Puberty is initiated by increases in hormones like leptin and kisspeptin which activate the hypothalamic-pituitary-gonadal axis, triggering the release of sex hormones and setting off physical changes. In females, puberty involves breast development, pubic hair growth, menarche, and ovarian and uterine maturation over 3-5 years starting around age 10. In males, it involves testicular growth, pubic hair growth, penis growth, voice deepening, and a growth spurt over 3-5 years starting around age 11. Throughout puberty, sex hormones influence brain development and increase emotional volatility and risk-taking behavior.

1. Hormonal Changes in puberty
MJ Rasaee
TMU Tehran 2022

3. 1. Puberty is the term used to describe the developmental changes a child undergoes to become sexually mature
and physiologically ready for reproduction and is composed of two phases: adrenarche and gonadarche. During
adrenarche, which typically begins around ages 7–8 years, the adrenal glands produce increasing levels of the
hormones dehydroepiandrosterone (DHEA) and testosterone . Gonadarche is a longer process that typically
takes 4–5 years, beginning around ages 9–10 and occurring on average a year earlier in girls than in boys
2. It normally begins between the ages of 8-14 in females, and between the ages of 10-16 in males.
3. During puberty, the production rate of growth hormone (GH) doubles and is associated with an increase in
growth velocity. Growth hormone appears to increase the rate of sexual maturation once a pubertal pattern of
pituitary gonadotropin secretion is established During puberty, The ovary is a site of GH reception and action,
where it can potentiate steroidogenesis and gametogenesis either directly or through endocrine actions. A
significant percentage of the final adult height is attained during puberty, then after puberty, the production rate
of GH decreases with age. In children with GH deficiency, it is known that the dosage of GH, in addition to the
duration of treatment, can greatly influence the final adult height. At present, the dosage of GH given to children
of short stature is kept at a constant rate throughout puberty.

4. 1. Adolescence (from Latin adolescentem, “the one who is growing”) is not the same as puberty, even
though both concepts are frequently confused. Adolescence comprises the adaptive period between
childhood and adulthood, and involves changes in psychological, social and physiological development
including the capacity to acquire affective and sexual behaviors typically feminine or masculine.
2. Adolescence is a time of transition from childhood to adulthood during which people experience significant
changes in almost all areas of their life, including biological functioning, cognitive capabilities, social
environments, and family and peer relation-ships. The prefrontal cortex of the brain undergoes change and growth
via the myelination and synaptic pruning process. other changes, adolescents experience an increase in
negative life events ,have more family conflict and often initiate romantic relationships.
3. Related psychological changes appear from 12 to 21 years of age. This period is characterized by the
modulation of the limbic-cortical circuits associated to the acquisition of adult cognition and the
establishment of neural information pathways required to promote emotional and social development
4. Psychological, emotional, and social changes :More sensitive to peer acceptance and rejection,
Develop functional and adaptive skills and competencies, Risk for depression , Question identity
,demonstrating expanding cognitive abilities.

5. 1. in fact, adolescents are easily overwhelmed by stressful situations, a fact evidenced by
their lack of control over stress. This explains the commonplace phrase, “they react
first, and they think second” when referring to teenagers. Then, since adolescents are
highly vulnerable to stressful factors, this transitional period of their development can
be particularly stressing for them
2. In addition, they show great difficulty in performing tasks involving inhibition of
impulsive behavior or continuous attention. Since youngsters seem to be unable to
perform such selective inhibition, they prefer pleasant activities offering immediate
reward, even if risky, because those activities appear to be more attractive and easily
gratifying than those offering long-term rewards

6. Brain maturation is influenced by
heredity and environment, prenatal
and postnatal insult, nutritional
status, sleep patterns,
pharmacotherapy, and surgical
interventions during early childhood.
Furthermore, physical, mental,
economical, and psychological
stress; drug abuse (caffeine, nicotine,
and ethanol); and sex hormones,
including estrogen, progesterone,
and testosterone influence the
development and maturation of the
adolescent brain. MRI studies have
suggested that neurocircuitry and
myelinogenesis remain under
construction during adolescence
because these events in the CNS
depend on sex hormones that are
specifically increased during puberty

7. Several executive brain functions are
governed by the prefrontal cortex,
which remains in a state of active
maturation during adolescence.
These complex brain functions are
regulated by the prefrontal cortex as
illustrated , adolescent teens may
take part in risk seeking behavior
including unprotected sex, impaired
driving, and drug addiction

8. The nucleus accumbens and amygdala
are the two most prominent parts of the
central nervous system involved in
riskier behavior and increased sex drive
among teenage adolescents. The
nucleus accumbens is highly sensitized
to accomplish desirable goals. A
decrease in dopamine in the nucleus
accumbens is involved in increased
vulnerability to drug addiction and risky
decisions. Sex hormones (estrogen and
testosterone) bind with their receptors to
induce increased sex drive and
emotional volatility and impulsivity. Due
to an immature prefrontal cortex,
adolescents also have an increased sex
drive and problems in self-regulation.

