By: Dr.Fareeda Banu Associate Professor Dept of Physiology USM-KLE IMP Learning Objectives

⚫ Introduction

⚫ : Definition, Stages, Causes, Signs and Physical features.

⚫ Secondary sexual characteristics.

⚫ Hormonal changes during puberty.

⚫ Abnormalities of puberty: and Delayed or Absent puberty. Female Reproductive System • - Primary sex organs - Acessory sex Organs:

• Duct System • Uterine tubes (fallopian tubes) • Uterus • Vagina

• External genitalia

Introduction ⚫ The reproductive axis is driven by releasing (GnRH); neurons in the mediobasal hypothalamus that secrete GnRH in a pulsatile pattern.

⚫ GnRH, in turn, stimulates production of pituitary (LH and FSH).

⚫ GnRH neurons display a significant increase in activity in the first 2 years of infancy (“mini- puberty of infancy”), followed by about a decade of very low activity of the reproductive axis. Introduction ⚫ Puberty and adolescence are the phases of growth between childhood and adulthood.

⚫ Which includes the final maturation of the reproductive axis & development of secondary sexual characteristics brought about by gonadotropins, adrenal and GH.

⚫ During childhood, before puberty: ⚫ Small amount of gonadotrophins are secreted by anterior pituitary. ⚫ Hormonal secretion from is too small to cause maturation of reproductive organs. PUBERTY

⚫ Defn: It is the period when the endocrine & gametogenic functions of the gonads have first developed to the point where reproduction is possible. Girls- 8-13yrs Boys- 9-14yrs Puberty ⚫ Another event that occurs in humans at the time of puberty is an increase in the secretion of adrenal androgens. ⚫ The onset of this increase is called . ⚫ It occurs at age 8–10 years in girls and age 10– 12 years in boys.

⚫ Dehydroepiandrosterone (DHEA) values peak at the age of 25 in females and slightly later in males. ⚫ Then they decline slowly to low values in old age. ⚫ The rise appears to be due to an increase in the activity of 17α-hydroxylase. Cause of puberty : ⚫ During childhood , the hypothalamus is extremely sensitive to the negative feedback exerted by the small quantities of steroid hormones produced by the child's ovaries/testis .

⚫ Hence there is very less or slow release of Gonadotropins (FSH & LH).

⚫ At the time of puberty, the hypothalamic cells become more mature and less sensitive for feedback suppression by steroid hormones. Cause of puberty : ⚫ As puberty approaches , in addition to the release from CNS inhibition, there is also strong evidence for the activation of stimulatory centers in the CNS that induces the pulsatile secretion of GnRH .

⚫ Hypothalamus is also stimulated by the critical body mass, visual, external, olfactory and other sensory stimuli.

⚫ Hence at puberty, the frequency and amplitude of the GnRH pulses increase. This change increases LH and FSH secretion throughout the day. ⚫ Primary effects of LH and FSH on Gonads: ⚫ Stimulation of and .

⚫ Stimulation of Gonadal hormone secretion.

⚫ Maintenance of Gonadal structure. Cause of puberty : ⚫ The ovaries respond to the increase FSH&LH secretion by follicular development & estrogen secretion

⚫ This together with adrenal androgens produces puberty changes.

⚫ Leptin : plays a permissive role in hypothalamic maturation and resurgence of GnRH secretion at the onset of puberty. Leptin deficient individual fail to enter puberty. Cause of puberty : ⚫ The ovaries respond to the increase FSH&LH secretion by follicular development & estrogen secretion

⚫ This together with adrenal androgens produces puberty changes.

⚫ Leptin : plays a permissive role in hypothalamic maturation and resurgence of GnRH secretion at the onset of puberty. Leptin deficient individual fail to enter puberty.

Factors stimulating the time of Puberty ⚫ The mechanism explaining pulsatile secretion of GnRH is unclear; proposed mechanism include 1. Melatonin secretion by Pineal gland: Decrease in rate of melatonin secretion during puberty. 2. Leptin secretion by adipose tissues: **Leptin accelerates GnRH pulsatility in hypothalamic neurons, and it has a direct effect on the anterior pituitary. Physiologic Changes Associated with Puberty ⚫ The developmental milestones associated with puberty in boys and girls were objectively described by Marshall and Tanner and are referred to as Tanner stages.

