Search

Purpose: To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls. Methods: Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis. Results: We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a significantly higher mean PI (mean, 6.70; SD, 2.15) than girls in initial puberty (mean, 4.14; SD, 1.55) and in late puberty (mean, 2.81; SD, 1.05) (P3.75 cm³ had a sensitivity of 73%, specificity of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty. Conclusions: The significant reduction in the PI during pubertal development combined with increasing uterine volume can be a valuable, highly specific, noninvasive tool to confirm the onset of puberty.

Purpose: This study aimed to evaluate the time interval to menarche after gonadotropin-releasing hormone agonist (GnRHa) treatment in females with central precocious puberty (CPP) and to identify factors contributing to timing of menarche.Methods: We retrospectively reviewed medical records of 39 females with CPP who reached menarche after GnRHa treatment (leuprolide or histrelin). CPP diagnostic criteria were breast development at

Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.

Precocious puberty is defined as the onset of secondary sexual characteristics before 8 years of age in girls and 9 years in boys. Central Precocious Puberty (CPP) is caused by early activation of the hypothalamic-pituitary-gonadal axis. Laboratory test of LH, FSH, and Estradiol is recommended for monitoring suppressive effects from GnRHa therapy in the early three months and every six months. This study aimed to report a case of CPP in a 3-year and 3-month-old girl. A 3-year and 3-month-old girl went to the hospital with vaginal bleeding (menstruation), breast development, and pubic and axilla hair for 7-month-old. Physical examination found moderately ill with obesity, body weight 20 kg, height 98 cm. Tanner stage was A2M3P2, café au lait was found in the left forehead with size 7x3.5 cm. In March 2015 before GnRHa therapy, LH, FSH and Estradiol level increased with levels of 4.32 mlU/mL, 6.01 mlU/mL, and 67 pg/mL, and after 3 months of the treatment was 0.87 mlU/mL, 2.51 mlU/mL and

Objectives In this study, we evaluated the concordance between the ultrasonographic stage of breast (US B) and Tanner stage of breast (TS B) for overweight and obese girls based on a school population study. Methods We conducted multistage, stratified cluster, and random-proportional sampling and ultimately included 221 girls (aged 6–10 years). Results This study revealed that the concordance was poor (accuracy=0.19 (95% confidence interval: 0.14, 0.25)) between US B and TS B among the 221 participants. When our subjects were stratified by weight, we observed a weak association between US B and TS B in the thin/normal weight group (r=0.34, p=0.001) but not in the overweight (r=0.097, p=0.38) or obese groups (r=–0.19, p=0.206), and as the body mass index (BMI) z-score increased, the overestimation ratio of TS B increased. US B manifested a positive correlation with breast bud diameter (BD) (r=0.885, p Conclusions As the BMI z-score increased, the correlation between the two methods declined, and the overestimation ratio of TS B increased. US B is an objective and quantitative method used to evaluate breast development, and whether BD might replace US B as a routine diagnostic method to evaluate breast development in clinical practice needs to be confirmed in larger-sample studies.

Substantial progress has been made in the treatment of Cystic fibrosis due to introduction of CFTR modulators. However, little is known about the long term side effects of treatment with these drugs. We here present a 7 year old girl with CF who presented with breast development as a rare dose dependent side effect of treatment with ivacaftor and we report data on the correlation between drug plasma concentration and clinical effect, bodyweight, and BSA in 16 patients. Higher plasma concentrations did not correlate with clinical effect, as change in FEV1 and sweat chloride concentration. Patients with low bodyweight or BSA tended to have higher plasma concentrations. This might indicate that the current recommended dose of ivacaftor is at the top of the dose-response curve and that some patients can be treated with lower doses of ivacaftor with similar clinical effect.

Objectives There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic–pituitary–gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. Methods Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. Results After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group’s basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). Conclusions In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

Breast tissue undergoes a series of changes from birth to puberty. The majority of the changes are transient, related to physiological hormonal changes. Although the breast is identical in both sexes at birth, its histology and development will eventually differ. It is important for radiologists to have a basic understanding of endocrinological changes and appearance on imaging to avoid potential pitfalls, particularly on ultrasound, which is the primary modality used to evaluate the breast.

Background. Breast cancer is one of the four types of cancer among women and is the most frequently diagnosed in most countries. Breast cancer occurs due to DNA damage and genetic mutations affected by exposure to estrogen, inheritance of damaged DNA, or pro-cancer genes such as BRCA1 and BRCA2. Therefore, a family history of ovarian cancer or breast cancer increases the risk of developing breast cancer. The embryo of the breast develops around the age of 6 weeks of pregnancy. Similar to breast development, fingerprint patterns also develop during the 6-13 weeks of pregnancy. Thus, the genetic message contained in the genome occurred during that period and was reflected in the dermatoglyphic pattern.Methods. The literature search was systematically used using PubMed, Cochran, Google scholar, and other Gray literature between 2010-2020. Of the 69 publications identified, 21 met the criteria and were included in the review. The review is carried out following the provisions of PRISMA (Preferred Reporting Items for Systematic Review).Results. This systematic review showed fairly consistent findings in breast cancer patients who tended to have more whorl fingerprint patterns and larger ATD angles. For radial loops, ulnar loops and arches were minor compared to the control group potential as an initial screening tool in at-risk groups.Conclusion. Long-term and follow-up studies with larger sample sizes in various ethnicities are needed to validate dermatoglyphics in anthropometric measurements as a promising marker of breast cancer.

Objectives We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy. Case presentation Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy. Conclusion Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.

Background There are many factors that lead to dwarfism, and the mechanism has not yet been elucidated. Next-generation sequencing may identify candidate-related gene mutations, which may clarify the molecular cause. Aim To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations. Methods Physical and laboratory characteristics, including clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1), IGF binding protein 3, other related tests, imaging examination, and chromosome karyotyping, were analyzed. Next-generation sequencing was performed to analyze pathogenicity variability. Results In the 39 dwarfism patients, 10 had pathogenicity variability. Gene variation was found in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes. Of the 10 patients with pathogenicity variability, the related physical characteristics included double breast development and growth hormone deficiency, enuresis and indirect inguinal hernia on the left, two finger distance of 70.2 cm, head circumference of 49.2 cm, ischium/lower body length of 1.8 cm, weak limb muscles, and partial growth hormone deficiency. After 6 mo of growth hormone therapy, the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2 ± 170.3 to 285.0 ± 166.0 and 3.9 ± 1.4 to 4.2 ± 1.1, respectively. Conclusion OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes may be related to the incidence of dwarfism, and more research needs to be performed to elucidate the mechanism.

