Why can intramucosal fibroids cause infertility?

Endometrial vascular disturbance, endometrial inflammation, and secretion of vasoactive substances Rx: hysteroscopic resection What is the medical treatment of fibroids? GnRH agonist decreases estrogen production and thus fibroid growth SE:  Hot flashes are experienced by >75% of patients, usually in 3-4 weeks after start of treatment and should not persist for longer than 1-2 months  After cessation of treatment, menses return in 4-10 weeks, and myoma and uterine size return to pretreatment levels in 3-4 months  The regrowth is consistent with the fact that reduction in size is not due to a cytotoxic effect  Not true that secondary to the GnRH agonist withdrawal they will grow at a more rapid rate.

Infections of the Lower Female Reproductive Tract
What is the most common infection of the lower GU tract? UTI  Sx: buring sensation through the urethra with micturation, urethritis, cystitis (pain in the mid suprapubic region and/or frequent urination)  Risk factors: DM, sickle cell dz  Rates are higher in women due to short length of the urethra and the proximity to the rectum  Dx: U/A hematuria, leukocytes, leukocyte esterase, nitrates with no vaginal infection  R/O pyleonephritis via costovertebral angle tenderness and fever  Rx: ampicillin, trimethoprim-sulfamethoxazole, macrodantin, or cephalexin  Rx: fluoroquinolones such as ciprofloxacin  If pyelonephritis is suspected should admit and treat with IV abs What are the most common organisms causing UTI?  E.coli  S. saprophyiticus  P. mirabilis  K. Pneumoniae  Enterococcus What should you consider when the urine culture is negative?  C. trachomatis and N. Gonorrhoeae or HSV What is vulvitis?  Pruritis, erythema, small satellite lesions of the vulva  Commonly caused by candidiasis  Rx: antifungals  R/O malignancy if chronic vulvar irritation is present What are common causes of ulcerative lesions of the vulva (vulvar ulcers)? SHCCL  STIs—  Herpes  Syphilis  chancroid  lymphogranuloma venerum

chrohn’s dz

What is syphilis?  Pathophysiology—treponema pallidum (sphirochetes) infect mucosal surfaces and skin thorugh minute abrasions  Presentation—non-tender plaques on vulva with brownish rash on palms and soles (dark-field examination of vulvar lesions will show evidence of coiled spirochetes  Locations—vulva, vagina, cervix, anus, lips, nipples  Stages: o Stage 1—painless red ulcer 1 cm in size with raised edges known as chancre develops 3 weeks after infection and is associated with regional adenopathy o Stage 2—1-3 months dissemination of the disease causes maculo-papular rash on skin or mucous membranes, palms and soles of feet have rash, condyloma latum; other systems may be affected o Latent phase can last for years o Stage 3—granulomas or gummas of the skin, bones, aortitis, neurosyphilis can cause tabes dorsalis  Dx: VDRL and RPR – remain + for 6-12 months following treatment of syphilis o There can be a delay in + testing where the test can be – early in the infection and should be repeated 1 and 3 months after the appearance of the ulcer o If +  confirmation via FTA-ABS (fluorescence treponemal antibody absorption test o Asymptomatic patients with a + test are considered to be in latent phase  Rx: penicillin (benzathin penicillin G 2.4 milion units IM weekly for 3 weeks)  Alternatives—tetracycline, doxycycline, ceftriaxone, azithromycin  Penicillin  only medication recommended for pregnancy  Neurosyphillis—crystalline penicillin G 3-4 million units IV every 4 hours for 10 to 14 days and then follow with benzathine penicillion 2.4 million for 3 weeks  Follow RPR and VDRL titers 6,12,24 months  SIDE EFFECTS: Jarisch-Herxheimer reaction acute febrile reaction, fever chills, HA, myalgia, malaise, pharyngitis, rash (may cause preterm contractions or fetal distress in pregnant women but should not delay therapy) o Cause: inflammatory reaction to killing of spirochetes that released endotoxins into circulation causing cytokine release  also seen in Lyme What is HSV?  Herpes simplex virus  Presentation— multiple painful ulcers involving the vulva, fluid filled, weeping and crusted, difficulty voiding fever, o HSV1—typically infects the mouth but 30-40% of genital herpes are caused by HSV1 o HSV2—typically infects the genitalia o Infection—begins with flulike sx: malaise, myalgias, nausea, diarrhea, fever followed by vulvar burning and pruritis, development of vesicles that evolve into painful ulcers o Recurring episodes—1-6x/year o Pregnancy—if herpes should have c/s  Dx—viral cultures = gold standard but have a low sensitivity 10-20% false negative rate, Tzank smear examines for multinucleated giant cells; serum antibody screening only indicates lifetime exposure and would not answer the question as to the etiology of the specific lesion  Rx: acyclovir 200mg 5x/day, acyclovir 400mg TID, famiciclovir 250mg TID, valacyclovir 1g BID  Rx in immunocompromised: IV acyclovir 5mg/kg every 8 hrs  Recurrences: prophylactic or suppression therapy of 400mg orally BID acyclovir