⚫ The progression of secondary sex characteristics was characterized as five stages, ending in adult as stage 5.

⚫ In both sexes, these stages reflect the progressive modifications of the external genitalia and of sexual hair. Physiologic Changes Associated with Puberty ⚫ For boys; changes begin with testicular enlargement followed by pubic hair and penile growth. ⚫ For girls; changes begin with development followed by pubic hair and . ⚫ Changes are driven by increasing sex steroids. ⚫ Also, adrenal androgens increase (adrenarche) before gonadal and hormonogenesis (gonadarche). ⚫ At about 6 to 7 years of age in girls and 7 to 8 years of age in boys. Adrenal androgens are converted to , DHT, and and therefore contribute to growth of pubic and axillary hair, particularly in girls. Puberty changes in Males ⚫ The testis respond to increase in gonadotropin secretion by increase in testicular size and Testosterone secretion.

⚫ Initiation of spermatogenesis.

⚫ Testosterone causes development of genital organs and appearance of secondary sexual characters. Puberty changes in Males ⚫ The first sign of puberty in males is an increase in testicular volume.

⚫ Puberty is associated with numerous primary and secondary sexual changes, including growth and onset of function of the prostate and seminal vesicles; increased growth of the penis; increased muscle mass; thickening of vocal cords; appearance of pubic (), facial, and body hair; and development of libido.

⚫ Many of these changes are dependent on the conversion of testosterone to DHT.

Puberty changes in Females

⚫ Ovaries respond to increase in gonadotropin secretion by follicular development and Estrogen secretion.

⚫ Estrogen causes development of genital organs and development of secondary sexual characteristics.

⚫ With increased Estrogen secretion Menarche occurs. Puberty changes in Females

⚫ In girls, the first event is (development of ) , followed by pubarche (the development of axillary and pubic hair), and then by menarche (onset of first menstrual period).

⚫ Also associated with growth of genital organs, secondary sexual changes and pubertal growth spurt.

⚫ At puberty, the increase in estrogen induces most of the changes. Stages of Puberty in Females

⚫ Puberty is divided into 3 stages: Stage1- Thelarche (development of Breast): Estrogen & progesterone are responsible for this

Stage2- Pubarche ( growth of Pubic & axillary hairs): Androgens(0.5mg per day) secreted by ovaries & adrenals are responsible for this

Stage3- Menarche (onset of cycles of ): controlled by ovarian hormones Estrogen & Progesterone

Signs of Puberty: Tanner Staging in Females Stage 1 Elevation of papilla only. No pubic hair. (Prepubert (Thelarche) (Pubarche) al) Stage 2 Elevation of breast and Sparse, long, pigmented papilla as small mound, hair, along labia majora. areola diameter enlarged. Stage 3 Further enlargement Dark, course, curled hair without separation of breast sparsely spread over and areola. mons . Stage 4 Secondary mound of areola Adult type hair, abundant and papilla above the but limited to mons. breast.

Stage 5 Recession of areola to Adult type spread in contour of breast. quantity and distribution. Tanner Staging Stages of Thelarche Stages of Pubarche

Stages of In Boys In Girls Puberty Stage 1 Preadolescent stage/ stage of childhood (7.5yrs)

Stage 2 (12yrs Beginning of enlargement Onset of Thelarche in boys, 10.5yrs in of testis girls) (appearance of breast bud)

Stage 3 (14yrs Appearance of pubic and Enlargement of breast, in boys, 11.5yrs in axillary hair and penile Onset of Pubarche & girls) enlargement Growth spurt Stage 4 Further growth of internal Projection of areolas and (15.5yrs in boys, and external genitalia & onset of Menarche 13yrs in girls) Growth spurt (appearance of Menses)

Stage 5 Adult genitalia with Adult breast and genitalia (16.5yrs in boys, secondary sexual with secondary sexual 14yrs in girls) characteristics characteristics Pubertal growth spurt ⚫ The pubertal growth spurt refers to a significant increase in growth velocity. ⚫ The growth spurt occurs early in puberty in girls, but toward the end of puberty in boys.

