Disorders of Female Sexual Maturation PDF

9: Disorders of Female Sexual Maturation (Baby Wolter) Baby Wolter Q’s 1. Teenager >15 yrs old, delayed puberty, cramping/bloating abdominal pain every 4 weeks & goes away after 3-4 days, don’t have period yet, tanner stage beyond 2-3 (have secondary sex characteristics) • Dx – imperforate hymen • G...

9: Disorders of Female Sexual Maturation (Baby Wolter) Baby Wolter Q’s 1. Teenager >15 yrs old, delayed puberty, cramping/bloating abdominal pain every 4 weeks & goes away after 3-4 days, don’t have period yet, tanner stage beyond 2-3 (have secondary sex characteristics) • Dx – imperforate hymen • Gonadotropin levels – LH/FSH are NORMAL 2. Precocious puberty, pt <8 yrs old, thelarche occurs & no pubarche/adrenarche → incomplete, no growth spurt, • First step → bone age o Bone age is normal (same as chronologic age) ▪ Dx – premature thelarche ▪ What do you do? Observation, do not intervene o If bone age abnormal (advanced) → next step is labs 3. pt is teenage <15, hasn’t started period, short stature, increased carrying angle, shield-shaped chest, wide spaced nipples Dx – Turner’s • Gonadotropin levels – LH/FSH high → hypergonadotropic hypogonadism 4. Pt with obesity, hypotonia when born, excessive hunger, small hands/feet • Dx – Prader Willi • Labs – LOW LH/GSH ***Know difference btw complete/incomplete precocious puberty & difference between premature thelarche vs. premature pubarche/adrenarche Notes Precocious Puberty – thelarche or pubarche < 8 yrs old • Incomplete – isolated premature thelarche OR isolated premature pubarche/adrenarche o Thelarche – breast development o Adrenarche – maturation of adrenal androgen system o Pubarche – pubic hair development o Isolated premature thelarche ▪ Get bone age • Normal – monitor 4-6 mo • Advanced – labs/imaging o Isolated premature pubarche/adrenarche ▪ Bone age → normal ▪ DHEAS, total & free testosterone, androstenedione, 17 OH progesterone → rule out virilization disorders ▪ Labs normal → monitor every 4-6 mo • Complete – premature thelarche AND pubarche/adrenarche o Central – gonadotropin dependent (CNS issues – infection, tumor, etc.) ▪ Height prediction – early tall stature with lower than predicted adult height • growth spurt early → growth plates close early → shorter than could be ▪ Hypothalamic Hamartoma – MC brain lesion causing precocious puberty→ • Behavioral issues, cognitive impairment, seizure o Peripheral – gonadotropin independent (adrenal, gonadal, exogenous estrogen, etc.) ▪ McCune Albright Syndrome – precocious puberty, gonadotropin independent, patchy cutaneous pigmentation, fibrous skeletal dysplasia • o Eval – H&P, bone age, labs (thyroid, LH/FSH, estrogen, etc.), pelvic US ▪ MRI for ALL complete precocious puberty girls <7 yrs old o Tx – based on cause ▪ Determine height potential → GOAL: preserve growth potential • Height at risk → GnRH antagonist (leuprolide) ▪ Psychosocial concerns addressed Delayed Puberty – no breast/pubic hair by age 13, absence of menarche by age 15 or w/in 5 years of pubarche • Hypergonadotropic Hypogonadism – HIGH FSH/LH o Turner’s syndrome (45, XO) – gonadal dysgenesis, ovarian failure, short stature, increased carrying angle, shield-shaped chest, wide spaced nipples, lymphedema ▪ Tx – GH → increase linear growth & estrogen/progesterone o Ovarian failure – radiation, chemo, infection, etc. o Resistant ovary syndromes – ovarian failure & short stature • Normal Gonadotropins – NORMAL FSH/LH o Constitutional delay of puberty – unexplained delay in HPG system at puberty ▪ MC cause of delayed puberty, typically familial ▪ Bone age – appropriately delayed (younger) ▪ No tx o Genital tract abnormalities – imperforate hymen, vaginal atresia, vaginal aplasia ▪ Cyclical cramping (every 4 weeks), no visible bleeding, “mass” felt on palpation ▪ Tx – surgery o Post-infectious or post-surgical scarring • Hypogonadotropic Hypogonadism – LOW FSH/LH o Hypothalamic dysfxn – nutrition, body comp, stress, exercise-induced, etc. ▪ Amenorrhea ▪ Female Athlete Triad – eating disorder, amenorrhea, osteoporosis • Associated risks – stress fx, osteoporosis, infertility o Isolated gonadotropin deficiency – Kallmann Syndrome ▪ Defect in KAL-1 gene on X chromosome ▪ Abnormal GnRH secretion ▪ Infertility, anosmia, sensorineural deafness, kidney malformations, pes cavus ▪ Delayed bone age ▪ Tx – GH and sex steroids o Prader Willi – 15q11-q13 microdeletion ▪ Hypotonia when born, obesity, excessive hunger, short stature, small hands/feet, hypogonadism, developmental delay ▪ Tx – GH and sex steroids, healthy diet, education, psych support o Pituitary abnormality – panhypopituitarism, hyperprolactinemia o Hypothyroidism – Tx with exogenous T4 • Do bone age, tailor labs to patient/suspected cause 10: Vaginitis & Diseases of the Vulva Normal Vaginal Flora – all about the pH • Lactobacillus – main bacteria of vagina o Produce lactic acid (pH <4.5) → prevents overgrowth of pathogens • Raise pH → Abx (destroy lactobacillus), menses (blood alkaline), decreased estrogen, STIs, hygiene products (douching), intercourse (semen alkaline) Wet Prep – sample from lateral vaginal walls with q tip Empiric Tx for all 3 – Diflucan + Metronidazole • Put on slide with 2 drops of saline → look under microscope • Also look at pH • Do on ALL pts with abnormal white discharge that has fishy odor Vaginitis: inflammation in vagina only Bacterial Vaginosis – MC vaginitis • Overgrowth of anaerobes – Gardnerella MC • CP – malodorous, gray-white discharge • pH > 4.5 – hallmark o Anaerobes produce enzymes that breakdown peptides to AA & amines → increase pH • RF – anything that raises pH (smoking, douching, loss of estrogen (post-menopause) o Estrogen makes glycogen → feeds Lactobacillus → produce lactic acid → low pH o Smoking reduces estrogen levels → impacts system above • Complications – pre-term delivery, premature rupture of membranes, postpartum endometritis, post-surgical infections • Wet Prep → clue cell – sharp edges, looks peppery • Add KOH Prep → get fishy odor → + Whiff test • Tx – ONLY if symptomatic o Not pregnant – Metronidazole o Pregnant – avoid tx, but if have to give them clindamycin for first trimester ▪ After 1st trimester → metronidazole Candida albicans – yeast vaginitis • 2nd MC cause of vaginitis – typically found in bowel/perianal region • CP – cottage cheese discharge o Hallmark → itching • RF – Abx, steroids/immunosuppressants, diabetes, pregnancy • Wet Prep → leukocytes • KOH Test→ lyses squamous cells → shows hyphae & budding yeast o Whiff test neg • pH acidic - <4.5 • Tx – Trichomonas vaginalis • Only STI causing vaginitis • CP – malodorous discharge, dysuria • PE – strawberry cervix – hallmark o Yellow-grey or green frothy discharge • Wet Prep → ONLY discharge that moves (has flagella) o pH > 4.6 • • Labs – check for other STIs (gonorrhea, chlamydia, HIV), also get a pregnancy test Tx – metronidazole 1 dose PID o MUST tx partner o Delay tx if pregnant o Test of cure 1 mo later Pelvic Inflammatory Disease (PID) – infection of PELVIS • CP – fever, pain, vaginal discharge o She has peritoneal signs!! o Chandelier’s sign – move cervix & the pt jumps off the table Fitz-Hugh Curtis • Labroscopy → Adhesions, R uterine tube is huge & inflamed o Fitz-Hugh Curtis Syndrome → PID spreads to liver & gets adhesions there Bartholin Cyst/Abscess • CP – painful bump at vaginal opening, hurts to sit, & can’t have intercourse o Cyst – can be asymptomatic and be there for years o Abscess – acutely inflamed, infected, and in lots of pain • If sexually active → tx for gonorrhea • If over 40 → consider biopsy for cxr (bc it’s rare to get these at this age) • Tx – insert a word catheter → drain the cyst o Leave in for ~ a week → allows continuous drainage o Give Abx – cephalexin (broad spectrum) Differential for Vulvar Dystrophies • Lichen sclerosis – so itchy → scarring → will get better with steroids but lifelong use • o Lichen simplex chronicus – hallmark is hyperkeratosis & deep rete ridges o • ANY lesion of vulva → BIOPSY! Vulvar Intraepithelial Neoplasia (VIN) • High risk HPV – 16, 18, 31, 33 • VIN 2/3 → progression to cancer • CP – pruritis • Dx – biopsy • Tx – repeat cytology, chemo (5FU), laser ablation, surgery VIN Squamous Cell Carcinoma HSV – bilateral kissing lesions, painful vesicular lesions on a red base = hallmark → Syphilis – painless ulcer chancroid 11: HPV, Pap Smear, Colposcopy, and Cervical Cancer Cervical Cancer – More in developing countries, but cases are dropping dt pap smears Cervical Intraepithelial Neoplasia (CIN) • CIN I – mild dysplasia, low grade intraepithelial lesion (LGSIL) • CIN II – moderate dysplasia, high grade intraepithelial lesion (HGSIL) • CIN III – severe dysplasia, HGSIL • CIS – carcinoma in situ • Invasive Cervical Cancer • Nucleus/Cytoplasm ratio increasing as more dysplastic, nucleus enlarging • HPV – human papillomavirus, 75-90% lifetime risk if sexually active o High risk - Most cancers from 16, 18, 31, 45 o Low risk – 6 and 11 ▪ Condyloma and LGSIL o Transmission – genital skin-to-skin contact (condoms only partially protective), fomite m,aybe o 64-70% male partners of women w/ cervical HPV will have penile lesions on exam, 65% chance of acquiring w/ 1 exposure o Usually takes 4 weeks – 8 months from exposure to development of genital warts • CIN RF o Persistent HPV infxn – longer chance for cells to become dysplastic ▪ RF for persistence – increasing age (<30), HPV 16, infxn w/ multiple types of HPV, smoking, Chlamydia, HIV, oral contraceptive use ▪ Encourage to quit smoking o Early age sexually active o Multiple partners or partner w/ hx of multiple o Smoking, immunosuppression (can become pregnant then warts appear) o DES exposure in utero o Hispanic/African American, low socioeconomic status • “very important slide to know” Bethesda System Pap Smear • Conventional Cytology vs. Liquid-Based Cytology – more modern/used more in US o Same sensitivity and specificity o We use Liquid-Based bc we can also do HPV testing at the same time • Transformation Zone – ~99% HPV-related genital cancers are from transformation zone of cervix o Use pap to get cells from this region for cytology screening o Metaplasia btw original and current squamocolumnar jxn • Abnormal Pap Follow up o Atypical Squamous Cells of Undetermined Significance (ASCUS) ▪ Negative High Risk HPV – repeat pap/HPV in 3 years ▪ Positive High Risk HPV – colposcopy if  25 years, repeat pap in 1 year if < 25 o LGSIL – colposcopy if  25 years, repeat pap in 1 year if < 25 o HGSIL – colposcopy o Atypical Glandular Cells of Undetermined Significance (AGUS) – colposcopy/endometrial biopsy ▪ Glandular cells become abnormal but don’t have features of adenocarcinoma in situ or adenocarcinoma ▪ More aggressive eval: colposcopy, biopsy, endometrial biopsy ▪ Associated w/ higher risk for HGSIL, adenocarcinoma in situ, cervical and endometrial cancers (up to 15 years) Colposcopy – looking at cervix, use acetic acid to turn tissue cells white • Adequate Exam – able to visualize transformation zone and entire lesion Cervical Dysplasia and Tx • LGSIL – follow w/ pap every 6 mo until normal for 3 in a row • HGSIL – ablation vs. excision, occasionally will recheck in 6 mo w/ pap and colpo in younger pts • LEEP o Colposcopy does not have to be adequate o Low risk but, bleeding, infxn, cervical incompetence • Cryoablation o Colposcopy must be adequate o Low risk but, bleeding, infxn, cervical stenosis • Choosing o Do you need specimen? If yes – no ablation o Excision must be used: colposcopy is inadequate, ECC is positive, 2 grade discrepancy btw pap and biopsy result, CIN III/CIS HPV Vaccine o Cervarix – 1st one ▪ HPV 16 and 18 o Gardasil – Quadrivalent ▪ HPV 6, 11, 16, 18 o Gardasil – Nanovalent – most used now ▪ 3 shots – HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 Hypothetical??? Questions at the end 1. 30 year old woman, normal pap 2 years ago, said shes here for pap smear – what do you tell her? a. As long as she brought proof (and they did HPV testing) , she doesn’t need another pap until next year 12&13: Amenorrhea Primary Amenorrhea • No menses by 13 with no secondary characteristics or no menses by 15 with characteristics • Menstrual cycle o First half = estrogen dominant o Second half = progesterone dominant ▪ Drop of progesterone = period o Lining of uterus being prepared for pregnancy o Estrogen is fertilizing the grass & then progesterone mows the lawn to keep the grass at the same level → then tornado kills the grass and estrogen starts over (he didn’t add the tornado part but tornado = menstruation, you’re welcome) • Hypogonadotropic hypogonadism o Kalman = no smell o Pituitary dysfxn – elevated PRL interferes with GnRH ▪ Pituitary tumor or Hypothyroidism • Hypergonadotropic hypogonadism o Turner’s – streak ovaries (XO) o Swyer syndrome – genetically male but presents female ▪ If XY but phenotypic female → need to remove gonads (risk of cancer) • Eugonadotrophic o Mullerian dysgenesis, intrauterine scarring, androgen insensitivity syndrome • Pt case – 15 yr old with primary amenorrhea & abdominal pain o Tests – labs, pregnancy test, CBC, urinalysis, hormones (FSH, thyroid, PRL) o Imaging – CT & US ▪ All labs normal → eugonadotrophic ▪ US – shows distended uterus filled with blood • Embryology o Mullerian ducts for upper 2/3 of vagina, cervix, uterus, and fallopian tubes • • • ▪ Tubes not fusing at center can cause abnormalities (Mullerian agenesis) Androgen insensitivity syndrome o XY karyotype o Androgen receptors do not respond to androgens → external genitalia is female ▪ Testes will be present internally & no internal female organs o Will not menstruate due to no internal female organs o Need a gonadectomy due to increased risk of malignancy Turner syndrome – XO genotype o Streak ovaries, amenorrhea, need growth hormones, estrogen & progesterone to develop at normal puberty Swyer syndrome – defective SRY region o Testes do not develop – patient presents as female with normal internal female organs & Mullerian development ▪ NEED AN ORICHETOMY – increased risk of malignancy Secondary Amenorrhea • Defined as absence of menstrual period for greater than 3 months in women with regular cycles or more than 6 months in women with irregular cycles o Oligomenorrhea – fewer than 9 menstrual cycles per year/cycle longer than 35 days • MC causes → pregnancy, PCOS, premature ovarian failure, outflow obstruction • Work up o Hypothalamic causes – stress, change in weight, change in diet or exercise, medication, signs of PCOS o Pituitary disease – headaches, visual field changes o Ovarian deficiency – signs of estrogen deficiency (hot flashes, night sweats) o Uterine – history of uterine trauma (d&c, c-section, etc.) o Look for hirsutism, acne, acanthosis nigricans (androgen excess) • Pt case – 29 yr old with no period for last 8 months o PE – hair growth, acanthosis nigricans o Tests – pregnancy, TSH, PRL, FSH, progesterone withdrawal test, testosterone, DHEAS ▪ Shot of progesterone – if causes period = lack of ovulation, if no period = menopause o Imaging – US o Pt – has cycle after progesterone shot, slightly elevated testosterone, ▪ String of pearls in ovaries = PCOS • PCOS o Menstrual irregularity – anovulation or oligo-ovulation o Hyperandrogenism – hair growth, acanthosis nigricans o Polycystic ovaries – US ▪ Need 2 of 3 to diagnosis ^^^ o Obesity common, excess production of androgens, overstimulation of uterus o Risk for Cardiovascular disease – BP, BMI, lipid profile, and insulin sensitivity need to all be checked ▪ T2DM common o Tx – weight loss, OCPs, ovulation induction if want to get pregnant, spironolactone (for hyperandrogenic symptoms) ▪ Estrogen increases sex hormone bind protein to decrease the testosterone in the blood = decreases hirsutism and androgen symptoms • Hirsutism • o PCOS, congenital adrenal hyperplasia, ovarian and adrenal androgen secreting tumor o Diagnosis – total testosterone, DHEAS, 17-OHP Virilization – more severe hyperandrogenism with masculinizing features o Clitoromegaly, deep voice, baldness, muscle growth o Typically from androgen secreting tumor 14: Abnormal Uterine Bleeding (AUB) and Leiomyoma Abnormal Bleeding • Normal – 3-7 days, 21-35 day cycle length, less than 80 cc o Postmenopausal vaginal bleeding – more than 12 months after last period o Acute bleeding – heavy bleeding constituting concern