Weeks 2 and 3 (Women's Health) Flashcards

Question

Causes of DUB by age

Answer 1

Adolescent: HPG axis maturing, **blood dyscrasias** (Von Willebrand's disease, PT deficiency, leukemia) Reproductive age: chronic **anovulation**, **lactation**, exogenous hormones, hematologic abnormalities, thyroid disorders, hypothalamic dysfunction (stress, exercise, weight loss) Reproductive/Perimenopause: **declining ovarian function**, vWD, leukemia, thyroid problem, etc

Answer 2

**CBC** for anemia, thrombocytopenia **Pregnancy** test **Coagulation** studies (PT/PTT, bleeding time) **Thyroid** function tests **Imaging** (pelvic ultrasound) **Endometrial** sampling

Answer 3

Any **postmenopausal bleeding**/spotting **Perimenopausal intermenstrual** (metrorragia) or abnormal bleeding Abnormal bleeding with **history of anovulation** Note: **transvaginal ultrasound** can be alternative to endometrial biopsy

Answer 4

**Oral contraceptives** (suppress FSH/LH, angrogen secretion; increase SHBG) **Progestins** (restore menstrual cycle, useful when estrogen contraindicated)

Answer 5

**Endometrial ablation** (freeze, burn, etc) You **won't fix** the anovulation, but will decrease amount of bleeding (don't do this if woman wants to get pregnant!)

Answer 6

**Uterine** cancer: screening **not necessary** because presents with symptoms early on **Cervical** cancer: **screen** **Ovarian** cancer: **no effective** screening yet (most lethal too)

Answer 7

**95%** of uterine cancers originate in **endometrium** (endometrioid, papillary serous, clear cell) 5% originate in **myometrium**/muscle walls (leiomyosarcoma, endometrial stromal sarcoma, mixed homologous/heterologous mullerian tumors)

Answer 8

5% of all endometrial cancers Usually bilateral Looks like **fallopian tube** tissue 50% present with extrauterine disease (**metastasized** already) **Aggressive** course

Answer 9

**Type I** (**90%** of cases): due to estrogen excess, PTEN, **Kras** mutations, **microsatellite** instability, diploid, majority are early stage and curable **Type II** (**10%** of cases): unclear etiology, Her2/neu, **p53** mutations, aneuploid, present at advanced stage and poor survival

Answer 10

**Atypical** endometrial hyperplasia **Obesity** \>50lbs Unopposed **estrogen** **Hereditary** syndrome **Postmenopausal** bleeding **Tamoxifen** Diabetes, nulliparity, hypertension (not necessarily causative but associated)

Answer 11

**Thin** endometrium \<4mm is **protective** **Thick** endometrium **\>/=5mm** more likely to have endometrial **cancer**, malignancy, atypical hyperplasia \<5mm cutoff rules out cancer!

Answer 12

**Locally** invades **muscle** within uterus, cervix, adnexa **Lymphatic** spread from pelvic to **para-aortic nodes** **Hematogenous** spread to **liver** and **lungs**

Answer 13

Note: during surgery, have pathologist in OR to look at the cancer and determine whether or not to do LN dissection 1) **Grade 3** lesions 2) **Grade 2** tumors **\> 2cm** in diameter 3) Non-endometrioid histologies 4) \>50% of **myometrial invasion** 5) **Cervical** extension of disease

Answer 14

Done **surgically**! Staging is critical to **prognosis** and choice of **adjuvant** treatment (many will not need radiation therapy)

Answer 15

**Second most common** gynecologic malignancy **Highest mortality** of any gynecologic malignancy Incidence increases with **advancing age** Almost 75% of cases present with advanced stage II/IV If we could find patients with EARLY ovarian cancer, would be good prognosis, but cannot do this well Risk of relapse of advanced stage disease is 70% Most begin in **epithelium**

Answer 16

5 year survival rate: Stage I: 90% (but only 20-25% present in this stage) Stage II: 65-75% Stage III: 35-60% (45-60% present here) Stave IV: 5-20% **Overall: 45-50%**

Answer 17

**Inceased** risk: **nulliparity**, family history, personal history of **breast** **cancer**, "**incessant** **ovulation**" (more lifetime ovulatory cycles) **Decreased** risk: **oral contraceptives** (greater than **5 years**), breastfeeding, **pregnancy**, bilateral tubal ligation, prior hysterectomy (both of these might prevent cancer starting in fimbria from falling onto ovarian surface by severing the connection)

Answer 18

Natural history poorly defined Anatomic barriers (intraperitoneal location, **hard to feel**) **Non-specific early symptoms** (although there ARE early symptoms, just very different in diff people) Poor sensitivity and specificity of available tests (**CA-125**, transvaginal ultrasound) Note: majority of early stage cancers that ARE detected are low malignant potential or stromal tumors

Answer 19

Marker that is used to look for **ovarian cancer**, but is elevated in a LOT of different things (**other cancers**, endometriosis, pelvic infection, alcoholism, pancreatitis, etc), so not a great test The higher the **Stage** of ovarian cancer, the more people have % **CA-125 above 35** Seems to be that an **increase** in CA-125 and **not absolute value** tells you whether a woman has ovarian cancer CA-125 obtained in all women undergoing **surgery** for pelvic mass, interpreted with caution in reproductive aged women though (\>200 still concerning), if greater than 35 in menopausal woman means cancer 25% of the time

Answer 20

**Do NOT** use CA-125 or ultrasound as screening for ovarian cancer However, there are some new biomarkers...are they used? DO screen those with hereditary susceptibility? 10% are hereditary and will have BRCA1, 2, or HNPCC

Answer 21

**Epithelial** ovarian cancer can be **serous** (looks like fallopian tube), **mucinous** (looks like endocervix), **endometrioid**, **clear**, **mixed**; median age 55 years Specialized gonadal stroma ovarian cancer can be **granulosa** or sertoli-leydig; median age 50 years **Germ cell** (unfertilized ovum) ovarian cancer median age 19-26 years

Answer 22

**Low grade pathway**: normal ovary to ovarian **cyst** to **serous cystadenoma** or cystadenofibroma to **serous tumor** of low malignant potential to low grade serous carcinoma **High grade pathway**: goes to high grade serous carcinoma

Answer 23

Type of epithelial ovarian carcinoma **"Beach ball"** and **multicystic** Unilateral

Answer 24

15-20% of all ovarian neoplasms (benign or malignant) 60-75% present at Stage I Tumor markers: **AFP**, LDH, beta-hCG Embryonic: **teratoma**, polyembryoma Extra-embryonic: endodermal sinus (**yolk sac**), **choriocarcinoma**

Answer 25

**Immature** teratoma: **malignant**, contains immature neural elements, includes all 3 layers (ectoderm, mesoderm, endoderm) **Mature** teratoma: **benign**, most common ovarian tumor in childhood

Answer 26

**Fibrous** strands/septa infiltrated lymphocytes Most common malignant ovarian germ cell tumor 5% arise in dysgenetic **XO Turner's** or XY gonads (Gonadoblastoma) Female equivalent seminoma

Answer 27

**Schiller-Duval bodies**, pseudopapillary bodies with central blood vessel **AFP** marker?

Answer 28

Stage I: cancer confined to **one or both ovaries**; tumor on surface of ovary Stage II: cancer involves one or both ovaries with extension into **pelvic region** (uterus, fallopian tubes, bladder, sigmoid colon or rectum) Stage III: cancer has spread beyond pelvis to abdominal wall or abdomen, small bowel, **lymph nodes** or liver surface Stage IV: cancer has spread to **distant** **organs** (liver, spleen, lung)

Answer 29

Cervical cancer is the biggest problem in **developing countries** (80% of cases) because of lack of screening Third most common cancer worldwide Withiin the US, more of a problem in black and hispanic populations

Answer 30

Inadequate screening **Asymptomatic** at early stage disease **False negative** pap smear (even with regular screening) **Endocervical adenocarcinoma** (origin within endocervical canal is more difficult screening)

Answer 31

**Conventional**: Ayres spatula placed in fixative; debris, non-uniform distribution of cells, **harder to read** **Liquid-based**: cervical broom multipronged; cells rinsed, **distributed evenly**, able to do **HPV testing**

Answer 32

**Latency** period from **dysplasia** to **cancer** of cervix is variable, but estimated **preclinical** **phase** SCIS to cancer is **5-10 years**

Answer 33

Sexually transmitted Colonizes entire genital tract Patient is generally **asymptomatic** Most infections **clear over time** Cervix is area at greatest risk because of **transformation zone** 75% of population in US has been exposed to HPV, 60% has HPV antibodies but cleared the infection (no HPV DNA) In addition to cervical cancer can cause **anal, vulvar, vaginal, penile, oropharyngeal cancer**

Answer 34

**Hybrid Capture II** Hybridize cervicovaginal cells with specific HPV RNA probe cocktain and see which ones "captured" by specific antibodies Immobilized hybrids (whatever you're positive for) will be detected by **chemiluminescence**

Answer 35

**Atypical squamous cells of undetermined significance** (ASC-US) Atypical squamous cells, **cannot rule out high grade lesion** (ASC-H) May be precancerous, so always **test these samples for HPV**

Answer 36

High grade (or low grade) **squamous intraepithelial lesion** No all people with HSIL or LSIL have prsence of HPV right now, but **at one point** they did!

Answer 37

**CIN 1**: mild dysplasia, includes condyloma (anogenital warts); have **koilocytes** (larger nuclei) in **lower 1/3** of biopsy from basement membrane **CIN 2**: moderate dysplasia; koilocytes occupy b**ottom 2/3 of epithelium** from basement membrane **CIN 3**: severe dysplasia, includes **carcinoma in situ**; dysplastic cells occupy entire thickness of epithelium **Invasive**: invasion of the basement membrane

Answer 38

**Gardasil**: strains 6, 11, 16, 18 **Cervarix**: strains 16, 18

Answer 39

Antibody titer after HPV vaccine is VERY **high** and remains high People who had HPV infection but cleared it had **lower** antibody titer

Answer 40

Age at **first** coitus **Number** of sexual partners (\>4) Venereal **warts** **Smoking**

Answer 41

**Squamocolumnar junction** (transformation zone)

Answer 42

75% **squamous** **cell** carcinoma on **ectocervix** 15-20% **adenocarcinoma** on **endocervix** (harder to detect) 1-2% **small cell**

Answer 43

Postmenopausal **bleeding** Irregular menses Postcoital spotting Vaginal **discharge** **Pain, leg edema**

Answer 44

Clinical staging Ia1: \<3mm depth, \<7mm wide, cannot see Ia2: 3-5mm depth, \<7mm wide, cannot see Ib1: \<4cm, seen on cone biopsy Ib2: \>4cm, seen on cone biopsy IIa: proximal vaginal disease (down) IIb: extends to parametria (out) IIIa: distal vaginal disease (all the way down) IIIb: extends to pelvic sidewall and obstructs ureter (all the way out)

Answer 45

5 year survival Stage Ia: 97% Stage Ib: 70-85% Stage II: 60-70% Stage III: 30-45% Stage IV: 12-18%

Answer 46

If only **Stage Ia1** and wants to have baby, can just do cervical **conization** Otherwise **hysterectomy** (simple vs. radical) or **radiation** or chemoradiation

Answer 47

HNPCC, or **Lynch II Syndrome** Caused by **defective DNA mismatch repair** MSH2, MSH6, MLH1 Earlier age at diagnosis (~45 years) **Right** side (proximal) colon tumor **Extracolonic** **cancers**: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors

Answer 48

* *Amsterdam II criteria** (diagnostic for HNPCC): * *3 relatives** w/HNPCC associated cancers; 1 case of first-degree relative in successive 2 generations; at least **1 cancer \<50**, exclude FAP **Bethesda criteria** (suggestive of HNPCC): colon or endometrial cancer at **age \<50**; **2 HNPCC cancers** in any person at any age; colon or endometrial cancer in person with **1 or more first degree relatives** with HNPCC cancer, with at least 1 diagnosed \<50; colon or endometrial cancer at any age, in an individual with 2 or more first or second degree relative with HNPCC

Answer 49

**Colonoscopy** at **age 20-25** every 1-2 years for **colorectal cancer** **Transvaginal ultrasound** or endometrial aspirate annualy starting at **age 25-35** for **endometrial** **cancer**

Answer 50

BRCA1 and BRCA2 complex with RAD51, are phosphorylated by cellular damage and BRCA1 **co-activates p53-related transcription** **Now** **can't do DNA double strand repair**, maintain chromosomal integrity, or transcriptional regulation **BRCA1 inactivation** may allow estrogen-promoted carcinogenesis

Answer 51

**BRCA1** has high risk of **breast** **cancer** and **ovarian cancer** **BRCA2** has high risk of **breast** **cancer** but lower risk for ovarian cancer; can cause **male breast cancer**; increased risk of **prostate**, **laryngeal** and **pancreatic** cancers

Answer 52

3 **Jewish founder mutations**: 2 in BRCA1 and 1 in BRCA2 1/40 Ashkenazi Jews carries BRCA mutation

Answer 53

**2 relatives** with breast cancer (same side of family) if **one occurred before age 50** **3 first or second degree** relatives with breast cancer at any age **Breast** and **ovarian** cancers in 2 first or second degree relative A first degree relative with **bilateral breast cancer** **Ashkenazi** ancestry with any first degree relative with breast or ovarian cancer **Male breast cancer** in family

Answer 54

Because most cancer detected is **already advanced stage**, majority of early stage cancers have low malignant potential or stromal tumors Cost to screening Sensitivity is only \<50% and PPV 17-40%

Answer 55

Increases uterine cancer risk Used to treat breast cancer--use for only 5 years??

