Week 2 - Female Repro Flashcards
Hormonal control of ovary
FSH (pituitary) mediated granulosa cells prolif and secretion. Also stimulates aromatase
LH (pituitary) stimulates theca cells androgen production and promotes follicle vascularization
Estrogen (ovarian follicles and CL) is anabolic and does lots of things
Estrogen Production
Theca cell: LH via cAMP stimulates cholesterol to pregnenolone to progesterone to androgens
Granulosa cell: can make progesterone like theca cells, but can also turn androgens into estrogens via aromatase (stim by FSH via cAMP)
Inhibins (role in cycle)
synthesized by granulosa cells
A: peaks in leuteal phase, suppresses FSH
B: index of granulosa cell volume in leuteal phase, suppresses FSH in midfollicular phase
Gonadal steroids (role in cycle)
Estradiol: increase in late follicular phase stimulates LH surge
Progesterone: increase in luteal phase suppresses GnRH pulses
Gonadotropins (role in cycle)
FSH: increase at end of luteal and beginning of follicular phase stimulates maturation of follicles
LH: surge stimulated by estrogen pos feedback stimulates ovulation
Effects of estrogen
Uterus: endometrium prolif Ovary: mitotic effect on granulosa cells Breast: ductal epithelium growth and differentiation Liver: metabolic modulation CNS: neuroprotective Bone: anti-resorptive
Things about female puberty that warrant evaluation
- breasts or pubic hair before 8yo
- absence of 2ndary sex char by 14yo
- absence of menstruation by 16yo
- absence of menses with a hx of menses for 3 cycles or 6mo
Breast and pubic hair hormones
breast= estrogen (ovarian axis)
pubic hair= testosterone (adrenal axis)
Physiological efects of estrogen
female sexual maturation and growth epiphyseal growth plate closure feedback regulation of GnRH positive effects on bone mass plasma lipids: inc trigs, lowers chol, inc HDL, dec LDL Increases coag, decreases anti-coag, increase fibrinolysis alters bile increases watery cervical mucus Promotes endometrial prolif** increases tubal contractility
Physiological effects of progesterone
decreases freq of GnRH pulses (supp gonadotropin)
decreases endometrial prolif
abrupt decline- end of cycle- onset of menstruation
maintenence of pregnancy
increases basal body temp mid-cycle
increases cervical mucus viscosity
decreases uterine contractions
Clomiphene
weak estrogen agonist and potent antagonist
induces ovulation
increases pulsitile gonadotropin release
reduces intracellular estrogen receptors, diminishes negative feedback, activates GnRH secretion
sides: hot flashes, multiple births
Tamoxifen
anti-estrogenic in the breast
treatment and prevention of breast CA
sides: hot flashes, risk of endometrial ca, thrombo ds
Raloxifene
estrogen agonist in bone
prophylaxis of osteoporosis
sides: hot flashes, thrombo, does not cause endometrial thickening
Aromatase inhibitors
Letrozole, Anastrozole (reversible)
Exemestane (irreversible)
tx breast ca
sides: hot flashes
Progestin drugs
Progesterone (low oral bioavail)
Medroxyprogesterone (ester, better)
Norethindrone and Norgestrel (oral, slower metabolism)
Drospirenone (spironolactone analog, monitor K)
Uses: pregnancy prevention, post-menopause hormone replacement (w/ estrogen)
Sides: breakthrough bleeding, androgenic action
Mifepristone
progesterone receptor antagonist
use: pregnancy termination (-49d)
usually given with misoprostol to ensure expulsion
Ulipristal
selective progesterone receptor partial agonist
use: emergency contraception (-5d)
inhibits LH release- inhibits ovulation
Leimyoma (uterine fibroids)
very common meno/menometrorrhagia intermenstrual spotting mass sx most prevalent during reproductive years Tx: surgery (myomectomy)
