Preconception Stress and the Secondary Sex Ratio A Prospective Cohort Study

Prospective longitudinal evaluation of preconception stress biomarkers in relation to the secondary sex ratio demonstrated a significant association between preconception cortisol concentration and decreased odds of a male birth.


Rebecca J. Chason, M.D., Alexander C. McLain, Ph.D., Rajeshwari Sundaram, Ph.D., Zhen Chen, Ph.D., James H. Segars, M.D., Cecilia Pyper, M.B., B.S., M.F.P.H., Germaine M. Buck Louis, Ph.D.

Vol 98, Issue 4, Pages 937-941



To study the association between salivary stress biomarkers and the secondary sex ratio.


Prospective, longitudinal cohort study.


Community setting in the United Kingdom.


Upon discontinuation of contraception for purposes of becoming pregnant, 338 women aged 18-40 years with complete data (90%) were followed until pregnant or up to six menstrual cycles.



Main Outcome Measures:

Secondary sex ratio.


Human chorionic gonadotropin (hCG) pregnancies were detected in 207 (61%) women and 130 (63%) delivered singleton infants with available gender data. The adjusted odds ratio for a male birth was decreased for women in the highest quartile (AOR = 0.26; CI = 0.09, 0.74) of salivary cortisol relative to women in the lowest quartile during cycle one. An inverse relation was observed between α-amylase and the 2˚sex ratio, though not statistically significant.


Our findings are consistent with a reversal in the 2 sex ratio with increasing preconception salivary cortisol concentrations. This relation suggests that activation of the hypothalamus-pituitary-adrenal axis may have implications in sex allocation and requires further study.

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