced risk of maternal metabolic disease. Additional studies will be needed to confirm these findings in other populations and to determine whether these associations are causal.