Answer 56

**No menses by age 16** when secondary sexual characteristics exist **No menses by 14** when no secondary sexual characteristics exist Prevalence is 1-2% in US

Answer 57

Absence of menses for **3 menstrual cycles** or a total of **6 months** in women with previously normal menses

Answer 58

Menses at **greater than 35 day** intervals

Answer 59

**Regular** intervals but **excessive** **flow** and duration

Answer 60

Menses at **irregular** intervals, **excessive** flow and duration

Answer 61

Menses at **intervals less than 21** days

Answer 62

Fetal **testis** necessary for **masculine** **genital** **development** **Ovary not essential for development** of fallopian tubes and uterus

Answer 63

**Vas deferens** **Seminal vesicles** **Epididymis** Regress in females without gonadal influence

Answer 64

**Fallopian tubes, uterus, upper vagina** Grow caudal and fuse in midline Regress in male secondary to MIF

Answer 65

Uterus and breasts: **secondary** amenorrhea, **hypothalamic**, **pituitary** or **ovarian** causes, **congenital** abnormalities of genital tract-**outflow** tract Uterus but no breasts: **gonadal failure**/agenesis, disruption of **hypothalamic** axis, **Turner Syndrome** No uterus and breasts: **mullerian agenesis** (XX), **androgen insensitivity syndrome** No uterus and no breasts: **gonadal agenesis** in 46XY, **17 alpha hydroxylase deficiency**, **5-alpha reductase deficiency**

Answer 66

**Hypergonadotropic** (high LH, FSH): postmenopausal, s/p oophorectomy or **ovarian failure** **Hypogonadotropic** (low LH, FSH): prepubertal **hypothalamic** or **pituitary dysfunction**

Answer 67

**Primary ovarian failure**: high LH, FSH and low estrogen **Gonadal dysgenesis**: defective embryonic development of the gonads (**Turner** **Syndrome**: 45XO, ovaries undergo rapid atresia and follicles don't mature properly, so no more primordial follicles by puberty) **Savage Syndrome**: receptor defect where ovaries do not respond to FSH and LH

Answer 68

**Phenotypic** **female** with **sexual infantilism** and a 46XX or 46XY karyotype Usually have **streak gonads** Note: gonadal dysgenesis most common cause of primary amenorrhea, but can also present with secondary amenorrhea

Answer 69

50% are **45X** 25% are **mosaic** 25% are **46 XX**

Answer 70

**45XO** **Short** stature, **webbed** **neck**, **shield** **chest**, widely spaced nipples, cubitus **valgus** (increased carrying angle at elbow), **streak gonads** **Primary amenorrhea** usually 40% are **mosaics** If Y present, gonads need to be removed as soon as the diagnosis is made (but this is not Turner's??)

Answer 71

AKA **XY gonadal dysgenesis** XY karyotype but **phenotypically female** because no MIF (have mullerian system) Treatment: **remove gonads** (prevent testicular cancer?)

Answer 72

Mutation in **StAR** protein **Block** in cholesterol to pregnenolone

Answer 73

Can be XX or XY with absent uterus (because have MIF) **Hypertension** and hypokalemia (because too much aldosterone)

Answer 74

**Imperforate hymen**: may have cyclical pain from blood accumulation **Transverse vaginal septum**: may be from failure to fuse mullerian derived upper vagina and UG sinus-derived lower vagina **Vaginal agenesis**

Answer 75

**Mayer-Rokitansky-Kuster-Hauser syndrome** **Primary amenorrhea** **No vagina**, but 46XX and ovaries seen on ultrasound and normal **ovarian** **function**, have **breasts** Reared as females Complete absence of uterus and complete vaginal agenesis or partial vaginal agenesis with rudimentary uterus and distal vagina 1/3 have urinary tract abnormality, 12% have skeletal abnormalities Treatment: **mechanical** (serial dilatation of perineal body), or **surgical** (create vagina via McIndoe or Vecchietti operation)

Answer 76

Formerly **testicular feminization** **Abnormal androgen receptors** (either absent, or abnormalities in binding) Normal **female phenotype**, normal **male karyotype**, normal or slightly elevated testosterone **46XY** and have **breasts** but **no uterus**, short **blind vagina** Secrete **MIF** and have no mullerian structures, but do have **male gonads intraabdominally** **Male** **pseudohermaphrodite** (XY with genitalia opposite from gonads--**vagina** but **testes inside**) Treatment: reased as females but need **gonadectomy** after full development, HRT, possible vaginal surgery

Answer 77

**Gonadal dysgenesis** (most common, 30%) **Mullerian agenesis** (14%) **Androgen insensitivity syndrome**

Answer 78

**Tumors** **Infarcts** **Surgery** **XRT**

Answer 79

**Malignant** **tumors** (very rare) **Benign tumors** (problem because of confined space) **Prolactinomas** and nonfunctioning adenomas are most common Symptoms include headaches and visual changes **Sheehan's syndrome** (post-partum necrosis of anterior pituitary)

Answer 80

OB **hemorrhage** results in pituitary insufficiency from ischemia and infarction

Answer 81

**Prolactin** elevated in **1/3 of women** with no obvious cause of amenorrhea 1/3 of women **with** **high prolactin** have **galactorrhea** 1/3 of women **with galactorrhea** have **normal menses** 1/3 of women **with secondary amenorrhea** will have a **pituitary adenoma** and if galactorrhea is present then 1/2 will have abnormal sella turcica

Answer 82

Comprise 50% of all pituitary adenomas Microadenomas (\<10mm) may not need tx but can use **dopamine agonist** (parlodel, cabergoline, bromocriptine) Macroadenomas (\>10mm) medical treatment or close f/u, **surgery**, and/or **radiation**

Answer 83

**Prolactinoma** **Primary hypoparathyroidism** (causes increased TSH and **TRH**) **Medications** that increase prolactin (dopamine antagonists: Haldol, TCA, MAO inhibitors and opiates) **Breast stimulation** **PCOS**

Answer 84

**Hypothalamic disorders** **Low LH, FSH** and low estrogen Tumors: **craniopharyngioma** **Kallman Syndrome**: congenital **absence of GnRH** and **anosmia** (uterus but no breasts) Eating disorders Extreme exercise/stress Constitutionally delayed puberty **Hyperprolactinemia** Note: amenorrhea without galactorrhea or other abnormalities and normal imaging studies is hypothalamic amenorrhea (hypogonadotropic hypogonadism)

Answer 85

Affects 5-10% of adolescent women High mortality **FSH and LH levels low** (like in **childhood**) **Hypercortisolism** TSH and T4 normal, but **T3 low** and **rT3 high** Relative **hypothyroidism** (constipation, cold intolerance, bradycardia, hypotension, dry skin, low metabolic rate, hypercarotenemia) 30% remain **amenorrheic** despite resumption of gonadotropin secretion with weight gain

Answer 86

**Decreased frequency of GnRH pulses** Rates of amenorrhea attributed to differences in body fat content (runners and ballet dancers at higher risk than swimmers)

Answer 87

**Pregnancy** **test** **TSH** **Prolactin** (can be increased due to TRH increased) **Progesterone challenge** **FSH/LH/estradiol**

Answer 88

1% of women Early **depletion of ovarian follicles** Ovarian failure **before 40 years** **Elevated gonadotropins** (LH, FSH) repeatedly Check TSH, thyroid antibody, T3, T4, fasting glucose, adrenal antibody, Ca2+, PO4, CBC, ANA, rheumatoid factor, consider Fragile X

Answer 89

**Primary** amenorrhea: 50% = **45X** 25% = Mosaic 25% = 46XX **Secondary** amenorrhea: **46XX** most common 45X/46XX mosaic Deletions in X and long arm 47XXY 45X

Answer 90

All patients **under age 30** with **amenorrhea** and elevated **gonadotropins**, presence of a **Y chromosome**, T**urner's (45XO)** Consider it in young woman less than 60 inches tall (Turner's) All women desiring future fertility (Turner's or Turner's mosaics)

Answer 91

**Age** and **dose** dependent 250-500 rads age 15-40 = 60% sterilized 500-800 rads age 15-40 = 65% sterilized \>800 rads = 100% permanently sterilized **Alkylating** agents are toxic (**cyclophosphamide**, **MTX**, **5FU**) = 2/3 of women treated with them have premature ovarian failure

Answer 92

Uterine syncechia Usually from **frequent D&C** C/s **myomectomies** or **infections** Results in **secondary amenorrhea** Treatment: hysteroscopic **lysis of adhesions** and **estradiol** post-op

Answer 93

**Hypothalamic** amenorrhea Weight loss, anorexia and bulimia Exercise and amenorrhea Treatment: treat cause, HRT, OCP if fertility not desired, ovulation induction medications if fertility desired

Answer 94

Chance of getting pregnant after... 3 months: 57% 6 months: 72% **1 year: 85%** 2 years: 93%

Answer 95

Failure to achieve a successful pregnancy after 1**2 months** or more of regular unprotected intercourse This is a disease Evaluation after **6 months if over 35** and evaluation immediately if over 40 7.4% of married couples infertile Causes: 27% **ovulation**, 25% **male factor**, 22% tubal factor, 5% endometriosis, 17% unexplained

Answer 96

**Positive feedback** during **follicular phase** **Negative feedback** during **luteal phase**

Answer 97

Beginning (**primordial** follicle to primary/pre-antral follicle) is **gonadotropin-independent** Then, remember the **"lucky egg"** is the one with the most **FSH receptors** End (**secondary**/anatral follicle to preovulatory follicle) is **gonadotropin dependent**

Answer 98

1) **Estrogen** increases **LH synthesis** in the pituitary but does not allow for LH release yet 2) As estrogen reaches high levels it causes release of all stored LH over a 24 to 36 hour period (**LH surge**) 3) LH surge increases **proteases** that digest ovary capsule and cause **extrusion of oocyte** and surrounding ganulosa cells (cumulus oophorus) 4) Oocyte enters **meiosis II** which is arrested until fertilization

Answer 99

WHO class 1: hypogonadotropic hypogonadal anovulation (**hypothalamic** amenorrhea, **hyperprolactinemia**) WHO class 2: normogonadotropic normoestrogenic anovulation (**PCOS**) WHO class 3: hypergonadotropic hypoestrogenic anovulation (**premature ovarian failure**)

Answer 100

**Cervical mucus** Basal body **temperature** Ovulation detection **devices** Day 22-24 progesterone

Answer 101

Cycle **day 3 FSH** and **estradiol** **TSH** **Prolactin** **Androgens** (T, DHEAS, 17-hydroxyprogesterone (?) if hirsutism) Evaluate ovarian age: basal FSH and estradiol, clomiphene citrate challenge test, inhibin B levels, antral follicle count/ovarian volume, MIF levels

Answer 102

**Blocked fallopian tube** Decrease in endometrial receptivity Direct embryotoxic effect Tubal fluid may mechanically flush embryo from uterus

Answer 103

**Estrogen agonist-antagonist** (SERM?) **ovulation induction** Depletes estrogen receptor concentrations by binding for extended periods of time (including on hypothalamic receptors) **Reduced estrogen negative feedback** alters pulsatile GnRH secretion **Stimulation** of pituitary gonadotropins (**FSH** and **LH**) Side effects: vasomotor flushes (hot flashes), mood swings, visual disturbances, breast tenderness, pelvic discomfort and nausea

Answer 104

**Oral biguanide** antihyperglycemic agent approved for treatment of **T2DM** **Decreases** blood **glucose** (decreases hepatic glucose production, decreases intestinal absorption of glucose, improves insulin sensitivity by increasing peripheral glucose uptake and utilization) As a result of **better insulin sensitivity** (decreased insulin concentrations) get **decreased** serum **androgens**, decreased **LH**, **increased SHBG**

Answer 105

**Clomiphene citrate** superior to metformin Combination is superior for ovulation, but NOT live births Just use clomiphene citrate (?)