To investigate the prevalence of precocious puberty in school-based population in Zhongshan, Guangdong, China. We recruited a total of 4058 students in grades 1–3 using a multistage stratified cluster random sampling method in a population-based cross-sectional study. We evaluated height, weight, and development of breast and pubic hair in girls, breast development was evaluated by inspection and palpation combined with ultrasound detection for overweight and obese girls, and testicular volume and development of pubic hair in boys. We estimated overall, sex-, age, and district-specific prevalence of precocious puberty and examined the association between prevalence of precocious puberty and body mass index (BMI). The unadjusted and adjusted prevalence of precocious puberty by Tanner stage was 4.74% (girls:8.78%, boys:2.58%) and 6.19% (girls:11.47%, boys:3.26%), respectively. In both urban and suburban areas, the prevalence of precocious puberty was higher in the overweight and obese group than in the normal-weight group (p

Context Breast development is important for most trans women. An important limitation of current breast development measurement methods is that these do not allow for 3D volume analyses. Objectives To examine breast development and change in anthropometry during the first 3 years of gender-affirming hormone treatment using 3D imaging. Associations with clinical or laboratory parameters and satisfaction with the gained breast development were also studied. Design Prospective cohort study. Setting Specialized tertiary gender identity clinic in Amsterdam, the Netherlands. Participants Participants were 69 adult trans women with a median age of 26 years (interquartile range, 21-38). Interventions Gender-affirming hormone treatment. Main Outcome Measures Volumetric and anthropometric breast development and satisfaction. Results Breast volume increased by 72 cc (95% confidence interval [CI], 48-97) to 100 cc (standard deviation 48). This resulted in a cup-size Conclusions Sustained breast growth and development during hormone treatment was observed during the full 3-year observation period. The breasts of trans women are positioned more laterally and caudally on the chest compared with cis women. Although modest breast volumes were observed, breast development was satisfactory to most trans women.

Objectives To identify the most eagerly anticipated change resulting from hormone therapy using gender-affirming hormones for patients with gender incongruence undergoing a clinical trial. Methods Patients diagnosed with gender identity disorders based on the International Classification of Diseases 10th revision classification at three institutions in Japan for whom hormone therapy using gender-affirming hormones was initiated were analyzed. They were asked what the most anticipated change was due to gender-affirming hormone that they had thought of between giving informed consent and the first administration of the drug. Results The responders were 336 transgender men who were administered androgens and 48 transgender women who received estrogens. The median age at commencement of hormone therapy was 24 years for transgender men and 28 years for transgender women. For transgender men, the most frequent answer was cessation of menses (52.7%) followed by a deepened voice (32.4%). For transgender women, breast development (35.4%) was the most anticipated change, followed by gynoid fat deposition (29.2%). Conclusions Cessation of menses in transgender men and breast development/gynoid fat deposition in transgender women might represent primary end-points in clinical trials evaluating the efficacy of hormonal treatment in these patients.

A disorder of sex development (DSD) is defined as a congenital condition in which development of chromosomal, gonadal, or anatomical sex is atypical. Swyer syndrome is an example of 46,XY DSD with a female phenotype. It usually becomes apparent in adolescence with delayed puberty and amenorrhoea. Spontaneous breast development is very rare. A 15-year-old girl was presented due to primary amenorrhoea with breast development compatible with Tanner stage V. Hormonal tests revealed hypergonadotropic hypogonadism with low level of oestradiol. Pelvic ultrasound and magnetic resonance imaging revealed a small uterus, and no ovaries were found. In the right lower abdomen, a structure of unknown origin was visible. The chromosome analysis revealed a 46,XY karyotype. The patient was qualified for a laparoscopic bilateral gonadectomy. Postoperative histopathological examination revealed gonadoblastoma. We underline the need to consider DSD 46,XY in the presence of primary amenorrhoea, even when pubertal development is present. Germ cell tumors have a tendency to grow and metastasize rapidly. Delayed diagnosis may increase the risk of malignant transformation and cause a poor diagnosis.Zaburzenia różnicowania płci polegają na niezgodności płci genetycznej i gonadalnej z fenotypem zewnętrznych narządów płciowych. Zespół Swyera jest przykładem DSD z kariotypem 46,XY i żeńskim fenotypem. Rozpoznanie jest ustalane głównie w wieku nastoletnim w związku z diagnostyką pierwotnego braku miesiączki i opóźnionego pokwitania. Prawidłowy rozwój piersi występuje u tych pacjentek niezwykle rzadko. Piętnastoletnia dziewczyna została przyjęta w celu diagnostyki pierwotnego braku miesiączki. W badaniu fizykalnym rozwój piersi wg skali Tannera oceniono na M5. W badaniach hormonalnych stwierdzono cechy hipogonadyzmu hipergonadotropowego z małym stężeniem estradiolu. W badaniu ultrasonograficznym i rezonansu magnetycznego miednicy małej zobrazowano małą macicę, brak prawidłowych jajników. W podbrzuszu prawym widoczna była struktura niewiadomego pochodzenia. W badaniu cytogenetycznym stwierdzono kariotyp męski – 46,XY. Pacjentka została zakwalifikowana do zabiegu usunięcia gonad. W pooperacyjnym badaniu histopatologicznym stwierdzono gonadoblastoma. Prezentowany opis przypadku podkreśla konieczność wzięcia pod uwagę zespołu Swyera w diagnostyce pierwotnego braku miesiączki, nawet w przypadku obecności drugorzędowych cech płciowych. Należy pamiętać, że nowotwory germinalne mogą szybko rosnąć i dawać przerzuty. Opóźnienie właściwego rozpoznania może zwiększać ryzyko zezłośliwienia nowotworu i niekorzystnie wpłynąć na rokowanie.

Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as “premature adrenarche.” It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene. Learning Objectives Identify the precise pathophysiologic mechanisms leading to virilization in girls at puberty considering that virilization at puberty may be the first manifestation of an endocrine active tumor or a disorder/difference of sex development (DSD) that remained undiagnosed before and may be life-threatening. Of the DSDs, nonclassical congenital adrenal hyperplasia occurs most often. Provide a step-by-step diagnostic workup plan including repeated and expanded biochemical and genetic tests to solve complex cases. Manage clinical care of a girl virilizing at puberty using an interdisciplinary team approach. Care for complex cases of DSD manifesting at puberty, such as the presented girl with a Turner syndrome-like phenotype and virilization resulting from a complex genetic variation.

