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
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2
Q

What are the pubertal “arches?”

A
  • Adrenarche
  • Thelarce: 8.9/10
  • Pubarche: 8.8/10.5
  • Gonadarche
  • Menarche: 12.2/12.9
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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
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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
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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
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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
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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
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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
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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
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10
Q

Why is bone devo important during puberty?

A

Adolescent years are a critical period for devo of peak bone mass

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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
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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
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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
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14
Q

Reiteration of simultaneous devo. Appreciate this.

A

Good job!

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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
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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
Q

How can you use the history to evaluate for precocious puberty?

A
  • 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
Q

How might this affect pubertal devo?

A
  • GIPP: adrenal tumor (if hormone secreting)
27
Q

How things can you examine in the PE to evaluate for precocious puberty?

A
  • Growth curve
  • Neurological exam
  • Thyroid
  • Breast development
  • Skin and pubic hair
  • Genitalia
  • Abdominal & pelvic palpation for mass
28
Q

What is the imaging/lab workup for PP?

A
  • 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
Q

What is some additional testing that can be done for GDPP? GIPP?

A
  • 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
Q

What are the txs for GDPP? GIPP? Goals?

A
  • 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
Q

What is delayed puberty? 3 types?

A
  • 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
Q

What are the causes of hypogonadotropic hypogonadism?

A
  • 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
Q

What are the causes of hypergonadotropic hypogonadism?

A
  • Ovarian Failure
  • Gonadal dysgenesis: normal or abnormal karyotype
  • Iatrogenic: cancer treatment, surgery
34
Q

What are the causes of eugonadism?

A
  • Mullerian agenesis
  • Outlet obstruction:
    1. Imperforate hymen
    2. Transvaginal septum
  • Androgen insensitivity
35
Q

How can you evaluate a pt for delayed puberty?

A
  • 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
Q

How do you manage a pt with delayed puberty?

A
  • Address surgical, medical causes
  • Induction of puberty using progressive doses of estrogens
  • Continued monitoring
37
Q

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?

A
  • 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