⚫ The growth spurt is under complex hormonal regulation, involving triiodothyronine (T3), GH and its target, insulin-like growth factor-1 (IGF-1), and sex steroids.

⚫ Estradiol promotes normal bone density in both sexes and also promotes the cessation of long bone growth by inducing the closure of the epiphyseal plates in both sexes

Secondary sexual characteristics In Boys In Girls

Body Broad shoulders and Narrow shoulders, broad configuration more muscular body hips, diverging arms(wide carrying angle), female distribution of fat in the breast and hips giving characteristic curves and contours to the body. Hair growth Appears all over the Appearance in axilla and body, in axilla, over the pubis (female pattern: pubis (male patterna- triangle with apex down), triangle with apex up), less body hairs and more face & chest; hair line scalp hairs. on scalp recedes anterolaterally. Secondary sexual characteristics ….. In Boys In Girls Voice Enlargement of larynx No enlargement of and increase in length larynx, hence Voice and thickness of vocal changes into high pitch cords: Voice becomes deep and breaks External Increase in length and Increase in length & genitalia width of penis, scrotal width of clitoris and skin thickens, becomes enlargement of labia pigmented and rugose. majora & minora.

Internal Seminal vesicle, Increase in growth and genitalia prostate and activity of Ovaries, bulbourethral glands uterus and vagina. enlarge & secrete. Secondary sexual characteristics ….. In Boys In Girls

Skin Appearance of pimples Appearance of changes /acne on face due to pimples/acne on face less increased sebaceous than males as estrogen gland secretion by the antagonizes action of action of androgens. androgen on sebaceous glands.

Psychologi Individual becomes Changes in mental and cal aggressive, active emotional behavior, changes attitude, interest in shyness & interest in opposite sex develops opposite sex develops Secondary sexual characteristics include: In Girls In Boys ⚫ Narrow shoulders, broad hips, ⚫ Broad shoulders and more female distribution of fat muscular body ⚫ Less body hair female pattern of ⚫ Hair appears all over body, male Pubic hair pattern of Pubic hair

⚫ Voice changes into high pitch ⚫ Voice changes into deep and breaks

⚫ External & internal genitalia enlarge to attain adult size & ⚫ External & internal genitalia their activity increases enlarge to attain adult size & their activity increases

⚫ Appearance of pimples on face less than males ⚫ Appearance of pimples on face

⚫ Shyness &interest in opposite ⚫ Individual becomes aggressive, sex develops active attitude, interest in opposite sex develops

Hormonal changes during Puberty ⚫ The entire endocrine system is altered during adolescence.

⚫ However, it is essentially the activation of the hypothalamic-pituitary-gonadal axis that induces and enhances the progressive ovarian and testicular secretion.

⚫ Which are responsible for the profound biological, morphological, and psychological changes to which the adolescent is subjected. Hormonal changes during Puberty ⚫ The rising levels of plasma gonadotropins stimulate the to produce increasing amounts of estradiol. ⚫ Estradiol is responsible for the development of secondary sexual characteristics, that is, growth and development of the breasts and reproductive organs, fat redistribution (hips, breasts), and bone maturation. ⚫ The maturation of the ovary at adolescence correlates well with estradiol secretion and the stages of puberty. Hormonal changes during Puberty ⚫ Besides ovaries and testes, other endocrinal glands (adrenal, thyroid and anterior pituitary) also grow in size and their activity increases at the onset of puberty. The hormonal changes are: ⚫ Gonadotropins: there is slow increase in FSH&LH from childhood to pre-adolescent age but at the time of puberty it peaks suddenly.

