Shephard - Female Puberty Flashcards
1
Q
What is puberty?
A
- Period during which adolescents reach sexual maturity, and become capable of reproduction
- Series of changes (physiologic + neuroendocrine) that result in ability to ovulate and menstruate:
1. Initial growth
2. Development of 2° sex characteristics
3. Growth spurt
4. Attainment of fertility - NOTE: girls hitting puberty earlier than ever
2
Q
What are the pubertal “arches?”
A
- Adrenarche
- Thelarce: 8.9/10
- Pubarche: 8.8/10.5
- Gonadarche
- Menarche: 12.2/12.9
3
Q
Adrenarche
A
- Before any perceived phenotypic change occurs; not visible b/c no physical manifestations (ages 6-8)
- Regeneration of inner layer of adrenal cortex (zona reticularis), and production of INC androgenic steroid hormones:
1. Dehydroepiandrosterone sulfate (DHEAS)
2. Dehydroepiandrosterone (DHEA)
3. Androstenedione - Production of these hormones INC from age 6-8 until age 13-15
4
Q
Gonadarche
A
- INC pulsatile GnRH secretion from hypothalamus leads to stimulation of ant pit to produce LH + FSH
1. Age 8, but a lot of ethnic variations in this - Initial INC mostly during sleep, and fail to lead to any phenotypic changes
- Eventually, LH + FSH pulsatility lasts throughout the day, leading to stimulation of ovary to produce estrogens
5
Q
What are the phenotypic changes of puberty? Cause?
A
-
Estrogen release triggers characteristic physical changes associated with puberty:
1. Breast development (thelarche)
2. Devo of pubic, axillary hair (pubarche)
3. Growth spurt: peak height velocity
4. Onset of menstruation (menarche) - Up, down, up, down: breast, pubic, axillary, menstruation
- Usually occurs over a 4-year period
6
Q
What is the age of onset of puberty? What things contribute to its variation?
A
-
Genetics account for the majority of the variability, but other factors include:
1. Overall health
a. Body fat important: gymnasts may go through puberty later on
2. Social environment: family stress, presence of an adult nonbiologically-related male
3. Environmental exposures: endocrine disruptors, environmental contaminants that may affect endocrine processes - While timing is variable, 98.8% of girls have first signs of sex devo ages 8-13
7
Q
Thelarche
A
- Typically the first phenotypic sign of puberty
- First stage of thelarche (development of breast buds) usually occurs around age 10
1. INC levels of circulating estrogens - As breasts are developing throughout puberty and adolescence, estrogenation of vaginal mucosa and growth of the vagina & uterus also occurring
8
Q
Pubarche
A
- Around age 11; onset of growth of pubic hair
1. Often growth of axillary hair too - 2° to INC in circulating androgens
-
Usually lags thelarche by ~6 mos, but pubic hair as the first sign of sex devo may be normal variant in some ethnic groups
1. Can see this as early as 6 years of age in AA girls, which is not terribly uncommon
9
Q
Peak growth velocity: timing, hormones
A
- “Growth spurt” characterized by acceleration in growth rate around age 9-10, w/peak growth velocity (~9cm/yr) around age 12
1. 17-18% of adult height accrued in puberty - Peak height velocity (PHV) attained in majority of girls before Tanner stages 3 in breast devo and 2 in pubic hair devo
1. On avg, 0.5 yrs prior to menarche - INC rate of growth is likely secondary to INC levels of GH and somatomedin-C that result from the INC levels of estrogen
10
Q
Why is bone devo important during puberty?
A
Adolescent years are a critical period for devo of peak bone mass
11
Q
Menarche: onset, cycles
A
- Average age of onset 12-13, or ~2.5 yrs after devo of breast buds
- During first 2 yrs after menarche, the majority of cycles are anovulatory (50- 80%)
- This accounts for the irregularity of cycles during this time period
12
Q
Tanner staging for pubic hair
A
- Stage 1 (preadolescent): NO sexual hair
-
Stage 2 (presexual hair): sparse, pigmented, downy hair mainly along the labia
1. PHV around this time - Stage 3 (sexual hair): darker, coarser, and curlier sexual hair appears
- Stage 4 (mid-escutcheon): hair distribution is adult in type, but decreased in quantity
- Stage 5 (escutcheon): hair is adult in type and quantity, with spread to medial thighs
- NOTE: can be difficult to detect this if the girl is shaving everything
13
Q
Tanner staging for breast devo
A
- Stage 1 (preadolescent): elevation of papillae only
- Stage 2 (breast bud stage): elevation of breast & papillae + areolar enlargement
-
Stage 3: further enlargement of breast & areolae w/o separation of contours
1. PHV around this time - Stage 4: projection of areolae & papillae to form a 2° mount
- Stage 5 (mature stage): projection of papillae only as areolae recess to breast contour
14
Q
Reiteration of simultaneous devo. Appreciate this.