Answer 106

Recombinant human **FSH** SQ injections Measure follicles then **give hCG** and time intrauterine insemination If using gonadotropins, also usually do intrauterine insemination (inject sperm into cervix)

Answer 107

Counted from **first day of full flow** menstrual bleeding and usually 28 days Two phases are **follicular** and **luteal** Uterine phases are **proliferative** and **secretory** Lose 10-80 ml during period

Answer 108

Very **little flow** (\<10ml)

Answer 109

Regular cycles with intervals of **21 days or fewer**

Answer 110

**Heavy** flows (\>80ml)

Answer 111

**Heavy** menstruation that occurs **frequently** and **irregularly**

Answer 112

This is **bad**! Means not as many eggs, **less fertile** Ovary should be able to do job with low FSH, so if it is high, means brain sending down signal to ovary with too much force and ovary not responding

Answer 113

**Primordial** follicle (resting stage): oocyte in **meiosis I** with **single** layer of **granulosa** **cells**; maturation is **independent of FSH and LH** As follicle mature, increase in granulosa cells Follicles need **FSH** **receptors** to survive, but only one with most FSH receptors gains **dominance** (due to positive feedback within granulosa cells) Follicle contains **no LH receptors** until final stages of development (**late** **follicular** phase)

Answer 114

**FSH** induces **estradiol** production through stimulation of **armoatase** activity in **granulosa** cells **Theca cell** synthesizes A4 and T under influence of LH (this allows **granulosa** cells to make **estradiol** using aromatase) Estradiol increaes 10 fold due to activity of dominant follicle, and increases **number FSH** (and eventually LH) **receptors** Estradiol also inhibits FSH release from pituitary so less mature follicles see very little FSH

Answer 115

Neuroendocrine neurons in **medial preoptic** and **arcuate nuclei**

Answer 116

1) **LH** binds receptors on **theca** **cells** and stimulates cAMP production to turn cholesterol to **androstenedione** 2) Androstenedione diffuses into circulation then into **granulosa** **cells** 3) **FSH** binds receptors on **granulosa cells** and stimulates cAMP to increase aromatase enzyme and conversion of androstenedione into **estrogen**

Answer 117

**Intraovarian** regulators In general, activins **activate** **LH** and **FSH** secretion and inhibins **inhibit** **LH** and **FSH** secretion

Answer 118

Excess FSH administration produces **multiple follicles** for pregnancy enhancement

Answer 119

Prophase of first meiotic division during fetal life First meiotic process arrested at **diplotene stage** of **prophase meiosis I** in **utero** Meiosis I resumed in adult ovary during **follicular maturation** (one menstrual cycle) but arrested at **metaphase meiosis II** Ovulation occurs at metaphase stage of second meiotic division and division **complete** only after **sperm penetrates egg** in fallopian tube

Answer 120

**Granulosa cells** become luteinized (terminally differentiated): bigger, ability to secrete large quantities of progesterone and some estradiol

Answer 121

**LH surge** results in partial 17-hydroxylase block in theca cells and granulosa cells, and stimulates progesterone production **Progesterone** stimulates **"secretory phase"** of endometrium, and also breast tenderness, bloating, affective lability Length of luteal phase is 14 days (+/- 2 days)

Answer 122

If **not pregnant**, corpus luteum gets **old** and produces less protesterone and estrogen --\> spasm of endometrial vasculature and breakdown of endometrium --\> **menses** If **pregnant**, embryo produces **hCG** which is **like LH** and **maintains CL** --\> endometrium maintaied and supports growing embryo

Answer 123

Ovarian: **insulin** **resistance**, ovarian tumors (Sertoli, leydig cell) Adrenal: nonclassical adrenal hyperplasia, **Cushing's** syndrome, glucocorticoid resistance, adrenal carcinoma Specific condition of pregnancy: luteoma of pregnancy (chest hair), hyperreactio luteinalis, **aromatase deficiency** in fetus Other: drugs (danazol), hyperprolactinemia, idiopathic

Answer 124

At least 2 of the following: 1) Oligo/**anovulation** 2) **Hyperandrogenism** 3) **Polycystic ovaries** Also, must exclude late onset adrenal-hyperplasia (CAH), androgen secreting tumors, hyperprolactinemia/thyroid disorder

Answer 125

1) **Sertoli-Leydig cell tumors** 2) **Thecoma** 3) **Hilar cell tumor** 4) **Luteoma of pregnancy**

Answer 126

**Increased** free and active **testosterone** Decreased clearance rate of testosterone **Decreased SHBG** **Anovulatory ovaries** usually source of increased testosterone and androstenedione

Answer 127

**DHEAS** 98% from **adrenal** glands **DHEA** 95% from adrenal glands **Testosterone** 25% from **adrenal** glands and 25% from **ovary** **Androstenedione** 50% from **adrenal** glands and 50% from **ovary**

Answer 128

**DHT** is strongest \> testosterone \> androstenedione \> DHEA \> **DHEAS** is weakest Note: concentrations of androgens are the opposite

Answer 129

PCOS is associated with **insulin resistance** Because of insulin resistance, patients are **hyperinsulinemic**, causing liver to **decrease SHBG** and **increase androgens**!

Answer 130

Short term: **acne**, **hirsutism**, **irregular menses**, **weight gain** Long term: **infertility**, **endometrial** **cancer**, androgenic alopecia, **insulin resistance**, **DM**, anxiety, depression, introversion, dyslipidemia, HTN, CVD

Answer 131

During follicular phase, measure **testosterone**, **DHEAS**, **17-hydroxyprogesterone** **TSH** and **prolactin** **HgA1C**, CMP (?) Fasting **lipid panel** 2 hour **OGTT** Cycle day 22-24 **progesterone** level

Answer 132

Normal weight: \<60 ul/mL insulin Obese: \<100 **Mild insulin resistance: 100-150** Moderate insulin resistance: 151-300 Severe insulin resistance: \>300

Answer 133

For infertility: **clomiphene citrate**, (metformin), ovarian **drilling**, **gonadotropins**, IVF, lifestyle modification For androgen suppression (hirsutism and endometrial protection): lifestyle modification, **OCPs**, **GnRH agonist**, **estrogen/progestin**, **metformin**, dexamethasone/prednisone, **spironolactone**, finasteride, flutaide, Vaniqua (topical)

Answer 134

They usually are **anovulatory** or oligooulatory and risk of endometrial cancer goes up when you have no ovulation This is because you have **rise in estrogen**, but since no ovulation then no corpus luteum formed so **no progesterone** from CL (?), which means **estrogen with unopposed progesterone** and increased **proliferation** of endometrium can increase risk for hyperplasia/carcinoma

Answer 135

Have to do with **unopposed estrogen** stimulation leading to **endometrial hyperplasia** Obesity Diabetes HTN Infertility Failure of ovulation Dysfunctional uterine bleeding Prolonged estrogen use Tamoxifen use

Answer 136

**Most common** malignant tumor of the ovary (~40% of all cancers of the ovary) Ovarian **non-germ cell tumor** Glandular complexity, branching papillary fronds, nuclear atypia, epithelial stratification, mitoses, stromal invasion Associated with **psamomma bodies** 65% bilateral Symptoms: lower abdominal pain, enlargement Labs: CA-125 present in 80% of serous and endometrioid carcinomas (but don't use this as a screening test?!) Prognosis: 35% 5 year survival (70% if only ovary and 25% if involves peritoneum) Risk factors: nulliparity, FH, gonadal dysgenesis, clomiphene, **HNPCC**

Answer 137

Agent that contributes to **abnormal fetal development** or function

Answer 138

Birth defect of **no limbs** or **tiny flipper-like arms and legs**, serious **facial** **deformities** and **defective organs**

Answer 139

Used in the 1950's-60's to **treat nausea and vomiting** caused by morning sickness of pregnancy Caused more than 10,000 birth defects before being withdrawn in 1962 Exposure during **day 21-40 of gestation** almost 100% of women had babies with defect Thalidomide is the reason why FDA approval process exists in its current form

Answer 140

**Synthetic nonsteroidal estrogen** DES marketed in 1940-70 to **prevent miscarriages** or premature deliveries Females exposed to DES in utero (DES daughters) were at increased risk of developing **clear cell adenocarcinoma** of the **vagina** and **cervix** 1/3 DES daughters have identifiable **genital abnormality**, and most have **ectopic pregnancy, miscarriage, premature birth** DES sons have increased incidence of **epididymal cysts**

Answer 141

Early 1980s, used as **antiemetic** for morning sickness Voluntarily removed from market in 1983 by manufacturer even though **FDA showed no association between Bendectin and birth defects** (false-positive)

Answer 142

1) Species sensitivity in preclinical testing (thalidomide tested in rodents did not show effect) 2) Importance of timing of human exposure (thalidomide caused defects specifically at week 3 to 6) 3) Specific type of congenital anomaly ("signature" effect of thalidomide was phocomelia) 4) Need for evidence of teratogenic effect 5) Long delay between exposure and identification of toxicity (DES showed effect of clear cell adenocarcinoma when affected fetuses were adults!) 6) Initial anecdotal findings can lead to false-positives; need for rigorous unbiased studies (Bendectin removed from market unnecessarily)

Answer 143

Maternal **albumin** concentration **decreases** during second trimester and only 70-80% of normal albumin at time of delivery --\> **increased** amount of **free drug** **Total body water** increases in pregnancy and **plasma** **volume** **increases** 30-50% --\> **lower concentration** of drug

Answer 144

Passive diffusion: **concentration**-dependent Solubility: **lipid** **soluble** molecules cross placenta and polar molecules do not Molecular size: most drugs **\<500Da**, drugs \>500Da transferred incompletely and drugs \>1000Da cross very poorly Ionization: only **neutral** form crosses placenta Protein binding: only **free drug** crosses placenta

Answer 145

Phase I: during first trimester, fetal liver cannot metabolize drugs using CYP450 enzymes; during organogenesis fetal CYP3A7 used for steroid metabolism Phase II: fetal liver can do sulfonation, glutathione conjugation and N-acetyltransferase; does not have adequate glucoronidation (for metabolism of lipophilic drugs) Note: good that fetus cannot metabolize drugs because they/metabolites may get stuck?

Answer 146

Study of all environmental contributions to **abnormal** **development**, including **chemicals**, **viruses**, environmental agents, physical factors and **drugs**

Answer 147

**Embryonic** exposure likely to lead to **structural** abnormalities or embryonic **death** **Fetal** exposure likely to lead to **functional** deficits or **growth restriction**

Answer 148

The "all or none" period Insult can damage large number of cells to cause death of embryo No teratogenic effects here because either the embryo **survives** and is fine, or does not survive and **dies**

Answer 149

1) **Preimplantation** period: **0-2 weeks**, **"all or none"** so either embryo fine or dies if exposed to teratogens 2) **Embryonic** period: **week 2-8**; organogenesis, more crucial for **structural** malformation 3) **Fetal** period: **week 9+**; maturation and **functional** **development** continues

Answer 150

**Case reports**: can never provide estimate of risk of disease after exposure **Descriptive** studies: information about distribution and frequency of outcome, resulting in rates of occurence that can be compared among populations, places or times **Case-Control** studies: groups of individuals with some outcome or disease of interest are compared with controls; are advantageous in testing outcomes of infrequent occurrence **Cohort** studies: groups defined by presence or absence of given factor then followed over time and compared for rate of ocurrence of outcome; prospective study **Clinical trials**

Answer 151

**After prenatal exposure** to registry medication, pregnancy registered prospectively and **adverse effects reported** through voluntary reports by health care providers Can provide margins of reassurance regarding lack of risk when precise measure is impossible, monitor for suspected risks, identify factors that affect risk of adverse outcomes (dose, timing, maternal characteristics), serve as hypothesis-generating tool

Answer 152

A: controlled studies in humans show no risk B: controlled studies in animals show no risk C: controlled studies in animals show risk **D**: studies in **humans** show risks **X**: **contraindicated** in pregnancy; only one where risks clearly outweigh potential benefits Note: the Teratology Society suggests abandoning FDA classification because these categories aren't absolute risk, they consider the **risk to benefit ratio** so don't tell you about risk in absolute terms

Answer 153

**ACE inhibitors**: captopril, enalapril, lisinopril **Antidepressants**: SSRIs (citalopram, fluoxetine, sertraline, paroxetine) **Anxiolytics**: benzodiazepines (alprazolam, clonazepam, diazepam, lorazepam) **Anti-epileptic drugs**: valproic acid and derivatives, carbamazepine, phenobarbital, phenytoin Other: **isotretinoid, warfarin, methotrexate**

Answer 154

Use **Tylenol** (**acetaminophen**) and not ibuprofen, ketoprofen, or naproxen

Answer 155

**Continue antiepileptic drugs** Increased risk of fetal malformations, **unclear whether epilepsy or drugs** Most frequent defects are **orofacial clefts** and **cardiac malformations** May cause **delayed development**, autism, behavioral disorders

Answer 156

**Behavioral** disturbances **Brain** defects **Cardiac** defects **Spinal** defects **Craniofacial** anomalies (microcephaly, short opening of eye, epicanthal folds, midface flat, nadal bridge low, philtrum indistinct, upper lip thin, micrognathia, ears have curve at top of outer ear (railroad track))

Answer 157

The permanent **cessation** **of** **menstruation** which results from the l**oss of ovarian function** Menopause is direct result of **ovaries** not working, whereas puberty begins in the **brain**

Answer 158

**Apoptosis** Apoptosis **accelerates** after woman is **35**

Answer 159

As ovaries fail, **less follicular estrogen** production by the dominant follicle (recruited from pool or primordial follicles) and **E2 cannot be produced** by aromatization of androstenedione

Answer 160

These drugs inhibit aromatase function so **less** androstenedione converted to **estrone** (then estradiol) Now commonly used to **treat breast cancer** Ex: **Anastrozole** (non-steroidal)**, exemestane** (irreversible, steroidal)

Answer 161

Cessation of menses for **12 months** Average age is **48-52** **Early** perimenopause: 2-8 years before cessation of menses, menstrual cycle lengths normal or **shorter** due to shorter follicular phase, **FSH higher**, get irregular menses, hot flashes, interrupted sleep, breast tenderness **Middle** perimenopause: variable time before menopause, less predictable menstrual cycle pattern, some cycles ovulatory **some** **anovulatory** (estrogen rises and falls without progesterone secretion), FSH higher, additionally get **dysphoric mood, depression, mild memory problems** **Late** perimenopause: **year** **after** final menstrual period, FSH high, same symptoms Postmenopause: symptoms improve

