10/14/14

Overview

• Context Physical Growth and Development • Features of during • Evaluation of pubertal development • Adolescent brain development • Resources

Annie Hoopes Adolescent Medicine Fellow/LEAH Senior Fellow November 8, 2013

Puberty Basics

• Outcomes of puberty • size and appearance • Clear distinction between sexes Features of • Ability to reproduce • Physical changes reflect hormonal changes Puberty • Onset • Girls: Age 7 to 13 years • Boys: 9 to 14 years • Rate • 5 years for girls • 6 years for boys • Differences in timing and rate by gender/ethnicity

1 10/14/14

Definitions of puberty

• – adrenal cortex starts producing • Hypothalamic-pituitary-gonadal axis androgens • Adrenal system • – activated by follicle-stimulating (FSH) and luteinizing hormone (LH) • – appearance of • – appearance of tissue • – age of onset of first menstrual period • – age at first

Hypothalamic-Pituitary-Gonadal (HPG) Axis HPG Axis: After Puberty

2 10/14/14

LH and FSH and Estrogen

Testosterone Estrogen LH FSH Growth of and **Peripheral conversion Growth of pubic/facial hair Testosterone production production Low levels: pubertal growth MALES Deepening of voice spurt, accrual of peak bone from Leydig cells from Sertoli cells MALES Increased libido mass Increased muscle mass High levels: closure of Androgen production Acne epiphyses from theca cells Ovarian follicle Thickening of cortical bone development Bone effects as in males Progesterone production FEMALES Growth of , , from the corpus luteum Estrogen vagina, uterus Thickening of cortical bone FEMALES Pattern of fat deposition production from Growth of pubic hair Mid-cycle surge ! granulosa cells Vaginal pH " and length # Proliferation of endometrium Triggers LH surge

Onset of Puberty Adrenal System

• Trigger for puberty not completely understood • 50-80% of variation in onset likely genetics • Change in body composition = permissive role • Threshold % of body fat is likely necessary but not sufficient for onset (↓Leptin ⟶ ↓ LH pulse ⟶ pubertal suppresion) • Other factors • Inhibitory central feedback mediated by Occurs peripherally neurotransmitters (GABA, neuropeptide Y) (outside of the • releasing adrenal gland) hormone pulse generator becomes increasingly active – first nocturnally then during the day

3 10/14/14

How do we measure puberty? SMR (Tanner) Stages - Males

1: Prepubescent, no pubic hair • Timing is variable but SEQUENCE is

predictable 2: Enlargement of testes >2.5cm or 4 cc volume, • Chronologic age correlates poorly with reddening of scrotum, no change in penis (**1.5 years before growth spurt), sparse pubic hair biological maturity • Assess maturity with Sexual Maturity Rating 3: Penis and scrotum grow, pubic hair darker and (Tanner) scale or skeletal age/bone age coarser

4. Scrotal darkening, penis grows in width (, voice changes), hair extends up

5. Adult size penis and testes, hair extends to thighs

SMR (Tanner) Stages - Males SMR (Tanner) Stages - Females

1: Prepubescent, no breast tissue

2. Breast buds, sparse pubic hair)

3: Enlargement of breast, no separation of from breast, pubic hair coarser and darker

4. Areola and papilla project above breast, forming secondary mound, pubic hair extends up

5. Areola recedes to match contour of breast, papilla projects beyond areola, pubic hair extends to thighs

4 10/14/14

SMR (Tanner) Stages - Females Peak height velocity

Timing of pubertal events Body Composition

5 10/14/14

Timing of pubertal events What’s too early? Or too late?

Girls Boys

Males Breast Changes: changes: • Early<7-8 in girls • Early <9 in boys • Late>13 in girls • Late >14 in boys Pubic Hair: Pubic Hair: • Early <9 in boys • Early<7-8 in girls • Late >15 in boys • Late>13 in girls Duration of Puberty: Menarche: • Too long>5 yrs from TS Females • Too late>15-6 (or > 5 yrs II-V from TS-II breasts)

Puberty – Getting Earlier? Case #1

Menarche: • A 14yo male comes into your office. You detect upon • 1850s!1950s - mean age of menarche ↓ walking into the room that he needs to start wearing from 17 yrs! 12.5 yrs in U.S./Western Europe deodorant. You also note that he has some mild facial • Timing of menarche relatively stable since acne and some axillary hair. 1960s in U.S.

