Effects of the Timing of Sex-Steroid Exposure in Adolescence on Adult Health Outcomes

Abstract

Abstract Context Variation in pubertal timing is associated with a wide range of adult risks and outcomes, but it is unclear whether these associations are causal, and it is largely unknown whether these associations can be modified by treatment. Evidence Acquisition We conducted PubMed searches to identify Mendelian randomization (MR) studies on the influence of pubertal timing on adult health and studies on sex-steroid treatment of the following conditions associated with reduced reproductive endocrine function in adolescence: constitutional delay, Turner syndrome, and Klinefelter syndrome. Evidence Synthesis Results of MR studies suggest that earlier pubertal timing increases body mass index; increases risk for breast, ovarian, endometrial, and prostate cancers; elevates fasting glucose levels and blood pressure; impairs lung capacity and increases risk for asthma; leads to earlier sexual intercourse and first birth; decreases time spent in education; and increases depressive symptoms in adolescence. Later pubertal timing appears to lower bone mineral density (BMD). Although studies of constitutional delay have not shown that sex-steroid treatment alters adult height or BMD, studies of girls with Turner syndrome and boys with Klinefelter syndrome suggest that earlier initiation of sex-steroid treatment improves physical and neurocognitive outcomes. Conclusions Despite having some limitations, MR studies suggest that pubertal timing causally influences many adult conditions and disease risks. Studies of Turner syndrome and Klinefelter syndrome suggest that earlier sex-steroid exposure may have short- and long-term benefits. The mechanisms underlying these findings and the effects of trends and treatments affecting pubertal timing remain to be determined.