Answer 162

No, not unless **symptoms** related to menopause (can treat those syptoms with hormones temporarily)

Answer 163

**Vasomotor** **instability** (hot flashes, sleep disturbance, depression, memory problems) gets better with time **GU-atrophy** related (dyspareunia, atrophic vaginitis, dysuria, stress/urge incontinence, urinary urgency) get worse with time

Answer 164

Abrupt **drop** in sex steroid levels: **menopause**, use of **GnRH** **agonists**/antagonists **Pituitary** **insufficiency** (or after hypophysectomy)

Answer 165

Under physiologic conditions in women, estrogen causes **tonic inhibition** of thermoregulatory center of **hypothalamus** NT and neuropeptide systems implicated in **hot flush mechanism**: **Serotonin**: estrogen withdrawal decreases blood serotonin, increases 5-HT(2A) receptor sensitivity in hypothalamus **Noradrenergic** neurons: modulate LHRH secretion and thermoregulation, hot flashes may be triggered by central alpha adrenergic receptor effects on noradrenergic neurons **Opioid**-containing neurons: modulate thermoregulation

Answer 166

Hormone therapy **most effective** treatment for vasomotor symptoms Reduction in symptoms of **80-90%** Reassess need for treatment of vasomotor symptoms every 6-12 months

Answer 167

**Risks**: breast cancer, total **cancer**, CHD, **stroke**, dementia, pancreatitis, **DVT/PE**, gallbladder disease, kidney stones, breast/bleeding side effects, possibly ovarian cancer **Benefits** (while on therapy): **vasomotor** symptoms, vaginal **atrophy**, **osteoporosis**, colon cancer, possibly skin preservation and depression

Answer 168

**Risks** (while on therapy): stroke, dementia, DVT/PE, **endometrial hyperplasia/cancer**, kidney stones, breast/bleeding side effects, pancreatitis, possibly ovarian cancer **Benefits**: vasomotor symptome, vaginal atrophy, breast cancer decreased, MI decreased, osteoporosis prevented while on therapy, possibly skin preservation and depression

Answer 169

CNS/neuromodulators SERMs Placebo effects Soy, vitamin E, black cohosh, oil of primrose, "yam progesterone," dong quai, red clover, ginsent, acupuncture For hot flashes: paroxetine, fluoxetine, sertraline, gabapentin, pregabaline, clonidine, venlafaxine Note: efficacy similar to placebo but placebo benefit is 25-50% reduction in vasomotor symptoms

Answer 170

Vaginal epithelium is **maintained by estrogen** so any situation or medication that decreases estrogen will be associated with atrophic vaginal epithelium Treatment: lubricants, local hormone therapy (Estring, Vagifem, low-dose topical estrogen), systemic hormone therapy (only if also using for vasomotor symptoms)

Answer 171

**Osteoporosis** BP, diabetes, cholesterol Screen for cancer: mammography, colonoscopy Mental health depression screening

Answer 172

Use **heparin** in pregnancy because **polar** and cannot cross placenta Do NOT use Warfarin because is fat soluble and can cross placenta

Answer 173

Because some of the drug is in **neutral** form and that can diffuse across the membrane

Answer 174

**Phenytoin**: fetal hydantoin syndrome (craniofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac defects, facial clefts) **Carbamazepine**: fetal hydantoin syndrome; spina bifida **Valproate**: neural tube defects **Phenobarbital**: clefts, cardiac anomalies, urinary tract malformations **Lamotrigine**: theoretical (may lower fetal folate levels by inhibiting DHFR) **Topiramate**: theoretical (has produced defects or abnormal pregnancy outcomes in all animals tested, even at low or therapeutic doses)

Answer 175

**NO regulations** for herbal remedies and nutritional supplements! No studies, so dietary supplements should NOT be assumed to be safe for the embryo/fetus

Answer 176

Usually is **anxiety** Also look for hypothyroidisn (?), infection, malignancy

Answer 177

Men with **prostate** **cancer** who are taking **GnRH** **continusously** (to block HPG axis) get sharp drop off in testosterone --\> can cause hot flashes!

Answer 178

**Exercise** works at the **hypothalamus** to decrease the action of GnRH

Answer 179

**Embryopathy** is exposure within **first 8** weeks and fetopathy is after 8 weeks

Answer 180

Study in the 1980s showed that tamoxifen given for only 5 years **prevented recurrence of breast cancer** better than tamoxifen given forever Something about **short** **exposure** then **stopping** that prevents breast cancer Note: similar effect from **estrogen** because if give for short period of time then stop see that people have lower incidence of breast cancer

Answer 181

Worse menopause symptoms: smoking, obesity, alcohol (maybe?), aspirin Better menopause symptoms: exercise (maybe?), aspirin, calcium, vitamin D, eating well

Answer 182

No! Tamoxifen is metabolized (to active metabolite) by **same CYP450** enzyme as paroxetine so if give both, tamoxifen will be **less effective** and women will get **more breast cancer** **recurrence**

Answer 183

Secreted by **trophoblast** Glycoprotein Alpha unit similar to LH and **TSH** (can act on TSH receptors to produce thyroxine so actual TSH may be lower in pregnancy) B sub-unit 8 days after ovulation, and **peaks** at 60-90 days (**10 weeks**) **Maintains corpus luteum** for up to 8 weeks Stimulates **placental** **steroid** production, **fetal adrenal steroid** production, **fetal testes testosterone** production

Answer 184

Similar to **GH** Linked to **placental mass**, produced by placenta, used to assess placenta function Stimulated by insulin and IGF-1 Inhibited by PGE2 and PGF2 **Maternal lipolysis** and increase in free fatty acids, providing energy for maternal metabolism **Anti-insulin** or "diabetogenic" action provides **glucose** and **AAs** for transport to fetus Potent **angiogenic** hormone; role in fetal vasculature formation

Answer 185

Produced by **corpus luteum** until 7-8 weeks, then by **placenta** and persists after fetal demise Level rises until delivery Maintains **uterine quiescence** (in woman at risk of preterm labor, can give progesterone to prevent preterm labor) Establishes immune tolerance for conception

Answer 186

**CRH** from the placenta stimulates **fetal adrenal glands** to produce **DHEA-S** which is converted to **16 OHDHEA-S** in **fetal liver** DHEA-S converted in **placenta** to **17-estradiol (E2)** **16 OHDHEA-S** is converted in **placenta** to **estriol (E3)** Near term, half of E2 is from fetal adrenal and half from maternal DHEA-S **90% of E3 in placenta from fetal** 16 OHDHEA-S and 10% from other sources

Answer 187

Outer cortex: **cortisol** (production stimulated by **CRH** from placenta) **Fetal zone: DHEAS** Medulla: catecholamine Cortisol induces fetal **lung maturity**; involved in **labor initiation** Note: adrenal in fetus is huge because large fetal zone

Answer 188

Stimulated by **estrogen** Postpartum **milk production** Fluid and electrolyte shifts across fetal membranes

Answer 189

**RBC volume increases** due to erythropoietic effect of placental human placental lactogen, progesterone and prolactin **Maternal blood volume increases** due to uteroplacental circulation functioning as low-resistance circuit This **increases cardiac output** and nutrient delivery for further growth of products of gestation Feedback mechanism: fetal growth/increasing steroidogeneiss by developing fetal adrenal gland results in maternal cardiovascular adaptations --\> maternal cardiovascular adaptations to pregnancy to optimize further fetal development Note: if no increased maternal blood volume, can get restricted fetal growth, preeclampsia, etc

Answer 190

Total peripheral resistance goes **down** in **mid-pregnancy** Due to prostacyclin (vasodilation), NO (vasodilation), aldosterone, ANP

Answer 191

**Fetus** controls this plasma expansion! 1) Fetal **DHEAS** production 2) Placental **estrogen** production 3) **RAAS** activation 4) Increased **aldosterone** production 5) Renal Na and **water reabsorption** 6) Plasma **volume increase** Note: also uteroplacental AV shunt

Answer 192

**Cardiac output increases** early in pregnancy, initially as result of increased **HR** then increase in **SV** CO continues to increase until midpregnancy then stable then small decline in last weeks of pregnancy **BP decreases**, reaches minimum at midpregnancy and normal at term **Peripheral vascular resistance reduced** throughout pregnancy Myocardial **contractility increased** (mild ventricular **hypertrophy**) **Increased preload** causes increased L atrial diameter During labor, CO and BP increase but after, CO decreases within first hour and reaches **baseline 2 weeks postpartum** 5 months postpartum, mild residual ventricular hypertrophy persists

Answer 193

1) Compress leg and pelvic veins: causes leg and vulva **edema**/varicose veins, hemorrhoids, **thrombosis** (also caused by increased clotting factors and low albumin) 2) Compress **vena cava**: cause nausea, **dizziness**, **syncope**, bradycardia, **fetal hypoxia** 3) Compress **aorta**: cause low femoral pressure, **fetal hypoxia** and Poseiro effect

Answer 194

Mostly **fetus** and **maternal** **stores** (fat) Also extravascular fluid, blood, uterus, amniotic fluid, placenta, breasts

Answer 195

**Increased lipolysis** with FFAs, tendency to ketones (accelerated starvation), FFA for mom, glucose and AA for fetus **Early** pregnancy: **increased fasting insulin**, **decreased fasting glucose**, increased glycogen synthesis and storage, decreased gluconeogenesis **2nd half** of pregnangy: **increased insulin resistance**, increased post-meal glucose **Anti-insulin effect**: HPL, cortisol, cytokines, progesterone, estrogens Get **higher spikes** of **glucose** and **insulin** after meal in pregnancy, which is due to **increased insulin resistance** in pregnancy

Answer 196

Due to **mechanical** effect of enlarging uterus, and need more oxygen uptake (**reflects** **increase in metabolism** that is happening in pregnancy) **Total lung capacity decreases** Decrease in expiratory reserve volume and residual volume (together are functional residual capacity) **Minute ventilation increases**, oxygen uptake increases Stimulant effect of **progesterone** **Hyperventilation** results in reduced maternal PCO2 (**respiratory alkalosis**), facilitates transport of CO2 from fetus to mom but impairs release of oxygen from maternal blood to fetus (**Bohr effect**) Increase in blood pH stimulates **increase in 2,3-DPG** in maternal RBC which counteracts Bohr effect, shifting oxygen dissociation curve back to the right, facilitating oxygen release to fetus **Dyspnea** in 60-70%

Answer 197

**Increase** in **GFR** (because increased plasma volume) --\> blood **cleared** of products **faster** (ex: creatinine clearance usually 120 but in pregnancy will be double that; serum creatinine and BUN decreased) **Increased** renal **size** **Dilatation** of pelves, calyces, ureters (uterus compresses ureters so urine backup in kidney; progesterone relaxes smooth muscles so get stasis) Changes in acid-base metabolism (serum **bicarb** and **PCO2** **lower**) Renal water handling (osmotic thresholds for ADH release and thirst decrease, **serum osmolality decreases**)

Answer 198

**Increased** small bowel **transit** **times** Morning sickness Stomach and intestines **displaced** Appendix displaced upwards Delayed gastric emptying increases **regurgitation** risk Esophageal pressures are lower and intragastric pressures higher Esophageal peristalsis is lower Gums hyperemic and softened Impaired gallbladder contraction Intrahepatic cholestasis Constipation

Answer 199

**Ductus venosus** shunts oxygenated blood away from liver, into right atrium, through foramen ovale to L atrium then L ventricle then to ascending aorta then to perfuse fetus' body R ventricle pumps mixed blood into pulmonary arteries then through **ductus arteriosus** (instead of to lungs) then to descending aorta

Answer 200

Innate: NK cells, macrophages, complement Adaptive: T cell recognition then IL-4, IL-5 cause B cell proliferation and antibody production for humoral antibody; or IL-2 causes T cell clonal proliferation for cell mediated immunity

Answer 201

Privileged immunologic site (decreased/altered afferent lymphatic) More **suppressor T cells** **Separation** of maternal and fetal **circulation** (tight intracellular junctions and fibrinous layer) **No class II HLA** antigen at maternal-fetal interphase which is necessary for immune response **Limited T response** to trophoblast HPL, hCG, estrogen, progesterone, pregnancy specific a2 globulins, 1-glycoproteins cause **local nonspecific immune suppression** Placenta as immuno-absorbent

Answer 202

Means **fetus is in jeopardy** Fetus produces most of the estriol during pregnancy, so if estriol low means something is wrong with the fetus

Answer 203

SOB Dyspnea on mild exertion Heat intolerance High HR Low BP Displacement of apical impulse Systolic murmur BIlateral lower limb edema Nausea, vomiting Heartburn Constipation Gallstones

Answer 204

**Lower** because more fluid than RBC mass in pregnancy

Answer 205

**6-12 weeks postpartum** these changes resolve

Answer 206

**Spontaneous** **abortion** if **before 20 weeks** gestation **Preterm** if **after 20 weeks** gestation Note: 37 weeks or later is term labor

Answer 207

Pregnancy loss within **first 2 weeks** before missed period **Don't even know** you were pregnant Occurs in 13-26%

Answer 208

90-96% Still really **good**! Note: up to 6-8 weeks, **hCG should double** every 48 hours, so can measure this twice and if doubling then have normal pregnancy

Answer 209

Absence of **yolk sac** when mean sac diameter 13mm Absence of **embryonic** **pole** when mean sac diameter 18mm Absence of embryonic **cardiac** **activity** with crown-rump length \<5mm Abnormal yolk sac **Slow fetal HR** \<100 (zero survival at HR\<70 at 6-8 weeks GA **Small gestational sac**, **irregular contour**, **minimal decidual thickness** or **low sac position** in uterus

Answer 210

**Bleeding** through **closed cervix** Bleeding of expected menses, decidual reaction, cervical lesions, no effective therapy **Half will abort** Increased risk for preterm delivery, low birth weight, and perinatal death Vaginal sonography, serial serum hCG levels, serum progesterone values 5% of Rh negative women become iso-immunized (make Rh antibodies if baby is Rh+)

Answer 211

**Leaking amniotic fluid** (membranes have ruptured) Cervical **dilatation**, heavy bleeding, severe pain, impending abortion Risk of incomplete abortion or sepsis Uterine evacuation (incomplete abortion can be dangerous...?)

