Puberty and Menstrual Disorders

when does puberty begin in girls

-around 8-9 yrs with thelarche(breast development)

-obese girls mature earlier, maybe bc of higher estrogen levels related to leptin and gonadotropin secretion

what systems are involved in puberty

-HPG axis, CNS, endocrine system

extrahypothalamic factors: cause hypothalamus to release GnRH

what does GnRH stimulate

stimulates anterior pituitary to secrete gonadotropins-FSH and LH(stimulate ovaries to secrete female sex hormones)

paracrine hormones

inhibin, activin, follistatin

-influence positive and negative feedback loops for HPG axis

adrenarche

increased production of adrenal androgens(occurs with regeneration of zona reticularis in adrenal cortex, usually at age 6-8, starts process before visualized changes)

gonadarche

gonadal maturation (decreases activation of HP gonadal axis, which involves pulsatile GnRH secretion stimulating anterior pituitary to produce LH and FSH, causes ovaries to produce estrogen)

-begins around 8

thelarche

breast development

-first phenotypic sign of puberty, development of breast buds

-occurs around 9 bc of increased estrogen

pubarche

pubic and axillary hair development

begins around age 11

menarche

onset of menstruation

-12-13 yrs average or 2.5 yrs after breast bud development

-adolescent menstrual cycle usually irregular for first 1-2 yrs, reflecting anovulatory cycles

what extrahypothalamic factors effect puberty

age and health

environment

stress

ovary development during puberty

-ovaries begin to release mature ova, puberty is complete at 1st ovulatory menstrual period(capable of reproduction)

-growth spurt occurs on average 2 yrs earlier in girls, peak velocity around 12(around 9 cm per year), due to direct effects of sex steroids on epiphyseal growth and increased growth hormone secretion

development of secondary sex characteristics

-average 4.5 yrs, range 1.5-6

-first physical sign is breast budding, followed by axillary or pubic hair

-next stage growth or peak height velocity

-next menarche

-final stage is adult pubic hair distribution and adult breasts

precocious puberty

-development of any secondary sex characteristic age 8 for girls, number 1 cause is idiopathic

-may cause psychological problems

tanner stage 1

-may be fine vellus hair that is no different than what is found over abdominal wall

-Preadolescent, elevation of papilla only

tanner stage 2

-growth of sparse straight hair, primarily along the labia

-Breast bud stage; elevation of breast and papilla as a small mound with enlargement of the areolar region

tanner stage 3

-hair increases in quantity and is curlier and darker

-Further enlargement of breast and areola without separation of their contours

tanner stage 4

-pubic hair resembles adult pubic hair

-Projection of areola and papilla to form a secondary mound above the level of the breast

tanner stage 5

-pubic hair has increased further in volume, spread onto medial thighs, taken on female configuration

-Mature stage; projection of papilla only, resulting from recession of the areola to the general contour of the breast

types of precocious puberty

-heterosexual(virilizing neoplasms, congenital adrenal hyperplasia, exposure to exogenous androgens)

-isosexual(incomplete, complete, pseudoisosexual)

heterosexual precocious puberty

development of secondary sex characteristics opposite of those of the anticipated phenotypic sex

isosexual precocious puberty

premature sexual maturation that is appropriate for the phenotype

complete isosexual puberty

full secondary sex characteristics and increased levels of sex steroids

incomplete isosexual puberty

early appearance of a single secondary sex characteristic

true isosexual puberty

premature activation involving the hypothalamic pituitary gonadal system, diagnosed by administration of exogenous GnRH with resultant rise in LH levels equivalent to normal girls going thru puberty

pseudoisosexual puberty

estrogen levels elevated, cause sexual maturation without activation of hypothalamic pituitary axis

which conditions are associated with pseudoisosexual puberty

-McCune Albright syndrome(sexual precocity, multiple cystic bone defects, cafe au lait spots)

-Peutz Jeghers(GI tract polyposis, mucocutaneous pigmentation)

-ovarian or adrenal neoplasm

-exogenous estrogen exposure, advanced hypothyroidism

Labs for precocious puberty

-LH and FSH

-dehydroepiandrosterone sulfate, testosterone

-17 hydroxyprogesterone, 11 deoxycortisol

-thyroid function tests

-GnRH stimulation test

X rays for precocious puberty

-serial bone age(looks more accelerated)

-MRI or CT of hypothalamic region and sella turcica

-MRI abdomen, pelvis, adrenal gland

tx true isosexual precocious puberty

-75% is constitutional or idiopathic(GnRH agonist therapy Leuprolide)

-needed to prevent accelerated epiphyseal fusion, or will be very short

delayed puberty

-secondary sex characteristics not appeared by 13

-no menarche by 15/16

-physiologic factors cause 95%

-some type of disruption of HPG axis

causes of delayed puberty

-constitutional(physiologic delay)