What is Chancroid?  Infection with haemophilus ducreyi  Presentation— o Painful ulcerated demarcated non-indurated ulcer located in the anogenital region accompanied by inguinal lymphadenopathy o Can be a cofactor for HIV o 10% of ppl are co-infected with HIV and syphilis  Dx: difficult to culture so often dx is made clinically  Rx: o ceftriaxone 250mg IM  3rd generation cephalosporin  MOA: bactericidal and disrupt the synthesis of the peptidoglycan layer of the cell wall beta-lactam; less susceptible to penicillinases  clinical use: activity against gram + and gram o azithromycin 1g orally once  macrolide  MOA: binds to 50S subunit of the ribosome so inhibits protein synthesis by blocking translation of mRNA  clinical use: gram negative o ciprofloxacin  fluoroquinolone  MOA: inhibits DNA gyrase needed to separate bacterial DNA and inhibiting cell division  Clinical use: gram – and gram +  Contraindicated in pregnancy o erythromycin What is lymphogranuloma venereum?  Infection with Chlamydia trachomatis – obligate intracellular parasite  Presentation o Stage 1: shallow ulcer or papule that is painless and often unnoticed o Stage 2: painful inflammation and enlargement of the inguinal nodes, fever, HA, malaise, anorexia o Stage 3: proctocolitis, rectovaginal fistula, rectal stricture, elephantiasis, anal pruritis develops with rectal discharge  Dx: direct immunofluorescence, nucleic acid detection  Rx: o doxycycline 100mg BID  tetracycline  MOA: protein synthesis inhibitor; binds to the 30S ribosomal subunit in the mRNA translation complex o erythromycin 500 mg orally QID What other sx can Chlamydia cause? o Causes cervicitis, urethritis, and PID – scarring of fallopian tubes and infertility o Typically presents asymptomatically o May infect ocular, respiratory, and reproductive tract o Doxycycline o Azithromycin What are causes of nonulcerative lesions?  Condyloma acuminata – warty lesions

   

Molluscum contagiosum—caused by the pox virus Phthirus pubis—crab louse Sarcoptes scabiei—itch mite Folliculitis—leading to abscess, boil, carbuncle due to inoculation with skin flora staph. Aureus

What is HPV?  Human papillomavirus causing condyloma acuminata or genital warts  Condyloma accumata-- Strain: 6 and 11  Cervical cancer – strain: 16, 18, 31  Presentation— o Condyloma accumata—raised papillomatous or spiked lesions that can be 1-5mm in size; can become pedunculated and form cauliflower-like growths o Arise in the anogenital region, anal canal, perineal body, vulva, walls of the vagina, and cervix  Dx: biopsy  Rx: o Local excision with cryotherapy o Topical trichloroacetic acid o Topical podophyllin o 5-FU cream—pyridine analog used in the Rx of cancer o imiquimod o podofilox o non-responsive CO2 laser to vaporize What is phthirus pubis?  Crab louse that infects pubic hair  Causes intense pruritis  Rx: permethrin cream, pyrethrins, piperonyl butoxide What is sarcoptes scabiei?  Itch mite that infects the skin and can infect the entire body  Rx: permethrin cream What are causes of various vaginal infections?  Imbalance of microflora caused by diet, illness, antibiotics, overgrowth, pathogen  Sx: itching, burning, discharge, odor, pain  Common infections: candida, trichomonas, garnerella What is bacterial vaginosis?  Infection with gardnerella vaginalis  Vagina usually colonized by lactobacillus that maintains the vaginal pH < 4 and BV can develop when there is a shift in the bacterial species in the vagina  BV RISK FACTORS: multiple sexual partners, douching, decrease in lactobacilli cigarette smoking  Sx: isolated increase in vaginal discharge w/ amine or malodorous fishy odor  Dx: whiff test  an amine odor with addition of 10% KOH, pH >4.5, clue cells  Rx: o metronidazole 500mg BID  MOA: metabolites are taken up by bacterial DNA to form unstable molecules  Clinical use: anaerobic bacteria o clindamycin 300 mg TID

 

MOA: bacteristatic effect; similar to macrolides in that binds to 50S ribosomal subunit Clinical use: anerobic

What are yeast infections?  Candidiasis – usually infection with candida albicans  Sx: vulvar and vaginal pruritis, burning, dysuria, dypareunia, vaginal discharge, cottage-cheeselike discharge  Dx: KOH preparation will indicate hyphae and spores  Rx: azole agents: terconazole, fluconazole What is trichomonas vaginalis?  Unicellar anerobic flagellated protozoan that can cause vaginitis  Pathophsyiology: increases the pH of the vagina to 6-7, sx worse following period due to transient increase in pH at this time  Sx: heavy discharge—yellow, green, fray or frothy; vulvar erythema, edema, and pruritis, cervix—puncatate epithelial papillae “strawberry” appearing  Dx: wet preps of vaginal swabs that show a protozoan that has 3-5 flagella, culture, nucleic acid probe  Rx: o metronidizole (Flagyl)— used against anaerobic bacteria; metabolites are intercalated in DNA to create unstable products o Tinidazole What organisms most commonly cause cervicitis?  Gonorrhea and Chlamydia What is Neisseria Gonorrhoeae?  Second leading cause of STI in US  Most cases occur between 15-29 y/o  RISK FACTORS: non-white, urban residence, low socioeconomic status, early age of first sex partner, drugs, being unmarried  PREVENTION: condoms, diaphragm, spermicide  Gonococcus infects the mucosa of the female more readily than the keratinized epithelium of the penis  Location: anal canal, urethra, oropharynx, bartholin glands  Sx: burning with urination, penile discharge, cervicitis, urethritis, PID, TOA (tubo-ovarian abscess), bartholin’s abscess, fever, macular skin lesions, tenosynotvitis, and septic arthritis  Dx: o Microscope—looks like paired kidney beans gram-negative dipplococcus, chocolate agar, NAAT (nucleic acid amplification tests)  Rx: o Ceftriaxone o Cefixime o Rx for Chlamydia – azithromycin since usually co-infected

