Puberty and Menstrual Disorders 1 Flashcards
Hypothalamic-pituitary axis
- GnRH (from hypothalamus)
- stim LH and FSH (from ant pit- stored in gonadotrophs)
- stim estrogen and progesterone (from ovarian follicle)
Ovarian Cycle- phases
- Follicular phase- onset of menstruation to surge of LH
- Luteal phase- LH surge to first day of menses
dec estradiol and progesterone from the regressing corpus luteum- initiates
-inc in FSH- stim follicular growth and estradiol secretion
2 cell theory of ovarian follicular development
- LH stim Theca cells- produce androgens (androstenedione and T)
- FSH stim Granulosa cells- convert androgens into estrogens
Luteal phase
- LH and FSH are suppressed (neg feedback of elevated estradiol and progesterone)
- if conception doesnt occur- progesterone and estradiol dec due to corpus luteal regression- FSH rises!- follicular growth
GnRH
- stim syn and release of LH and FSH (from ant pit)
- estradiol enhances hypothalamic release of GnRH to induce the midcycle LH surge
ovarian cycle- estrogen
- early follicular development- estradiol is low
- 1 wk before ovulation- estradiol starts to inc- reaches a maximum 1 day b/f LH peak
- after LH peak- estradiol falls
- luteal phase- estradiol rises for 5-7 days after ovulation and then returns to baseline b/f menstruation
ovarian cycle- progestins
- follicular development- ovary secretes small amt of progesterone
- prior to ovulation, the grafian follicle begins to produce progesterone
- secretion of progesterone by corpus luteum reaches a max 5-7 days after ovulation- returns to baseline b/f menstruation
ovarian cycle- follicular development
- primordial follicles mature into a graafian follicle
- follicle ruptures- releases an ovum
- luteinization of ruptured follicle= corpus luteum
- 8-10 wks of fetal development- oocyte-granulosa cell complex= primordial follicle
- adult- graafian follicle
- granulosa cells adhere to ovum- cumulus oophorus- antrum forms along the granulosa cells- innermost layer forms corona radiata- corona radiata and oocyte is released at ovulation
ovarian cycle- ovulation
- LH surge causes ovulation
- stigma forms- ruptures the follicular basement membrane- oocyte is expelled
ovarian cycle- luteinization and corpus luteum fxn
- after ovulation- granulosa cells of rupture follicle undergo luteinization= forms corpus luteum
- corpus luteum produces progesterone!!
- if pregnancy doesnt occur, corpus luteum is replaced by a scar (corpus albicans)
overall cycle
- corpus luteum dies- E and P fall
- inc FSH
- follicles grow, secrete E
- E neg feedback on FSH
- dec FSH levels- causes selection of dominant follicle- produces high levels of E
- high E- positive feedback on LH
- LH surge- ovulation- corpus luteum produces high P
- high P, E- neg feedback on LH and FSH
Endometrium-2 zones
- outer portion (functionalis)- sloughed off at menstruation, contains spiral a’s
- inner portion (Basalis)- remains unchanged, basal a’s
Endometrial cycle- 3 stages
- menstrual
- proliferative (estrogenic)
- secretory (progestational)
Menstrual phase
- 1st day of menstruation- day 1
- sloughing of functionalis layer, compression of basalis layer
Proliferative phase
- endometrial growth due to estrogenic stim
- inc in spiral a’s, mitoses
Secretory phase
- after ovulation- progesterone secretion by corpus luteum stim glandular cells to secrete mucus, glycogen
- glands become tortuous and lumens dilated
- stroma is edematous
- spiral a’s
- endometrial lining- maximal thickness
Secretory phase- if no conception
- corpus luteum regress- dec progesterone- endometrium undergoes involution
- constriction of spiral a’s- ischemia of endometrium- necrosis- sloughing of endometrium
Secretory phase- coag pathway is necessary
- menstruation disrupts BVs- normal hemostasis allows for the to rapidly repair
- warfarin, aspirin, clopidogrel- heavy bleeding
Menarche- median age
- 12.43 yrs
- 2-3 yrs after thelarche, at Tanner stage IV
Primary amenorrhea
-no menstruation by 13 W/O secondary sexual development
OR
-age of 15 W/ secondary sexual development
normal cycle length
- 21-35 days long in adults
- irregular thruout adolescents
excessive menstrual flow
- mean blood loss= 30 cc (change pad 3-6x/day)
- > 80 cc= anemia (change pad 1-2 hrs)
puberty- occurs when?
10-16 yo (mean is 12.4)
- genetic factors
- geographic location
- nutritional status
Fetal/newborn and childhood period
- HPO axis is suppressed b/w 4-10 yo
- low levels of gonadotropins and sex steroids:
- gonadostat sensitivity to neg feedback of low estradiol
- CNS inhibition of GnRH secretion
late childhood
- ages 8-11- inc in DHEA, DHEA-S, and androstenedione
- androgen prod- diff of zona reticularis- initial endocrine changes!!!