Answer 212

**Partial expulsion** with **retained products of conception** (POC) (seen with US or pelvic exam) More common **after 12 weeks** GA Open internal cervical os, bleeding Hemorrhage, sepsis Uterine evacuation

Answer 213

Closed internal cervical os Ultrasound shows **normal endometrial stripe**

Answer 214

**Dead** products of conception (POC) retained inside uterus for long time with closed cervix May not feel "pregnant" anymore May be associated with coagulation defects Expectant, medical or surgical management

Answer 215

**3 or more consecutive** spontaneous abortions Risk of 1 loss: 10-15%; 2 losses = 2.3%; 3 losses = 0.34% Parental cytogenetic analysis **Antiphospholipid** (anti-cardiolipin) antibodies bind placenta and cause pregnancy loss If previous liveborn then risk for subsequent abortion 30% If no liveborn, risk of subsequent abortion 46%

Answer 216

**Fetal**: abnormal zygotic development (40%), aeuploid abortion (50%) **Maternal systemic**: infections, chronic diseases, TB, carcinomatosis, celiac, antiphospholipid antibodies, inherited thrombophilia **Maternal local**: uterine leiomyoma, Asherman syndrome, Mullerian duct defects, DES offspring, incompetent cervix, physical trauma **Maternal endocrine**: hypothyroidism, DM, progesterone deficiency **Maternal environment**: tobacco, alcohol, caffeine, radiation, IUD failure, anesthetic gases **Paternal factors**

Answer 217

Many in **first trimester**, some in second, few in third and very few live born

Answer 218

52% autosomal trisomy (trisomy 16 common and always lethal) 22% Polyploidies (tri and tetra) 19% Monosomy X 7% other

Answer 219

**Painless cervical dilatation** in **2nd trimester** with prolapse and ballooning of membranes into the vagina, followed by expulsion of an immature fetus Transvaginal ultrasound to measure cervical length and funneling Previous trauma to the cervix (dilatation and curettage, conization, cauterization or amputation, traumatic delivery) Abnormal cervical development (DES daughter) Treatment: **McDonald cerclage** or Shirodkar cerclage

Answer 220

Persistent **nausea and vomiting** associated with **ketosis** and **weight loss** (\>5% of pre-pregnancy weight) Etiology: unknown for the most part (socioultural, psychological, hCG levels, estradiol levels, gastric dysrhythmias, vestibular and olfactory dysfunction) Note: 50-90% of women have morning sickness but is only HEG if ketosis and weight loss!

Answer 221

Treat with **IV fluid**, antihistamines, anti-emetics, promotility agents, diet, B6, ginger, parenteral nutrition If low pregnancy weight gain, increased risk of: low birth weight, small for gestational age, preterm delivery, 5 minute apgar \<7 (bad!)

Answer 222

**Malformation**: **programmed** to develop abnormally; thus intrinsically genetically abnormal **Deformation**: genetically normal structure develops abnormal shape because of **mechanical** forces imposed by uterine environment **Disruption**: severe change in form or function when genetically normal tissue is modified due to a **specific insult** **Phenocopies**

Answer 223

**Spina bifida** **Anencephaly** **Omphalocele**: abdominal wall defect where bowel into umbilical cord covered by membrane; malformation **Gastroschisis**: bowel in abdominal cavity with no membrane; disruption Endocardial cushion defect: center of heart missing Hypoplastic left heart: left ventricle smaller than right

Answer 224

**Isoretinoin**: ear defects, cardiac outflow tract defects, hydrocephaly system, thymus aplasia **Diethylstilbestrol** (**DES**): vaginal clear-cell adenocarcinoma, adenosis, cervix/vagina defects, hypospadias **Antifungals**: CNS and skeletal defects **ACE** **inhibitors**: oligohydramios, growth restriction, limb shortening, maldevelopment of calvarium; via renal ischemia? **Tobacco**: ileal atresia, hydrocephaly, hand defects, microcephaly, omphalocele, gastroschisis, cleft lip/palate; via vascular disruption **Methyl mercury**: microcephaly and severe brain damage; via neuronal and cell division migration **Cocaine**: skull defects, cutis aplasia, porencephaly, subependymal/periventricular cysts, ileal atresia, cardiac anomalies; visceral infarcts; via vascular disruption **Anti-neoplastic drugs**: IUGR, craniosynostosis, microcephaly, limb defects **Coumadin (warfarin)**: nasal and midface hypoplasia; stippled vertebral and femoral epiphyses, dorsal CNS dysplasia, mental retardation; via inhibiting posttranslational carboxylation of coagulation proteins; in 2nd and 3rd hemorrhage leading to disharmonic growth and deformation from scarring **Phenytoin**: cradiofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac defects, facial clefts; via accumulation in fetal tissues of free oxide radicals with toxic/carcinogenic/mutagenic effects **Carbamazepine** and **valproate**: neural tube defects **Phenobarbital**: clefts, cardiac anomalies, urinary tract malformations

Answer 225

Toxoplasma gondii Rubella CMV HSV, HIV Syphilis (and varicella)

Answer 226

Intracranial infections: dilated ventricles with bilateral preventricular calcifications Hepatomegaly, splenomegaly Hydrops: scalp edema, ascites

Answer 227

**13, 18, 21** 13: Patau 18: Edward 21: Down's syndrome

Answer 228

**Trisomy**: nondisjunction of meiosis I **Monosomy**: nondisjunction of meiosis I **Triploidy**: fertilization of one egg by diploid or 2 sperm (partial hydatidiform mole) **Deletions**: during meiosis from mal-alignment/mismatching at pairing chromosomes **Translocations**

Answer 229

Achondroplasia Huntington Factor V leiden Marfan syndrome Neurofibromatosis Von Willebrand Disease BRCA1 and BRCA2

Answer 230

Cystic fibrosis Thalassemia Tay Sachs Albinism Sickle cell anemia Phenylketonuria Homocystinuria Congenital adrenal hyperplasia

Answer 231

Duchenne muscular dystrophy G-6-P deficiency Androgen insensitivity syndrome X-linked dominant disorders affect mainly females and usually lethal in males Hemophilia A Color blindness Fragile X

Answer 232

**First trimester** (11-14 weeks) look at beta-hCG, PAPP-A, and on ultrasound look at nuchal translucency (NT) **Second trimester** can determine **trisomy 21** (low AFP, **high HCG**, low unconjugated estriol, **high inhibin**) and **trisomy** **18 (**low AFP, **low hCG**, low unconjugated estriol, **low inhibin**)

Answer 233

Do it at **14-20 weeks** gestation (later than CVS) Ultrasound guidance to pass 20 to 22-gauge spinal needle to collect 20mL fluid for fetal karyotype and AFP Complications: fetal loss (0.5%), transient vaginal spottins or amniotic fluid leakage (1-2%), chorioamnionitis (\<0.1%) Indications: advanced maternal age, previous aneuploidy, couple with translocation, history of genetic disease, abnormal serum screen, fetal defects noted

Answer 234

Also to identify congenital defects Done earlier in pregnancy, but more technically difficult procedure Done **10-12 weeks** after missed period

Answer 235

BP **140/90 mmHg** diagnosed before pregnancy or **before 20 weeks** gestation Hypertension diagnosed after 20 weeks gestation and **persistent after 12 weeks postpartum** 5% of pregnancies, advanced maternal ages, AA women, 95-98% have essential hypertension

Answer 236

BP \>/= 140/90 mmHg for **first time** during pregnancy **after 20 weeks** **No proteinuria** BP return to **normal \<12 weeks postpartum** (final diagnosis made postpartum) No other signs of preeclampsia

Answer 237

Caused by **reduced uteroplacental perfusion** --\> endothelial cell activation --\> vasospasm --\> regional organ failure, capillary leak, activation of coagulation --\> hypertension, proteinuria, thrombocytopenia BP **\>/= 140/90** mmHg after 20 weeks gestation, **proteinuria \>/= 300** mg/24h or \>/= **1+ dipstick** 6% of pregnancies Related to **trophoblast** or **placenta** so always due to pregnancy!

Answer 238

BP **\>/= 160/110** **Proteinuria 3+** Visual disturbance, headaches, epigastric pain, convulsions, pulmonary edema, abruption Retinal changes, CVA, oliguria, elevated creatinine, thrombocytopenia, liver enzymes elevated, DIC, oligohydramnios, fetal distress, IUGR

Answer 239

Mechanism: **vasospasm** (vessels narrowed), glomerular capillary endotheliosis, acute **atherosis** in uteroplacental arteries, lack of invasion of spiral arteries by trophoblasts Note: increased vascular sensitivity to pressor agents, new father syndrome (immune tolerance to your spouse but more likely to have preeclampsia with new mate) Pathology: prostacyclin thromboxane ratio low (too much **thromboxane** means more vasoconstriction), **NO decreased**, endothelin, VEGF, soluble FMS-like tyrosine kinase 1 (blocks VEGF), placental growth factor, oxidative stress, endothelial cell activation, genetic predisposition

Answer 240

Occurrence of **convulsions** in a woman with preeclampsia without other neurological diagnosis Occurrence is a sign of inadequate prenatal care Etiology: cerebral **edema**, cerebral **vasospasm** (?) Incidence really **low** because we can treat preeclampsia

Answer 241

**Hemolysis**: abnormal smear, bilirubin \>/= 1.2 mg/dl, LDH \> 600 U/L **Elevated liver** enzymes: sgot \> 70 U/L **Low platelets**: class 1, 2, 3 Adherence of platelets to damaged vascular endothelium, increased platelet aggregation and consumption Hepatic necrosis --\> hematoma --\> rupture Microangiopathic hemolysis

Answer 242

Definitive treatment is **delivery** Control or prevent seizures with **magnesium sulfate** Control BP with hydralazine, lebatalol, nifedipine Mild preeclampsia: expectant management if preterm, induction and delivery at term Severe preeclampsia: stabilize and deliver regardless of gestational age

Answer 243

Assess maternal condition: **CBC**, **LFT**, **uric acid**, **urinalysis**, coagulation profile, electrolytes

Answer 244

Blocks neuromuscular and cardiac conducting systems (by **competing with Ca2+** at the motor end plate) **Decreases** smooth muscle **contractility** **Depresses CNS irritability** Relaxes vasculature, IV 4-6g loading dose then 1-4g/h 10g IM with 5g Q 4h IM Phenytoin less effective, **contraindicated** in **renal** **failure** and myasthenia gravis Effect of **increasing** magnesium **levels**: first **anticonvulsant** prophylaxis, then EKG changes, then loss of deep tendon reflexes, then respiratory paralysis, then general anesthesia, then **cardiac arrest**

Answer 245

Patient education to come to hospital for: headaches, visual disturbance, epigastric pain, N/V Prophylaxis: **baby** **aspirin** for at risk pregnancy initiated before 16 weeks GA

Answer 246

**90%** of diabetes in pregnancy is GDM Carbohydrate intolerance of variable severity first recognized in pregnancy May be due to relative impairment from pregnancy changes or Type 2 DM unmasked 35-50% of cases may have no risk factors **50g glucose test** if positive **(140 mg/dl)** followed by 3 hour oral glucose test

Answer 247

Maternal: **UTI**, **candidiasis**, **preeclampsia**, cesarean delivery, genital trauma, **polyhydramnios**, 50% develop overt DM within 5 years Neonatal: unexplained **stillbirths**, **macrosomia** (big baby), shoulder dystocia, **erbs' palsy** and other birth trauma, **hypoglycemia** (**after birth bc too much insulin**), respiratory distress syndrome (insulin suppresses formation of type 2 pneumocytes), hypocalcemia, hypomagnesia, neonatal jaundice, polycythemia, obesity, diabetes

Answer 248

Maternal: worsening of proliferative retinopathy, **increased mortality with heart disease**, diabetic ketoacidosis, hypoglycemia, no effect on nephropathy Neonatal: abortions, embryonic delay, **birth defects**, hypertrophic/congestive cardiomyopathy, **IUGR** (small baby) with Class C and worse, **preterm delivery**

Answer 249

From **DKA**, maternal hypotension causes **decreased placental perfusion** which causes fetal **hypoxia** and fetal compromise Fatty acids, glucose and ketones cause fetal **hyperglycemia** and **ketoacidosis** which cause fetal hypoxia and fetal compromise Result in fetal loss in 20-50%