Infections of Upper Female Reproductive Tract
What is endometritis? o Infection of the endometrium that can sometimes infect the myometrium causing endomyometritis o Can advance to cause PID

o Cause: D&C, D&E, C/S, IUD placement o Sx: usually asymptomatic but clinically can lead to PID so is worth recognizing; pts pay have chronic irregular bleeding, discharge, pelvic pain o Dx: pain with bimanual exam causing uterine tenderness, fever, elevated WBC o Rx: clindamycin and gentamicin (aminoglycocide—binds to 30S ribosomal subunit and interfere with bacterial cell membrane, good for gram -), cephalosporins such as cefoxitin (add doxycycline if suspect Chlamydia) What is PID? o Pelvic inflammatory disease  most common serious consequence of STI (usually caused by gonorrhea or Chlamydia infection but typically polymicrobial  with Gardernella, E.coli, bacteroides, streptococci) o Complications: infertility and ectopic pregnancies o RISK FACTORS: non-white, multiple sexual partners, prior hx of PID, age 15-25, cigarette smoking, IUD o Preventation: barrier contraceptives and OCT o Sx: lower abdominal pain, cervical motion tenderness, adnexal tenderness, uterine tenderness, acute salpingitis-- burning, cramping, stabbing (unilateral or bilateral), vaginal discharge, vaginal bleeding, GI disturbances, abnormal odor o Dx: o Empiric Rx for the following—lower abdominal pain + cervical motion tenderness, uterine tenderness, adnexal tenderness o Other criteria: fever, cervical or vaginal mucopurulent discharge, high WBC, infection with Chlamydia, Gonorrhea o Labs: high WBC, ESR elevated, elevated CRP o Laproscopy, endometrial biopsy, pelvic imaging o Laproscopy typically reserved for cases when appendicitis can’t be ruled out o Fitzhugh-Curtis Syndrome—PID causes adhesions from the liver to the diaphragm results in RUQ pain, elevation of LFTs o Rx: o Broad-spectrum cephalosporin—cefoxitin + doxycycline o Allergic to cephalosporin—gentamicin, clindamycin o Pregnant: clindamycin, gentamicin How will acute salpingitis present?  Sx—fever, abdominal pain with guarding of lower quadrants, acute salpingitis (pelvic inflammatory disease)  Mucopurulent cervicitis with peak sx during and after menstruation is classically gonorrhea  Chlamydia is frequently associated with gonorrhea and also causes cervicitis and pelvic inflammatory disease  Gonorrhea cultures require specialized media, specifically chocolate agar (Thayer-Martin.)  A quick diagnosis of gonorrhea can be made on gram stain--not very sensitive, the finding of gram-negative intracellular diplococci is highly specific for gonorrhea  Trichomonas may cause a yellow frothy discharge, and Candida may cause a thick white cottage cheese like discharge, but neither would cause fever and abdominal pain What is tubo-ovarian abscess? o Can actually be tubo-ovarian complexes that differ from TOA in that they are not walled off and are easier to Rx o PID can progress to TOA in 3-16% of cases o Sx: abdominal/pelvic pain

o Dx: elevated WBC, elevated ESR, culdocentesis can reveal gross pus, US imaging study of choice, CT o Rx: ampicillin, gentamicin, + clindamycin or metronidazole o Rx for serious TOA—if failure to respond to medication or rupture surgical intervention is indicated: drainage of TOA using US guidance or laparoscopy, unilateral salpino-oophorectomy What is TSS? o Toxic Shock Syndrome associated with high-absorbency tampons o Other causes: postpartum endometritis, laser Rx of condylmata, miscarriage, C/S, vaginal infection, vaginal delivery o Pathophysiology: colonization with staph aureus that produces an exotoxin that is absorbed through the vaginal mucosa o Sx: fever, hypotension, desquamation of the plams and soles, erythematous macular rash, GI disturbances—abdominal pain, vomiting, diarrhea, myalgias, mucose membrane hyperemia o LABS: increased BUN, Cr, platelets < 100,000 o Rx: hospitalization to stablize with fluids – IV antibiotics consist of clindamycin and vancomycin What is HIV? o Human immunodeficiency virus o CONTRACTION— o Breast feeding o Sexual contact o Parental inoculation o Vertically mother to child o EPI: rising among women in the US o Pathophysiology—infects CD4 cells, T-cells, B-cells, monocytes, and macrophages o Sx: AIDS-related complex—lymphadenopathy, fever, malaise, diarrhea, weight loss, night sweats, infections like oral candidiasis, varicella zoster, HSV o Opportunitic infections: pneumocystitis carinii, pneumonia, toxo, mycobacterium avium intracellulare, CMV, Kaposi sarcoma, non-Hodgkins lymphoma o Dx: ELISA confirmed with Western o Rx: o Prevention and prophylaxis of OIs, clean needles o Nucleoside analogs—AZT, 3TC, abacavir, didanosine, stavudine (act to inhibit reverse transcriptase and interfere with viral replication) o Protease inhibitors—lopinavir, atazanavir, indinavir, saquinavir, ritonavir (interfere with synthesis of viral particles that have been effective in increasing the CD4 counts and decreasing the viral load) o Non-nucleoside analogs o High incidence of cervical cancer in pregnant women with HIV so screen o Pregnant HIV patients—ZDV should be administered during pregnancy and labor o Start therapy in the second trimester to suppress viral load by third trimester o If viral load >1,000 indication for C/S o Screen pregnant women in first and third trimester o Breast-feeding is contraindicated

Pelvic Organ Prolapse
How are the pelvic organs supported?  Muscles—levator muscles  Fascia—urogenital diaphragm, endopelvic fasica  Nerves and ligaments—uterosacral and cardinal ligaments (attaches the cervix to the side pelvic wall contains the uterine artery and vein)

What is a cystocele and urethrocele?  Protrusion of the bladder/ ureter through the anterior vaginal wall What is a rectocele?  Protrusion or herniation of the rectum through the posterior vaginal lumen What is uterine prolapse?  Prolapse of the uterus through the vagina due to weakening of the cardinal ligaments and other pelvic support structures What is an enterocele?  Protrusion of the small intestines through the vagina What are risk factors for prolapse?  Increased pelvic pressure, chronic cough, hysterectomy, vaginal deliveries, heavy lifting, intrinsic weakness and atrophic changes  Postmenopausal due to decreased estrogen, tissue is less resilent What are sx of prolapse?  Pelvic pressure, pain, dyspareunia, bowel and bladder dysfunction, urinary incontinence, increased urinary frequency, vaginal bulge  Dx—split speculum exam, urine cultures, cystoscopy, urethroscopy, and urodynamics  DDx: skene gland cysts, tumours of the urethra, urethral diverticula, gartner cysts  Rx: reinforcing the pelvic muscles—hormonal therapies, kegel exercises mechanical devices like pessaries (indicated in patients whose sx are severe enough to require Rx but cant have surgery), surgical correction of the fascial defects, uterine prolapse—hysterectomy