Progesterone (Pg) is a pregnancy-related hormone that prepares the endometrium for the implantation of the fertilized zygote and suppresses myometrial contractility for the maintenance of pregnancy. At high concentrations, it acts as a natural immunosuppressant avoiding the rejection of a half allogeneic foetus. It is the precursor of many other related steroid hormones, but what is its role in the human breast? In this chapter, we will discuss some aspects related to Pg and its role in breast development and in the neoplastic disease. Understanding the mechanisms related to Pginduced effects in the normal and neoplastic mammary gland will light the way to exploit this hormone signalling pathway therapeutically. We will introduce some aspects of the effects of progestins in normal breast development, breast cancer risk and in neoplastic growth, and we will describe ongoing clinical trials in breast cancer using progestins or antiprogestins. Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Earlier pubertal development is only partially explained by childhood body mass index; the role of other factors, such as childhood infections, is less understood. Using data from the LEGACY Girls Study (North America, 2011–2016), we prospectively examined the associations between childhood viral infections (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) 1, HSV2) and pubertal timing. We measured exposures based on seropositivity in premenarcheal girls (n = 490). Breast and pubic hair development were classified based on mother-reported Tanner Stage (TS) (TS2+ compared with TS1), adjusting for age, body mass index, and sociodemographic factors. The average age at first blood draw was 9.8 years (standard deviation, 1.9 years). The prevalences were 31% CMV+, 37% EBV+, 14% HSV1+, 0.4% HSV2+, and 16% for both CMV+/EBV+ coinfection. CMV+ infection without coinfection was associated with developing breasts an average of 7 months earlier (hazard ratio (HR) = 2.12, 95% confidence interval (CI): 1.32, 3.40). CMV infection without coinfection and HSV1 and/or HSV2 infection were associated with developing pubic hair 9 months later (HR = 0.41, 95% CI: 0.24, 0.71, and HR = 0.42, 95% CI: 0.22, 0.81, respectively). Infection was not associated with menarche. If replicated in larger cohorts with blood collection prior to any breast development, this study supports the hypothesis that childhood infections might play a role in altering pubertal timing.

BackgroundEarlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort.MethodsWomen ages 35–74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure.ResultsDuring follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03–1.46 for ConclusionsEarlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.

We aim to report outcomes and safety with hormonal suppression to facilitate gonadal preservation in a select group of patients with 46,XY differences in sex development (DSD) who are raised and identify as female yet have diagnoses with potential for androgenization at puberty. We performed a retrospective review of the past 10 years of DSD patients treated by a multidisciplinary program. Inclusion criteria were 46,XY DSD, female sex of rearing, risk of androgenization at puberty, and plan for hormonal suppression at puberty. Patients on hormonal suppression had at least 6 months of follow-up from initiation. We excluded those with complete gonadal dysgenesis or complete androgen insensitivity. Four patients met inclusion criteria. Initial evaluation by DSD team was at a mean age of 6.6 years (3 weeks–16 years). All patients were evaluated in a coordinated multidisciplinary clinic. The diagnoses are listed in Table 1. Mean follow-up was 5.7 years (1.2–10.9 years). One patient presented as an infant, and is being monitored until Tanner stage 2 and/or serum hormonal evidence to initiate hormonal suppression. Three patients have been receiving hormonal suppression for 1.4 years (1.1–1.9 years) without side effects or complication. Three patients were initiated with estrogen replacement to promote desired breast development. At last follow-up, all patients had retained their gonads, all have female gender identity with no reported gender dysphoria, and no progression of androgenization. In our initial experience, gonadal preservation with hormonal suppression is a tool in multidisciplinary management of select DSD patients with female gender identity with conditions associated with androgenization at puberty. Patients’ growth, bone health, and overall psychosocial well-being will need to be monitored closely.

Background Body-image dissatisfaction among children and adolescent has become increasingly serious, and may be the result of staged differences in the puberty-development process. The aim of this study was to compare differences in body-image dissatisfaction among children and adolescents at different pubertal stages. Methods A total of 574 students aged 8-15 years were recruited from two nine-year schools via stratified cluster sampling, their secondary sex characteristics and external genital development examined, and body-image cognition surveyed using the teenage body-image annoyance questionnaire. This questionnaire covers body-shape, gender, sexual organ, and appearance dissatisfaction. Lower scores indicate a more negative body image. Results Total, gender, and appearance-dissatisfaction scores in girls were significantly lower than in boys (P

BACKGROUND The earliest onset of puberty had shifted downward, which may be due to the role of early growth and development factors in childhood. METHODS All of 1575 Kindergarten Two (K2) children from Anhui province, China were followed up to elementary school. Girls (n = 342) with available data on AR and breast development were included for this analysis. Polygenic risk score (PRS) was computed based on 17 single nucleotide polymorphisms for early puberty. Accelerate failure time (AFT) model was used to describe thelarche timing by early AR among girls with different polygenic susceptibility. RESULTS After adjustment for perinatal anthropometric, household income, parental education and prepuberty BMI-Z score, puberty started 4.12-month earlier in early AR girls compared with normal AR girls (TR: 0.96; 95% CI: 0.95, 0.98, p

Context In trans women, hormone treatment induces feminization; however, the degree of feminization varies from person to person. A possible contributing factor could be estrone, a weak estrogen that interferes with the estrogen receptor. Objective We assessed whether estrone is involved in feminization induced by hormone treatment. Methods This prospective cohort study, with follow-up of 1 year, included 212 adult trans women at a gender identity clinic, who were starting gender-affirming hormone treatment between July 2017 and December 2019, median age 25 years. Change in fat percentage and breast development were assessed. Results After 12 months of hormone treatment, estrone concentration was 187 pmol/L (95% CI, 153-220) in transdermal and 1516 pmol/L (95% CI, 1284-1748) in oral estradiol users. Fat percentage increased by 1.2% (interquartile range [IQR], 0.3-4.8) in transdermal and 4.6% (IQR, 2.5-5.9) in oral estradiol users. This was not associated with estrone concentrations in transdermal (+4.4% (95% CI, −4.0 to 13) per 100 pmol/L increase in estrone concentration) nor in oral estradiol users (−0.7% [95% CI, −1.7 to 0.3]). Breast volume increased by 69 mL (IQR, 58-134) in transdermal and 62 mL (IQR, 32-95) in oral estradiol users. This was not associated with estrone concentrations in transdermal (+14% [95% CI, −49 to 156] per 100 pmol/L increase in estrone concentration) nor oral estradiol users (+11% [95% CI −14 to 43]). Conclusions Change in fat percentage and breast development in trans women were not associated with estrone concentrations nor with administration route. Therefore, measurement of estrone concentrations does not have a place in the monitoring of feminization in trans women.