⚫ Adrenal androgens: There is an increase in secretion of adrenal androgens at puberty (8-10yrs of age in girls and 10-12yrs in boys), which is known as adrenarche. They help in growth of pubic and axillary hair in both sexes and growth of muscle mass and strength in boys. Hormonal changes during Puberty ⚫ Growth hormone: ⚫ Normally from birth to pre-pubertal stage, the GH secretion is intermittent (few paeks/24hr) but at the time of puberty, there is an increase in the frequency and amplitude of the peaks. ⚫ It is responsible for generalized growth spurt at adolescence. ⚫ Thyroid gland secretion: ⚫ Also increases during puberty ⚫ Responsible for normal growth and development. ⚫ Role of IGF-I and Insulin in Puberty: The synergetic effect of gonadal sex steroids, growth hormone, and IGF-I production, shows a significant increase in pubertal growth acceleration. ABNORMALITIES OF PUBERTY ➢ Disorders of puberty are related to the time of its onset: ▪ Early onset of Puberty (precocious puberty) and

▪ Late onset of Puberty (delayed or absent puberty) Abnormalities of Puberty ➢ PRECOCIOUS PUBERTY: Onset of puberty in a child before 8yrs in girls and 9yrs in Boys. Commonly seen in girls. Two types- 1.True precocious puberty [central precocious puberty (CPP)]: It is gonadotropin-dependent and involves the premature activation of the hypothalamic- pituitary-gonadal (HPG) axis.

2. Pseudo Precocious puberty-[peripheral precocious puberty (PPP)]: It is gonadotropin-independent, and the presence of sex steroids is independent of pituitary gonadotropin release Abnormalities of Puberty 1.True precocious puberty (CPP/Gonadotropin dependent ) ▪ Associated with the full spectrum of physical and hormonal changes of puberty. ▪ Early development of secondary sexual characters with premature development of Gonads (with gametogenesis). ▪ Due to early maturation of Hypothalamo Pituitary Gonadal axis, either due to increased secretion of gonadotropins or decreased inhibition on release of GnRH from hypothalamus. Abnormalities of Puberty…. 2. Pseudo Precocious puberty- ▪ Early development of secondary sexual characteristics without development of Gonads (without gametogenesis) ▪ Caused by abnormal exposure of immature males to androgen or females to estrogen. ▪ In this, child may show altered sequence of events of puberty. ▪ Causes: 1. Congenital virilizing adrenal hyperplasia 2. Androgen secreting tumor in males. 3. Estrogen secreting tumor in females. Astrocytomas & Gliomas Abcess, Encephalitis and Trauma

Congenital adrenal Hyperplasia

Constitutional precocious puberty; that is, precocious puberty in which no cause can be determined, is more common in girls than in boys. Delayed or Absent Puberty: ⚫ Puberty is considered to be pathologically delayed in case of female, if menarche does not occur by 17yrs of age, or in case of male, testicular development and maturation fails to occur by the age of 20yrs. ⚫ More common in boys. ⚫ Causes: a. Panhypopituitarism: failure of hypothalamus/pituitary to secrete gonadotropins. b. Primary gonadal failure: refers to developmental failure or gonadal dysgenesis, which occurs in Chromosomal abnormality, Klinefelter syndrome (XXY pattern) in Males and Turner’s syndrome (XO pattern) in females. Delayed or Absent Puberty: ⚫ Features: ⚫ Lack of pubertal development. ⚫ Short stature ⚫ Associated with other endocrinal abnormalities, ⚫ Low levels of gonadotropins.

Genetically female with normal male Ovarian dysgenesis genitalia MCQs ⚫ What is the age of onset of Puberty in girls? A. 7-10years B. 8-13years C. 11-15years

⚫ Select the option with stages of puberty in proper order. A. Menarche – Thelarche-Pubarche B. Pubarche-Menarche-Thelarche C. Thelarche-Pubarche-Menarche Important Questions ⚫ Describe the stages of puberty in girls/boys and explain the hormones responsible for each.

⚫ List out the secondary sexual characteristics in a boy/girl during puberty.

⚫ Explain the hormonal changes during puberty.

⚫ SBQ on precocious / Delayed puberty. References:

1. Endocrine and reproductive physiology; the Mosby physiology monograph series by Bruce and Susan, 4th Edition. 2. Guyton and Hall, textbook of medical physiology 12th Edition. 3. Ganong’s Review of Medical physiology 24th Edition. 4. Medical physiology for Undergraduate students by Indu Khurana. 5. Text book of Physiology by Dr. A K Jain, 6th Edition.