Urinary Incontinence
What are the types of incontinence?  Stress incontinency: o Urine loss with exertion or straining (laughing, coughing, exercising) o Usually when urethra is positioned correctly pressure is equally displaced onto the bladder and urethra but when hypermobile urethra more pressure on bladder with increased intrabdominal pressure o RISK FACTORS: pelvic relaxation, increased intra-abdominal pressure and menopause o Rx: maximize pelvic support, fluid intake regulation, change in medications (diuretics) biofeedback, bladder training, estrogen , kegel exercises, pessaries to reposition the urethrasurgery to resuspend the hypermobile urethra  Urge incontinence o Urine leakage due to involuntary and uninhibited bladder contractions o Detrusor overactivity—idiopathic, UTI, bladder stones, urethral diverticular, and foreign bodies (neurologic disease such as stroke, AD, PD, MS, DM) o Sx—incontinence w/ or w/o full bladder, urinary frequency, nocturia, stress incontinence o Rx: bladder training (establishing a regular voiding schedule), medical therapy (anticholnergic to suppress micturition [parasymp] or alph-adrenergic to support continence [sypath]) o Pro-banthine, oxybutynin (anticholinergic) o Smooth muscle relaxants (detrol and tolterodine)—increased blasdder capacity  Mixed incontinence o Both stress and urge incontinence

o Imipramine—good for mixed incontinence both anticholinergic and alph-adrenergic  Overflow incontinence o Due to poor or absent bladder contractions that lead to urinary retention with overdistension of the bladder and overflow o Destursor insufficiency or detrusor arelexia o Sx: incomplete voiding, dribbling, urinary retention, and overdistension of the bladder o Causes-- fecal compaction, medication, LMN disease, DM, spinal cord injuries o Rx:  reduce closing pressure of urethra (prazosin, terazosn, phenoxybenxamine)  Cholinergic agents used to increased bladder contractility and intermittent selfcatheterization  Surgery if have What is bypass incontinence?  Continuous urine flow duet o urinary fistula formed betwe the bladder and the vagina or urethra and vagina  Cause—obstetric trauma, pelvic radiation and surgery, vag hyst accounts for 50% (higher risk if have PID, endometriosis, radiation)  Dx: methylene blue dye into the bladder and tampon test  Rx: surgery repaire immediately give antibiotics or urinary infection and estrogen and steroids have been used to decrease inflammation What is functional incontinence?  Problem psychologically with voiding or due to dementia, geriatrics What anatomy contributes to urination?  Detrusor muscle or bladder is a meshwork of smooth muscle that ends with the trigone area at the base  Internal sphinctor  UVJ—urethrovesical junction  Urethra—suspended by the pubourethral ligaments that originate lower pubic bone and extend to the middle third of the urethra to form the external sphincter  Urinary continence—result of intraurethral pressure > intravesicular pressure (internal sphinctor contraction creates this pressure differential and external sphinctor is second line protection; also can have pressure that is transmitted equally to the bladder and proximal third of the urethra)  Submucosal vasculature—engorges and creates pressure (decreased estrogen decreased capacity for mucosal coaptation) What is the neurological control of the bladder?  Sympathetic—contraction of bladder neck and internal sphinctor through hypogastic nerve  Parasympathetic --- pelvic nerver from S2-4  Somatic—external sphinctor and pelvic floor muscles pudendal nerve  Urge to go—somatic and sympathetic release followed by parasympathetic activation and bladder contraction  Dx:voiding diary, standing stress test, urine culture, cotton swab test, urodynamic studies, cystometrogram (measures blasdder pressure), uroflowmetry (rate of urine flow)

What are the types of amenorrhea? Primary—have not undergone menarche by age 16

Secondary—absence of menstrual cycle for total of 6 months in women who previously had normal menstruation What are causes of primary amenorrhea?  Outflow tract obstruction—imperforate hymen, transverse vaginal septum, vaginal agenesis, vaginal atresia, o testicular feminization: phenotypically female due to absence of testosterone receptor but 46, XY—patients have testes b/c of MIF early in development and they’re undescended or have migrated down to the labia majora, lack pubic hair and axillary hair uterine agenesis, MRKH syndrome  End-organ disorders – ovarian agenesis o ovarian failure: low estradiol but high GnRH hypergonadotropic hypogonadism; savage syndrome (failure to respond to FSH), Turner syndrome (45, XO) o enzymatic defects that lead to decreased steroid biosynthesis: 46, XY defect in testicular steroid production b/c of lack of 17-alpha-hydroxylase or 17,20 desmolase—results in phenotypically female o turner syndrome  Central regulatory disorders – o Hypothalamic: hypogonadotropic hypogonadism—GnRH pulses not present (causes: tumor mass effect, trauma, sarcoidosis, TB, irradiation, stress, athletics, hyperprolactinemia, hypothyroidism, rapid or severe weight loss, delayed puberty) o Pituitary: tumours, hemosiderosis (iron deposits in the pituitary), infarcts—causes decreased LH and FSH When do we see a lack of uterus?  Testicular feminization, mullerian agenesis, 46XY, steroid enzyme defects, pure gonadal dysgenesis, anorchia  Wkup—karyotype, FSH, testosterone levels When will breasts be present?  Uterus absent – testicular feminization, mullerian agenesis  Give estrogen so that breasts develop and prevent osteoporosis How do we work up patients with primary amenorrhea?  Ask: is there a uterus?  If there is a uterus then is there a patent vagina?  If there is no patent vagina than it may be imperforate hymen, transveres septum or vaginal agenesis  If there is a patent vagina then ask are there breasts?  If there are breasts then progesterone challenge—ovarian failure hypergonadotropic hypogonadism  If there are no breasts then consider as if progesterone challenge negative – hypogonadotropic hypogonadism What is the most common cause of secondary amenorrhea?  Pregnancy What are other causes of 2nd amenorrhea?  Anatomic— asherman syndrome (adhesions in the uterus caused by previous surgery, D&C, myomectomy, c/s, endometritis), cervical stenosis  Ovarian dysfunction— premature ovarian failure, ovarian torsion, irradiation  PCOS—hirsutism, obesity, polycystic ovaries, oligomenorrhea, amenorrhea, anovulation