Androgen insensitivity syndrome (AIS) is a rare condition caused by an X-linked mutation of the androgen receptor with an estimated incidence of 1–5 per 100,000 individuals. Varying degrees of presentation exist for complete, partial, or mild depending on the severity of androgen resistance. Patients with complete AIS (CAIS) are born phenotypically female but have male XY chromosomes and testes instead of ovaries. They exhibit normal secondary female sex characteristics such as breast development and external female genitalia but lack a uterus and other Mullerian duct structures due to testicular production of Mullerian-inhibiting factor (MIF). Due to androgen-resistance, androgen-dependent Wolffian duct products fail to develop such as the epididymis, vas deferens, and the seminal vesicles. These patients often present either during infancy with inguinal hernias or sublabial masses, or during adolescence with primary amenorrhea. On physical exam, they will typically have normal breast development, lack pubic or axillary hair, and will have a blind-ending vaginal pouch of varying vaginal lengths. Diagnostic work-up is often conducted using ultrasound or MRI, serum hormone levels, and karyotype analysis. For patients with CAIS, their testes can be located within the inguinal canal, sublabially or intra-abdominally. Following puberty, patients with intra-abdominal testes are at a 15% increased risk (range 0–22%) of developing germ cell tumors (GCT). Management consists of prophylactic gonadectomy with subsequent hormone replacement therapy (HRT) to maintain normal pubertal development and promote adequate bone health. The debate regarding the timing of prophylactic gonadectomy is ongoing with some patient support groups arguing against gonadectomy citing concerns with long-term hormone therapy and the desire to preserve fertility. The current convention promotes delaying gonadectomy until after physiologic puberty has been achieved as the risk of developing prepubertal GCT is relatively low (0.8–2%). We outline the presentation, diagnosis, intraoperative techniques, and postoperative considerations for managing CAIS via bilateral laparoscopic gonadectomy.

Objective To describe the case of a 17-year-old transgender boy who experienced breast development while on testosterone, having been suppressed with a gonadotropin-releasing hormone (GnRH) agonist prior to testosterone therapy Case report A 17-year-old transgender boy presented with breast development after having been on a GnRH agonist and then testosterone since the age of 11 years, having never experienced breast development before, which was consistent with pubertal gynecomastia. A small decrease in the testosterone dose resulted in a significant reduction of gynecomastia. Despite the improvement, he went on to undergo chest surgery with the removal of the breast tissue. Discussion Pubertal gynecomastia is a common phenomenon in the cisgender male population. However, it has not been previously described in transgender boys. The potential mechanisms for its occurrence were discussed. Conclusion Transgender boys who undergo GnRH agonist treatment for puberty suppression and subsequently receive testosterone therapy for puberty induction may develop gynecomastia. Judicious adjustment of the testosterone therapy may lead to an improvement.

Fibroadenomas are one among the foremost common benign tumors of the breast within the adolescent population. They account for 68% of all breast plenty and 44%–94% of all biopsied breast lesions. Fibroadenomas can vary from well masses to painful and speedily growing tumors which will cause vital esthetic distortions of the breast. Given the prevalence of fibroadenomas in the adolescent population and also the psychosocial morbidity of finding a mass in the adolescent breast, it's imperative for physicians treating adolescent patients to be acquainted and up to this point with this sickness process. The goal of this text is to produce a brief review of the classification, etiology, symptoms, initial work-up, and update on the management of breast fibroadenomas within the adolescent population by a proper homoeopathic miasmatic reportorial approach.

Central precocious puberty (CPP) is defined by the appearance of secondary sexual signs in girls younger than 8 years of age or the onset of menarche before the age of 10. Gonadotropin-releasing hormone analogs (GnRHa) are the most effective therapy in CPP. Drug-induced hypersensitivity vasculitis is an inflammation of blood vessels due to the use of several pharmacologic agents. We present the first pediatric case of vasculitis induced by Decapeptyl. 7 years and 3 months old girl admitted to Pediatric Endocrinology outpatient clinic with a complaint of premature breast development. The patient diagnosed CPP with her physical examination and laboratory findings and tripoteline acetate (Decapeptyl) treatment initiated. She experienced multiple rushes on her body with a mild abdominal pain and high temperature after 8 hours from the second dose of Decapeptyl administration. She hospitalized with the diagnosis of drug-induced vasculitis and single dose of iv metyl-prednisolone 1 mg/kg treatment and oral cetirizine initiated. Her blood and urine analysis revealed no other organ involvement rather than skin. On the third day, all the purpuric lesions started to resolve and completely disappeared on the 6th day. Hereby, we described first pediatric case of CPP experiencing vasculitis due to tripotelin injection. Her treatment for PCC was switched to Depot Leuprolide acetate and she continued her treatment for 2 years uneventfully. It should be kept in mind that in pediatric PCC patients who develop side effects like cutaneous vasculitis, the treatment may be continued by changing the preparation.

Objective: Contrast-enhanced brain magnetic resonance imaging (MRI) is routinely performed in children with central precocious puberty (CPP). We evaluated the value of a dedicated sellar MRI protocol without contrast enhancement in girls with CPP. Subjects and methods: This study included 261 girls diagnosed with CPP. We performed sellar MRI scanning without gadolinium enhancement of the hypothalamic-pituitary area (HPA) at the pituitary level, including additional T2-weighted imaging of whole-brain scans to check for other lesions. We evaluated the prevalence of intracranial lesions via this MR protocol. In addition,the correlation between the clinical parameters and morphology of the pituitary gland on the images was assessed. Results: Intracranial lesions were detected in 17 (6.5%) of the 261 girls. Of the 17 girls with abnormalities, 16 (94.1%) had findings in brain areas other than the HPA. The weight, height, Tanner stage of patients were significantly (p < 0.05) higher in the group with greater pituitary height. Patient weight and height, Tanner stage of breast development, and luteinizing hormone (LH) levels were significantly (p < 0.05) greater in those with a higher pituitary grade as determined on sellar MRI. Conclusion: A dedicated unenhanced sellar MRI protocol provides valuable information on brain lesions and pituitary morphology. We found a significantly low prevalence of brain lesions among girls with CPP. Analysis of the height or shape of the pituitary gland on sellar MRI revealed significant correlations with the weight, height, Tanner stage, and LH levels of the patients.