9. Injury and violence are the two most common
leading causes of death during adolescence.
Out of 19 million adolescents (15–24 years) in
the US that were diagnosed with HIV/AIDS,
39% admitted that they had unprotected sex. In
addition to risky sex behavior, 30% of
adolescents had been involved in motor vehicle
accidents, with 41% of these linked to deaths;
12% committed suicide; and 15% were victims
of homicide

10. influence of sex steroids on the
organizational and activational
effects that shape the
adolescent brain. Organizational
effects such as epigenetic
mechanisms, neuronal (and
receptor) pruning, remodeling of
dendritic spines, myelination,
and apoptosis are common
during adolescence. These
effects lead to the maturation
and remodeling of cortical and
limbic circuits, a fact that favors
the expression of certain
behaviors in adulthood, if
activational effects occur.

11. MRI studies have provided evidence that in
addition to the prefrontal cortex and limbic
system, myelinogenesis and neurocircuitry
remains under construction during
adolescence. Myelinogenesis requires
precursors such as polyunsaturated fatty
acids, of which many seafood's are a rich
source. Hence, consuming seafood may
accelerate brain maturation in adolescents.
However, malnutrition and substance abuse
may inhibit maturation of the adolescent
brain. (+) induction; (−) inhibition.

12. 1. we now know that one of the milestones that signal its beginning is the activation of the hypothalamic–
hypophyseal–gonadal axis ,a process in which a number of signaling biomolecules play a crucial role, among
them, peptide hormones, neurohormones kisspeptin and neurokinin B, gonadotropin-releasing hormone
(GnRH), the adipocytokine leptin, and growth hormone (together with its main effector, insulin-like growth
factor 1)
2. puberty begins with an increase in the child's adiposity (i.e., an increase in the size and number of
adipocytes); such change causes adipocytes to release more leptin, with a subsequent increase of this
hormone on the blood
3. At the kisspeptinergic nuclei of hypothalamus , when leptin binds leptin receptor-expressing neurons, these
cells increase the expression of the gene encoding kisspeptin
4. the neurons that secrete GnRH possess kisspeptin receptors (also known as GPR54). Kisspeptin, when
binding, causes an increase in the GnRH secretion pulses to the anterior portion of the pituitary gland . This,
in turn, leads to release of follicle stimulating hormone and luteinizing hormone, which, in general, exert their
action at the gonadal level increasing biosynthesis and secretion of sex steroid hormones . Finally, the steroid
surge triggers the expression of the secondary sex characters, e.g., breast development and widening of the
hips in women, and appearance of facial hair and broadening of the torso (especially chest and shoulders) in
men

13. Organ Systems Involved
The two major systems involved in puberty are the reproductive and endocrine systems. The hypothalamus,
pituitary gland, adrenal glands, ovaries, and testes all produce hormones involved in the changes of
puberty. However, these hormones produced during puberty affect nearly every system within the body, causing
both internal and observable changes. The skeletal system changes, muscles grow, the circulatory and respiratory
systems undergo rapid growth and development, and nervous system changes occur. During puberty, increases in
estrogen and testosterone bind receptors in the limbic system, which stimulates the sex drive and increases
emotional volatility and impulsivity

14. negative feedback
positive feedback
Key regulatory hormones involved in female puberty