Answer 250

**Nutritional counseling**, exercise **Insulin, glyburide**, blood glucose monitoring Increased clinic visits, US for anatomy and fetal growth, fetal testing Planned delivery, elective cesarean delivery for macrosomia, postpartum and annual diabetic screen

Answer 251

**Mother Rh-** and **fetus Rh+** Fetomaternal hemorrhage must occur (usually during delivery, but also can happen during abortion) Mother must mount anti-D antibody response and have failure of antibody-mediated immune suppression First pregnancies not at risk (IgM vs. IgG!!!) Anti D antibodies cross placenta and cause fetal hemolysis and cause **jaundice**, **kernicterus**, **hydrops** in second/affected baby 16% of Rh- women sensitized by first Rh+ baby (1-2% before delivery, 3-4% after first trimester SAB, 5% after induced AB)

Answer 252

10 fold reduction by giving 300ug Rh-immune globulin (RhIg; Rhogam) **within 72 hours** of delivery (also at **28 weeks** to prevent sensitization during 3rd trimester) **10ug** RhIg neutralized **1ml of fetal blood** Note: 72 hour time limit is arbitrary and can be given up to 28 days post delivery

Answer 253

This is how they used to assess for Rh antibody response on the fetus, but **not done anymore** because MCA peak velocity is better Do fetal blood sampling and intrauterine blood sampling every few weeks based on how many **antibodies seen in amniotic fluid** (OD450 measured) Do intrauterine transfusion if fetus is at risk of death

Answer 254

Do **ultrasound** to measure **middle cerebral artery peak velocity** **High** MCA peak velocity is good indicator of **anemia** so can tell if **hemolysis** due to Rh reaction is happening If high MCA velocity then get **intrauterine transfusion** but if normal/low MCA velocity just keep doing weekly/every 2 weeks ultrasounds to monitor

Answer 255

Follow MCA dopplers **every 1-2 weeks** (begin at **18 weeks** if previous affected fetus or infant) If value **\>1.5 MOM** proceed with **cordocentesis** (intrauterine transfusion for fetal hct \<30%) If value remains **\<1.5 MOM**, **continue** and induce at 38 weeks

Answer 256

HbSS, HbSC, HbS/beta thalassemia Complications for mother: **anemia**, infection, cholecystitis, pulmonary embolism, crisis (venooclusive, aplastic, sequestrative, hemolytic) Obstetric problems: 20-25% preterm labor, IUGR, stillbirths, vasoocclusive crisis, 25% inheritance Management: pneumovax, hydration, oxygen, antibiotics, analgesics, **blood transfusions** (keep hematocrit above 30%), folate, fetal testing

Answer 257

Second most **common** in pregnancy (after HTN) Course during pregnancy is variable: improve, remain stable or worsen If symptomatic, weeks 24-36 most difficult (10% have intrapartum asthma exacerbation) Generally follows similar course with subsequent pregnancies Effect on pregnancy: fetal risks due to **hypoxia**, increased spontaneous abortions (preterm labor, **low birth weight**, neonatal hypoxia), maternal death (status asthmaticus, associated complications)

Answer 258

Produce and mineralize bone matrix ("**build bone**") After incorporation into matrix they become **osteocytes**

Answer 259

Multinucleated cells which are responsible for bone **resorption**

Answer 260

Account for **90-95% of bone cells** and are involved in **regulation** of bone formation and resorption

Answer 261

**Bone formation**: **BMP**, beta blockers, **intermittent PTH**, mechanical **load**, androgens; NOT SOST, leptin, beta-adrenergic stimulation, immobilization, aging **Bone resorption**: **estrogen deficiency**, immobilization, l**ow Ca (PTH)**, NOT estrogen, SERMs, bisphosphonates, calcitonin, Ca2+, vitamin D

Answer 262

Systemic skeletal disease characterized by l**ow bone mass** and **microarchitectural deterioration** of bone tissue, with a consequent increase in bone fragility and **susceptibility to fracture**

Answer 263

Pain Height loss Kyphosis Activity limitations Restrictive lung disease Altered abdominal condition Psychological symptoms

Answer 264

1) **Endocrine** abnormality: estrogen deficiency, testosterone deficiency, Cushing's syndrome, thyrotoxicosis (hyper?), primary hyperparathyroidism, diabetes mellitus 2) **Genetic**: polygenic, osteogenesis imprefecta, Ehlers-Danlos syndrome, homocystinuria, Marfan's syndrome, Menkes' syndrome, lysinuric protein tolerance 3) **Rheumatoid arthritis** 4) **Inflammatory bowel disease** 5) **Chronic alcoholism** 6) **Cigarettes** 7) **Juvenile** osteoporosis 8) **Chronic hypophosphatemia** 9) **Renal hypercalciuria** 10) **Nutritional abnormality** (Ca2+ deficiency, Vitamin D deficiency, protein deficiency) 11) **Systemic mastocytosis** 12) **Weightnlessness**/immobilization (sclerostin-mediated) 13) **Proton pump inhibitors** 14) **Anticonvulsants** 15) **Thiazolidenediones** 16) **Heparin** 17) **Depression** and its **Rx** 18) **Chronic liver disease** 19) **Hematologic malignancy** (multiple myeloma, leukemia, lymphoma) 20) **Aging** 21) **Idiopathic**

Answer 265

**Diagnose osteoporosis** **Assess fracture risk** **Monitor therapy**

Answer 266

Dual x-ray absorptiometry (**DXA**) Quantitative computerized tomography (**QCT**) Quantitative ultrasound (**QUS**) **FRAX**: determination of fracture risk using risk factors with or without DXA

Answer 267

**Osteoblasts**: serum alkaline phosphatase (total and bone specific), N-terminal propeptide of type 1 collagen, osteocalcin **Osteoclasts**: serum and urine N and C terminal telopeptides **Osteocytes**: serum sclerostin, **FGF-23**

Answer 268

**Anti-resorptive** drugs: **estrogen**, **SERMs** (raloxifene, tamoxifen), **bisphosphonates** (alendronate, risedronate, pamidronate, ibandronate, zoledronic acid), salmon calcitonin, denosumab (Ab against RANKL) **Anabolic** drugs: **human parathyroid hormone** 1-34 (**teriparatide**: only drug that increases bone density AND bone mass), anti-sclerostin antibody romosozumab (experimental)

Answer 269

**Excess of unmineralized bone** (osteoid) which results from an impairment of bone mineralization Serum **alkaline phosphatase** is **elevated** and serum **Ca2+** and/or **PO4** are usually **decreased**

Answer 270

In **children**, causes **epiphyseal dysplasia**, impaired growth and **skeletal deformities** Can result from disorders that cause reduction of circulating vitamin D metabolites (peripheral resistance to 1,25 (OH)2D3, chronic hypophosphatemia from FGF-23 excess)

Answer 271

**Inadequate UV exposure** and inadequate vitamin D Vitamin D **malabsorption** (small intestine disease or surgical bypass, pancreatic insufficiency, insufficient bile salts) Abnormal vitamin D **metabolism** (liver disease, chronic renal failure, drugs (anticonvulsants, glutethimide), mesenchymal tumors, prostatic cancer, vitamin D-dependent rickets type I (25-hydroxyvitamin D-1 alpha hydroxylase deficiency)) **Renal loss** (nephrotic syndrome)

Answer 272

**Renal phosphate wasting**: hypophosphatemic rickets (familial X-linked, autosomal recessive, sporadic), hypophosphatemic osteomalacia (familial X-linked, sporadic), familial renal phosphate leak with hypercalciuria, nephrolithiasis and osteomalacia and rickets, Fanconi's syndrome, mesenchymal tumors, fibrous dysplasia, epidermal, nevus syndrome, prostatic cancer, primary hyperparathyroidism **Malnutrition** **Malabsorption** due to GI disease or phosphate-binding antacids **Chronic dialysis**

Answer 273

**Vitamin D dependent rickets, Type II** **Anticonvulsant drugs** **Chronic renal failure** Therapy: correct vitamin D deficiency, correct hypophosphatemia, high dose 1,25 (OH)2D3 and calcium

Answer 274

Evolves from **initial osteolytic lesion** into **sclerotic phase** over **decades** Numerous, large **osteoclasts** produce initial lesion --\> **secondary** increase in **osteoblasts** --\> increase in **bone mass** of **chaotic** structure Localized disorder initiated by **osteoclast** **overactivity** Paget's disease of bone: osteolytic phase, sclerotic phase; **osteoblasts** cause **increased serum alkaline phosphatase**; **osteoclasts** cause **increased bone collagen components**; nuclear and cytoplasmic inclusions in osteoclasts Susceptibility genes which may predispose to Paget's disease: sequestosome 1, colony stimulating factor 1 (CSF-1), TNFRSF11A, optineurin, UCMA/GRP, TM7SF4, valosine containing protein; **familial in 20%** Many people are asymptomatic but can have bone pain, hearing loss with skull disease or secondary arthritis with pelvic/lower extremity disease Treatment is **bisphosphonates** (oral or IV): single IV infusion of **zoledronic acid** restores SAP to normal range and produces remission up to 6.5 years!

Answer 275

**Osteoblasts** secrete **osteocalcin** (uncarboxylated) which increases **insulin** secretion and sensitivity Insulin receptors on osteoblasts allow for forward feedback loop in which insulin secretion activates osteocalcin which promotes glucose metabolism Osteocalcin may also stimulate **testosterone** secretion **Osteocytes** secrete **FGF-23** which **inhibits** renal tubular **reabsorption of phosphate** and **synthesis of 1,25 (OH)2D** (thus, may cause hypophosphatemic bone disease) Osteocytes also secrete **sclerostin** which regulates osteoblast and osteoclast activity (decreases bone formation and **increases bone resorption**)

Answer 276

**49%** of pregnancies are unintended 22% result in birth 20% result in abortion 14% result in fetal loss

Answer 277

**Hormonal contraception** most common for younger women (until age 30) **Sterilization** becomes more common after age 30

Answer 278

20 mcg levonorgestrel per day **5 year** use Primary mechanism is **fertilization inhibition** Causes **cervical mucus thickening**, **inhibit** **sperm motility** and function, **inhibit tubular motility** Inhibition of **implantation** is secondary mechanism

Answer 279

Copper ions **10 year** use Primary mechanism is **prevention of fertilization** (copper is a spermicide) **Inhibits sperm motility**, **inhibits acrosomal enzyme activation**, induces **endometrial** sterile **inflammatory** reaction resulting in **phagocytosis of sperm** Inhibition of **implantation** is a secondary mechanism (however, must be an action because copper IUD is most effective **emergency contraception**)

Answer 280

Highest patient satisfaction among methods Rapid **return of fertility** Safe **Immediately** **effective** Long-term protection Highly effective (perfect use first year failure rate 0.6%)

Answer 281

Placement **within 5 days** of unprotected sex is most effective form of emergency contraception Also effective when placed within 5 days of known ovulation

Answer 282

Relatively involved compared to other barrier methods Must be fitted by clinician Place prior to intercourse, maintain between **8-24 hours after intercourse** Must coat inner surface with **spermacide**

Answer 283

Detergents attack sperm **flagella** and body, **reducing motility** **Nonoxynol-9** is most common Apply **less than 1 hour prior** to coitus (foam, gel, cream) or at least **15 minutes before** (film ,suppositories, tablets) **Complete coitus within 60 minutes** after application No bathing or douching for 6 hours after application **Not very effective**: perfect use failure is 15% and typical use failure is 29% (greater than withdrawal method)

Answer 284

Perfect use failure rate is **2-4%**, typical use failure rate **18-27%** Note: more effective than spermacides alone

Answer 285

Predicting time of ovulation by **cervical mucus, calendar, cycle beads, basal body temperature** Perfect use failure rate is 1-9% Typical use failure rate is 12-25%

Answer 286

**Nursing delays ovulation** resumption after childbirth If **not** breastfeeding, begin ovulating within **6 weeks postpartum** If **breastfeeding**, 50% of women don't ovulate until **24 weeks postpartum** Possible to have delay longer than 1 year Definition: **amenorrhea**, **fully breast feeding**, **infant less than 6 months old** (if 3 criteria are met then risk of pregnancy \<2%)

Answer 287

More common in women then men Permanent **Female**: interruption of **fallopian tubes** to prevent fertilization **Male**: interruption of **vas deferens** to prevent passage of sperm into seminal fluid and female reproductive tract

Answer 288

Can do it immediately postpartum, or any time Partial **salpingectomy** (1% failure) **Coagulation** (3% failure) Silicone **band** (2% failure) Spring **clip** (4% failure) **Hysteroscopic** **implant** (becoming more common, best method)

Answer 289

Surgical ligation and resection of segment of vas deferens Follow-up for sperm counts Failure rate 1%

Answer 290

Can do medication abortion up to about **11-12 weeks gestation** **Mifepristone**, **RU-486**: similar to progesterone, and binds tightly to progesterone receptor without activating it; prostaglandin-mediated **cervical ripening** (softer and more dilatable) and **rhythmic contractions** **Misoprostol**: induces **uterine contraction** and **softens os**; also is an inexpensive gastroprotectant (Cytotec) but used off-label for abortion; is absorbed from oral, vaginal, buccal, sublingual or rectal routes; **prostaglandin E1 analogue** misoprostol is active ingredient **Mifepristone + misoprostol** together used to induce abortion: block progesterone to cause decidual necrosis, rhythmic uterine contractions and cervical ripening which cause detachment, expulsion and abortion