and intervention • Heavy bleeding - >7 days, heavy flow, irregular flow o Menometrorrhagia: heavy, irregular o Dysmenorrhea: painful menses o Break through bleeding: birth control pills, etc. • Red flags for heavy bleeding – changing pads/tampons every hour, clots >1in Structural Causes – PALM • Polyp o Focal, benign process o Premenopausal or immediately postmenopausal o MC symptom – abnormal uterine bleeding (spotting) but regular periods!!! • Adenomyosis o Endometrial tissue (glands) in myometrium (muscle) o MC symptoms – extremely painful menses, heavy prolonged bleeding, chronic pelvic pain (OUCH) o A lot like endometriosis (glands in wrong place) – they’re cousins • Leiomyomas o Proliferation of smooth muscle cells surrounded by capsule of compressed muscle (fibroids) o Premenopausal women o RF – early menarche, fam hx, Caucasian women in 30s-40s, or African Am women 4-6 yrs earlier o MC symptom – painful, heavy bleeding ▪ Dependent on size/location – anemia, infertility, dyspareunia, pelvic pressure (ant – bladder pressure, post – constipation, back pain, hydronephrosis) ▪ Can still get pregnant, but fibroids will grow as pregnancy progresses o PE – uterus larger than normal, palpable mass o Diagnosis – transvaginal US/hysterosonogram o Tx – ▪ Meds – OCPs only tx symptoms, doesn’t reduce size • GnRH agonist or antagonist – shrink up to 50%, grow back if stop – best when close to menopause • Mirena IUD – progesterone will reduce lining, will “lose” fibroid (hard to find) • Antifibrinolytics (tranexamic acid) – helps blood clot • NSAIDs ▪ Surgery • Endometrial ablation or radiofrequency ablation • ▪ Myomectomy – larger operation than hysterectomy, only for people that want to keep fertility • MC indication for a hysterectomy → 100% definitive tx Interventional Radiology • Uterine Fibroid Embolization – poor surgical candidate & does NOT want fertility o Short recovery but more complications/readmissions, DO NOT get preg Asymptomatic – observation, no tx ▪ • Malignancy o Leiomyosarcoma – postmenopausal woman with rapidly enlarging mass & postmenopausal bleeding (fibroid gone rogue) – muscular part of uterus o Endometrial cancer – cancer of lining of the uterus o NEED TO EVALUATE THE ENDOMETRIUM OF WOMEN WITH: ▪ Menorrhagia & > 35 years old OR prolonged AUB (abnormal uterine bleeding) ▪ Postmenopausal bleeding (more than 12 months after last cycle) ▪ *****to rule out endometrial cancer***** ▪ NEED A BIOPSY – cancer until proven otherwise Non-Structural Causes – COEIN • Coagulopathy o MC – Von Willebrand’s disease – missing or defective von Willebrand factor (VWF) o MC CP – newly menstruating girl with very heavy periods & anemia • Ovulatory Dysfxn o Endocrinopathies (hypothyroid, hyperprolactinemia, PCOS), mental stress, obesity, anorexia, weight loss, extreme exercise in elite athlete o Anovulatory CP – won’t have period for 6 months, then will bleed for 3 months ▪ Estrogen is high, no progesterone → endothelium keeps growing until outgrows blood supply → starts breaking off & bleeds • Endometrial – less common o Intermenstrual spotting – can’t repair endometrium, endometrial infection o Heavy, prolonged bleeds – deficiency in endothelium 1 & prostaglandin F2, accelerated lysis of endometrial clots o Atrophic endometrium • Iatrogenic o Hormone therapy (OCPs leading to break through bleeds) ▪ Oral contraceptives (OCPs) – usually combination pills with both estrogen/progesterone, want to keep endometrial lining same thickness (low) • If lining too small → will bleed randomly o IUDs, anticonvulsants, Abx, meds impacting dopamine metabolism (tricyclic antidepressants, phenothiazines) • Not yet described Etiology depends on age • Young o Menarche (10-14) – anovulation bc immature HPO axis, von Willebrand disease, PCOS o Reproductive (15-29) – PREG!!, structural lesions, PCOS, hormonal contraception, endometrial hyperplasia • Older o Perimenopause (40s-50s) – structural lesions, anovulatory cycles, endometrial hyperplasia/cxr o Post-menopause – hyperplasia/cxr until proven otherwise!!!!! ▪ Endometrial atrophy 15: Pelvic Pain Syndromes Chronic Pelvic Pain • CPP evaluation – detailed history, old records, PE, imaging, etc. o Tx – NSAIDs, OCPs, Opioids, TCAs, SSRIs Gabapentin, etc. or surgery – depends on what you find • Dysmenorrhea – painful menstruation o Primary – within first 6 months of menarche o Secondary – structural or disease process of the uterus o Symptoms – colicky, spasmodic, like labor pains, N/V, fatigue, anxiety, dizziness, headaches o Etiology ▪ Intramural – adenomyosis, leiomyomata ▪ Intrauterine – polyps, IUD, infection, cervical stenosis ▪ Extrauterine – endometriosis, tumors (benign/malignant), inflammation, adhesions, psychogenic o Adenomyosis ▪ Endometrial glands and stroma in myometrium ▪ MC in parous women • Endometriosis o Presence of endometrial glands/stroma outside endometrium o RF – family hx, cycles <28 days, menses >7 days, menarche <12 yrs old, nulliparous o Pathogenesis – 3 theories – said not on boards but might want to know? ▪ Sampson’s theory – retrograde menstruation → go into pelvic cavity ▪ Halban’s theory – vascular/lymphatic dissemination → distant sites ▪ Meyer’s theory – coelomic metaplasia → stem cells in peritoneal cavity that differentiate into endometrial glands o CP – dysmenorrhea worsening over time, dyspareunia, chronic pelvic pain, cyclic rectal bleeds (dyschezia), bladder/bowel pain, tender nodule in abdominal incision when