Normal Q Onset

[Kristin Banyas]

Pubertyis a time of rapid and complex changes involving overlapping components: hormonal, physical, and cognitive. Tanner Staging, also known as Sexual Maturity Rating (SMR), is an objective classification system that providers use to document and track the development and sequence of secondary sex characteristics of children during puberty. It was developed by Marshall and Tanner while conducting a longitudinal study during the 1940s to the 1960s in England. Based on observational data, they developed separate scales for the development of external genitalia: phallus, scrotum, and testes volume in males; breasts in females; and pubic hair in both males and females.

The physical changes of puberty require a concerted effort from many organs; these changes are initiated by the activation of the hypothalamic-pituitary-gonadal (HPG) axis (gonads refer to ovaries in females and testes in males). The first hormonal change in puberty is the pulsatile release of GnRH triggered by disinhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Although the cause of this disinhibition is largely unknown, the subsequent release of GnRH then stimulates the pulsatile release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH act on specific gonadal cells to stimulate the release of androgens, estrogens, and the process of gametogenesis. LH stimulates the theca cells in the ovary to produce estrogen precursors and the Leydig cells of the testes to produce testosterone. On the other hand, FSH works on the ovarian follicle to convert the thecal estrogen precursors to estrogen and on the Sertoli cells in the seminiferous tubules of the testes to help create sperm. This complex process leads to increased estrogen and testosterone production that then facilitates the development of breasts and the formation of adult male genitalia.[1][2][3]

The adrenal glands also contribute to the formation of secondary sex characteristics, particularly pubarche, which is the development of pubic and axillary hair. Although adrenal maturation often coincides with HPG axis maturation, it is important to note that these processes occur independently of each other and that pubarche itself is not the best indicator of pubertal development.[4]

The normal onset and sequence of physical maturation vary greatly based on sex, race and ethnicity, and environmental factors. Tanner Stages are utilized in pediatric and adolescent practice to counsel patients about the timing of anticipated body changes, perform appropriate medical screenings, and monitor for deviations in normal timing and sequence of physical signs of puberty that may represent physiologic problems. Changes that are associated with but not directly measured by Tanner staging include bone growth and fusion, body composition and linear growth, and hematocrit values. Tanner Staging, rather than chronological age, should be used in assessing pubertal development. Clinical examples of use include delivering timely anticipatory guidance on menstrual hygiene needs (menarche occurs about 2 years post-thelarche/tanner 2 breasts) or targeting scoliosis exams at well-visits before and during peak height velocity (Tanner 2 to 3, depending on sex).[4][5][6]

In females, the normal onset of puberty ranges from 8 to 13 years old, averaging age 10 years in White Americans and age 8.9 years in African-Americans. Puberty in females begins with the development of breast buds under the areola, also known as thelarche, and represents entry into Tanner Stage 2. As puberty progresses, the glandular tissue of the breast increases in size and changes in contour. In females, thelarche is followed in 1 to 1.5 years by the onset of sexual hair (pubic and axillary), known as pubarche. Menarche, the onset of menses, arrives on average at age 12.5 years, regardless of ethnicity, following thelarche on average by 2.5 years (range 0.5 to 3 years). Between Tanner Stage 2 and 3 breast development, females experience peak height velocity. African-American females have closer to 3 years between their thelarche and menarche, accounting for greater height potential.

In males, the onset of puberty ranges from 9 to 14 years of age. The first secondary sexual characteristic visible is gonadarche when the testicular volume reaches greater than or equal to 4 mL (or long axis greater than or equal to 2.5 cm) and enters tanner stage 2. During Tanner Stage 3 genital development, males undergo peak height velocity. Spermarche, the counterpart of menarche in females, is the development of sperm in males and typically occurs during genital Tanner Stage 4.

Pubertal development generally follows a predictable pattern of onset, sequence, and velocity. However, population norms are published to help clinicians determine which adolescents fall outside two standard deviations of the mean and require further investigation. Precocious puberty is defined as the onset of Tanner 2 secondary sexual characteristics before age 8 years in females or age 9 years in males if the continued progression of pubertal development occurs soon after. Delayed puberty should be considered if females have not reached Tanner 2 thelarche by age 13 years old or if males have not reached Tanner 2 gonadarche by age 14 years. Primary amenorrhea is defined as a failure to start menses within 3 years of Tanner Stage 2 (thelarche) or by age 15 years. It is important to note that some males will temporarily develop glandular breast tissue (pubertal gynecomastia) between genital tanner stage 3 and 4, which may be emotionally troubling but not physically harmful. Abnormalities may be caused by idiopathic conditions, nutritional deficiencies,[7][8] HPG axis variations, or neoplastic and genetic disorders. Describing these disorders is outside the scope of this article.