15. Female Development During Puberty
1. Thelarche :refers to breast growth, typically the first sign of puberty in girls, occurring around 9 or 10. An
increase in estrogen causes the lactiferous duct system to develop, while an increase in progesterone causes
the lobular alveoli at the ends of lactiferous ducts to increase in number.
2. Pubarche :Approximately six months after thelarche begins, pubarche, or growth of pubic hair, will typically
occur. Pubic hair initially appears light, sparse and straight but will become coarse, thick, and dark throughout
the course of puberty. Approximately two years after pubarche, axillary hair will begin to grow, a secondary
sexual characteristic mediated by testosterone.
3. Menarche :Menarche is the female's first menstrual period, caused by an increase in FSH and LH. Menarche
typically occurs 1.5 to 3 years after thelarche at approximately 12.8 years of age in White race girls and 3-8
months later in African-American girls. During puberty, the uterine endometrium undergoes cycles of proliferation
and regression due to fluctuating plasma estradiol levels. This occurs until a point is reached when substantial
growth occurs so that withdrawal of estrogen results in the first menstruation (menarche). Plasma progesterone
levels remain low until a rise occurs after menarche, indicating that ovulation has occurred. The first ovulation
takes place approximately 6 to 9 months after menarche due to an immature positive feedback mechanism of
estrogen.
4. Ovarian Development :The rise in gonadotropins during puberty stimulates the ovary to produce estradiol,
which is responsible for developing secondary sexual characteristics such as thelarche, growth of reproductive
organs, fat redistribution to the hips and breasts, and bone maturation. Ovarian size increases from prepubertal
volume (approximately 0.5 cm^3) to a post pubertal volume (approximately 4.0 cm^3).
5. Uterus Size :The uterus of a prepubertal female is tear-drop shaped, with the neck and isthmus accounting for
up to two-thirds of the uterine volume. An increase in estrogen production causes the uterus to become pear-
shaped, with the uterine body increasing in length and thickness.
6. Vaginal Changes :Puberty brings about an enlargement of the labia major and labia minora. Clear to white
vaginal discharge may also be seen prior to the onset of menarche.

16. Several factors may promote the increase in GnRH that precedes puberty, including: reduced sensitivity to inhibition of GnRH secretion by the sex steroids; increased leptin, which
reduces inhibition of gonadotropins and their releasing hormones by the gonadotropin inhibiting hormone (GnIH); decreases in melatonin, with an associated reduction in GnIH production;
and increases in kisspeptin, perhaps triggered by a “somatometer” or “pubertal clock,” which acts to further increase GnRH secretion.
Key hormones involved in the initiation of puberty

17. Male development during puberty
1. Testicular Size :An increase in testicular size is typically the first sign of puberty in boys. Testes
increase in size during puberty due to the development of the seminiferous tubules. Increased LH
stimulates the synthesis of testosterone by Leydig cells, while increased FSH stimulates the
production of sperm by Sertoli cells. Testicular size increases throughout puberty .An increase in
testicular size causes the scrotal skin to become thinner and darker in color. Boys typically
experience their first ejaculation approximately one year after the testicles begin to grow. The first
ejaculation, however, does not automatically signal an ability to procreate. On average, fertility is
achieved one year after the first ejaculation.
2. Pubarche :The growth of pubic hair at the penile base typically occurs alongside testicular
development. Pubic hairs initially appear light, straight and thin; then become darker, curlier, and
thicker as puberty progresses. Approximately two years after the onset of pubarche, axillary,
chest, and facial hair begin to grow.
3. Penis Size :The growth of the penis occurs after testicular enlargement. The penis grows in
length, then width, and the glans penis and corpus cavernosum also enlarge.
4. Growth Spurt : results from interactions between sex steroids (estradiol/testosterone), growth
hormone, and IGF-1. The rise in sex steroids leads to an increase in growth hormone levels,
which causes an increase in IGF-1. IGF-1 causes somatic growth via its metabolic actions (e.g.,
increases trabecular bone growth). Following the growth spurt in males, the larynx and vocal
cords enlarge, and the boy's voice may 'crack' as it deepens in pitch.
5. Adrenarche : refers to the increased secretion of adrenal androgen precursors
dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and
androstenedione from the adrenal zona reticularis, which typically occurs prior to puberty in
children around the ages of 6-8 years. The eventual phenotypical result of adrenarche is
pubarche, as well as apocrine odor, increased oiliness of hair and skin, and acne.

18. Kisspeptin (KP) Expression in the Ovary Mainly Occurs in the
Granulosa Cells (GC) in Response to Preovulatory LH
SurgeLH surge also induces the expression of the full length
NTRK2 receptor, which with kisspeptin signaling drives oocyte
survival through the PI3K/AKT pathway. In addition, kisspeptin
stimulates steroid secretion by theca (TC) and luteal cells (LC).
Onset of Puberty in Female RatsAt around the time of
pubertal onset, decreased expression of PcG proteins by DNA
methylation along with histone 3 modifications increase Kiss1
mRNA expression resulting in elevated kisspeptin levels; this
rise is accompanied by increased sensitivity to it and number of
KISS1 neurons as well as enhancement of GPR54 signaling
efficiency and expressio Abbreviations: PcG;Polycomb group,
H3K9/14ac; Histon H3 acetylated at lysines 9/14, H3K4me3;
Histon H3 trimethylated at lysine 4, H3K27me3; Histon H3 tri-
methylated at lysine 27, E2; Estradiol.

