Introduction

The onset of and successful progression through puberty carries significant implications for an adolescent’s development, with puberty radically altering a child’s physical, psychological, and social baseline. Puberty depends on properly developing the hypothalamic-pituitary-gonadal (HPG) and adrenal axes, with hormones from these sources resulting in observable changes. In 1962, James M Tanner developed the Sexual Maturity Rating (SMR).[1] This scale, also known as the Tanner stages, granted providers objective criteria for monitoring an adolescent’s puberty progression. By evaluating the development of the testes, breast tissue, and pubic hair, a clinician can appropriately counsel and manage patients through this critical period of life.

Issues of Concern

It is crucial to understand the limitations of the Sexual Maturity Rating when evaluating patients. As the SMR only measures the external signs of sexual development obtained via physical exam, their use is limited in non-clinical settings.[2] Additionally, the time of onset and rapidity of sexual maturity varies among different ethnicities. There is evidence of advancement in the timing of sexual maturation among various populations, observable within developed and underdeveloped societies. While the underlying causes of the differences in sexual maturation timing remain unidentified, it is highly likely to be a multifactorial issue that relies on social and physiological components. To properly use the SMR, it is imperative to have recent and reliable data from a similar ethnic population subset while evaluating a patient.[3]

Development

The onset of puberty in both males and females relies on the hypothalamus. The intermittent release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, also known as the hypothalamic pulse generator, signals the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary.[4] There is a belief that the neurotransmitters GABA and kisspeptin inhibit the release of GnRH. As an individual matures, the hypothalamus becomes less sensitive to this inhibition and eventually shifts towards pulsatile surges.[5]

LH stimulates Leydig cells in males' testes to produce testosterone, typically occurring between ages 9 to 14. Testosterone can then be peripherally converted into its more potent counterpart, dihydrotestosterone (DHT), via the 5-alpha-reductase enzyme. Acting on intracellular androgen receptors, testosterone is responsible for the pubertal growth spurt, closure of the epiphyseal plates, deepening of the voice, penile and testicular enlargement, muscle growth, and libido.[6] DHT acts similarly on intracellular receptors yet contributes to facial hair growth, sebaceous gland secretion, and male pattern baldness. 5-alpha-reductase inhibitors have become the first-line therapy for treating male pattern baldness.[7]

In females, both LH and FSH contribute to the development of secondary sexual characteristics.[8] FSH promotes follicular maturation within the ovary. Theca cells within the follicle are responsive to LH surges releasing testosterone into the periphery. Adjacent granulosa cells, stimulated by FSH, convert testosterone to estrogen via aromatase. Estrogen then acts on intracellular receptors within various tissues, resulting in growth spurts, closure of the epiphyseal plates, genital enlargement, and breast tissue development.[9]

Puberty is also marked by a period of increased adrenal androgen production, termed adrenarche, which typically occurs around age 6. While a specific signaling molecule has, to date, eluded researchers, it results from increased androgen-producing enzymes within the adrenal gland's zona reticularis (ZR) layer. Dehydroepiandrosterone (DHEA) acts on intracellular receptors promoting androgen-dependent hair growth. Adrenarche is a common period between both sexes, resulting in shared pubic hair growth patterns.[10]

Organ Systems Involved

Breasts

The onset of breast tissue development (thelarche) in the female is the first secondary sexual characteristic to develop in puberty. Free estrogen acts on intracellular receptors to promote the development of both ductal and stromal elements. The fatty stromal elements compose most of the breast growth during puberty; by its completion, only a minor amount of ductal tissue remains within the breast.[11] Pregnancy and its associated hormonal changes result in the progression towards increased ductal tissue versus stroma.

Due to relative estrogen dominance during puberty, up to 40% of boys may develop transient breast enlargement (gynecomastia), which is secondary to ductal and stromal hypertrophy.[11] Clinicians should be aware that while male gynecomastia during puberty is typically short-lived, it can significantly affect the male child's psychological well-being, and their fears and distress should be addressed appropriately.

Testicles

Pre-adolescent males typically have a testicular length of less than 2.5 cm or a testicular volume of less than 4 mL. It is the growth of the testes beyond these measurements which marks the onset of puberty.[12] Testicular growth during puberty is facilitated by androgens causing germ cell growth and expansion in seminiferous tubule diameter.[13]

Pubic Hair

DHEA and dehydroepiandrosterone sulfate (DHEAS) both result in the production of pubic and axillary hair growth. These hormones act on hair follicles, causing both the thickening and darkening of the pubic hair. The distribution of hair follicles highly responsive to these hormones is genetically determined; thus, certain individuals may be predisposed to a lesser or greater distribution of darkened body hair.[14]

Function

The function of the Sexual Maturity Rating is to present a standardized scale of physical development in children and adolescents. Knowing this scale allows clinicians to counsel patients on anticipated physical changes, monitor for deviations in the normal sequence and timing of physical changes, and perform the appropriate medical screenings.[15]

Related Testing

Alternative methods have been developed to assess a patient’s pubertal development. The Pubertal Development Scale (PDS) is a questionnaire that covers typical changes manifested throughout puberty (eg, growth spurt, body hair growth, voice deepening, etc.) and asks patients to answer whether they’ve experienced these changes. Features not assessed with SMR can be evaluated through this system. Additionally, the PDS assesses a patient’s understanding of their progression through puberty.[16]

Picture-based interview about puberty (PBIP) measures pubertal development based on a conversation between clinician and patient. With a set script and photographs, clinicians discuss changes in the adolescent body with the patient, after which the patient reports their assessment of their pubertal stage.[2] This method of measuring stages of puberty allows the clinician to engage the patient in a conversation about their body and the changes they may be going through. It also allows the patient to play an active role in diagnosing which stage of puberty they are in and what changes in their body they can expect to occur. 