Breast Development: (1) Should you conclude that he is going through puberty • ? ↓ since the 1970s in the United States: normally? 1970s : age 8 1997 : age 7 (white girls) and age 6 (African American girls) (2) Which system causes these changes? ! ? Due to changes in nutritional, health, & SES, other causes (?endocrine disruptors?)

6 10/14/14

Case #1 Acne

• A 14yo male comes into your office. You detect upon • Can be part of normal walking into the room that he needs to start wearing development deodorant. You also note that he has some mild facial • Can contribute to negative acne and some axillary hair. self-image • Caused by the adrenal (1) Should you conclude that he is going through puberty system normally? • If severe acne and other • Not necessarily. signs/symptoms of (2) Which system causes these changes? androgen excess • These are all signs that his ADRENAL SYSTEM is producing • Consider endocrine disorder hormones, but does not tell you anything about the H-P-G axis. (eg non-classic congenital adrenal hyperplasia)

Case #2 Case #2

• A 12 yo male presents with pain • A 12 yo male presents with pain and swelling in his right and swelling in his right nipple

(1) What do you want to know? (1) What do you want to know? • Is puberty progressing (2) What can you tell him about normally? this condition? • Is he on any medications? Taking any drugs? • Does he have any chronic illnesses?

7 10/14/14

Gynecomastia Case #3

• Glandular development due to changes in hormone • An 11 year old female comes into your office for a sports levels during puberty (estrogenic-androgenic balance) physical. Name 2 common musculoskeletal complaints • 1/3 of healthy guys that occur in adolescence and are impacted by skeletal maturity. • Usually resolves in 3-24 mos without intervention • Assessment/management • Careful history for common drug culprits (drugs of abuse, antipsychotics, reflux meds, antifungals) or chronic disease • Physical exam to assess for true vs. pseudogynecomastia • Monitor every 3-6 mos until resolved • Consider treatment or surgical referral is lasting longer than 12 mos, causing discomfort/embarrassment, and adult testicular size has been attained

Hints! Answers

• Osgood Schlatter: • Caused by overuse!chronic avulsion of tibial tubercle growth plate • Usually happens in athletic adolescents right after growth spurt (i.e., age 13-14 in boys, age 11-12 in girls) • Clinical diagnosis: appropriate history, tibial tubercle swelling

• Scoliosis: • 80-85% adolescent onset • Progression more common in girls once diagnosed • Once skeletal maturity occurs, will not progress • Indications for referral to an orthopedic surgeon • Angle of trunk rotation (as measured with the scoliometer) of ≥7º, Cobb angle ≥20º, and progression of Cobb angle of >5º

8 10/14/14

Other common issues

• Anemia (9% of adolescent girls = iron deficient) • Myopia (caused by growth in axial diameter of the eye) • Dysfunctional uterine bleeding (80% due to anovulation) • STIs (peak incidence of many STIs 15-24 years) Adolescent Brain Development

Adapted with permission from Doug Diekema, 2013

Previous knowledge of adolescent brain

• Adolescents often do not perform at a level commensurate with their cognitive abilities • Middle adolescents are more likely than younger Adolescent Brain adolescents to rely on analytic processing, but this is not their primary means of decision making Development • Middle and older adolescents have the ability to make adult-level decisions (ie possess competence) but frequently do not use that ability or maximize use of those abilities

Klucyznski. 2001; 72:844

Adapted with permission from Doug Diekema, 2013

9 10/14/14

New Science of the Teenage Brain “Two” Brain Systems

• Balance between the two systems: • “Rational” : pre-frontal cortex • “Emotional” : Limbic structures, ventral striatum • Both have value, either can mislead • “Emotional” systems most adaptive for humans living in small communities (responds to individuals, crisis, reward – less utilitarian)

Epstein. Stanford Social Innovation Review. Spring 2006.

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

Scarecrow and Tin Man “Emotional” Brain

• Picks up patterns before consciously aware of them • Motivates behaviors change through feelings, autonomic repsonses • First impressions • Often based on a “thin-slice” of available information

Gladwell. Blink. NY: Little, Brown, & Co, 2005.