Turner syndrome has an incidence of 1/ 2500 female live births. Clinical signs such as lymphoedema in childhood, as well as short stature and delayed puberty, are common reasons for screening for Turner syndrome. Almost all affected females experience ovarian failure. We present a 15-year-old female with short stature and delayed puberty. Her mother remembered noticing swelling in both hands and feet as a child but made no sense of it. The patient's weight and height were both below the third percentile, and she exhibited no secondary sexual characteristics. The diagnosis was confirmed by the patient's karyotype (45, XO).Her serum estradiol level was low, her uterus was small, and her ovaries were atretic. Primarin was used to stimulate puberty for two years, during which she gained 3kg of weight, 4cm of height, and breast development from Tanner stage 1 to 4. Clinicians must be on the lookout for common clinical signs of Turner syndrome in order to make an early diagnosis, refer, and manage affected children for optimal growth and development.

Simple Summary Primary prevention approaches are urgently needed to curb the growing global breast cancer burden. Mammographic density, also known as breast density, is one of the most significant and common independent risk factors for breast cancer. As such, it is an exciting new potential target to reduce the incidence of breast cancer; we could in the future identify women with high mammographic density at an increased risk of breast cancer and take steps to reduce that risk. However, more research is needed to understand the biological mechanisms that underlie high mammographic density and how these might be used to develop new prevention strategies. Here, we review the current knowledge around the biology of mammographic density with a particular focus on immune system factors that could provide new therapeutic targets. Abstract Mammographic density is an important risk factor for breast cancer; women with extremely dense breasts have a four to six fold increased risk of breast cancer compared to women with mostly fatty breasts, when matched with age and body mass index. High mammographic density is characterised by high proportions of stroma, containing fibroblasts, collagen and immune cells that suggest a pro-tumour inflammatory microenvironment. However, the biological mechanisms that drive increased mammographic density and the associated increased risk of breast cancer are not yet understood. Inflammatory factors such as monocyte chemotactic protein 1, peroxidase enzymes, transforming growth factor beta, and tumour necrosis factor alpha have been implicated in breast development as well as breast cancer risk, and also influence functions of stromal fibroblasts. Here, the current knowledge and understanding of the underlying biological mechanisms that lead to high mammographic density and the associated increased risk of breast cancer are reviewed, with particular consideration to potential immune factors that may contribute to this process.

Breast cancer (BrCa) as one of the major malignancies threatening women's health worldwide occurs due to the genetic and environmental interactions. Epidemiological studies have suggested that exposure to endocrine disrupting chemicals (EDCs) can elevate the risk of breast cancer. Di-(2-ethylhexyl)-phthalate (DEHP) and bisphenol A (BPA) are known as two typical EDCs. Although several studies have implied that there appear to have adverse effects of exposure to BPA or DEHP alone on breast development, no study to date has demonstrated the exact toxic effect of combined exposure to DEHP and BPA on breast tumorigenesis. In the present study, we performed an in vivo experiment including 160 female Sprague-Dawley (SD) rats, in which 80 rats were randomly allocated to 4 groups including control group given to normal diet, DEHP (150 mg/kg body weight/day), BPA (20 mg/kg body weight/day), and DEHP (150 mg/kg body weight/day) combined with BPA (20 mg/kg body weight/day) by gavage for 30 weeks. Additionally, a DEN/MNU/DHPN (DMD)-induced carcinogenesis animal model was also established to assess their effect on tumor promotion. Namely, the other 80 SD rats were separated into another 4 groups: in addition to DMD initiation each group treated with vehicle, DEHP, BPA and the combination of BPA and DEHP respectively. Our data demonstrated that BPA alone or in combination with DEHP may induce hyperplasia of mammary glands, including the proliferation of ductal epithelial cells and an increase in the number of lobules and acinus after a 30-week exposure. Notably, co-exposure to DEHP and BPA increased the incidence and reduced the latency of mammary tumor, which seemed to enhance the susceptibility of carcinogens-induced tumor. Mechanistically, our results supported the hypothesis that exposure to BPA and DEHP might promote breast cancer dependent on Esr1 and HDAC6 as pivotal factors, and further lead to the activation of oncogene c-Myc. Our study suggested that BPA combined with DEHP facilitate the occurrence of mammary tumors, which contributed to advance our understanding in the complex effects of compound exposure to endocrine disrupting chemicals.

Precocious puberty refers to the appearance of signs of puberty at an earlier age than is considered normal. It occurs ten times more commonly in girls than in boys. The overall incidence ranged from 1/5000 to 1/10,000 children. The cause is idiopathic in 90% of cases of female precocious puberty. We present BA a 24 month old female toddler who presented with one year history of progressive breast development and 6 month history of pubic hair growth. There was associated increasing weight, height and vaginal secretion. There was no similar occurrence in the family. Mother attained menarche at 14 years of age. Essential finding at presentation revealed a toddler who is heavy and tall for age with a weight of 17kg (>95th percentile for age and sex), height of 90.5cm (90th percentile for age and sex), Occipito-frontal circumference of 49cm (normal). Her sexual maturityrating was Tanner stage 3 for breasts and stage 2 for pubic hair. An assessment of precocious puberty was made. Her investigation result showed an advanced bone age of 5 years; elevated serum gonadotrophins in the pubertal range; and essentially normal cranial CT. Abdomino-pelvic USS showed an enlarged uterus for age, and a dominant right follicle with internal echo measuring 17.1mm X 15.2mm. Parents were counseled on the need for treatment to arrest the progression of precocious puberty but yet to respond because of financial constraint after 2 years of diagnosis. Female precocious puberty is ten times more common than male precocious puberty. The aetiology is idiopathic in 90% of cases and It is amenable to treatment. Integration of the investigation and treatment of childhood endocrine disorders into the National Health Insurance scheme will be a great panacea to the challenge of prompt management in developing countries. Keywords: Precocious, puberty, 24 months old, female, idiopathic, poverty, Nigeria

BackgroundPuberty is the period of human growth and development. To determine the onset of puberty with regards to the effect of higher adiposity, together with growth parameters of the participants at various stages of sexual maturity for both sexes.MethodsThe study was conducted on 1944 children (8–16) years; 1022 girls (52.6%) and 922 boys (47.4%) were taken at random. Pubertal assessment was done using Tanner staging that assigned breast development in females and pubic and axillary hair in males and females. Testicular volume was recorded using a Prader orchidometer. Height, weight, body mass index (BMI), body mass (BM) fat, body fat percentage, through applying a body impedance analyzer, and others were recorded.ResultsThe mean ages at the onset of puberty for females and males in our study were 10.29 ± 1.1 and 11.34 ± 1.02 years, respectively. Pubic hair (stage PH2) was attained at mean age of 10.72 ± 0.84 and 11.98 ± 1.03 years for females and males, respectively. For axillary hair (stage AH2), the mean age was 12.47 ± 0.68 years for females and 13.8 ± 0.58 years for males. The mean age at menarche was 12.41 ± 0.65 years. In concordance to BM fat and percentage, all pubertal stages started earlier in females with BMI ≥85th percentile comparable to females within average BMI. As for males, no significant relation was noted between mean pubertal ages and BMI values.ConclusionsA significant association of mean ages of Tanner stages to excess weight especially in females warranted the increasing awareness about health care, nutritional aspects, and living circumstances.