Answer 291

**FDA-approved**: Mifepristone 600mg PO on day 1, then **misoprostol 400ug PO on day 3**, then **follow up on day 14**; up to 49 days of gestation **Evidence-based**: Mifepristone 200mg PO on day 1, then **misoprostol 800mcg at home 0-72 hours later**, then **follow up on day 14**; up to 63 days of gestation

Answer 292

Assess **completion** **of** **abortion** by patient history, serial hCGs, sonography, speculum and/or bimanual exam Document missed follow-up If procedure incomplete or unsuccessful, repeat **misoprostol** **or MVA** can be used for retained products of conception

Answer 293

**Manual vacuum aspiration (MVA)**: option **up to 12 weeks** of pregnancy; requires syringe that creates suction; procedure complete under 5 minutes; useful for post-abortal care and management of early pregnancy failure **Electric vacuum aspiration (EVA)**: option **up to 16 weeks** of pregnancy; suction catheter removes products of conception; requires 5-10 min from cervical dilation to procedure completion

Answer 294

**Medication**: private, non-invasive, two visits required, **2-5% failure** require surgical procedure **Surgical**: single visit complete in 5-10 min; **99% effective** Note: these are in **first trimester**--if you want second trimester must do **induction of labor for medication** and **dilation and evacuation for surgery**

Answer 295

**17-beta-estradiol** Major estrogen secreted by the ovaries Adding ethinyl to 17 carbon position created 17-alpha-ethinylestradiol which leads to ORAL activity

Answer 296

**1st** generation: \>/= 50ug EE **2nd** generation: 30-35ug EE combined with norethindrone, norgestrel, levonorgestrel, norgestimate **3rd** generation: = 30ug EE combined with desogestrel, 10ug

Answer 297

Don't have to know them all, but are: norethindrone, norethynodrel, norethindrone acetate, **ethynodiol diacetate (low androgenicity)**, **norgestrel (most androgenic)**, norgestimate (less side effects), desogestrel, **drospirenone (similar to spironolactone, low androgenicity)** Each has **different side effect profile** so if one giving bad side effects to a patient, try another

Answer 298

Remove a methyl group from testosterone to get **norethindrone** (high progestational activity, high oral activity, almost no androgenicity) Add additional methyl group to form ethyl group to produce **norgestrel** (greater progestational activity than norethindrone) Norgestrel synthesized into dextro-norgestrel (inactive) and **levonorgestrel** (active form)

Answer 299

**Gonanes** have **17** carbons (related to norethindrone) **Estranes** have **18** carbons (related to norgestrel: levonorgestrel, desogestrel, gestodene, norgestimate) Drospirenone: analog of spironolactone (4th generation)

Answer 300

**Monophasic** have one level of hormone throughout the month (**Alesse**, Loestrin, **Yaz**, Yasmin, Ortho-Cyclen) **Biphasic** have 2 levels of hormone during the month (**mircette** (good for women w/headaches)) **Triphasic** have 3 levels of hormone during the month (**Ortho Tri-cyclen**); progestin increases from week 1 to 3

Answer 301

Used in women who **cannot take estrogen**-based medications (blood clots, migraine with aura) Ex: **Ovrette, Micronor**

Answer 302

**Seasonale**: 84 days 30ug EE-0.15mg levonorgestrel and 7 days inactive **Seasonique**: same as seasonale except 7 days of 10ug EE pills so no spotting on other 84 days **Lybrel**: 20ug EE-0.09mg levonorgestrel for 1 year; 99% resume ovulation within 3 months of discontinuation Continuous administration of active pills used in order to reduce frequency of menses-linked events or disease processes (endometriosis, severe dysmenorrhea, menstrual migraine)

Answer 303

They need only have range from **80-125% of values** for reference drug If only 70% dose, would impair efficacy in obese woman on low hormone pill!

Answer 304

**ER-alpha** and **ER-beta** Majority of tissues contain both receptors but in different distribution Note: **colon has only ER-beta** and studies showed that HRT causes reduction in risk of colon cancer--could be due to ER-beta

Answer 305

**hPR-B** and **hPR-A** Derived from same gene and exist in target cells Similar structurally but different functionally **PR-B is stronger transcriptional activator** than PR-A Cellular responsiveness modulated by PR-A to PR-B ratio (more responsive if more PR-B?) **PR-B** present in excess in **uterus**

Answer 306

**Stops ovulation**, changes **cervical mucus** to prevent sperm fertilization (**thicker**), alters **lining of uterus** to prevent embryo reception (**thinner**) Ovulation prevented by **inhibiting LH and FSH** by acting on pituitary and hypothalamus **Progesterone** agent suppresses **LH** (especially the LH surge) and **estrogen** agent suppresses **FSH** (prevents emergence of dominant follicle) Protesterone agent **thins endometrium** and **thickens cervical mucus** and **decreases tubal peristalsis**

Answer 307

**Decreases**: Ectopic pregnancy Dysmenorrhea Oligomenorrhea Acne Ovarian androgens PID Menorrhagia Anemia **Ovarian cancer** **Endometrial cancer** Perimenopausal symptoms Endometriosis Benign breast disease Rheumatoid arthritis Fibroids Ovarian cysts **Colon cancer**

Answer 308

**Cervical cancer**: with more than 5 years use, reaching 2x increase after 10 years (Breast cancer: 20% increase of early premenopausal breast cancer; but no effect of past use or duration of use up to 15 years on risk; previous OCP use may be associated with reduced risk of metastatic breast cancer later in life; OCP does not further increase risk in women with positive family history or benign breast disease --\> OVERALL NO INCREASED RISK)

Answer 309

**"New" progestins** (desogestrel, gestodene; also drospirenone) associated with **1.7x greater risk** than older progestins Risk increase concentrated in **first year of use** After discontinuation, VTE risk returns to that of non-users within 3 months Risk concentrated in **overweight** women **\>10 cigarettes** per day increases risk further Specific effects: increased prothrombin, factor 7, 8, 10, fibrinogen, decreased factor 5, resistance to activated protein C, fibrinolytic but also increase TAFI which inhibits fibrinolysis --\> NET PRO-THROMBOTIC

Answer 310

**Migraine with aura** **Smoking**

Answer 311

Breast tenderness Decreased libido Headache/migraines Nausea Bloating Chloasma/molasma (pigmentation on face and areola) Increased appetite and weight gain (not really!) Mood changes Changes in vaginal bleeding (lighter periods, BTB, amenorrhea)

Answer 312

**Increase SHBG** **Decrease T**

Answer 313

**Prior blood clot** Impaired liver function History of **CAD** or **CVD** **Migraine with aura** **DM** with **vascular disease** Known or suspected **breast cancer** Undiagnosed **vaginal bleeding** Known or suspected **pregnancy** **Smoker \>35** Severe **hypercholesterolemia**/hypertriglyceridemia Uncontrolled **HTN** (risk of stroke)

Answer 314

Migraines w/o aura Controlled HTN Fibroids H/o gestational DM DM Elective surgery Seizure disorder Obstructive jaundice in pregnancy Sickle cell disease or sickle C disease GB or liver disease Mitral valve prolapse Lupus Hyperlipidemia Smoking

Answer 315

Former smoker must have **stopped for 6 months** and preferably 12 months to be regarded as a nonsmoker Women who have nicotine in their bloodstream obtained from **patches** or **gum** should be regarded as **smokers**

Answer 316

**Anticonvulsants**: barbituates (phenobarbital, primidone), **phenytoin**, **carbamazepine**, topiramate, vigabatin Anti-infectives: **rifampin**, **griseofulvin** Note: doxycyclin, ampicillin, metronidazole and quinolone antibiotics do NOT decrease effectiveness of OCPs

Answer 317

Miss **3 or more active pills** or start pack 3 or more days late Take active pills as soon as possible then continue 1 pill/day; use condoms until active pills taken for 7 consecutive days If missed pills **in 3rd week**, finish active pills in current pack and then start new pack, **do not take 7 inactive pills** Note: if taking **20ug pills**, only have to miss **2 active** pills/start pack 2 days late to be at risk for unintended pregnancy and have to take 7 inactive pills

Answer 318

**High doses** of estrogen and/or protestins to **disrupt ovulation, prevent fertilization** and **prevent implantation** Effective up to **5 days post coitus** Ex: ulipristal acetate, Yuzpe, Plan B (progestin only), mefisterone (RU-486), IUD

Answer 319

**Stroke** **MI** **DVT** Gall bladder disease Benign liver tumors (hepatomas) BP elevation

Answer 320

Measure **hCG** and if **high**, do **ultrasound**, which will show you **NO intrauterine pregnancy** (not necessarily presence of ectopic) --\> can say it is ectopic pregnancy **Surgical** treatment: if contraindications to medical tx, if fetus larger than 3cm or if fetal heart beat; if unruptured, **laparoscopy** (salpingostomy) to incise tube, clean it out and let it heal itself; if ruptured, **laparotomy** (open surgery) instead **Medical** treatment: **methotrexate** 90% successful in resorbing pregnancy; contraindications are renal disease, liver disease, hematological disease

Answer 321

**Benign**: cyst, **fibroadenoma**, intramammary lymph node, cystosarcoma phyllodes **Malignant**: intracystic cancer/DCIS, invasive cancer/DCIS, breast lymphoma, metastatic tumor, malignant cystosarcoma phyllodes

Answer 322

**Benign**: fibrocystic changes **Malignant**: invasive lobular carcinoma

Answer 323

**Benign**: eczema, psoriasis **Malignant**: Paget's disease (intraepithelial carcinoma)

Answer 324

**Benign**: congenital or acquired **Malignant**: subareolar invasive cancer

Answer 325

**Benign**: mastitis, abscess **Malignant**: inflammatory breast cancer

Answer 326

**Benign**: hormone-mediated mastalgia **Malignant**: invasive cancer

Answer 327

**Benign**: sebaceous cyst **Malignant**: superficial invasive cancer, apocrine cancer

Answer 328

**Ultrasound**: most important for characterizing **benign** breast lesions **Mammography**: **cancer** screening and diagnosis **MRI**: adjunct modality, for implants/silicone leak, role in **screening** for **high risk** patients, useful for imaging patients with **dense** breasts **Needle biopsy**: mandatory for **all solid masses**

Answer 329

Can detect **tumors** as small as **5mm** and **cystic** lesions as small as **2mm** Can determine **solid vs. cystic** Can visualize lesions in mammographic-**dense** **breasts** Benign characteristics have \>99% negative predictive value in ruling out malignancy **Benign**: **oval** or gentle lobulations, **parallel** to skin, **circumscribed** margins **Malignant**: **irregular**, **taller than wide**, **indistinct**, **spiculated** borders

Answer 330

**Do not do mammogram on women under 35** because accuracy is low because dense breasts For women \>45, false negative is 10% but \<45 is 40-50%

Answer 331

**Fine needle aspiration**: aspirate fluid and cellular material, cytological analysis, variable sensitivity and specificity, unable to evaluate histology, good for **low suspicion lumps** in young women **Core needle biopsy**: multiple cores of tissue obtained, permits **histologic** examination, highly sensitive and specific All biopsies should be performed with imaging guidance

Answer 332

**Only if FNA and core needle biopsy non-diagnostic** Pros: large amount of dissue for analysis, eliminates possibility of sampling error Cons: most invasive, expensive, unnecessary, may make subsequent surgery more difficult if cancer identified

Answer 333

**Nonproliferative** and **no increased risk**: cysts, ductal ectasia, simple fibroadenoma, mastitis, fibrosis, mild hyperplasia **Proliferative** and **slightly increased risk**: complex fibroadenoma, papilloma, sclerosing adenosis **Proliferative with atypia** and **increased risk**: atypical ductal hyperplasia, atypical lobular hyperplasia

Answer 334

**Breast pain** (cyclical, noncyclical) Abnormalities of **nipple** **areolar** **complex** (nipple discharge, inversion) **Fibrocystic changes** **Infections** (mastitis, breast abscess) Dominant **breast masses** (simple cyst, fibroadenoma, phyllodes tumor, fat necrosis)

Answer 335

10% of women affected (60% have mild discomfort) Affects **younger** women, **late in luteal phase**, exogenous and endogenous estrogen stimulation, frequently bilateral, poorly localized, heaviness or soreness Possibly exacerbated by methylxanthine stimulation (caffeine, chocolate, soft drinks), fat intake, psychological factors Treatment: reassurance, **NSAIDs**, examine exogenous hormone use, eliminate caffeine, Vitamin E, evening primrose oil, bra fitting; for severe debilitating pain use danazol (antigonadotropin with hirsutism, acne, weight gain, and teratogenicity as side effects), bromocriptine, tamoxifen

Answer 336

More frequently related to **anatomic cause** Examine breast and chest wall thoroughly **Ultrasound** (and mammogram if over 35) for macrocyst, fibroadenoma, lipoma, infection \<10% of carcinomas associated with focal pain Could be radicular pain from cervical arthritis, costochondritis (Tietze's syndrome), thrombophlebitis (Mondor's syndrome)

Answer 337

In **50-60%** of women without breast disease **Blockage of milk ducts** leads to dilation **Lumpy, bumpy** breasts on examination Common in women **30-40** Hormonally responsive, can **enlarge with estrogen**, and cysts often involute after menopause No increased risk of breast cancer

Answer 338

75% of patients with delayed diagnosis fulfill these criteria: 1) Young age **\<45** 2) **Self-discovered** breast mass 3) **Negative mammogram** Important to **ignore negative mammogram** in this scenario and don't even get a mammogram if women \<35!