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

10 10/14/14

What does the prefrontal cortex do? Adolescent Brain Development

• High level reasoning • Extensive Remodeling and Pruning • Decision-making • Increased Linkages • Impulse control • Assessment of consequences • Corpus Callosum thickens • Planning, strategizing, organizing $ • Stronger links between Hippocampus • Inhibit inappropriate behavior (memory) and Frontal areas (goals and • Adjust behavior when agendas) situation changes • Increased Myelinization • Setting priorities • Estimating and understanding probabilities

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

Impact of Changes Adolescent Brain Development

• Improved balancing of impulses, desires, goals, self- • Not fully matured till mid 20s interest, rules, ethics, etc. • Maturation occurs “back to front” $ • Integration of memory and experience into decision- making • Pre-frontal cortex is last to mature • Improved planning • Imbalance: Less active pre-frontal, more active • Improved balance in considering immediate rewards and reward response system (ventral striatum) and future consequences limbic system • Males vs. Females

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

11 10/14/14

Prefrontal Cortex vs. Limbic System “The adolescent brain has a • PFC: well-developed accelerator but • Situation % assess % plan $ • (STOP) of survival only a partially developed • Limbic System: brake” • Situation % emotion/feeling % react --Laurence Steinberg

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

Why? Why?

• Once myelinization is complete and connections are • Evolutionary perspective established, learning slows down and the brain becomes • Adolescent: Movement from safety of home to less nimble and adaptable. complex outside world

• If the brain completed development earlier, the period of • Requires adaptability, willingness to take risk learning would be lost. • Sensation seeking: enhances learning, social connections • “If we smartened up sooner, we’d end up dumber” (David • Risk-taking: The young warrior Dobbs in National Geographic, October 2011)

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

12 10/14/14

Implications: PFCDD? The Adolescent Brain: Summary

• Impulsive, inflexible • Imbalance between development of pre-frontal (later) • Aggressive, Reckless and sub-cortical areas (early) • Emotionally volatile • Very sensitive to environmental cues, affective elements, • Risk-taking: less sensitive to risks and more sensitive to rewards and punishments possible rewards • Thrill seeking and risk taking. Impulsive • Reactive to stress • Brain is very good at decision-making tasks • Vulnerable to peer pressure • Brain is not very good at making decisions in emotionally charged situations • Respond to short term- rewards, excitement, arousal • Underestimate long-term consequences • Decisions may weigh current rewards and feelings at expense of future implications • Overlook alternatives NCHS Data Brief ■ No. 37 ■ May 2010

Adapted with permission from Doug Diekema, 2013 Adapted with permission from Doug Diekema, 2013

What are the leading causes of death for teenagers? Implications Putting it all into context

• Adolescents are capable of making rational decisions

• Less likely to be able to do so under conditions of high emotion or intense pressure (including peer pressure) • More likely to act impulsively without full consideration of consequences • Psychosocial and emotional contributors interact with cognitive aspects of decision-making • Emotional or “Gut Response” vs. Reason

Adapted with permission from Doug Diekema, 2013

13

■ 2 ■ 10/14/14

Putting it all into context Resources

• http://www.greatconversations.com • www.scarleteen.com • http://www.pbs.org/wgbh/pages/ frontline/shows/teenbrain/

No. 95 December 2011 The Teen Brain: Behavior, Problem Solving, and Decision Making

Many parents do not understand why their teenagers occasionally behave in an impulsive, irrational, or dangerous way. At times, it seems like they don’t think things through or fully consider the consequences of their actions. Adolescents differ from in the way they behave, solve problems, and make decisions. There is a biological explanation for this difference. Studies have shown that brains continue to mature and develop throughout childhood and adolescence and well into early adulthood.

Scientists have identified a specific region of the brain called the amygdala which is responsible for instinctual reactions including fear and aggressive behavior. This region develops early. However, the frontal cortex, the area of the brain that controls reasoning and helps us think before we act, develops later. This part of the brain is still changing and maturing well into adulthood.

Other specific changes in the brain during adolescence include a rapid increase in the connections between the brain cells and pruning (refinement) of brain pathways. Nerve cells develop myelin, an insulating layer which helps cells communicate. All these changes are essential for the development of coordinated thought, action, and behavior.

Changing Brains Mean that Adolescents Act Differently From Adults

Pictures of the brain in action show that adolescents’ brains function differently than adults when decision-making and problem solving. Their actions are guided more by the amygdala and less by the frontal cortex. Research has also demonstrated that exposure to drugs and alcohol before birth, head trauma, or other types of brain injury can interfere with normal brain development during adolescence.

Based on the stage of their brain development, adolescents are more likely to:

act on impulse misread or misinterpret social cues and emotions get into accidents of all kinds get involved in fights engage in dangerous or risky behavior

Adolescents are less likely to:

think before they act

14