Benign neoplasms
endometrial polyps (endometrium) endocervical polyps (cervical mucosa) adenomyosis (invasion of endometrium into myometrium)
Anovulation and abnormal uterine bleeding
common at extremes of reproductive ages
result of chronic estrogen without cyclic postovulatory progesterone
endometrium becomes abnormally thickened
results in asynchronous shedding of endometrium unaccompanied by vasoconstriction
predisposes to endometrial hyperplasia and cancer
Endometrial atrophy
“spotting”
hypoestrogenism
must be eval bc looks similar to cancer
Endometriosis
presence of endometrial glands and stroma outside of endometrial cavity and uterine musculature
can cause adhesions, pain, infertility, inflammation
can have chocolate cysts
Tx: hormonal suppression (oral contraception, GnRH agonists, aromatase inhibitors), NSAIDs
Ovarian reserve
“biological clock”
inversely proportional to LH/FSH levels
proportional to antimullerian hormone (secreted by granulosa cells)
Anatomic causes of hypogonadotropic hypogonadism (2ndary amenorrhea)
tumors (craniopharyngioma)
infiltrative ds
cranial irradiation
Sheehan syndrome (pituitary ischemia postpartum)
lymphocytic hypophysitis (pituitary infiltration of lymphocytes)
Endocrine causes of hypogonadotropic hypogonadism (2ndary amenorrhea)
hyperprolactinemia
thyroid ds
hypercortisolism
hyperandrogenism
Uterine cervical lesions
Cervicitis (infxns, STDs)
Neoplasia (squamous or glandular, caused by HPV)
Non-HPV (benign polyps, cysts, leiomyoma, sarcomas)
HPV
super common, peaks in 20s-30s, have vaccine now
6,11= low risk= condyloma
16,18= high risk= CIN(mucosa)- higher grade- invasive carcinoma- metastasis
stains with p16
Lichen sclerosis (vulva)
increased risk of squamous cell carcinoma usually non-menstruating painful, itchy epithelial thinning, inflammation white plaques
Lichen simplex chronicus (vulva)
no risk of cancer
epithelial thickening
white plaques
Neoplasms of vulva
condylomas (dysplasia, warty)
carcinoma (VIN) (squamous cell or adeno) (HPV-assoc)
Paget disease (glandular cells in epidermis, LMCK:CK7)
Mesenchymal lesions
Vagina pathology
vaginitis rare stuff: squamous dysplasia and carcinoma(VIN) (HPV) clear cell carcinoma (DES exposure) Sarcoma botryoides (young kids)
Fallopian tube pathology
inflammation (salpingitis) (plasma cells)
ectopic pregnancy
endometriosis
tumors: BRCA assoc, serous carcinoma
Ovary pathology
follicle and luteal cysts
polycystic ovarian disease
tumors: surface epithelial, sex cord, germ cell
Functional cysts of ovary
follicular
luteal
inclusion
hemorrhagic
Ovarian neoplasms
usually in reproductive age, usually benign, 20% malignant
Surface epithelial: most common, inc risk with obesity, estrogen use
also: germ cell (teratoma(mature,capsule), yolk sac (a-fetoprotein)) and sex-cord (estrogenic, thecoma, granulosa cell, steroid, )
Most are sporadic, 10% are familial
Type 1: low grade, most common, genetically stable, KRAS, BRAF, PTEN, ERBB2
Type 2: high grade, genetically unstable, p53, Her2, AKT
can be papillary serous (psammoma bodies)
or clear cell
CA125 is blood test marker (non-specific)
Fallopian tube tumors
cause ovarian cancer too
BRCA-1 assoc
also p53
Abnormal uterine bleeding DDX
uterine polyps leiomyomas (fibroids) adenomyosis endrometriosis ectopic pregnancy blood dyscrasias medical/endocrine disorders other tumors
Endometrial adenocarcinoma
Type 1: estrogen dependent, hyperplasia-carcinoma sequence
assoc with obesity
endometrial hyperplasia (excess estrogen)
(microsatellite path, PTEN, KRAS, B-catenin)
Type 2: usually atrophic background, older women, more aggressive, p53
Also assoc with HNPCC (lynch), Cowden’s syndrome
