Effects of Pubertal Maturation on ACL Forces During a Landing Task in Females

Background: Rates of anterior cruciate ligament (ACL) rupture in young people have increased by >70% over the past two decades. Adolescent and young adult females are at higher risk of ACL injury as compared with their prepubertal counterparts. Purpose: To determine ACL loading during a standardized drop-land-lateral jump in females at different stages of pubertal maturation. Study Design: Controlled laboratory study. Methods: On the basis of the Tanner classification system, 19 pre-, 19 early-/mid-, and 24 late-/postpubertal females performed a standardized drop-land-lateral jump while 3-dimensional body motion, ground-reaction forces, and surface electromyography data were acquired. These data were used to model external biomechanics, lower limb muscle forces, and knee contact forces, which were subsequently used in a validated computational model to estimate ACL loading. Statistical parametric mapping analysis of variance was used to compare ACL force and its causal contributors among the 3 pubertal maturation groups during stance phase of the task. Results: When compared with pre- and early-/midpubertal females, late-/postpubertal females had significantly higher ACL force with mean differences of 471 and 356 N during the first 30% and 48% to 85% of stance, and 343 and 274 N during the first 24% and 59% to 81% of stance, respectively, which overlapped peaks in ACL force. At the point of peak ACL force, contributions from sagittal and transverse plane loading mechanisms to ACL force were higher in late-/postpubertal compared with pre- and early-/midpubertal groups (medium effect sizes from 0.44 to 0.77). No differences were found between pre- and early-/midpubertal groups in ACL force or its contributors. Conclusion: The highest ACL forces were observed in late-/postpubertal females, consistent with recently reported rises of ACL injury rates in females aged 15 to 19 years. It is important to quantify ACL force and its contributors during dynamic tasks to advance our understanding of the loading mechanism and thereby provide guidance to injury prevention. Clinical Relevance: Growth of ACL volume plateaus around 10 years of age, before pubertal maturation, meaning that a late-/postpubertal female could have an ACL of similar size to their less mature counterparts. However, late-/postpubertal females have higher body mass requiring higher muscle forces to accelerate the body during dynamic tasks, which may increase ACL loading. Thus, if greater forces develop in these females, in part because of their increased body mass, these higher forces will be applied to an ACL that is not proportionally larger. This may partially explain the higher rates of ACL injury in late-/postpubertal females.

Timing of pubertal development and midlife blood pressure in men and women: A Mendelian randomization study

Introduction Observational studies suggest earlier puberty is associated with higher adulthood blood pressure (BP), but these findings have not been replicated using Mendelian randomization (MR). We examined this question sex-specifically using larger genome-wide association studies (GWAS) with more extensive measures of pubertal timing. Methods We obtained genetic instruments proxying pubertal maturation (age at menarche (AAM) or voice breaking (AVB)) from the largest published GWAS. We applied them to summary sex-specific genetic associations with systolic and diastolic BP z-scores, and self-reported hypertension in women (n=194174) and men (n=167020) from the UK Biobank, using inverse-variance weighting meta-analysis. We conducted sensitivity analyses using other MR methods, including multivariable MR adjusted for childhood obesity proxied by body mass index (BMI). We used late pubertal growth as a validation outcome. Results AAM (beta per one-year later = -0.030 [95% confidence interval (CI) -0.055, -0.005] and AVB (beta -0.058 [95% CI -0.100, -0.015]) were inversely associated with systolic BP independent of childhood BMI, as were diastolic BP (-0.035 [95% CI -0.060, -0.009] for AAM and -0.046 [95% CI -0.089, -0.004] for AVB) and self-reported hypertension (odds ratios 0.89 [95% CI 0.84, 0.95] for AAM and 0.87 [95% CI 0.79, 0.96] for AVB). AAM and AVB were positively associated with late pubertal growth, as expected. The results were robust to sensitivity analysis using other MR methods. Conclusion Timing of pubertal maturation was associated with adulthood BP independent of childhood BMI, highlighting the role of pubertal maturation timing in midlife BP.

6-Month Subcutaneous Leuprolide Acetate Effectively Suppresses Clinical Signs of Puberty in Children With Central Precocious Puberty