19. Changes in pubertal hormone levels
according to Tanner stage and
approximate age.

20. •skeletal homeostasis is regulated by
reproductive hormones and their fluctuations
throughout life
•Prevalent reproductive disorders, including
premature ovarian insufficiency, hypothalamic
amenorrhea and hyperprolactinemia, are
common causes of low bone mass
•While it is traditionally held that gonadal sex
steroids play a major role in skeletal
homeostasis, research has advanced into the
influence of other reproductive hormones on
bone physiology

21. Suicide is the second leading cause of death among adolescents ages 10–24 years
worldwide and accounts for 17.7% of all deaths in youth ages 15–24 years in the United
States . Although suicide has a relatively low prevalence, over the past 10 years suicide
rates in the US have increased by 76% in youth ages 15–19 years and, more alarmingly, by
300% in youth ages 10–14 years
suicidal thoughts and behaviors (STBs)
Graphical depictions of prevalence
rates of suicidal ideation,
concentrations of sex steroids, and
brain volume as a function of age.
Shaded region indicates puberty. The
schematized trajectories of gray
matter volume adjusted for total brain
volume are based on data reported in
. B) Summary of typical associations
between pubertal hormones and brain
structures from both adolescent and
adult samples. ACC anterior cingulate
cortex, AMYG amygdala, HPC
hippocampus, MPFC medial
prefrontal cortex, OFC orbitofrontal
cortex, STM striatum.

22. Publication
Sample size and
characteristics
Age (years) Sex Psychiatric condition
Suicide-related
outcome
Study design and
methods
Findings Additional notes
Afzali et al. 2012
81 suicide
attempters
Mean = 23.63 SD = 8.
41
Range = 15–55
F
Assorted
(25 Past mental
disorder, 22 Previous
suicide attempt)
History of Suicide
Attempts
Structured interview
over 6 months after
attempt
Suicide attempts
were not associated
with menstrual cycle
phase.
Patients with
irregular menstrual
cycles were
excluded.
Baca-Garcia et al.
2010a
281 suicide
attempters
176 healthy controls
Mean = 30.8 SD = 8.8
Range = 18–92
F
Assorted
(229 Mood disorder,
229 SUD, 275
Previous psychiatric
treatment)
Recent Suicide
Attempts and Recent
Suicidal Ideation
Blood sample within
24 h of attempt:
estradiol,
progesterone, LH,
FSH
Suicide attempts
were was more likely
during the follicular
phase.
Suicide intent
severity was elevated
during low-
estrogen/low-
progesterone states
(pre-menstrual
phase, amenorreha,
menopause)
Butterfield et al.
2005
130 inpatients
Mean = 49.4 SD = 8.1
3
M PTSD
Recent History of
Suicide Attempts
(past 6 months) and
Suicidal Ideation
Blood: DHEA,
androstenedione,
testosterone,
estradiol
Suicide attempters
had higher DHEA
than nonattempters
Cayköylü et al. 2004a
52 suicide
attempters
50 healthy controls
Mean = 26.51 SD = 7.
82
Range = Not
Reported
F
Assorted
(8 PMDD, 1 SCZ, 2
MDD, 1 OCD)
Recent Suicide
Attempts
Blood sample within
12 h of attempt:
estradiol,
progesterone
Menstrual status
determined with
self-report.
Suicide attempts
were more frequent
during the follicular
phase.
Estradiol and
progesterone levels
were not different in
suicide attempters
compared to healthy
controls.
Patients attempting
suicide with OD or
admitted to the ICU
were excluded.
cyclical hormone changes may play an important role in “acute risk for
daily suicidal ideation, planning, and intent” in individuals with
sensitivity to hormone changes

23. Experiences of early adversity affect the programming and development of endocrine and neural systems
which undergo significant maturation during puberty. Puberty-related changes in ovarian, gonadal, and other
related hormones shape the neural circuits underlying social cognition, emotion regulation, and impulse control
(which include structures such as the amygdala, hippocampus, striatum, anterior cingulate cortex, and portions
of prefrontal cortex). Alterations in these circuits may partially explain the ways in which changes in sex
hormones are linked with the emergence of suicidal thoughts and behaviors during adolescence. Moderators
of these processes, including a neurobiological sensitivity to ovarian hormones, experience of ongoing life
stressors, and underlying mental disorders, are highlighted in red.