Pathophysiology

Precocious Puberty

Premature activation of the HPG axis underlies the etiology of precocious puberty, with the defining characteristic being pubertal characteristics manifesting before age 8 in girls and 9 in boys. While the exact cause of precocious puberty is unknown, congenital malformations and acquired insults have both merited consideration as potential etiologies.[17]

Delayed Puberty

Delayed puberty is a diagnosis of exclusion most often cited in males, typically resulting in delayed skeletal maturation compared to individuals of the same age within the same population. Delayed puberty commonly resolves without issue and can be seen amongst multiple familial generations. Proper counseling of patients is imperative as delayed puberty can result in potential stigma among their peers. It is essential to exclude possible causes of delayed maturation, such as hypogonadism, as these conditions require pharmacologic treatment.[18]

Hypogonadism

Male and female hypogonadism results from the underproduction of their respective hormonal counterpart. Proper diagnosis requires a complete history, physical exam, and laboratory evidence. Male hypogonadism refers to symptomatology secondary to the underproduction of testosterone with a proper formation of spermatozoa. With testosterone playing a pivotal role in growth spurts, facial hair growth, penile elongation, and testicular enlargement, a deficiency can result in underdevelopment in these areas. Primary and secondary subsets result from pathology in the testicles or the hypothalamus/pituitary.[19] Female hypogonadism results from dysfunction within the hypothalamic-pituitary-ovarian (HPO) axis. Whether this dysfunction is acquired or congenital, the primary manifestation is menstrual cycle disturbances. However, underdevelopment of breast tissue can also occur.[20]

Precocious puberty, delayed puberty, and hypogonadism all require evaluation by a pediatric endocrinologist. Depending on patient presentation, hormonal therapy may be utilized, as it allows for the halting or the initiation of puberty and is the mainstay of treatment.[21]

Clinical Significance

The Sexual Maturity Rating grants providers a lens to evaluate and counsel patients through puberty. A patient’s age of pubertal onset, estimated final height, and potential environmental exposures can all be correlated through proper physical examination and SMR.[22] Remembering the hormonal axes contributing to each examined aspect's development is crucial. When examining males, long bone growth, deepening of the voice, and facial hair, all rely on gonadal hormones. When examining females, long bone growth, breast enlargement, and the onset of menarche also rely on gonadal hormones. Pubic and body hair both rely on adrenal hormones.[2] Thus, inconsistencies within a particular subset of the Sexual Maturity Rating allow for a focused examination of the adrenal axis versus the HPG axis. Listed below are the criteria for the Sexual Maturity Rating.

Sexual Maturity Rating    

Pubic Hair Scale: (both males and females)

• Stage 1: Absent hair
• Stage 2: Downy hair present
• Stage 3: Scant terminal hair present
• Stage 4: Terminal hair that fills the whole triangle overlaying the pubic area
• Stage 5: Terminal hair extending beyond the inguinal crease onto the thigh area

Female Breast Development Scale:

• Stage 1: No glandular breast tissue palpable
• Stage 2: Breast bud palpable under the areola (first pubertal sign in females)
• Stage 3: Breast tissue palpable outside areola; no development of areola
• Stage 4: Areola elevated above the contour of the breast, forming a “double scoop” appearance
• Stage 5: Areolar mound recedes into a single breast contour along with hyperpigmentation of the areola, papillae development, and nipple protrusion [23]

Male External Genitalia Scale:

• Stage 1: Testicular volume less than 4 ml or long axis less than 2.5 cm
• Stage 2: 4 ml to 8 ml (or 2.5 to 3.3 cm long) (first pubertal sign in males)
• Stage 3: 9 ml to 12 ml (or 3.4 to 4.0 cm long)
• Stage 4: 15 to 20 ml (or 4.1 to 4.5 cm long)
• Stage 5: greater than 20 ml (or over 4.5 cm long) [15]

Utilizing an ultrasound to assess testicular volume is the gold measurement standard; however, this method may be inconvenient, costly, or inaccessible.[23] While examinations with a centimeter ruler or orchidometer are often performed, these methods may result in inaccuracies.

Ages associated with SMR Stages (female)

• Stage 1: 0 to 15 years
• Stage 2: 8 to 15 years
• Stage 3: 10 to 15 years
• Stage 4: 10 to 17 years
• Stage 5: 12.5 to 18 years

Ages associated with SMR Stages (male)

• Stage 1: 0 to 15 years
• Stage 2: 10 to 15 years
• Stage 3: 10 to 16.5
• Stage 4: 12 to 17
• Stage 5: 13 to 18

Additional body changes seen in females that may correlate to SMR stages

• Peak growth velocity typically occurs soon after stage 2.
• Menarche occurs in approximately 2% of girls in late stage 3.
• Menarche typically occurs in stage 4, approximately 1 to 3 years after thelarche.
• Approximately 10% of girls undergo menarche in stage 5.

Additional body changes seen in males that may correlate to SMR stages

• Development of axillary hair and facial hair begins around stage 4.
• Approximately 20% of boys reach peak growth velocity during stage 5.

It is important to remember that the Sexual Maturity Rating is not used for the age estimation of an individual. As the name alludes to, the Sexual Maturity Rating corresponds to the maturity stage of an individual rather than their chronological age.[24] The Sexual Maturity Rating is an important tool used in managing HIV, with the SMR stage of a patient used to guide the antiretroviral therapy regimen.[25]