Below are the Tanner Stages described in detail for clinical reference. Tanner Stage 1 corresponds to the pre-pubertal form for all three sites of development with progression to Tanner Stage 5, the final adult form. Breast and genital staging, as well as other physical markers of puberty such as height velocity, should be relied on more than pubic hair staging to assess pubertal development because of the independent maturation of the adrenal axis.

An interprofessional team of clinicians and nurses should provide the screening evaluation of pediatric patients. All healthcare workers, including nurses, nurse practitioners, physician assistants, and physicians who evaluate pediatric patients, should know the Tanner stages. This will allow them to know if sexual development is normal or abnormal; the earlier the referral to the appropriate specialist, the better the outcomes.[6]

Menarche is defined as the first menstrual period in a female adolescent. Menarche typically occurs between the ages of 10 and 16, with the average age of onset being 12.4 years.[1] The determinants of menarcheal age are continuously being researched; socioeconomic conditions, genetics, general health, nutritional status, exercise, seasonality, and family size are thought to play a role.

Menarche tends to be painless and occurs without warning. The first cycles are usually anovulatory with varied lengths and flow. Menarche signals the beginning of reproductive abilities and is closely associated with the ongoing development of secondary sexual characteristics.[2]

The absence of normal menstrual periods, unrelated to pregnancy, is termed amenorrhea. Primary amenorrhea is the complete absence of menstruation by 15 years of age in the setting of normal growth and secondary sexual development or the absence of menses by age 13 in the absence of normal growth or secondary sexual development. Secondary amenorrhea is the absence of menses for greater than three cycle intervals or six consecutive months in a previously menstruating female.[3]

Of specific concern is when menarche occurs too early, too late, or not at all, as these scenarios have future adverse outcomes. Menarche is considered early if it occurs at or before ten years of age and late if it occurs at or later than 15 years of age.[4]

Numerous studies have shown the kiss1 gene, which produces kisspeptin, and its receptor G protein-coupled receptor 54 (GPR54) to be necessary for normal reproductive function. Kisspeptin and GPR54 are expressed in hypothalamic gonadotropin-releasing hormone (GnRH) neurons. The hypothalamic kiss1 system relays metabolic information to the gonadotropic axis. Circulating estradiol activates kisspeptin, which in turn activates GnRH neurons. Puberty is initiated when GnRH is secreted in a pulsatile manner by hypothalamic neurons.[5]

GnRH neurons are found in the olfactory pit at post-conception week six, then migrate via the forebrain to the hypothalamus by week nine. The pituitary begins to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH) into the fetal circulation by week 12, with LH and FSH reaching peak levels at midgestation, around 20-24 weeks. LH and FSH levels are low at birth but begin to increase upon withdrawal of placental estrogens.[7] As previously discussed, the pulsatile release of GnRH, and thus, LH and FSH, is necessary for puberty and menarche. The onset of female puberty is marked by thelarche (breast budding), which typically occurs after eight years of age. Thelarche is followed by pubarche (pubic hair development), growth spurt, and finally, menarche.

Menarche occurs 2-3 years after thelarche and six months after peak height velocity (PHV) is achieved. PHV is defined as the highest velocity observed during the pubertal growth spurt.[8] Menarche most commonly occurs in sexual maturity rating (SMR) or Tanner stage IV. It is abnormal for menarche to occur before the appearance of secondary sexual development. Sexual abuse, genital trauma, tumors, or bleeding disorders should be considered in the differential diagnosis of prepubertal females who experience vaginal bleeding.

By 15 years of age, approximately 98% of females will have undergone menarche, signaling the maturation of the adolescent female body. Menarche is commonly associated with the ability to ovulate and reproduce; the onset of menarche does not guarantee either ovulation or fertility. Menstrual cycles are frequently irregular during adolescence, particularly during the interval from the first to the second cycle.[9] Immaturity of the HPO axis during the early years after menarche results in anovulation and irregular cycles, which can range from short cycles ( 45 days). By the third year after menarche, 60-80% of menstrual cycles are 21 to 34 days long, typical of an adult cycle. In females who undergo early menarche, 50% of their cycles are ovulatory in the first year, and nearly all are ovulatory by the fifth year post-menarche. In contrast, it takes approximately 8 to 12 years for all cycles to be ovulatory in females who experience a later onset of menarche.[10]

3a8082e126