A
Good job!
15
Q
What is precocious puberty? Epidemiology?
A
- Physical and hormonal signs of pubertal devo at an earlier age than is considered normal (2-3 SD)
1. Breast, pubic hair devo precocious if <7 for white girls and <6 years of age for black girls - Incidence in US is 0.01% to 0.05% per year, so not very common
1. 4-10x more frequent in F than M
2. More common among African-American than Caucasian children
16
Q
What causes the onset of puberty in females? What mechanisms suppress its onset?
A
- Onset of puberty via secretion of high- amplitude pulses of GnRH by hypothalamus => pulsatile INC in pituitary gonadotropins, LH and FSH
1. INC LH => production of sex steroids by ovarian granulosa cells
2. INC FSH => enlargement of gonads and follicular maturation - Mechanisms that suppress puberty onset:
1. HPO axis -> highly sensitive to feedback INH by small amounts of sex steroids
2. Central neural pathways that suppress the release of GnRH pulses
17
Q
What is the chronicity of normal pubertal devo in females (chart)?
A
18
Q
What are the risk factors for precocious puberty?
A
- Female gender
- AA race
- Obesity
- Exposure to sex hormones: taking mom’s birth control pills, for example
- Other medical conditions: McCune Albright, CAH
19
Q
What are the diagnostic criteria for precocious puberty?
A
- First noticed physical changes of puberty at a pre- pubertal age
1. Girls -> breast development - A growth spurt
- Skeletal maturity > chronological age (x-ray)
- Pubertal range hormone levels
1. Estradiol > 5 pg/mL
20
Q
What are the 3 classifications of percocious puberty?
A
- Gonadotropin-dependent: central or true precocious puberty
- Gonadotropin-independent: peripheral or pseudo- precocious puberty
- Incomplete precocious puberty: only one part, i.e., just breast, pubic hair, or rarely, just menses
21
Q
GnRH-dependent precocious puberty? Types?
A
- Early maturation of hypothalamic-pituitary- gonadal axis, but normal pattern, timing of steps
- F>M
- INC GnRH pulses => INC LH, FSH => INC ovarian estrogen production & ovulation
- CAUSES: 80-90% idiopathic, or CNS-related:
1. Tumors: astrocytoma, ependymoma, pineal tumor, optic and hypothalamic gliomas
a. Hamartoma: most frequent CNS tumor cause -> contain GnRH neurons, and act as ectopic hypothalamic tissue
2. Lesions: hydrocephalus, cysts, trauma, CNS inflammatory disease
3. Primary hypothyroid: TSH directly activates the FSH receptor
a. Google says: extreme TSH elevation seen in profound hypothyroidism induces FSH like-effects on the gonads, resulting in multicystic ovaries, uterine bleeding, and breast enlargement
22
Q
GnRH-independent precocious puberty? Causes?
A
- Excess secretion of sex hormones (estrogens or androgens) derived from the gonads or adrenal glands, or exposure to exogenous sex steroids
1. FSH, LH levels suppressed; estrogen INC
2. GnRH agonists are ineffective - CAUSES: follicular ovarian cysts most common; pts often present after episode of vaginal bleeding
1. Ovarian tumors: granulosa-cell tumors, leydig cell tumors, and gonadoblastoma are rare causes of precocious puberty
2. Exogenous estrogen
3. Adrenal pathology: androgen-secreting tumors, CAH
a. Attached image GIPP via adrenal adenoma in 3-y/o
4. McCune-Albright syndrome
23
Q
What is McCune Albright?
A
- Peripheral (GnRH-independent) precocious puberty + café-au-lait skin pigmentation + fibrous dysplasia of bone
- Girls usually present w/premature vaginal bleeding that usually occurs before significant breast development
- F>M
- Tx varies by gender: girls tend to overproduce estrogen, and boys overproduce androgens
24
Q
What is incomplete precocious puberty? 2 types?