Answer 339

First do focused breast **ultrasound** If **cystic**, **aspirate** fluid (cytology if bloody) --\> repeat US 6 weeks later, excise for intracystic abnormality and consider excision for symptomatic recurrence If **solid**, do UC-guided **fine needle biopsy** --\> if **benign**, **excise** with narrow margins; if **malignant**, do **cancer** **workup** (bilateral and diagnostic mammogram)

Answer 340

**Age \<30**: firm, rubbery lump is **fibroadenoma** **Age 30-50**: firm, discrete lump could be **fibroadenoma**, **cyst**, **fibrocystic changes**, usual **ductal hyperplasia**, **atypical** ductal hyperplasia, atypical lobular hyperplasia **Age \>70**: firm, discrete lump is **cyst**, **DCIS**, **invasive cancer** Note: 9 out of 10 new nodules in premenopausal women are benign

Answer 341

**Fluid filled** Lined by **apocrine** **cells** and derived from **terminal duct lobular unit** On exam, may feel **firm or rubbery** 7% of Western women, with peak in 40s Hormonally responsive and **uncommon after menopause** Dx with **ultrasound** **No risk for malignancy**, so no need for treatment but can be aspirated (but 10% recur) However, **bloody** cyst raises suspicion for **malignancy** (send cytology, obtain imaging, consider excision)

Answer 342

**Benign tumor** arising from **epithelium** and **stroma** of **terminal duct lobular unit** Common in 20-40 Account for 75% of breast biopsies in women \<20 Hormonal factors affect growth (**increase during pregnancy**) **Rubbery** texture, sharply **demarcated**, **mobile** within breast, may be **tender** Dx with **US** and **needle biopsy** Begin as **noncalcified** but may develop coarse calcifications in periphery Treatment: **observe** if unambiguous, \<25, small (\<3cm), surgery (**enucleation** with narrow margin) if need to r/o phyllodes tumor, symptomatic, growing, extensive (would interfere with future breast imaging)

Answer 343

**Uncommon**, varying malignant potential Palpable mass indistinguishable from fibroadenoma on CBE 4-5cm with **rapid growth** **Core biopsy** for diagnosis 20% recur after local excision, but **do not metastasize** Treatment: **wide excision** with 1-2cm margins, but do not need lymphadenectomy

Answer 344

No cause in 50%, but can be secondary to **trauma, breast surgery, infection, radiation therapy** May **mimic** **carcinoma** on CBE and imaging: skin thickening, dimpling, retraction, calcifications, architectural distortion, spiculated masses Generally, need a **biopsy** to exclude malignancy

Answer 345

Occurs in 10-30% **breastfeeding** women, uncommon in non-lactating women **Bacteria** enter through cracks in skin: **S. aureus** most common but also **Strep** (epidermidis) Treatment: **continue** **nursing** **or pump** and discard, oral **antibiotics**, consider ultrasound to rule out abscess (milk flow decreases incidence of abscess)

Answer 346

Occurs in 5-10% of women **with mastitis** Difficult to distinguish from mastitis on exam Commonly present with advanced infection **US** is diagnostic and may show multiple collections of pus **Drainage** of abscess is essential (needle aspiration or surgical drainage), use antibiotics only if surrounding/systemic infection If infection does not regress, investigate for **inflammatory cancer**

Answer 347

**Congenital** **inversion**: aberrant development of terminal ducts, predisposes to terminal duct obstruction, periductal mastitis, and subareolar abscess, **can be everted on exam** **Retraction**: develops **rapidly** (months), decreased local mobility of the breast tissues, **cannot be everted**, need to **investigate for mass/malignancy**

Answer 348

**Physiologic**: with nipple compression, originates from **multiple ducts**, often bilateral **Pathologic**: spontaneous (may be bloody), usually localized to **one duct**, possibility of malignancy (32% of women over 60 and 7% of women under 60) **Galactorrhea**: (milk) endocrine abnormalities, medication side effects

Answer 349

Increased **TSH** (TRH stimulates prolactin secretion) Increased **prolactin**

Answer 350

Most common specific cause of **unilateral bloody nipple discharge** Rarely palpable 92% within 2cm of nipple Peak incidence age 40-50 Localization: pressure/stroking, galactography **Ductal excision** for papilloma: methylene blue dye helpful, can place probe in duct to guide surgery Papillomas are **benign**, but carcinoma is unexpectantly found in 5% of cases

Answer 351

**Rash, ulcer, crusting of NAC**: punch biopsy **Nipple/skin retraction**: imaging to rule out underlying mass; imaging-guided needle biopsy if mass identified **Breast skin lesion**: punch biopsy **Mastitis**: antibiotics, US to rule out abscess, if \>35 then mammogram for breast cancer screen **Breast abscess**: US guided needle drainage or open surgical drainage **Cyst**: drain if symptomatic and send fluid for cytology (maybe), excise if solid intracystic abnormalities **Fibroadenoma**: excise with narrow margins (enucleation) **Benign phyllodes tumor**: wide excision with 1-2cm margins **Intramammary lymph node**: US to characterize, needle biopsy, excise, send for flow cytometry **Intraductal papilloma**: duct excision **Fibrocystic changes**: symptomatic pain management **Gynecomastia**: look for underlying cause (hormonal, meds), r/o breast cancer in older patients, surgical excision if symptomatic

Answer 352

**DCIS**: at risk for subsequent cancer in that breast and contralateral **LCIS**: marker for malignancy, doesn't need to be excised because **LCIS itself doesn't develop** into breast cancer, but both breasts at **risk** for cancer (infiltrating ductal carcinoma); treatment is just watch or remove both breasts!

Answer 353

Most **frequently diagnosed** cancer (23% of cancer in women) **Leading cause of cancer death** in females Half breast cancer and 60% of deaths occur in developing countries

Answer 354

**15%** of women diagnosed have positive **family history** 1. 8x risk if one first degree relative 2. 9x risk if two first degree relatives Higher risk if affected relatives **younger** or **h/o ovarian cancer** Specific genetic mutations (**BRCA**, p53, PTEN, MLH1, MSH2) only account for 5-10% breast cancers Average lifetime risk of breast cancer if **no FH: 11-12%** Average lifetime risk of breast cancer if **first deg rel: 20-25%** Average lifetime risk of breast cancer if **BRCA1 or 2 mutation: 65-85%**

Answer 355

**1.3-2x** risk for **proliferative lesions without atypia** (complex fibroadenoma, sclerosing adenosis, intraductal paipllomas, hyperplasia) **3-6x** risk in ipsilateral breast if **atypical** ductal or lobular hyperplasia **1% per year** for lobular carcinoma in situ (**LCIS**) **5% 10 year risk** of invasive breast cancer in contralateral breast if ductal carcinoma in situ (**DCIS**) **1% per year** for **premenopausal** and **0.5% per year** for **postmenopausal** women for contralateral breast cancer if **already invasive cancer** of other breast

Answer 356

**Early menarche** **Nulliparity** **Age at first live birth \>30** **Older age at menopause** No breast feeding **Hormone replacement post-menopause** High socioeconomic status **High BMI** Increased dietary fat intake Young when ionizing radiation

Answer 357

Avoid extended hormone replacement (progesterone) **Early pregnancy** and breast feed \>6 months Low fat, low alcohol **Tamoxifen**: may reduce breast cancer by 50% in high risk; take for **5 years** Exemestane: real benefit but very small

Answer 358

**Women over 40** should have annual mammogram (American Cancer Society, American College of Radiology) If life expectancy is greater than 5 years, will benefit from screening

Answer 359

**Infiltrating ductal cancer**: when DCIS is associated, goal is to obtain surgical margins clear of both invasive tumor and DCIS to reduce risk of recurrence **Invasive lobular cancer**: associated with either LCIS or DCIS; higher frequency **bilateral** and multicentric and spreads to unusual locations (meninges peritoneum, GI)

Answer 360

T0: no evidence of primary tumor Tis: carcinoma in situ T1: tumor **T2**: tumor **\>2cm** and \<5cm **T3**: tumor **\>5cm** **T4**: any size with direct extension to **chest** **wall** or **skin** pN0: no LN metastasis **pN1**: **micrometastases** or up to **3 axillary LN** **pN2**: **4-9 axillary LN** or \>/= **1 internal mammary LN** **pN3**: **10+ LNs** or ipsilateral **supraclavicular LNs**

Answer 361

Stage 0: Tis N0 M0 Stage I: T1 N0 M0 Stage IIA: T0-1 N1; T2 N0 **Stage IIB**: **T2 N1**; **T3 N0** Stage IIIA: T0-2 N2; T3 N1-2 **Stage IIIB**: **T4** (any N) **Stage IIIC**: any T **N3** **Stage IV**: **metastases**

Answer 362

H&P CBC, LFTs Screening bilateral then diagnostic **mammogram** **Ultrasound** **MRI** in some patients (**high risk**, young?) **Biopsy** and pathology review Genetic counseling if high risk for hereditary breast cancer If **stage IIIA+** or symptoms: **chest** **CT**, abdominal CT/MRI, bone scan, **FDG PET/CT**

Answer 363

**Primary** **tumor**: breast conserving surgery or mastectomy **Lymph node evaluation**: sentinel lymph node biopsy (for clinically negative axilla) or axillary lymph node dissection

Answer 364

Indications: if tumor too **large** for breast conserving surgery, if **multicentric**/multifocal, if **genetic predisposition** to breast cancer, patient preference Types of mastectomy: **simple** (entire breast removed and SLN biopsy), **modified radical** (entire breast and axillary lymph nodes removed), **skin sparing** (remove breast and nipple with minimal surrounding skin--for immediate reconstruction)

Answer 365

They are **equivalent** in terms of survival!

Answer 366

**Blue dye and/or radioisotope** injected near tumor or under areola SLNs identified by color/radioactivity and excised from axilla If **no tumor** identified in SLN, **95% chance no other nodes** involved If **positive** SLN, generally **complete axillary lymphadenectomy** indicated

Answer 367

Use **after breast conserving surgery** because 30-40% have **residual** microscopic disease after margin negative resection Use **after mastectomy** for patients at risk (\>/= 4 positive axillary LNs; 1-3 LNs and tumor \>5cm; T4 disease (skin, chest wall involvement)) Adverse effects of radiation: fatigue, skin irritation, desquamation, breast volume loss, fibrosis, retraction, secondary cancer (sarcoma, lung cancer, contralateral breast cancer), injury to heart and lungs

Answer 368

**Neoadjuvant**: to shrink large tumor **before surgery** if patient wants breast conserving surgery rather than mastectomy (no difference in survival with or without neoadjuvant) **Adjuvant**: after surgery for early (stage I-III)

Answer 369

60-75% of breast cancer is **estrogen receptor positive** **Tamoxifen** blocks estrogen **receptor** **Aromatase inhibitors** decrease peripheral **production** of estradiol

Answer 370

**Decrease** **production** of estradiol by blocking the enzyme aromatase (in granulosa cells?) Anastrozole (Arimidex), letroxole (Femara), Exemestane (Aromasin) Appropriate only for **post-menopausal** women with ER+ and/or PR+ tumors 2-6% reduction in risk of breast cancer recurrence compared to tamoxifen

Answer 371

**Human PTH 1-34** **Anabolic** agent Only approved agent that increases both bone density AND **bone mass** Acts in part by **suppressing sclerostin** secretion Reserved for more severe cases of osteoporosis

Answer 372

**Prolong pregnancy** for 48 hours or longer **Calclium** **channel** **blockers**: delay delivery 2-7 days by blocking voltage-dependent channels to inhibit Ca2+ entry into smooth muscle cells **Oxytocin antagonists** **Beta-mimetic drugs** (terbutaline, ritrorine): delay delivery by 48 hours but greater side effects; relax smooth muscle in myometrium through stimulation of beta2-adrenergic receptor **COX inhibitors**: block production of prostaglandins (which usually increase free Ca2+ in myometrial cells, increase activation of MLCK to induce uterine contractions) **Magnesium sulfate**: act by competition with Ca2+ at the motor end plate

Answer 373

**Stimulate uterine contractions** for induction of labor and prevention of postpartum hemorrhage **Oxytocin**: nine AA peptide; G-protein coupled receptor on myometrial cells causes IP3 increase, Ca2+ increase and smooth muscle contraction **Methylergonovine**: stimulates smooth muscle directly; partial alpha agonist **Carboprost** **tromethamine**: methylated analog of PGF2a **Dinoprostone**: PGE2 **Misoprostol**: PGE1 analog originally intended for use to prevent NSAID-induced gastric ulcers; has cervical ripening and uterotonic properties

Answer 374

1st trimester: week 1-12 2nd trimester: week 13-26 3rd trimester: week 27-end (40?)

Weeks 2 and 3 (Women's Health) Flashcards

(402 cards)