What is adrenarche?
The production of sex hormones from the adrenal gland
When does adrenarche begin in girls?
6-8 yo. This occurs before any perceived phenotypic changes occur and is associated with regneration of androgen production from the zona reticularis
What are the main phases of female puberty in order?
-gonadarche (the increase in estrogens leads to the following stages)
1) growth acceleration
2) Thelarche, or development of breasts (stimulated by estradiol form the ovaries)
3) Pubarche, or the development of pubic hair (stimulates vy androgens from the adrenal gland)
4) Maximum growth rate
T or F. Mild to moderate obesity leads to earlier puberty
Notes about Gonadarche: this occurs when increased pulsatile GnRH secretion leads to subsequent release of LH and FSH and begins around age 8 in girls. Intitially these increases occur mostly during sleep and fail to lead to any phenotypic changes, but eventually LH and FSH pulsatility lasts throughout the day leading to stimulation of the ovary to begin estrogen production
T or F. During puberty there is up to 2x higher rates of depression in girls than in boys
T. Girls tend to struggle with the changes more. This trend has been found to be more pronounced in white girls
What is precocious puberty?
The onset of secondary sexual development prior to the age of 7 in white girls and 6 in AA girls
The timing of puberty is variable but 99% have the frist signs of sexual development between 8-13.
What are some GnRH-dependent causes of precocious puberty?
-Most commonly idiopathic (80-90%)
-Infection/Inflammation of CNS
-Rarely a tumor of the hypothalamic- pituitary stalk (hamartomas, astrocyotmas, ependymomas, pineal tumors, etc.)
-Primary hypothyroidism (TSH directly activates the FSH receptor)
What are some GnRH-independent causes of precocious puberty?
McCune Albright Syndrome (independent production of estrogen from the ovaries without FSH stimulation, bone fractures, and cafe au lait spots
-Adrenal tumors or CAH
-Iatrogenic estrogen administration
-ovarian cysts (most common cause: follicular cysts of the ovaries)- pts. often present with episodes of vaginal bleeding
A rapid-progression of precocious puberty suggests what as a potential cause?
GnRH-indepenedent cause such as a tumor
Evaulation of precocious puberty
1) Hx with pubertal staging
2) Radiographic evaluation of bone age
3) baseline LH level (high suggest GnRH dependent)- then go to brain imaging
4) GnRH agonist
What is delayed puberty defined as?
The lack of development of secondary sex characteristics by age 13
no evidence of menarche by age 15-16
no menses within 5 yrs of thelarch
How would hypergonadatropic hypogonadism cause of delayed puberty present in labs?
elevated FSH and LH
Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism, is a condition which is characterized by hypogonadism due to an impaired response of the gonads to FSH and LH and in turn a lack of sex steroid production and elevated gonadotropin levels (as an attempt of compensation by the body)
What is the most common cause of hypergonadatropic hypogonadism?
Turner Syndrome (XO), the lack of an X chromosome that present with short statue, webbed neck, solid chest, and streak ovaries
How is Turner syndrome treated?
estrogen administration which will stimuate breast development and genital tract maturation
What is the most common cause of a hypogonadotropic hypogonadism (lack of GnRH secretion) cause of delayed puberty?
constitiutional delay- tends to be familial
anorexia, exercise, stress
Causes of primary amenorrhea in girls with normal breast development
1) Mullerian agenesis (Mayer-Rokitansky Kuster Hauser Syndrome)- congenital absense of the vagina and/or uterus and fallopian tubes. Pt. will have normal ovaries
2) Imperforate hyman- obstruction of menstrual blood. Pt will have uterine pain
Adrenarche is one of the first manifestations of puberty, occurring at age 6-8, and characterized by the production of increased quantities of adrogenic steroid hormones such as DHEAS, DHEA, and Androstenedione from the adrenal cortex.
Production of these hormones increases from age 6-8 till age 13-15
What is Gonadarche?
In response to increased pulsatile secretion of GnRH from the hypothalamus, the ovaries in girls and the testes in boys begin to grow and increase the production of the sex steroids, especially estradiol and testosterone in response to LH and FSH.
Initially, these increases occur mostly during sleep and fail to lead to any phenotypic changes, but eventually LH and FSH pulsatility lasts throughout the day leading to stimulation of the ovaries to produce estrogens
When does gonadarche typically begin?
The increase in estrogen levels following gonadarche lead to what?
the characteristic physical changes assoicated with puberty incuding:
1) Breast development (Thelarche)
2) Development of pubic hair, and then axillary hair
3) Gorwth Spurts
In this order!
What factors influence the age of onset of puberty and menarche?
Genetics account for the majority of the variability but other factors include:
-social environment and exposures
T or F. The timing of events is variable but 98.8% of girls have the first signs of sexual development b/n the ages of 8 and 13
What is typically the first phenotypic sign of puberty?