o Chronic anovulation leads to elevated levels of estrogen and androgen o This leads to decreased SHBG and even higher levels of free estrogens and androgens o Increased LH:FSH ration and atypical follicular development, anovulation, and increased androgen production o Rx: Clomid (ovulation induction); insulin resistance – metformin; not interested in fertility use progestins or Depo-Provera prolactinoma, hyperprolactinemia— o excess prolactin leads to amenorrhea and galactorrhea o menstrual irregularities due to increased dopamine that cause increased FSH and LH o prolactin is inhibited by dopamine and stimulated by serotonin and TRH (thyrotropinreleasing hormone) o dopamine inhibits prolactin o serotonin and TRH stimulate prolactin o if you have suppression of prolactin by hypothalamic release of dopamine then you will increased FSH and LH since prolactin inhibits GnRH and FSH o cause of hyperprolactinemia—hypothyroidism causing elevated TSH and RRH that cause hyperprolactimenia; dopamine antagonists (Haldol, reglan, phenothiazines, TCAs, estrogen MAO inhibitors, opiates), pregnancy and breast-feeding CNS or hypothalamic disorder – anorexia, weight loss, stress, exercise, hypothalamic dysfunction

How do we workup someone with secondary amenorrhea?  B-hCG to R/O pregnancy  Hypothyroidism – letahry, weight gain, cold intoleramce  Hyperprolactinemia—nipple dicharge  Hyperandrogenism—hirsutism, acne, virilism  Check TSH, prolactin levels  Normal prolactin check progesterone challenge test – 10mg orally for 7-10 days to mimic withdrawal – see if bleeding occurs – if bleeding then you know disorder is a pituitary/gonadal feedback issue like PCOS, thyroid  If no bleeding administer progesterone and estrogen—if bleeding bow occurs this suggests intact anf functional uterus without adequate estrogen stimulation – measure FSH and LH (low—pituitary and high—ovarian failure)  Rx: hyperprolactinomic—bromocriptine and follow with serial prolactin level; PCOS – progesterone; hypoestrogenic—OCPs  Patients who respond to progesterone challenge test have evidence of estrogenation—ovulation can be induced with clomid that acts as antiestrogen to stimulate GnRH release, elevated androgens may need both Clomid and corticosteroids  If don’t respond to progesterone alone have low estrogen levels and may respond to Clomid or to hMG or GnRH to stimulate ovulation – careful to monitor ovarian hyperstimulation

Benign Disorders of the Lower Genital Tract
What are congenital abnormalities of the vulva and vagina?  Labial fusion o Cause—excess androgens; lack of enzyme 21-hydroxylase can lead to congenital adrenal hyperplasia that can cause

ambiguous genitalia, hyperandrogenism with salt wasting, hypotension, hyperkalemia, and hypoglycemia o Dx: elevated 17-alpha hydroxyprogesteroneor urine 17-ketosteroid with decreased serum cortisol o Rx: cortisol (administering cortisol will cause neg feedback on ACTH that will decrease stimulation of adrenal gland that is shunting all the steroid precursors into androgens o Rx: labial fusion—surgery Imperforate hymen o During development there is junction between the urogenitla sinus and the sinovaginal bulbs – tissue should degenerate o At birth there is a thin membrane at the vaginal introitus or hymenal ring o If degeneration fails the hymen remains intact – causing obstruction to outflow o Mucous and menstrual flow accumulation causing primary amenorrhea and pelvic pain o Rx: surgery Transverse vaginal septum o The upper vagina is formed as the paramesonephric duct (mullerian ducts) elongate and meet in the midline o The internal protion canalizes and the septum dissolves o Caudal mullerian duct form the uterus and upper vagina o Lower vagina is formed as the urogenital sinus elongates (sinovaginal bulb) and a hole forms from below canalizing and working its way up toward the mullerian system o No canalization there may be tissue left that forms a vaginal septum o Dx: made when presents w/ primary amenorrhea and cyclic pelvic pain; US, MRI o Rx: surgical correction Vaginal atresia o Lower vagina doesn’t develop and is replaced by fibrous tissue but there is normal upper genital tract o Presents with primary amenorrhea and cyclic pelvic pain o Rx: vaginal pull-through procedure—excise fibrous portion and evacuate hematocolpos Vaginal agenesis or MRKH o Absence of a vagina – normal external genitalia and ovarian function o Present with primary amenorrhea o Rx: motivated pts can have serial vaginal dilators pressed into the perineal body (Frank and Ingram procedures)  creates a neovagina o Rx: McIndoe procedure that utilizes a split-thickness skin graft from the butt and is molded to create a tube that is closed at one end; mold is inserted into the vagina

What are benign disorders of the vulva and vagina?  Non-neoplastic epithelial disorders of the vulva include atrophic and hypertrophic lesions  Require histologic exam  Lichen sclerosis: found on the vulva of females of all age groups but mostly postmenopausal women 5-15% risk of cancer—complications: labial fusion, contracture, thinning of the skin and skin fragility  squamous cell hyperplasia: chronic scratching causes localized thickening of the skin presenting as hyperkeratotic changes  Lichen planus: shiny flat, purple papules that may have aginal adhesions resulting in vaginal stenosis o Rx:  Lichen chronicus: thickened white epithelium, slight scaling, usually unilateral and circumscribed  Vulvar psoriasis: chronic inflammation in areas rich in sebaceous glands

Vaginal adenosis: palpable red glandular spots and patches in the upper third of the vagina on the anterior wall