Exposure to phthalate derivatives has adverse effects on the health and development of humans, especially for children. A growing body of evidence supports the idea that exposure to phthalates can change an individual's physiological set point and the time of puberty in both genders. In this systematic review and meta-analysis, recent studies were evaluated to obtain systematic and regulation results in relation to puberty status and phthalate exposure in girls and boys. We searched English-language papers using Scopus, ISI, and PubMed databases as search engines, with no restriction of time, until the end of July 2019. A comprehensive literature search for an association between phthalate exposure and signs of puberty as well as levels of different types of hormones was carefully performed. Of the 67 studies retained for full-text screening, 39 studies were eligible for data management and extraction. For conducting a meta-analysis, four studies had appropriate effect size and metrics for pooling in the meta-analysis. Our findings revealed that low and high exposure to phthalates could alter pubertal development in both genders; the effects were either early or delayed puberty such as changes in the pubarche, thelarche, and menarche time, as well as in testicular volume. We statistically analyzed the association of pubic-hair development, breast development, and menarche time with exposure to phthalates in girls. For example, the pooled odds ratios of mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) in relation to breast development were (OR: 1.48, 95% CI: 1.11–1.85) and (OR: 1.52, 95% CI: 1.15–1.58) (P-value < 0.001), respectively. In addition, we analyzed the correlation between pubic-hair development and testicular volume with exposure to phthalates in boys. To the best of our knowledge, this is the first systematic review and meta-analysis of its kind for girls and boys. In conclusion, we found that a positive association exists between phthalate exposure and pubertal timing in the pediatric age group. Therefore, prevention of exposure to phthalates and reduction of their use should be underscored in the strategies for primordial prevention of pubertal timing and related consequences.

Background: A random ultrasensitive luteinizing hormone (LH) (LH-ICMA) ≥0.3 mIU/L is highly accurate in confirming a diagnosis of central precocious puberty (CPP). However, a prepubertal value does not exclude the diagnosis. The clinical differences between patients with CPP who have a pubertal versus prepubertal LH-ICMA have not been clearly defined. Furthermore, there is minimal information regarding the utility of this test in boys with CPP. The objective of this study was to analyze differences between patients diagnosed with CPP who had a pubertal versus prepubertal LH-ICMA, including a cohort of boys. Methods: A retrospective chart review of children diagnosed with CPP within the last 10 years who had a baseline LH-ICMA obtained was performed. Variables analyzed included sex, age, ethnicity, bone age, BMI, etiology, Tanner stage (TS), testicular volume, and menarchal status. Results: Of 27 boys and 126 girls who qualified for the study, the LH-ICMA was pubertal in 87% and prepubertal in 13%. Girls with a pubertal LH-ICMA had higher baseline estradiol concentrations (p < 0.001) and more advanced breast development (p = 0.015) compared to girls with a prepubertal LH-ICMA. Of girls with a prepubertal LH-ICMA, 74% had at least TS 3 breast development and 1 was post-menarchal. The LH-ICMA was pubertal in 96% of the boys with CPP in this study. Conclusions: The LH-ICMA can be prepubertal even in girls with advanced development. To our knowledge, ours is the largest cohort of boys in whom the accuracy of a random LH-ICMA has been reported.

BackgroundPremature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible for the onset of PT have not yet been fully investigated. This study aimed to evaluate the relationship of nutrient intake, insulin resistance and lipid profile with PT.MethodsTwo hundred sixty-three girls with PT, and 222 healthy girls of similar age were enrolled into this study. Their demographics, Tanner stage of breast development, nutrient intake, insulin resistance and lipid profiles were compared.ResultsDaily protein and fat intakes, insulin resistance parameters including serum insulin-like growth factor 1, fasting glucose to insulin ratio, quantitative insulin check index and homeostasis model of assessment of insulin resistance, as well as serum levels of triacylglycerol, total cholesterol and low-density lipoprotein, were all significantly altered in PT patients. Daily intake of energy and carbohydrate, and serum level of high-density lipoprotein protein were statistically indistinguishable between PT patients and healthy controls.ConclusionChinese girls with PT are potentially insulin resistant, which warrants more clinical attention and further investigation to address the underlying etiology.

OBJECTIVE To determine basal and gonadotrophin-releasing hormone analogue (GnRHa)-stimulated peak luteinising hormone (LH) cut-offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III). DESIGN, PATIENTS AND MEASUREMENTS A retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost-effectiveness analysis was performed. RESULTS In comparison with basal LH cut-off of 0.3 IU/L, basal LH cut-off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut-off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut-off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost-saving when compared with using the cut-off of 0.3 IU/L. Moreover, using basal LH cut-off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients. CONCLUSIONS Basal serum LH cut-off of 0.2 IU/L could be a simple and cost-saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing.

Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 ± 0.065 g/cm2 vs 0.822 ± 0.113 g/cm2, P = 0.008) and total hip BMD (0.777 ± 0.118 g/cm2 vs 0.903 ± 0.098 g/cm2, P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 ± 0.049 vs 0.820 ± 0.105 g/cm2, P = 0.0047) and total hip BMD (0.752 ± 0.093 vs 0.908 ± 0.097 g/cm2, P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.