- rise in adrenal androgens- pubarche/adrenarche (axillary/pubic hair)
Onset of puberty
- 11 yo- intrinsic loss of CNS inhibition of GnRH release, dec sensitivity of the gonatostat to neg sex steroid feedback
- sleep-assoc inc in GnRH secretion
- inc GnRH- ovarian follicular maturation and sex steroid production- secondary sex characteristics
- positive-feedback mech of estradiol on LH release
Stages of Normal Pubertal Development
TAG ME
- Thelarche (breast development)- requires estrogen
- Adrenarche/pubarche (pubic/axillary hair)- requires androgens
- Growth spurt (1 yr before onset of menses)
- Menarche- requires pulsatile GnRH
Breast development- Tanner Staging
- 1- preadolescent- papilla elevation
- 2- breast bud stage- small mound
- 3- enlargement of breast and areola w/o separation of contours
- 4- projection of areola and papilla- form secondary mound
- 5- mature- projection of papilla only- recession of areola to general contour of breast
Pubic hair- Tanner Staging
- 1- preadolescent- absence of pubic hair
- 2- sparse hair along labia, slight pigment
- 3- sparsely spread, darker and coarser
- 4 adult-type hair
- 5- spread to medial thighs
precocious puberty
- secondary sexual characteristics prior to an age 2.5 standard deviations early than expected
- 8 yo- girls
- 9 yo- boys
- 75% idiopathic
- need to evaluate to eliminate a serious dz
2 groups of precocious puberty
- Heterosexual (opp gender characteristics)- virilizing neoplasms, CAD, exogenous androgens
- Isosexual (same gender)- constitutional, brain dz
Heterosexual precocity
- virilizing neoplasms, CAD, exogenous androgens
- androgen secreting neoplasms- Sertoli-leydig cell
CAD
- def of 21-hydroxylase
- excessive androgen prod
- classical- ambiguous genitalia at birth- if untreated, progressive virilization and short adult status
- Nonclassical (late onset)- premature pubarche
- salt wasting
Isosexual Precocity
- True- premature act of HPO axis
- Pseudo-isosexual- exposure of estrogens indep of HPO axis (tumors)
True Isosexual Precocious Puberty
- 75% constitutional or idiopathic
- dx- admin exogenous GnRH- resultant rise in LH
- 10% caused by CNS disorder
- dx with MRI of head
- tx- GnRH agonist (leuprolide acetate)- suppresses release of FSH and LH- decline of gonadotropins
- if untreated- 50% will < 5 ft height
Pseudoisosexual precocity
(w/o act of HPO axis!!)
- ovarian tumor
- exogenous estrogen
- McCune-Albright syndrome
- Peutz-Jeghers Syndrome
McCune-Albright Syndrome
(polyostotic fibrous dysplasia)
- somatic mutation during embryogenesis- fxn indep of their normal stim H’s
- mult cystic bone defects, cafe au lait spots
Peutz-Jeghers syndrome
- sex cord tumor- secretes estrogen
- GI polyposis, mucocutaneous pigmentation
Delayed puberty
- secondary sex characteristics not appeared by age 13
- no thelarche by 14
- no menarche by 15-16
- menses hasnt begun 5 yrs after onset of thelarche
Delayed puberty- causes
- Hypergonadotropic Hypogonadism (FSH, LH inc)
- Hypogonadotropic Hypogonadism (FSH, LH dec)
- Anatomic causes
Amenorrhea- types
(absence of menses)
- primary- no menses by age 13 W/O secondary sex characteristics; or no menses by age 13 W/ secondary sex characteristics
- secondary- prior menses, but has absent menses for 6 months
Primary amenorrhea- then do what?
- if NO sex characteristics- measure FSH and LH
- if sex characteristics- do US of uterus
primary amenorrhea- no secondary sex characteristics- measure what?
- FSH and LH!!
- if low- hypogonadotropic hypogonadism
- if high- hypergonadotropic hypogonadism- do karyotype analysis!!- 46,XX (premature ovarian failure) or 45X (turner’s syndrome)
Hypogonadotropic Hypogonadism
- low FSH and LH
- MRI
- exercise
- physiologic delay- most comon cause!!- hereditary- dx of exclusion
- Kallman syndrome
Kallman syndrome
- mutation of KAL gene on X chrom- prevents migration of GnRH neurons into hypothlamus
- anosmia!!!
Hypergonadotropic hypogonadism
- inc FSH and LH
- chromosomal or injury to ovaries by surgery, chemotherapy, radiation tx)
- 46,XX- premature ovarian failure
- 45X- turner’s syndrome
Turner’s syndrome
(45 X karyotype)
- most common form of female gonadal dysgenesis
- no signs of secondary sex characteristics
- mosaicism in 25%
- webbing of neck, broad flat chest, widely spaced nipples, short stature, streaked ovaries, absent puberty, coarctation of aorta
Primary amenorrhea + secondary sex characteristics- do what
US of uterus!!!
- absent or abnormal- Karyotype analysis: 46X,Y (androgen insensitivty syndrome); 46XX (mullerian agenesis)
- uterus present- outflow obstruction- imperforate hymen or transverse vaginal setpum
Primary amenorrhea + secondary sex characteristics- uterus abnormal
- AIS (androgen insensitivity syndrome)
- Mullerian agenesis
AIS (androgen insensitivity syndrome)
- 46,XY
- male levels ot T
- defect in androgen R
- testes are in abd wall- secrete antimullerian H’s- no uterus is formed
- external female genitalia, absent pubic hair
- small breasts
- tx- gonadectomy after puberty to avoid neolasm
Mullerian Dysgenesis
(karyotype 46,XX)
- mullerian defects that cause obstruction of vaginal canal- imperforate hymen or transverse
- MRKH syndrome- absence of uterus- failure of mullerian ducts to fuse distally; renal abnormalities
MRKH syndrome
(Mullerian Agenesis)
- normal secondary development and external female genitalia
- normal female range of T
- absent uterus and upper vagina
- 46,XX
- renal anomalies
- most common cause of primary amenorrhea in women with normal breast development!!
Primary amenorrhea + Secondary characteristics + uterus present- then what?
check of outflow obstruction!!
- no- evaluate for secondary amenorrhea
- yes- imperforate hymen or transverse vaginal septum
Outflow obstruction
- normal uterus on US
- imperforate hymen- monthly dysmenorrhea w/o bleeding- vaginal bulge- tx with hymenectomy
- transverse vagnal septum- no bulge- dx on MRI