on period (if had Csection) o Complications – dysmenorrhea, pelvic pain, AUB, infertility or “sub-fertile”, back pain, rectal bleeds, may have adhesions ▪ “Powder burn” lesions → look like gunpowder → o PE – classic finding is uterosacral nodularity ▪ Pelvic mass, immobile ovary/uterus ▪ CA-125 might be elevated o US – endometrioma (ground glass appearance) → “chocolate cyst” ▪ o Definitive Dx – biopsy o Tx – meds or surgery (laparoscopy, laparotomy, hysterectomy once done having kids) ▪ OCPs used to be first line, but better treatment → progesterone ▪ Leuprolide (GnRH agonist) – put them in “medical menopause” for 6 mo, add progesterone on top ▪ Orilissa (GnRH anatogonist) – less menopause sympt & can stay on it for 2 yrs ▪ Minera IUD – progesterone secretion, good if want contraceptive, not many ADRs ▪ Androgens (danazol) – ADRs limit use (get male pattern baldness) • Interstitial Cystitis – “probably won’t be a question about this” o Chronic inflammation of detrusor m. caused by “potholes” in lining of bladder o CP – constant & dull suprapubic pain that gets worse with exercise, intercourse & certain foods (caffeine, dairy, alcohol, etc.) ▪ Hallmark sympt – urinary frequency, nocturia, hematuria, incomplete emptying, dyspareunia, post-coital dysuria o PE – pain over bladder o Dx – potassium sensitivity test & cystoscopy o Tx – diet modification • Vulvodynia o Burning pain of vulva without a neurologic disorder ▪ Pain is neuropathic, intercourse may be impossible o RF – Latina women, hx of vaginitis, OCP use ▪ NOT associated with STI/physical abuse o Cotton or Q-tip swab test – apply gentle pressure around exterior vestibule (labia minora) using cotton swab, go in clock-wise fashion to test different areas o Tx – meds (lidocaine gel, gabapentin, amitriptyline, venlafaxine), PT, acupuncture Acute Pelvic Pain • Ask about prior surgery → worry about adhesions or bowel obstruction work through this → • • Check for pregnancy!! Best test to cover everything → CT 16: Endometrial Hyperplasia & Endometrial Cxr Endometrial cxr – 4th MC cancer in women • Typical CP – post-menopausal uterine bleeding • RF – exposure to unopposed estrogen → increased proliferation o HTN & DM – at risk for basically everything in gyn o Fam hx or personal hx • Protective factors – decreased estrogen exposure or increased progesterone levels o OCPs (progesterone wins), smoking Endometrial Hyperplasia • Simple – glands & stromal proliferation (gland:stromal ratio increased) o Variable size of glands, nuclei still at bottom of cell & look normal o NOT commonly associated with progression to endometrial cxr o Tx – progesterone • Simple with atypia – rare • Complex – abnormal proliferation of glands only (gland:stromal ratio increased), but glands are crowded & have branching • Complex with atypia – glandular elements lose cellular polarity, increased nucleus:cytoplasm ratio, dense chromatin & prominent nucleoli o Largest risk of progression to endometrial cxr – treat it like they have cxr o 30% risk of developing cancer CP for both – MC abnormal bleeding • PAP smear on postmenopausal pt & see endometrial cells → be concerned • Uterus in normal size/shape • No gross vaginal bleeding • Advanced sympt (Late CP)→ uterine enlargement with adnexal masses, bowel/bladder sympt, pain, bloating, ascites, weight loss • Always get biopsy if … o Menorrhagia & > 35 years old OR prolonged AUB (abnormal uterine bleeding) o Postmenopausal bleeding (more than 12 months after last cycle) o o If try to get biopsy & can’t get any endometrial tissue (indeterminate result) → do a D&C o Dilatation & curettage (D&C) = GOLD STD ▪ Dilate cervix → camera to find abnormal → take biopsy of abnormal → use curettage that scrapes off inner lining of uterus • Definitive dx Screening • Post-menopausal women on unopposed estrogen (estrogen therapy) • Women with family hx of HNPCC (Lynch’s Syndrome) • Premenopausal women with anovulation (PCOS) • Women on tamoxifen for breast cxr with abnormal thickened endometrium >10mm or bleeding Endometrial Cancer Types • Type 1 – Endometroid, MC type, estrogen dependent, arise out of hyperplasia o Endometrial cancer/adenocarcinoma • Type 2 – later than type 1, from atrophy not hyperplasia, NOT estrogen dependent o Serous & clear cell endometrial cancer (lowest survival rates) Tx of Endometrial Cancer – surgery • Dependent on surgical staging o FIGO stage 1 – limited to uterine body o FIGO stage 2 – cervical involvement o FIGO stage 3 – vaginal or pelvic sidewall, parametrium or adnexa, lymph nodes → but confined to pelvis o FIGO stage 4 – involves bowel, bladder & distant metastases • Grade = single most important prognostic factor o G1 – well differentiated → G3 – poorly differentiated o Depth of invasion of myometrium is 2nd most important prognostic factor • Initial approach → hysterectomy, bilateral salpingoophorectomy, bilateral pelvic & para-aortic lymphadenopathy o Low risk patient → no adjuvant therapy recommended o Intermediate risk patient → whole pelvic radiation & vaginal brachytherapy o High risk – stage 3 & 4 → combination radiation and chemo • Surveillance o Pelvic exams every 3 months for 2 years → 6 months for 3 years → yearly o CA 125 levels every 6 months – specifically in type 2 pt o Yearly CT for potential metastases Endometroid Adenocarcinoma • MC type of endometrial cancer & best prognosis • Risk factors → unopposed estrogen or PCOD o PCOS – if endometrial lining is >10 mm → endometrial