STUDY QUESTION What are the levels of breast development and satisfaction in women with a Disorder/Difference of Sex Development (DSD)? SUMMARY ANSWER Compared with normative data, women with DSD reached lower Tanner stages and reported less breast satisfaction. WHAT IS KNOWN ALREADY Women with DSD may have chromosomal and hormonal variations that can impact typical breast development. While much emphasis is placed on genital development in this group, little is known about breast development, satisfaction and their association. STUDY DESIGN, SIZE, DURATION Data collection was part of the cross-sectional European multicenter dsd-LIFE study. Fourteen recruiting sites included 1040 participants between February 2014 and September 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 695 female-identifying participants were included (Turner n = 332, 46,XY DSD n = 141 and congenital adrenal hyperplasia n = 222), with a median age of 28 years. Clinical (i.e. history of hormone and surgical treatments, Tanner breast examination) and patient-reported (i.e. breast satisfaction, relationship status, sexual satisfaction and experienced femininity) data was collected by independent trained research staff. The relationship between breast development, satisfaction and femininity was assessed. Control data on breast development and satisfaction in women without DSD was retrieved from the literature. MAIN RESULTS AND THE ROLE OF CHANCE Of the 695 participants, 61% had received estrogen replacement and 51% puberty induction therapy, whereas 2% had received breast augmentation surgery. Approximately 65% of participants had reached Tanner breast stage 5, which is substantially less than the general population (90%). Breast satisfaction was lower than normative data as well (P LIMITATIONS, REASONS FOR CAUTION Limitations include the sample representativeness (e.g. regarding the clinical heterogeneity) and the limited in-depth knowledge on (prior) hormonal regimens. Furthermore, no (matched) control data was collected as part of this study. WIDER IMPLICATIONS OF THE FINDINGS In order to support the psychosexual well-being of women with DSD, enhancing breast development by sufficient hormone replacement and possible augmentation surgery is advocated. The scope of DSD management should be beyond genital development only and consider breasts as well. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the European Union Seventh Framework Program (FP7/2007–2013) under grant agreement no. 305 373. There are no competing interests. TRIAL REGISTRATION NUMBER German Clinical Trials Register: Registration identification number: DRKS00006072.

BackgroundEarlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk.MethodsFrom 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.ResultsThe mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (ptrend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (ptrend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)).ConclusionsOur results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

Turner syndrome (TS) with an isochromosome mosaic karyotype 45,X/46,X,i(X) (q10) is an unusual variant, with only an 8-9% prevalence among women with TS based on international studies and 15% of all TS in the Philippines. Clinical features are atypical and any case should be investigated to detect potential complications. A 20-year-old female came in due to amenorrhea and alopecia. Physical examination revealed short stature, cubitus valgus and Tanner Stage 1 pubic hair and breast development. Transrectal ultrasound revealed absent ovaries and infantile uterus. Hormonal evaluation revealed hypergonadotropic hypogonadism. Bone aging was that of a 13-yearold for females with non-fusion of epiphyseal plates. Cytogenetic study revealed 45,X [37]/46, X, i (X) (q10)[13]. This is consistent with a variant Isochromosome Mosaic Turner Syndrome (IMTS). She was screened for medical complications. Audiogram and two-dimensional echocardiography were unremarkable. She has dyslipidemia and was given a statin. She has subclinical hypothyroidism with positive test for anti-thyroglobulin antibody. Her intelligence quotient (IQ) was below average. She received conjugated estrogen and progesterone that patterned the hormonal changes in a normal menstrual cycle. On the third week of hormonal therapy, she developed breast mound and on the fourth week, she had her first menstrual period. Her alopecia spontaneously resolved. The case is a variant of Turner Syndrome requiring supportive, medical and psychological care.

This article will provide an overview on female breast development and focus on common abnormalities of growth, the emerging role of breast self-awareness, and discuss trends in the evaluation and treatment of the breast masses and disorders most often encountered in the female adolescent population.Although the embryology of breast development is unchanged, data are emerging on the role of environmental factors on the timing of puberty and thelarche. As breast development occurs, the role of breast self-awareness is also a new trend that allows teens to be cognizant of changes in their own breast and to become more comfortable with their own anatomy. Finally, when breast treatments are needed or desired, the timing of breast treatments is a subject that must be individualized.There are numerous conditions that can result from disruption of normal breast development. These resultant breast disorders are generally benign but can still cause emotional distress to both the patient and family. It is thus imperative that healthcare providers be educated on breast development, the common breast masses that occur in the adolescent population and be prepared to discuss breast self-awareness and shared decision-making in this population.

Purpose Precocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls l8 years old (CPP) and for girls 8-9 years old (early puberty, EP). Methods From January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles. Results Basal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8-9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect. Conclusion Basal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.

Introduction There is paucity of literature and research on puberty among girls with cerebral palsy especially from India. Knowledge of sexual development and menstrual issues can guide towards better care for these girls. Objective To study the onset of sexual development and patterns of menstrual issues among girls with cerebral palsy who attended cerebral palsy clinic. Methods A cross sectional study of 93 girls with cerebral palsy(GMFCS levels-I toV), aged 5–19 years, attending the cerebral palsy clinic at a tertiary care hospital, was conducted. Data was obtained by interviewing the parents of the girls with cerebral palsy using a semi structured questionnaire followed by examination of the girls. Results Mean age of the girls in the study was 11.27 ± 4.46 yrs. The average height of the girls with cerebral palsy were found to be lesser than the published standards. 36(38.7%) girls had attained menstruation. Average age of menarche was 12.54 ± 1.37yrs. There was one case of delayed puberty. 75% of the girls had regular cycles while 47.2% had dysmenorrhoea. 69.4% used sanitary pads and mothers changed the pads in 38.8% of the girls. 58.3% of them had signs of vaginal infection while 25% of them showed signs of premenstrual syndrome. Conclusion Girls with cerebral palsy required extra support from their care-givers during the menstrual cycles. Usage of sanitary pads was not widely prevalent with signs of vaginal infection. Breast development was delayed but pubic hair development was found earlier among the study participants.

Purpose This study investigated whether size at birth and infant growth were associated with age of indicators of pubertal development in boys and girls. We hypothesized that restricted fetal growth and accelerated infant growth lead to earlier pubertal age. Patients and methods In total, 15,822 boys and girls answered questionnaires half-yearly with information on pubertal development: age at menarche, first ejaculation, voice break, Tanner stages, axillary hair, and acne. Birth weight and gestational age were used to calculate birth weight Z-scores. Changes in infant weight Z-score from 0 to 5, 5 to 12, and 0 to 12 months were estimated. We estimated the mean monthly difference in timing of puberty between children born small-for-gestational age (SGA) and large-for-gestational age (LGA) with children born appropriate-for-gestational age (AGA) as reference. We further investigated whether increasing infant weight Z-scores were associated with age at attaining indicators of pubertal development. Results Girls born SGA reached all pubertal markers at an earlier mean age than girls born AGA, as indicated by mean age differences below zero (eg, age at menarche: -2.3 months, 95% CI: -3.4, -1.2), except for breast development. Girls born LGA reached pubertal markers later than girls born AGA (eg, age at menarche: 1.7 months, 95% CI 0.5, 2.9). Boys born SGA and LGA achieved puberty earlier than boys born AGA, though with CIs crossing zero (eg, age at voice break for SGA: -0.7 months, 95% CI -2.1, 0.7 and for LGA: -0.7 months, 95% CI -2.1, 0.8). A 1-unit increase in weight Z-score from 0 to 12 months was associated with a mean age difference of -1.7 to -0.3 months for pubertal development in both sexes. Conclusion Small size at birth and rapid infant growth were associated with early pubertal age, most consistent and pronounced in girls.

