Week 2 - Female Repro Flashcards by Matt Doers

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

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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)

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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

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Gonadal steroids (role in cycle)

Estradiol: increase in late follicular phase stimulates LH surge
Progesterone: increase in luteal phase suppresses GnRH pulses

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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

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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

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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

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Breast and pubic hair hormones

breast= estrogen (ovarian axis)

pubic hair= testosterone (adrenal axis)

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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

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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

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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

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Tamoxifen

anti-estrogenic in the breast
treatment and prevention of breast CA
sides: hot flashes, risk of endometrial ca, thrombo ds

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Raloxifene

estrogen agonist in bone
prophylaxis of osteoporosis
sides: hot flashes, thrombo, does not cause endometrial thickening

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Aromatase inhibitors

Letrozole, Anastrozole (reversible)
Exemestane (irreversible)
tx breast ca
sides: hot flashes

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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

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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