Objective: Gonadotropin-releasing hormone (GnRH) agonists, such as intramuscular leuprolide acetate, triptorelin and the subcutaneous histrelin implant, are standard treatment for central precocious puberty (CPP). Implants require surgery and sometimes anesthesia, while frequent intramuscular injections can be painful. A shift to longer acting-formulations and subcutaneous injections has been proposed for the treatment of CPP. Therapies with convenient administration, prolonged duration of action and favorable safety profile may be beneficial, improving patient adherence. 87% of subjects achieved stimulated LH suppression to <4 IU/L by Week (W) 24 in a Phase III trial evaluating the efficacy and safety of the first6-month subcutaneous injectable in situ gel leuprolide acetate for CPP. We present secondary analyses of bone age (BA) advancement, weight, BMI, and pubertal maturation from this trial. Methods: 62 children (60 girls, 2 boys) with CPP (naïve to treatment) received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals, constituting the intent-to-treat population. Radiographs of the left hand and wrist were used to determine BA using the Greulich and Pyle method. BA was assessed by a blinded central reader. Rate of BA advancement was determined by the ratio of BA to chronological age (CA, BA/CA). Pubertal maturation was categorized with the Tanner staging system using breast development, external genitalia, and pubic hair. Safety outcomes were measured. Results: Mean age at onset of treatment was 7.5 ± 0.9 (SD) (range 4-9) years. BA/CA consistently declined throughout treatment, from 1.4 ± 0.2 at baseline, to 1.3 ± 0.1 at W24 and 1.3 ± 0.1 at W48. Although mean weight increased 8.7% from screening to W24 (34.8 kg vs 37.7 kg) and 16.9% from screening to W48 (40.4 kg), mean BMI remained stable throughout the study. The proportion of girls with early breast Tanner stage development (stage 1 and 2) increased from 9% at baseline to 37% at W48. The proportion of girls with late breast Tanner stage development (stage 4 and 5) decreased from 18% at baseline to 5% at W48. Both boys regressed from Tanner stage 3 to stage 2 for external genitalia development by W48. Tanner staging for pubic hair development remained stable for approximately 80% and decreased for 7% of children by W48. 52/53 treatment emergent adverse events were mild or moderate. Conclusions: 6-month 45 mg subcutaneous leuprolide acetate is a promising treatment for CPP. It effectively suppressed LH, suppressed clinical signs of pubertal maturation and demonstrated a good safety profile. It also has the beneficial features of subcutaneous administration, small injection volumeand twice a year dosing. This may be a welcome addition to the armamentarium given the proposed shift in CPP therapies towards longer-acting formulations and subcutaneous injections.

Characterization of pubertal development of girls in rural Bangladesh

This study aimed to describe the timing and patterns of pubertal maturation of girls living in rural Bangladesh. Starting in September 2015, a total of 15,320 girls from a birth cohort, aged 9 to 15 years at initial encounter, were visited twice at about a one year interval, typically in their birth month. Participants were asked to self-report extent of pubertal maturation, including breast development, pubic hair growth and age at menarche, if applicable. Pubertal stage (abbreviated as B2 and B3-4 for breast development and PH2 and PH3-4 for pubic hair growth) was assigned. Data from both visits were pooled, yielding a total of 29,377 age-related observations per pubertal characteristic. Probit regression models were used to estimate distributions of age at which each stage of pubertal development was attained. Before age 8, <3% of the study population initiated pubertal maturation as indicated by onset of breast development (B2). The median (95% confidence interval) age of B2 and B3-4 was 11.02 (11.00–11.04) and 12.82 (12.80–12.83) years, respectively; and 12.93 (12.91–12.94) and 14.29 (14.27–14.31) years for the onset (PH2) and advanced stage (PH3-4) of pubic hair growth, respectively. Median age at menarche was 13.17 (13.15–13.19) years, with 2.15 years of timespan from B2 to menarche. Girls in rural Bangladesh progressed through puberty following a well-documented sequence of sexual maturation stages. The age at which each pubertal milestone took place was somewhat later, but the tempo from breast development to menarche was comparable to that observed elsewhere. Our findings present a current norm of pubertal maturation in a typical, rural adolescent population in South Asia, which could help inform future studies and interventions to preserve or improve early adolescent health and development.

PRECOCIOUS PUBERTY AND PEER RELATIONSHIPS OF PREADOLESCENT GIRLS

This article discusses the relationship between precocious puberty and the peer relationships of preadolescent girls in public primary schools in Kiambu County, Kenya. This article is based on a case study of twelve selected public primary schools (representing the 12 constituencies) of Kiambu County, Kenya. The sample population was a total of four hundred and ten pre-teenage girls drawn from eight to twelve-year-old girls, and eight class teachers, who were purposively sampled from twelve randomly selected public primary schools in the study location. This was a mixed study that utilized both quantitative and qualitative data collection methods. The self-rating scale for pubertal maturation and the peer connectedness scale was used to assess for signs of precocious puberty and the quality of peer relationships respectively. In addition, structured interviews and focus group discussions were used to gather additional primary data. The instruments were pilot-tested on a sample of thirty-six respondents who were purposively sampled from three public primary schools in the sample location, and who were omitted from the actual study sample. The quantitative data was analysed using the Statistical Package for Social Sciences (SPSS) version 26, while the qualitative data was analysed using the content analysis approach. Analysed data was presented using both figures and tables. This study found a significant relationship (β=0.258, p=0.011) between precocious puberty and peer relationships among preadolescent girls. This was confirmed by the interview responses and the focus group narratives. The study concluded that earlier pubertal maturation led to strained peer relationships among preadolescent girls. This article recommends that forums to educate children on the stages of development and how to handle each of them be incorporated in the curriculum, to prepare girls for pubertal maturation whenever it occurs.

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study

AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9–10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study—a multi-site sample of 9–10 year-olds (n = 11,875)—and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child’s weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9–10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.