Insulin Resistance and Pubertal Changes

Abstract

Temporal changes (or secular trends) in the onset of menarche and pubertal maturation have been observed over the past two centuries.Europeanpopulationshaveshownmarkedreductionsintheage at menarche over the last 150 yr; the mean age at menarche was approximately16–17yrinthemid-19thcentury(1).InEasternEuropean countries, these decreases in age at menarche have occurred at a surprisingly consistent rate of around 1–3 yr for every 100 calendar years or 1–3.6 months per decade (2). A slower rate of decline for the timing of menarche has been reported in the United States. The National HealthExaminationSurveyreportedadropofabout2.5monthsinthe average age of menarche during the time period between 1963–1970 and 1988–1994 (3). More recently, the age of menarche in the NationalHealthandNutritionExaminationSurvey III (1988–1994)and National Health and Nutrition Examination Survey 1999–2002 reportedafurtherdeclinefrom12.5yrin1988–1994to12.3yrin1999– 2002 (4). Thus, these two national surveys indicate a decline in age at menarche of about 1 month per decade (approximately 1 yr for every 100 yr) in the United States. Reported differences in age at menarche across ethnic and racial groups indicate that Black girls on average experience menarche about 6 months earlier than White girls (4, 5). The mean menarcheal age in Black girls, however, is similar to the declineobserved inWhitegirls ( 6months)during the sameperiodof time. Girls with early menarche tend to be more obese and to have higher rates of cardiovascular risk factors as adults. A recent commentary by Slyper (6) provided an excellent summary of many of the key issues related to pubertal timing in American girls. He noted that insulin resistance “may be more prevalent in US children than previously recognized.” He raised concerns that such insulin resistance may be accompanied by dyslipidemia (elevated triglycerides and low high-density lipoprotein cholesterol) and accelerated atherogenesis. The Bogalusa, LA, study, a long-term community-based study of cardiovascular risk factors since childhood, reported that both White and Black adult women who reported an age of menarche before age 12 have, on average, greater weight ( 10 kg), body mass index ( 4 kg/m), and skin fold thicknesses ( 6 mm) than women who underwent menarche after age 13.5 yr. In addition, the women with earlier menarche had a higher prevalence of hypertension and increased cardiovascular risk profiles (5). In addition, Bogalusa investigators reported that early menarche is associated with increased prevalence of hypertension, dyslipidemia, and insulin resistance, and the estimated odds for developing metabolic syndrome in adulthood was 1.54 (95% confidence interval, 1.14–2.07), regardless of race (7). Thus, a history of early menarche appears to increase future risk of developing diabetes, hypertension, and cardiovascular disease. Data supporting this have also been reported by European investigators who reported a long-term follow-up investigation of Danish schoolchildren (7–9). The article by Casazza and colleagues (10) in this issue of JCEM investigates the determinants of pubertal transition in AfricanAmerican and European-American girls. In contrast to previous epidemiological surveys on pubertal changes and age of menarche that used population approaches and cross-sectional or longitudinal designs, this study is a prospective study and includes dualenergy x-ray absorptiometry to assess adiposity, insulin response to an iv glucose challenge to evaluate insulin resistance, and endocrine hormone levels. Overall, these methods provide more detailed assessments than what has been generally available. Casazza and colleagues’ (10) baseline data are based on findings in prepubertal girls at a mean age of 8 yr. They reported greater fasting insulin concentrations and evidence for more insulin resistance during an iv glucose tolerance test in Blacks compared with Whites. The Black girls subsequently experienced adrenarche approximately 0.8 yr earlier and menarche 0.9 yr earlier than their White counterparts. Multivariable regression analyses showed no relation between baseline levels of total fat mass, estrogen levels, and insulin resistance with age of menarche or between total fat mass estradiol levels and insulin levels or androgenic hormone levels dihydroepiandrosterone sulfate with adrenarche. On the other hand, Black race was significantly associated with greater insulin resistance during pubertal years (especially age 9–14 yr) and estradiol levels (generally age 7–13 yr) as well as lower age of both adrenarche and menarche. Even when adjusted for fat mass, Black girls tended to experience adrenarche and puberty earlier than White girls, and it is likely