biopsy o Pt case – biopsy shows complex hyperplasia with atypia ▪ Shows endometrial carcinoma grade 1 • Tx – hysterectomy or progestin (if want future fertility) o If progestin working → regression in 6 mo Lynch Syndrome • AD, hereditary disorder with risk of endometrial, ovarian, and colorectal cancer (& breast) • Get genetic testing for Lynch syndrome if pt with endometrial cancer that is less than 50 yoa Questions What is not a risk factor for endometrial cancer? – smoking & progesterone tx What is the MC histological type? – endometroid Tx for stage 1 endometrial adenocarcinoma? – simple hysterectomy, lymphadenectomy, maybe or maybe not take ovaries Gold standard for dx of endometrial adenocarcinoma? – Dilatation & curettage 17: Urinary Incontinence & Pelvic Organ Prolapse Urinary Incontinence • Stress incontinence – involuntary leakage of urine due to intraabdominal pressure increase o Pressure in bladder exceeds pressure in urethra = leaky o Loss of support of the urethral-vesical jxn o Valsalva causes the urethra to be placed downward & decreases intraurethral pressure = bladder is higher pressure o RF for incontinence → age, previous vaginal deliveries, body weight, previous pelvic surgery, environmental factors o In office tests – Q-tip test, stress test, post void residual, urodynamics (complicated only, previous surg hx), urinary diary ▪ Q-tip test – put into urethra, ask them to cough → if Q tip rotates up 30 deg, + test o Tx – pelvic floor exercises/Kegels, pessaries, surgery (Burch, sub urethral), slings • Urge incontinence – involuntary contractions of the bladder o Unstable bladder with contractions ▪ Intense urge to void and leaks on way to restroom, worse at night • Latch key incontinence – bladder doesn’t wait for brain to say ok go • Urinary diary is important to diagnose o Tx – Kegel, vaginal estrogen = key, bladder training (void by the clock), beta 3 adrenergic, antimuscarinic, Botox, neurostimulation (stim sympathetic, can get pacemaker eventually) • Mixed incontinence – occurs when both stress incontinence and urge incontinence are present o Tx – replace vaginal estrogen, meds, surgery • Overflow incontinence – bladder is unable to contract and overfills and spills past urethra, leak randomly (roll over in bed, pick something up) o Neurological issue with no bladder contraction o High post void residual volume o Will NOT respond to surgery – may need self cath Pelvic Organ Prolapse • Cause – break/tear in connective tissue & endopelvic fascia → lose support → descend through urogenital hiatus (aka hernia through vagina) • Components o Cystocele – weakness in anterior vaginal wall → bladder descends ▪ Typically, mild/asymptomatic – not leaking bc being compressed ▪ Severe → incomplete emptying or inability to void ▪ When repair → move bladder back & give them a sling so you don’t cause incontinence o Rectocele – weakness in posterior vaginal wall → trapping effect → difficult to defecate ▪ “splinting” – put hand in vagina to hold rectum wall down → then can defecate o Cervico-uterine prolapse – defect/loss of cardinal & uterosacral ligament support → cervix goes through vagina or introitus ▪ If totally outside vagina → procedentia o Vaginal apex prolapse o Enterocele – small intestine prolapse • Eval – POPQ scoring – basically see how far they are herniating • Management – dependent on symptoms o Asymptomatic → follow unless end organ damage possible • Tx – pelvic floor exercises, changes in activities, pessaries (plastic that prevents bulge to fall down) o Surgery – tailored to restore anatomy/fxn 18: Ovarian Neoplasm Ovarian cancer • Risk factors – genetics, age, family hx, eastern European Jewish, endometriosis, never had birth control pills, infertility o BRCA 1 & 2 – increased risk of ovarian cancer (1 more than 2) o Lynch syndrome – increases risk for colon cancer, endometrial & ovarian cancer, and gastric cancer o Reduce risk – OCPs, breastfeeding, kids, BTL/salpingectomy (tubes tied) • Symptoms o Abnormal vaginal bleeding or discharge, pain in pelvis or abdomen, back pain, bloating, fill quickly, change in bowel habits, increase in abdominal size, weight loss, SYMPTOMS PRESENT FOR MONTHS • Diagnosis o Physical exam ▪ If ovary palpated on exam & pt is menopausal, get CT and US for concern for cancer o Imaging ▪ Transvaginal US is gold standard ▪ CT or MRI ▪ Abdominal US if large cyst o Laparoscopy – if not sure what’s going on • Functional Cyst o Follicular ovarian cyst from corpus luteum or theca lutein o US shows round, anechoic, thin and normal walls o Hemorrhagic – varied appearance, may look like blood in the ovaries o Management – resolves within 1-2 cycles, maybe OCPs, large ones need repeat US • Benign Neoplasm o Serous cystadenoma – unilocular, can be large, filled with watery fluid ▪ Remove it o Mucinous cystadenoma – lined by columnar epithelium similar to cervix, secrete thick, gelatinous mucous, larger than serous, multilocular, thin septations ▪ Take it out (can cause mass effect) o Mature ovarian teratoma – calcifications, smooth, round, ovoid, slow growing, can contain hair, fat, & teeth ▪ Rupture can cause acute peritonitis ▪ Remove it o Endometrioma – chocolate cyst ▪ Ground glass appearance, excise it • Germ cell tumors o Germ cell tumors – younger patient, good prognosis, stage 1 typically at diagnosis ▪ • • • CP – subacute abdominal pain, menstrual irregularity o Dysgerminoma ▪ Secrete LDH (can monitor) ▪ Tx – unilateral