What is the first typical stage of thelarche and what drives it?
The first stage is the development of breast buds around the age of 10 driven by increased levels of estrogen. Note that as the breasts are developing throughout puberty and adolescence, estrogenation of the vaginal mucosa and vaginal and uterine growth are also occurring
What is Pubarche?
Pubarche is the development of pubic hair usually occurring around age 11, and typically followed by the appearance of axillary hair secondry to increases in circulating androgens from the ovaries
How long does pubarche typically lag thelarche?
Usually by 6 mos but pubic hair can be the first sign of development in some ethnicites
How much growth typically occurs during female puberty?
Approximately 17-18% of adult height accrues during puberty, marked by a 'growth spurt' around age 9-10 with peak growth velocity occurring around age 12
This occurs AFTER thelarche and pubarche normally!!
When does peak height velocity typically occur in relation to thelarche and pubarche?
PHV is attained in the majority of girls before they reach Tanner stages 3 in breast development and 2 in pubic hair development
NOTE: PHV occurs on avg 0.5 yrs before menarche
What is thought to cause the growth spurt in femal puberty?
It is likely secondary to increased levels of GH and somatomedin C that result from the increasing levels of estrogen from gonadarche
When does menarche typically occur in female puberty?
Avg. age is between 12-14 (or 2.5yr after the development of breast buds in most girls)
Notes about menarche and early menstruation
During the first 2 yrs after menarche, the majority (50-80%) of cycles are anovulatory- this accounts for the irregularity many girls experience during this time period
Stage I correlates to preadolescence and the complete lack of sexual hair and only slight papillae elevations of the breast
What is precocious puberty?
The appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal (2-3 SD) OR
Breast or pubic hair development is precocious if under 7 years of age for white girls and 6 yo for black girls
T or F. Precocious puberty is more common in AA girls than white girls
T. And 4-10x more common in girls than boys
Precocious puberty is inhibited both by the central HPO axis, which is very sensitive to small amounts of sex hormones, as well as central inhibitory neural pathway that suppress gnRH releases
What are the risk factors of precocious puberty?
-female gender, AA race
-exposure to exogenous sex hormones
-McCune-Albright syndrome or CAH
Describe GnRH-dependent precocious puberty
This is the result of early secretion of GnRH causing accelerated development that is marked by early appearance of puberty BUT in a normal pattern and with appropriate intervals between phases
What are the most common causes GnRH-dependent percocious puberty?
Hamartomas- contain GnRH neurons and act as ectopic hypothalamic tissue (most frequent CNS tumor to cause)
-astrocytoma, ependymoma, pineal tumor, optic and hypothalamic gliomas
primary hypothyroid (TSH directly activates the FSH receptor)
What is GnRH-independnent precocious puberty?
Excess secretion of sex hormones (estrogens or androgens) derived from the gonads or adrenal glands or exposure to exogenous sex steroids. Here FSH and LH levels are suppressed, while estrogen is increased
GnRH agonists are ineffective in GnRH-independent precocious puberty
What are the msot common causes of GnRH-independent precocious puberty?
-Ovarian cysts (most commonly follicular)
-CAH and McCune Albright Syndrome
What is McCune-Albright Syndrome?
It is the replacement of trabecular bone with fibrous tissue that is characterized by multiple bone fractures, cafe-au-lait skin spots, and precocious puberty. Girls typically present with premature vaginal bleeding (usually will occur before significant breast development)
How is McCune-Albright Syndrome treated?
Trmt varies by gender as girls tend to overproduce estrogen and boys overporduce androgens
What are some types of incomplete precocious puberty (i.e. the appearance of some parts of puberty early, but not all)?
-Premature thelarche, or the isolated appearance of breast development (unilateral or bilateral) usually in girls younger than 3 yrs old. Growth rate is normal
-Premature adrenarche/pubarche, or the appearance of pubic hair without signs of puberty in children younger than 7-8 yo. Risk factor for PCOS
What is the goal of treatment of precocious puberty?
To arrest/diminish sexual maturation until normal pubertal age and to maximize adult height
What is delayed puberty defined as?
The absence of sexual maturaiton by the age of 13
No evidence of menarche by age 15-16
When menses have not begun 5 yrs after thelarche
What are the categories of causes of delayed puberty?
Hyper- and hypogonadotropic hypogonadism
What are some causes of Hypogonadotropic hypogonadism?
-GnRH insufficiency (inherited, nutrition, stressors)
-CNS disorders or trauma
What are some causes of Hypergonadotropic hypogonadism?
Gonadal dysgenesis (normal or abnormal karyotype)
Iatrogenic (cancer tx., surgery)
What are some causes of eugonadism?
-Outlet obstruction (imperforate hymen, transvaginal septum)