Background Girls who are overweight/obese (OB) develop breast tissue but do not undergo menarche (the first menstrual period) significantly earlier than girls of normal weight (NW). It has been proposed that estrogen synthesized by adipose tissue may be contributory, yet OB do not have higher serum estrogen levels than NW matched on breast stage. We hypothesized that estrogen synthesized locally, in mammary fat, may contribute to breast development. This hypothesis would predict that breast development would be more advanced than other estrogen-sensitive tissues as a function of obesity and body fat. Methods 80 pre-menarchal girls (26 OB, 54 NW), aged 8.2–14.7 yrs, underwent dual-energy x-ray absorptiometry to calculate percent body fat (%BF), Tanner staging of the breast, breast ultrasound for morphological staging, trans-abdominal pelvic ultrasound, hand x-ray (bone age), a blood test for reproductive hormones, and urine collection to determine the vaginal maturation index (VMI), an index of estrogen exposure in urogenital epithelial cells. Results When controlling for breast morphological stage determined by ultrasound, %BF was not associated with serum estrogen or gonadotropin (LH and FSH) levels or on indices of systemic estrogen action (uterine volume, endometrial thickness, bone age advancement, and VMI). Tanner breast stage did not correlate with breast morphological stage and led to misclassification of chest fatty tissue as breast tissue in some OB. Conclusions These studies do not support the hypothesis that estrogen derived from total body fat or local (mammary) fat contributes to breast development in overweight/obese girls.

Objective:To examine adherence to a Mediterranean-like diet at age 9–10 years in relation to onset of breast development (thelarche) and first menstruation (menarche).Design:We evaluated the associations of adherence to a Mediterranean-like diet (measured by an adapted Mediterranean-like Diet Score, range 0–9) with thelarche at baseline, age at thelarche and time to menarche. Data were collected at baseline during a clinic visit, complemented with a mailed questionnaire and three 24 hour telephone dietary recalls, followed by annual follow-up questionnaires. Multivariable Poisson regression, linear regression and Cox proportional hazards regression were used to evaluate timing of pubertal development in relation to diet adherence.Setting:New Jersey, USA.Participants:Girls aged 9 or 10 years at baseline (2006–2014,n 202).Results:High Mediterranean-like diet adherence (score 6–9) was associated with a lower prevalence of thelarche at baseline compared with low adherence (score 0–3; prevalence ratio = 0·65, 95 % CI 0·48, 0·90). This may have been driven by consumption of fish and non-fat/low-fat dairy. Our models also suggested a later age at thelarche with higher Mediterranean-like diet adherence. Girls with higher Mediterranean-like diet adherence had significantly longer time to menarche (hazard ratio = 0·45, 95 % CI 0·28, 0·71 for highv. low adherence). Further analysis suggested this may have been driven by vegetable and non-fat/low-fat dairy consumption.Conclusions:Consuming a Mediterranean-like diet may be associated with older age at thelarche and menarche. Further research is necessary to confirm our findings in other US paediatric populations and elucidate the mechanism through which Mediterranean-like diet may influence puberty timing.

Context The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset. Objective We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones. Design and Setting Longitudinal observational study. Participants and Main Outcome Measures In 269 girls, serum concentrations of steroid sex hormones [estradiol (E2), estrone, testosterone, and dehydroepiandrosterone sulfate] were measured by HPLC-mass spectrometry at time points before, at, and after thelarche. Girls were classified into four hormone phenotypes using objective principal components and cluster analyses of longitudinal hormone data. The association between the identified phenotypes and age of pubertal milestones was estimated using Cox proportional hazards modeling. Results Mean ages at thelarche, pubarche, and menarche were 9.02, 9.85, and 12.30 years, respectively. Girls with low levels of all four hormones, phenotype 3b, were youngest at thelarche (8.67 years); those in phenotype 2, with the highest E2 levels and E2 surge 6 months after thelarche, were youngest at menarche (11.87 years) with shortest pubertal tempo. When controlling for race, maternal age of menarche, caregiver education, and body mass, different phenotypes were associated with the age of pubertal events. Conclusions Hormone phenotypic clustering can identify clinically relevant subgroups with differing ages of thelarche, pubarche, and menarche. These findings may enhance the understanding of timing of pubertal milestones and risk of adult disease.

ContextPrevious case reports associated prepubertal gynecomastia with lavender-containing fragrances, but there appear to be no reports of premature thelarche.ObjectiveTo add to a case series about lavender-fragranced product use and breast growth in children and to measure endocrine-disrupting chemical activity of essential oil components.Design, Setting, and PatientsPatients experiencing premature thelarche or prepubertal gynecomastia with continuous exposure to lavender-fragranced products were evaluated in the pediatric endocrinology departments of two institutions. Mechanistic in vitro experiments using eight components of lavender and other essential oils were performed at National Institute of Environmental Health Sciences.Main Outcome MeasuresCase reports and in vitro estrogen and androgen receptor gene expression activities in human cell lines with essential oils.ResultsThree prepubertal girls and one boy with clinical evidence of estrogenic action and a history of continuous exposure to lavender-containing fragrances were studied. Breast growth dissipated in all patients with discontinuation of the fragranced products. Some of the components tested elicited estrogenic and antiandrogenic properties of varying degrees.ConclusionWe report cases of premature thelarche that resolved upon cessation of lavender-containing fragrance exposure commonly used in Hispanic communities. The precise developmental basis for such conditions could be multifactorial. In vitro demonstration of estrogenic and antiandrogenic properties of essential oil components suggests essential oils in these cases could be considered a possible source and supports a possible link with idiopathic prepubertal breast development. Whether the level of lavender oil estrogenic potency is sufficient to cause these effects is unknown.

Adolescence is a vulnerable period of breast development, and environmental chemical exposures that occur during this period can increase the risk of breast cancer in adulthood. Discussing breast health with adolescent girls can be difficult for several reasons. In this project, we worked to not only inform adolescent researchers about environmental risks for breast cancer but to also involve them in research studies. We taught adolescents about the stages of mammary gland development using samples collected from mice, with a specific focus on pre-pubertal and pubertal stages of development. Our analysis shows that adolescent researchers, with relatively modest training, can collect reliable and reproducible data on aspects of mammary gland biology that are known to be disrupted by environmental chemicals, with coefficients of variation