A
- Early devo of 2o sexual characteristics; variant of normal puberty, but close monitoring needed
- X-ray of bone age to confirm that growth is NOT accelerated -> normal results = no further testing
-
Premature thelarche: isolated appearance of breast development (unilateral or bilateral)
1. Usually girls <3-y/o with normal growth rate -
Premature adrenarche/pubarche: pubic hair w/o signs of puberty in children younger than 7-8 years
1. Risk factor for PCOS (50%) - Can look at vagina to see if pt is IPP or complete precocious puberty:
1. Attached image shows progressive effects of estrogen on hymen and tissue of vestibule
25
How can you use the history to evaluate for precocious puberty?
- Age of onset + rate of progression of puberty
- Growth velocity
- _Hx suggesting CNS pathology_, i.e., headache, visual impairment, seizures, etc.
- _Hx of exposure to sex steroid_
- _Family hx_: puberty onset age/patterns, parental height
26
How might this affect pubertal devo?
- GIPP: adrenal tumor (if hormone secreting)
27
How things can you examine in the PE to evaluate for precocious puberty?
- Growth curve
- Neurological exam
- Thyroid
- Breast development
- Skin and pubic hair
- Genitalia
- Abdominal & pelvic palpation for mass
28
What is the imaging/lab workup for PP?
- _Bone age x-ray_: skeletal maturity ≥ 2yrs greater than chronologic age
- _LH, FSH levels_: pubertal range or overlapping pubertal and pre-pubertal levels
- _Sex hormone levels_: estradiol \> 5pg/mL
- Can also do GnRH stimulation to determine if GnRH-dependent or independent
29
What is some additional testing that can be done for GDPP? GIPP?
- _GnRH-dependent (GDPP)_:
1. MRI-brain: to check for brain abnormalities
2. Thyroid testing (for hypothyroid)
- _GnRH-independent (GIPP)_:
1. Additional blood tests
2. Pelvic ultrasound to check for ovarian cyst or tumor (of adrenal or ovary)
3. Bone scan
30
What are the txs for GDPP? GIPP? Goals?
- _GDPP_: GnRH analogue therapy
1. Monthly injection of leuprolide or other med to stop HPO axis and delay further devo until child reaches puberty (whenever determined)
- _GIPP_: treat underlying medical condition; remove exposure
- _Goals_: arrest/diminish sexual maturation until normal pubertal age and maximize adult height
31
What is delayed puberty? 3 types?
- Absence of sexual maturation by the age of _13_
- No evidence of menarche by age _15 – 16_
1. Menses not begun 5 years after thelarche
- TYPES:
1. _Hypogonadism_: hypogonadotropic or hypergonadotropic
2. _Eugonadism_
32
What are the causes of hypogonadotropic hypogonadism?
- Pituitary tumor
- GnRH insufficiency: inherited, nutrition, stressors
1. _Anosmia-Kallmann syndrome_: hypothalamic GnRH neurons fail to migrate to hypothalamus during embryonic development
- _Hyperprolactinemia_: prolactin INH FSH, LH
- Constitutional delay
- Chronic Disease
- CNS disorders or trauma
33
What are the causes of hypergonadotropic hypogonadism?
- Ovarian Failure
- Gonadal dysgenesis: normal or abnormal karyotype
- Iatrogenic: cancer treatment, surgery
34
What are the causes of eugonadism?
- Mullerian agenesis
- Outlet obstruction:
1. Imperforate hymen
2. Transvaginal septum
- Androgen insensitivity
35
How can you evaluate a pt for delayed puberty?
- _History and PE_, including looking for signs of Turner syndrome (attached)
1. Vaginal patency
2. Pelvic masses
3. Tanner Staging
- _Labs/imaging_: FSH, TSH, PRL, estrogen effect (if any)
1. Pelvic ultrasound
2. Karyotype
3. MRI (brain)
36
How do you manage a pt with delayed puberty?
- Address surgical, medical causes
- Induction of puberty using progressive doses of estrogens
- Continued monitoring
37
15-y/o F comes in for exam, and she has NOT had a period. Normal breast devo started 3 years ago. Normal height and weight, and has not had any significant medical illnesses. ROS, family hx (-).
Active in school and a cheerleader. Has boyfriend, but not sexually active —\> hopefully NOT pregnant.
BP 100/60. Weight 130. Breast stage 5. Soft, straight pubic hair covering mons, but not extending to thighs.
FSH/LH normal. Estrogen and thyroid normal. US: has ovaries, but no uterus.
What is going on here? What things are important?
- This girl has **mullerian agenesis**
- Hormonal tests are normal, but structural tests abnormal
- Would expect her pubic hair devo to be a little further along considering her stage 5 breast development
