LEPTIN IS INVERSELY RELATED TO AGE AT MENARCHE IN HUMAN FEMALES

Over the last century there has been a trend toward an earlier onset o f menarche attributed to better nutrition and body fatness. With the d iscovery of the obesity gene and its product, leptin, we reexamined th is hypothesis from a new perspective. As delayed menarche and leanness are considered risk factors for osteoporosis, we also evaluated the r elation between leptin and bone mass. Body composition and serum lepti n levels were measured, and the timing of menarche was recorded in 343 pubertal females over 4 yr. Body composition was measured by dual x-r ay absorptiometry, and leptin by a new RIA. All participants were prem enarcheal at baseline (aged 8.3-13.1 yr). Leptin was strongly associat ed with body fat (r = 0.81; P < 0.0001) and change in body fat (r = 0. 58; P < 0.0001). The rise in serum leptin concentration up to the leve l of 12.2 ng/mL (95% confidence interval, 7.2-16.7) was associated wit h the decline in age at menarche. An increase of 1 ng/mL in serum lept in lowered the age at menarche by 1 month. A serum leptin level of 12. 2 ng/mL corresponded to a relative percent body fat of 29.7%, a body m ass index of 22.3, and body fat of 16.0 kg. A gain in body fat of 1 kg lowered the timing of menarche by 13 days. Leptin was positively rela ted to bone area (r = 0.307; P < 0.0001) and change in bone area (r = 0.274; P < 0.0001). A critical blood leptin level is necessary to trig ger reproductive ability in women, suggesting a threshold effect. Lept in is a mediator between adipose tissue and the gonads. Leptin may als o mediate the effect of obesity on bone mass by influencing the perios teal envelope. This may have implications for the development of osteo porosis and osteoarthritis.