salpingoophorectomy with staging & chemo (depending on stage) o Endodermal Sinus – yolk sac tumor ▪ Secrete AFP, poor prognosis o Embryonal ▪ Secrete hCG & AFP ▪ Younger patients o Immature teratoma ▪ Secrete AFP & Ca 125 ▪ Three germ layers o Choriocarcinoma ▪ Not associated with pregnancy ▪ Secrete hCG o Gonadoblastoma ▪ Typically found on right side, associated with Y chromosome o Tx of Germ Cell Tumors ▪ Attempt fertility sparing treatment (unilateral salpinoophorectomy – SPO) ▪ Bilateral SPO ▪ Chemo or radiation in advanced cases Stromal tumors (sex cord tumors) o Granulosa cell tumor ▪ MC sex cord tumor, can cause hyperestrogenism, precocious puberty o Thecoma ▪ Hyperestrogenism o Ovarian fibroma ▪ MC tumor to cause Meigs syndrome • Meigs syndrome – ascites, pleural effusion & soild ovarian mass • Symptoms resolve after removal o Tx – fertility sparing treatment, bilateral SPO, chemo & radiation Ovarian Carcinoma o High grade cancers of the ovary, tubes or peritoneal ▪ Epithelial cancer o Leading cause of death from gynecological malignancy o US shows – multilocuated, solid ocmponents, echogenic, large, thick septa, papillary projections, nodularity o Key to survival is tumor debulking – need to leave less than 1cm of tumor left o Tx – debulk down to less than 1 cm, CA 125 levels checked after chemo/surgery ▪ Surgery + chemo (no radiation) Workup for ovarian cancer o Pt presents with abdominal bloating ▪ Transvaginal US – shows cyst ▪ Check CA 125 level – elevated ▪ Take it out o Pt presents with simple cyst ▪ Check CA 125 level – normal = leave it & check a couple months later o Pt (30 yoa) with 5 cm cyst with blood in cyst ▪ Leave it & recheck 19: Menopause Menopause • Climacteric: gradual decline in ovarian function • Menopause: 12 months without a period & no other reason for that • Premature ovarian failure: menopause before age 40 • Perimenopause: time immediately before, during, & after menopause • Age of menopause o Typically, 51-52 yoa o Smoking – decrease estrogen levels can lead to earlier menopause o Genetics • Pathophysiology of menopause o Progressive ovarian senescence with consistent decrease in estrogen & less functional follicles o Follicular atresia = decreased sex steroids • Diagnosis – MOST RELIABLE TESET IS FSH o FSH >10 is first clinical sign o >25 is late menopause transition o But menopause cannot be considered a lab diagnosis → need 12+ months of amenorrhea o Androgens – LH stimulates ovaries to produce testosterone & androstenedione ▪ Testosterone declines in menopause ▪ Post-menopausal → some testosterone & some leftover estrogen related to body fat increase • Physiologic changes o Menstrual changes, vasomotor symptoms (hot flashes), genitourinary changes, skin/hair/teeth, pelvic floor relaxation o Menstrual changes – irregular bleeding & fluctuating FSH o Hot flashes – flushing, sweating, sensation of heat, palpitations, anxiety ▪ 3-5 min 5-10x a day ▪ Night sweats – fatigue & bad mood ▪ Central disturbance of hypothalamic body temp regulation center secondary to rapid decrease in estrogen levels ▪ Tx – hormone replacement (estrogen replacement), gabapentin, progestins, SSRIs, clonidine, black cohost ▪ If pt has uterus → need both estrogen & progesterone to prevent endometrial cancer o Genitourinary complaints ▪ Vaginal atrophy & dryness (due to lack of estrogen) ▪ Dryness, pruritus, dyspareunia, pelvic relaxation, pelvic organ prolapse, frequency, dysuria, asymptomatic bacteria o Other ▪ Decreased hair growth on head, increased on face & body • SHBG decreases & more free testosterone is present ▪ CNS – sleep disturbances, headaches ▪ Decreased libido & dyspareunia ▪ Thinning of skin, decreased collagen in dermis • Pt case – presents with no symptoms & wants to be put on hormone therapy – NO SYMPTOMS = NO HORMONE THERAPY • Effective theory to tx symptoms of hot flashes & vaginal atrophy → oral estrogen & progesterone • Pt present with vaginal dryness as only symptoms → tx with vaginal product (estrogen localized) 20: Common Procedures of the GU System Informed Consent (PREPARED) – Procedure, Reasons, Expectations (outcome/recovery), Preference of pt, Alternatives, Risks, Expense ($ and loss of work), Decision (shared) • Does NOT waive your liability Sonohysterogram – inject uterine cavity with saline → see structures with US • Indications – abnormal uterine bleeds MC, uterine abnormalities, infertility • Risks – infection, false + • Contraindication – known infection, pregnancy Colposcopy – use microscope to see cervix, add acetic acid to see abnormal tissue of cervix, take biopsy to dx • Indication – abnormal pap smear, high risk HPV, DES exposure in utero • Risks – infection, bleeding • Contraindication –biopsy in pregnant pt Colposcopy with Leep – dx & tx of abnormal cervical tissue • Remove whole transformation zone → o Good margins = pts are treated o Cone specimen can be analyzed further → will tell you if tissue was worse than you thought • Indication – cervical dysplasia on biopsy (not pap) • Risks – bleeding, cervical insufficiency (take too much → cervix prematurely opens in preg) or stenosis • Contraindications – pregnancy Hysterosalpingogram – Xray of uterus/fallopian tubes using fluoroscopy & contrast • Looking for abnormal uterus & to see if fallopian tubes are open • Do btw days 1-14 of menstrual cycle • Indication – infertility (assess tube patency), confirmation of tubal occlusion after Essure, recurrent miscarriage • Risks – PID, allergic to dye • Contraindications – pregnancy, PID, heavy uterine bleeding Dilation & Curettage (D&C) – gold std for endometrial biopsy • Indications – abnormal uterine bleeding, evacuate products after spontaneous abortion • Complications – blind procedure → perforation, infection or hemorrhage Hysteroscopy – replaced Sonohysterogram – look into uterus with scope (direct visual) • Dx – abnormal bleeds or recurrent miscarriage (abnormal uterine architecture) • Tx – place permanent birth control, remove polyp, endometrial ablation, remove adhesions, locate/remove IUD if you can’t find it • Need distention media – low viscosity fluids (saline) • Risks – perforation, infection, thermal energy complications, scarring Hysteroscopic Endometrial Ablation – coagulate entire uterus • Indications – heavy periods o Will get rid of lining so they can’t shed it (aka will have no period or very light periods) Hysteroscopic polypectomy – Myosure device that Pac Mans the polyp Tubal Ligation – MC permanent contraception in US • Do it postpartum or between pregnancy (interval) • Pomeroy – plain gut suture (only lasts 2 days) → tubes separate so the tubes can’t grow back together • Bipolar Coagulation – cauterize tubes, be careful of getting wrong structure • Falope Ring or Fishie Clip are other options • Salpingectomy for sterilization – lowers risk of ovarian cancer Hysterectomy – complete removal of uterus (+ cervix) • Supracervical hysterectomy – take out uterus but NOT the cervix o Indication – severe endometriosis & can’t get cervix out o Contraindications – malingnant/pre-malignant = must get cervix out o No benefit of doing it this way • MC gyn surgical procedure • Vaginal route- uterine size, accessibility, pathology only in uterus, operator experience o Vaginal hysterectomy = ACOG says it’s the approach of choice ▪ Lowest complication rate & cost effective • Post-op – early Radical hysterectomy – surgical removal of uterus, tubes, cervix, surrounding tissue, upper vagina & LN • If have cervical cxr → MUST have this 21: Radiology of Female Reproductive System Order of Imaging Choices – US → MRI → CT → X-ray → fluoroscopy Learn these US – MC for examining female pelvis • MegaHz – 3.5 MHz (abdominal wall, pelvic cavity) to 18 MHz (superficial glands like thyroid) • Doppler effect – speed/direction of blood flow (pregnancy or malignancy) • Pros – nonionizing radiation!!, real time imaging • Cons – bowel gas, bone, significant pain o Need highly trained individual to perform these • Can find IUD on US – creates lots of shadowing • Indications – pelvic pain, dysfunctional uterine bleeding, + pregnancy test, dysuria o Transvesical – bladder imagine, large masses, NOT sexually active transvesicular ▪ Need full bladder – used as acoustic window o Transvaginal – better fine detail, early pregnancy visualization, ovarian torsion • Intrauterine pregnancy – make sure has HR (not “live” until can live on own” • o Live ectopic pregnancy transvaginal • o o Tx – methotrexate Ovaries o Need to see blood coming into & over ovary (low resistance wave form) o Ovarian torsion → surgical emergency ▪ No doppler flow over one of the ovaries → L ovarian torsion Normal ovary MRI – 1.5-3T magnetic field • H molecules line up → add radiofrequency pulse from another section → Normal MRI flips the protons → measure how long it takes them to come back • Pro – no ionizing radiation, good soft tissue o Can way more detail of endometrium • Cons – expensive, no metal, long exams o Safety concerns – no metal, no pacemaker, or implantable pumps (pain/insulin pump) • Indications – infertility (congenital uterine anomalies), fibroids before surgery, placental abnormality Bicornate uterus o MC abnormality – bicornate uterus → o Gadolinium – NOT used in pregnancy – can accumulate in amniotic fluid & be ingested by fetus CT • Pros – 2D & 3D images, super thin slices, super fast (30s) • Cons – ionizing radiation • Indications – additional eval of non-OB pelvic pain, trauma, pelvic masses o Avoid if possible in OB patients o Calcified fibroids – highly vascular, common cause of abnormal bleeds Normal CT ▪ ▪ Can be embolized → arteriogram→ fill arteries with tiny particles to limit blood flow → necrosis of fibroids & they shrink Xray • • • • Usually order this bc of hip pain & have incidental GU findings Pro – quick, inexpensive, portable Cons – poor soft tissue resolution, ionizing radiation Calcified Fibroid – asymptomatic, in lots of women >50 yrs old → o CP – LBP & pelvic pain, heavy menstruation Fluoroscopy • Hysterosalpingogram (HSG) – bilateral tubes fill & spill into peritoneal cavity o Indication – uterine abnormality, verify tubal occlusion, infertility o Hydrosalpinx – result of previous PID ▪ Blind sac – terminal fluid collections o Tubal-occlusion (Essure birth control) Normal Endometrial polyp Hydrosalpinx Tubal-occlusion Other Images • Tubo-ovarian Abscess (TOAs) – “dirty” bc complex, contrast-enhanceing walls, not clear fluid • Ovarian Dermoid/Teratoma – at least 2/3 germ cell layers – fat, hair, teeth, cartilage o Asymptomatic, but if grow → pelvic pain + ovarian torsion • Ovarian Cystadenoma – MC benign epithelial neoplasms o Thin septations – can see better on US o CT – shows big bag of fluid-filled cyst ▪ ▪ TOAs Teratoma Metastatic • • can see mets in peritoneum (L image), pleural effusion (R image), etc. Endometrial Carcinoma • Best method – MRI o Thin myometrium, looks like fluid filled canal, advanced