What are the sx of patients with benign lesion of the vulva or vagina?  Vulvar itching, irritation, and burning, dysuria, dyspareunia, and vulvodynia  Skin may be tender, bumpy or thickened  Dx: biopsy the lesion, colposcopy  Rx: o Avoid tight clothing o Maintain good hygiene—no douching, powders, feminine scents, detergents o High-potency topical steroids for lichen sclerosus and planus o Low-medium potency steroids for mild cases of dermatoses What are the types of vaginal/vulvar cysts?  Epidermal cyst found on the vulva usually from blocked hair follicle—lined with squamous epithelium and contain tissue that would normally be exfoliated – can develop into an abscess  Sebaceous cyst—sebaceous gland becomes blocked and sebaceous cyst forms; sebum accumulates in this cyst and can become infected with local flora  Apocrine sweat gland—sweat gland found on mons pubis and labia majora and can become occluded and form a cyst—if infected can form multiple abscesses, hidradenitis suppurativa can result  Skene’s gland cysts—paraurethral glands are located next to the urethra meatus that can become obstructed due to inflammation and result in cystic dilation  Bartholin’s duct cyst—glands located at 4 and 8 clock on posteriorlateral aspect of the vaginal orifice that are mucous secreting with ducts that popen just external to the hymenal ring; if obstructed can causes cyst o Rx: resolves on its own or with sitz baths  To prevent recurrence—word catheter placement, marsupialization and warm sitz baths are recommended for relief  Antibiotic therapy recommended if gonorrhoeae or staph o Dx: if > 40 R/O bartholin’s gland carcinoma What are benign solid tumours of the vulva and vagina?  Lipoma – soft pedunculated made of fat or fibrous strands  Hemangioma—elevated soft red tumours  Urethral caruncles and urethral prolapse—fleshy tumor at urethral meatus What is a double cervix?  Uterine didelhs can have a double vagina or a double cervix (bicollis)  High risk—DES daughters  Increased risk for cervical insufficiency  Increased risk for clear cell adenocarcinoma of cervix What are some cervical cysts?  Nabothian cysts, mesonephric cyst, endometriosis can implant on or near the cervix What are cervical polyps?  Pedunculated or broad-based asymptomatic or symptomatic—intermenstrual or postcoital spotting  Cervical fibroids can also form and cause sx of intermenstrual bleeding, dyspareunia, problems in pregnancy

What is cervical stenosis?  Asymptomatic and doesn’t usually affect menstruation or fertility  Can be treated with dilation

Benign Disorders of the Upper Genital Tract
What does the Mullerian duct system fuse to create?  Cervix, upper vagina, uterus, fallopian tubes  Lower vagina urogenital bulb  Ovaries—genital ridge  Anamolies—most common condition—septate uterus due to malfusion of the paramesonephric ducts/ inguinal hernias and urinary tract anomalies Why is the incidence of uterine abnormalities higher?  DES daughters in 1940-1971 What are some sx of uterine anomalies?  Dysmenorrheal, cyclic pelvic pain, dyspareunia, infertility, recent pelvic pain What is the problem with uterine septums?  Vertical and can vary in length and thickness and composed mostly of collagen fibers and lack adequate blood supply to facilitate placentation and maintain a growing pregnancy  Usually suffer first trimester pregnancy loss What are bicornuate uteruses associated with?  Pregnancy loss in the second due to preterm labor  Dx: MRI or CT HSG What are uterine lyeiomyomas?  Benign proliferation of smooth muscle cells of the myometrium  most common reason for surgery for women in US  usually only a problem when someone is experiencing pelvic pain or heavy irregular bleeding or a mass effect on other pelvic structures  pathogenesis—monoclonal develop from a single smooth muscle cell, have estrogen and progesterone sensitive growth activity  types—subserosal (exterior portion of the uterous beneath the uterine serosa), intramural (in the uterine wall), submucosal (beneath the endometrium), parasitic (adheres to the pelvic wall and develops own blood supply)  degenerative changes—can outgrow their blood supply, infarct, and begin to degenerate causing pain or hemorrhaging  epidemiology—50% of AA develop fibroids and 30% of whites  risk factors— smoking, green veggies, injectable depot medroxyprogesterone acetate, OCPs reduce risk  sx: abnormal bleeding is the most common sx (increased duration and heaviness of menses), other sx, menorrhagia, metorrhagia, menometorrhagia, blood loss that can cause anemia, postcoital spotting, sometimes can have pelvic pressure, constipation, hydronephrosis, and venous stasis, 2-10% difficulty with fertility  PE: non-tender irregularly enlarged uterus, pelvic US (hypoechogenicity) HSG, SIS, MRI  Rx: depends on future fertility, age, size and location of the tumours

o Medical—provera (medroxyprogesterone), danazol, and GnRH agonsits MOA: decrease ciculating estrogens that will reduce size of fibroids o UAE—uterine artery embolization; cath the femoral artery under local anesthesia in order to inject an embolizing agent into each uterine artery and decreased the blood supply to the fibroid causing ischemic necrosis degeneration and reduction of fibroid size (uterine blood supply and ovarian can be compromised) o Myomectomy – symptomatic fibroids who wish to preserve fertility o Hysterectomy—definitive Rx What are endometrial polyps?  Overgrowths of endometrial glands and stroma over a vascular core  Found in women 40-50  Tamoxifen increases risk  Presentation—metrorrhagia, menorrhagia, or heavy irregular bleeding menometrorrhagia  Dx: US  Rx: removal b/c can mask bleeding from other sources such as endometrial hyperplasia without atpia or endometrial cancer What is endometrial hyperplasia?  Abnormal proliferation of the endometrial lining glandular and stromal elements of the endometrial lining due to unopposed estrogen  Can be just focal patches and can progress to endometrial cancer  Cause—unopposed estrogen (endogenous – obesity; exogenous—HRT)  Sx: bleeding—oligomenorrhea or amenorrhea followed by irregular or excessive uterine bleeding, postmenopausal uterine bleeding  PE: enlarged uterus, pelvic exam unremarkable, obesity, acanthosis, acne, hirsutism  Dx: tissue is required – endometrial biopsy (if can’t get good biopsy do a D&C)  Rx: o medical—progestin therapy (Provera/ medroxyprogesterone or injectable DepoProvera) Megace, or norethindrone that is oral progesterin; IUD (Mirena)  MOA—stromal decidualization and thinning of the endometrium  3 mos and re-biopsy o surgical—hysterectomy if atypical complex hyperplasia; endometrial curettage, weight loss, ovulation induction  Simple hyperplasia—abnormal stromal and glandular proliferation  Complex hyperplasia—crowded glands  Atypical simple hyperplasia—atypia and mitotic figures to glandular crowding and complexity  Atypical complex hyperplasia—most severe and progresses to 29%  Risk factors—DM, HTN What are ovarian cysts?  Neoplastic or functional; benign or malignant neoplasms  Functional cysts result from normal physiology— o Follicular cysts—failure of the follicle to rupture so just keeps growing 3-8cm  Can cause ovarian torsion (waxing and waning nausea)  Long intermenstrual events but typically asymptomatic  Should spontaneously regress o Corpus luteum cysts  Corps leuteum fails to regress after 14 days and becomes enlarged or hemorrhagic  Sx—delay in menstruation, aching and dull lower quadrant pain; if rupture can cause pain and signs of hemoperitoneum