-chronic anovulation(PCOS)

-anatomic-outlet obstruction or agenesis

-androgen insensitivity syndrome

-hypogonadotropic hypogonadism

-Turner, Kalmann syndrome

turner syndrome

-XO karotype, causes delayed puberty

-often present with hypergonadotropic hypogonadism and features like short stature and infertility

Kalmann syndrome

-hypogonadotropic hypogonadism, anosmia/hyposmia

-may result from mutation of KAL gene on x chromosome or from autosomal mutations that prevent embryologic migration of GnRH neurons into hypothalamus-> decreased GnRH production and release

establishing the ovarian cycle

-before puberty, ovaries secrete small amounts of estrogen, inhibiting hypothalamic release of GnRH

-as puberty nears, if leptin adequate, hypothalamus becomes less estrogen sensitive, so GnRH is released, stimulates FSH and LH release by pituitary then acts on ovaries

-events continue until adult cyclic pattern is achieved and menarche occurs

how many days does each phase of uterine cycle last

menstrual phase days 1-5

proliferative(preovulatory) days 6-14

secretory(postovulatory) days 15-28

menstrual phase

-days 1-5

-ovarian hormones at lowest levels

-gonadotropin begins to rise

-stratum functionalis detaches from uterine wall and is shed(menstrual flow of blood and tissue)

-by day 5, growing ovarian follicles start to produce more estrogen

proliferative(preovulatory phase)

-days 6-14

-rising estrogen prompts generation of stratum functionalis(as layer thickens, glands enlarge, spiral arteries increase in number)

-estrogen increases synthesis of progesterone receptors in endometrium

-thins out normally thick mucus to facilitate sperm passage

-ovulation occurs at then end on day 14

secretory(postuvulatory phase)

-most consistent in duration(14 days)

-endometrium prepares for embryo to implant

-rising progesterone levels from corpus luteum-> functional layer becomes secretory mucosa, endometrial glands enlarge and secrete nutrients into uterine cavity, thickened mucus forms cervical mucus plug that blocks entry of more sperm, pathogens, or debris

what happens in secretory phase if fertilization does not occur

-corpus luteum degenerates towards end of phase and progesterone falls

-causes spiral arteries to kink and spasm

-endometrial cells die, glands regress

-spiral arteries constrict again, then relax and open wide, causing rush of blood into weakened capillary beds

-blood vessels fragment, functional layer sloughs off

-cycle restarts on 1st day of period

normal menses

regular bleeding, average every 28 days, lasts 3-5 days, average 30-50 mL

menorrhagia

heavy bleeding(>80 mL), or prolonged bleeding (>7 days), at regular intervals

hypomenorrhagia

light flow)<30 mL), at regular intervals

metrorrhagia

any bleeding between normal menses

menometrorrhagia

excessive or prolonged bleeding at irregular intervals

oligomenorrhea

irregular cycles >35 days apart

polymenorrhea

frequent regular cycles but <21 days apart

amenorrhea

-no menses by age 16 in presence of secondary sex characteristics

-no menses by age 14 in absence of secondary sex characteristics

dysfunctional uterine bleeding

idiopathic heavy/irregular bleeding with no identifiable cause

dysmenorrhea

pain and cramping during menstrual cycle with absence of pain between cycles

classifications of primary amenorrhea

1: disorders of outflow tract or uterine target organ

2: disorders of an ovary

3: disorders of anterior pituitary gland

4: disorders of CNS or hypothalamic factors

secondary amenorrhea

absence of menstruation for time equivalent to 3+ cycles or 6 months in women who have previously menstruated

causes of secondary amenorrhea

pregnancy

anovulation

dramatic weight loss

malnutrition or excessive exercise

hypothyroidism

PCOS

common during adolescence, perimenopause, lactation

manifestations of secondary amenorrhea

infertility, vasomotor flushes, vaginal atrophy, acne, osteoporosis, hirsutism, hyperprolactinemia

secondary amenorrhea tx

-replace deficient hormones(estrogens, thyroid hormones, glucocorticoids, gonadotropins)

-correct underlying pathology

vellus hair

non pigmented, soft and covers entire body

-converted to terminal hair by androgens at puberty

terminal hair

pigmented, thick, covers scalp, axilla, pubic region

hirsutism

-increase in terminal hair on face, chest, back, lower abdomen, inner thighs of women

virilization

development of male features in female(deepening of voice, frontal balding)

causes of non neoplastic ovarian disorders

PCOS

hyperandrogenic insulin resistance/acanthosis nigricans

-theca lutein cysts

Rotterdam criteria

Need 2/3:

-clinical or biochemical hyperandrogenism(LH:FSH ratio, testosterone)

-oligomenorrhea or amenorrhea

-polycystic ovaries(but not required for diagnosis)