   

o Theca letuin cysts—bilateral filled with straw-colored fluid and result from stimulation of high B-hCG EPI: 75% of ovarian masses are functional cysts; most commonly occur between puberty and menopause Dx: pelvic US; CA-125 can be used if at high risk of ovarian cancer DDx: torsed adnexa, ectopic pregnancy, PID, tubo-ovarian abscess, endometriosis, fibroids, and ovarian neoplasm Rx: if suggestive of neoplasm should be closely investigated with dx laparoscopy or laparotomy; not resolved in 60-90 consider cystectomy, OCPs

Endometriosis and Adenomyosis
What is endometriosis?  When endometrial tissue grow outside of the uterine cavity—can grown anterior cul-de-sac, posterior cul-de-sac, uterine-sacroligament, broad ligament  Forms endometriomas or cystic collections of endometriosis  Spreads—lymphatically, retrograde periods, or de-differentiation of cells into endometrium  Dx: only can be dx’d surgically; dark brown powder burns, reactive fibrosis, cystic collections, chocolate cysts  DDx: PID, endometritis, fibroids, adhesions, hemorrhagic corpus luteum cysts, ectopic pregnancy, and ovarian neoplasms  Rx: o suppression and atrophy (if not trying to conceive)—OCPs, progestns, NSAIDs, pseudomenopause—GnRH, Danocrine, LUpron, Dynarel want to decrease amount of estrogen released o conservative surgical therapy involves laparoscopy and fulguration of endometrial implants o TAHBSO o No role for medical rx in patients trying to conceive  SE—hot flashes, HA, decreased bone density, vaginal atrophy, dryness – can use GnRH therapy with add-back estrogen  Sx—chronic pelvic pain and infertility; cyclic pain 1-2 weeks bf period that subsides at the onset of flow and peaks at 1-2 days bf onset of menses , dysmenorrheal, dyspareunia, abnormal bleeding, and infertility  Infertility occurs due to adhesions and distortion of the pelvic anatomy  PE—perform early in menses to assess tender and size (may have fixed retroverted uterus)  RISK FACTORS—first-degree relatives 7x more likely, autoimmune dz like lupus What is adenomyosis?  Extension of endometrial tissue into the uterine myometrium that results in menorrhagia or metromenorrhagia  Layer between the endometrial tissue and myometrium is broken down (endometritis may be predisposing factor)  Causes the uterus to become enlarged and globular due to hypertrophy and hyperplasia – into the fundus and posterior uterine wall  Not responsive to regulation with OCPs or hormonal Rx  EPI—develops in parous women in late 30-40s  RISK FACTORS—adenomyosis, endometriosis, uterine fibroids coexists  Sx—most are asymptomatic; most common are secondary dysmenorrheal or menorrhageia or both (dysparenunia, dyschezia, menorrhagia)  PE—diffusely enlarged globular uterus 2-3x larger <14cm

 

Dx: MRI pelvic US distinguishes adenomyosis from fibroids; R/O other things with TSH and endometrial biopsy Rx: hysterectomy; NSAIDs, OCPs, menstrual suppression w/progestins can be helpful

Puberty, the Menstrual Cycle, and Menopause
What occurs during puberty? Adrenal cortex: Regeneration of the zona reticularis in the adrenal cortex and production of androgens Anterior Pituitary: pulsatile GnRH secretion begins stimulating ap to produce LH and FSH Ovary: LH and FSH cause the release of estrogen Result physical changes Breast: breast buds Pubic and axillary hair: hair begins to develop Growth spurt: increase to peak height velocity Menstruation: first menstrual period Length of time from breast buds to menarche 2.5 years What is adrenarche and gonadarche? o Adrenarche begins at ages 6-8 with the regeneration of the zona reticularis where increased production of androgens are produced  DHEAS, DHEA and androstenedione

o Gonadarche pulsatile release of GnRH from the hypothalamus at night which causes pulsatile release of LH and FSH and stimulation of the ovary which will trigger physical changes and the initiation of the LH surge What is thelarche? o First phenotypic sign of puberty and occurs in response to increased estrogen causing breast bud formation and vaginal mucosal development with growth of the vagina and uterus What is pubarche? o Growth of pubic hair usually around age 11 and axillary hair What causes increased growth velocity? o Estrogen causes increased GH and somatomedin-C resulting in 9cm/yr around age 12

When does menarche occur? o 2.5 years following breast bud development usually around age 12-13 o Delay in gymnasts, distance runners, ballet dancers due to insufficient body fat % and stress on the body that may inhibit ovulation through positive effects on NE and GnRH Describe the menstrual cycle.

Defined by ovary and endometrial development— o Ovary: follicular and luteal phase o Endometrium: proliferative and secretory phase Follicular phase— o Withdrawal of estrogen and progesterone from prior luteal phase cause a rise in FSH o FSH stimulates the growth of primordial ovarian follicles and one becomes the dominant follicle and matures until ovulation o Estrogens are produced by theca internal cells producing androstenedione in response to LH stimulation and the granulosa cells convert this androstendione to estrodiol

o Estrogen levels negatively feed back on pituitary FSH secretion but the number of FSH receptors are also decreased so the dominant follicle is not affected by FSH decrease o Estrogen levels increase causes LH surge Lutueal phase— o Follicle ruptures and releases the mature ovum o Ovum is swept toward the uterus – takes 3-4 days o Fertilization should occur in 24 hours o Granulosa cells and theca cells form the corpus luteum which secretes progesterone o Endometrium becomes more glandular and secretory to prepare for implantation o Fertilization—if fertilization then development of trophoblast secreting hCG similar to LH to allow for continuation of corpus luteum secreting estrogen and progesterone until the placenta 8-10 weeks can take over o No fertilization—withdrawl of progesterone after degeneration of the corpus luteum causes the endometrium to slough off and at the same time FSH will begin to rise again What is menopause? o Menopause – 12 mos of amenorrhea after a final menstrual period o Cause: oocytes have undergone atresia; ovarian follicular depletion, eggs stop responding to FSH and LH and leads to absence of ovarian estrogen secretion and increase in FSH and LH o EPI: usually occurs at age 51 but in 5% of women occurs at 55 and 5% can occur between 40-45 yrs o early menopause is more common in women with a hx of smoking, nulliparity, type 1 DM, short cycles, fam hx of early menopause o Sx: hot flashes, night sweats, mood swings, depression, vaginal dryness, osteoporosis, insomnia, vaginal atrophy o Dx: decreased estrogen levels, FSH (increased, but if perimenopausal won’t tell us much b/c elevated or decreased) o Should be used for patients with amenorrhea, oligomenorrhea, menopause What are the long-term effects of lack of estrogen?  Increased risk of coronary artery disease: Cardiovascular effects of estrogen on the lipid profile – estrogen increases HDL and decreases LDL, prevents atherogenesis, increases vasdilation and inhibits platelet adherence  Osteoporosis: increases bone resorption b/c estrogen regulates osteoclast activity What is PMOF? o Premature ovarian failure—spontaneous onset of menopause before age 40 What are risks of HRT and ERT?  HRT—hormone replacement therapy includes both estrogen and progestin  ERT—only estrogen and should only be used in patients who have had hysterectomy o Unopposed estrogen can cause endometrial hyperplasia  CON: both can have cardiovascular risks such as stroke and heart attacks  PRO: osteoporosis  DOSE: used for short period (6-12mos) of time and smallest dose to Rx the Sx—sleep, mood, vasomotor flushing, vaginal atrophy, improvement of skin and muscle tone  Contraindications: liver, pregnangy, estrogen-dependent neoplasms, DVT, undx’d vaginal bleeding What are some other therapies for menopause sx?

Sx Cardiovascular changes Osteoporosis risk

Option Blood pressure and lipid control meds, smoking cessation, exercise, weight loss Calcium, calcitonin, bisphosphonates, raloxifene, HRT, weight bearing exercise


Raloxifene: SERM; blocks binding of estrogen to estrogen receptor, agonist for bone, antagonist in breast and endometrial antagonist (used for osteoporosis and breast cancer) Calcitonin: tones down calcium levels so decreases calcium release from bone and (controlled by increased serum calcium) Bisphosphonates: etidronate, pamidronate, alendronate, risdronate; MOA inhibits osteoclastic activity and reduces formation and activity of hydroxyapatite

Hot flashes Vaginal dryness/dyspareunia Mood Disturbances

HRT, clonidine, SSRIs, black cohosh, evening primrose, dong quai HRT, vaginal estrogen, water-based lubricant, isoflavones, chasteberry, ginseng HRT, SSRIs, St. John’s wort, black cohosh

Abnormalities of the menstrual cycle
What is dysmenorrhea?  Pain with menstruation that can interfere with normal activityes  Primary dysmenorrhea—caused by menstrual pain o Cause—increased levels of endometrial PG production o Dx—differentiate from endometriosis (dysmenorrhea begins on the day of menstruation where as pain from endometriosis begins 1-2 weeks before menstruation and worsens 12 days before and is relieved with menstrual flow o Sx—nausea, vomiting, HA o Rx—NSAIDs, aspirin, ibuprogen, naproxen, OCPs, (decrease in ovulation or decrease in endometrial proliferation that decreased PG production)  Secondary dysmenorrheal—painful meses due to underlying pathology (endometriosis, fibroids, adenomysosis, PID, cervical stenosis) o Cervical stenosis—obstruction of flow can cause cramping and pain  Rx—dilation of cervix surgically or laminaria o Pelvic adhesions—adhesions may cause dysmenorrhea (PID, tubo-ovarian abscess, other inflammatory diseases)  Rx—anti-PGs, laparotomy for lysis of adhesions What is PMS and PMDD?  Premenstrual syndrome— o A constellation of physical and psychological changes including HA, depression , anxiety, fatigue, bloating, weight gain, feeling like being out of control  Premenstrual dysphoric disorder— o More severe version of PMS  Pathogenesis: multifactorial—abnormalities in estrogen-progesterone balance and disturbance in RAA pathway, excess PG and prolactin production, and psychogenic factors such as changes in serotonin and ovarian steroids  Rx: o SSRIs—mood sx (prozac), celexa, paxil, Zoloft o SNRIs—effexor, xanax

o o o o

Lupron and danocrine Yaz – OCP with low estrogen and spirolactone Vitamins Carb-rich beverage

What are patterns of uterine bleeding? Bleeding Pattern Definition Normal Regular bleeding; q28 days (21-35) lasting 35 days and bleeding on avg. 30-50mL/cycle Menorrhagia Regular bleeding heavy (>80mL) or prolonged (>7days) menstrual flow occurring at regular intervals Cause—adults: polyps, fibroids, adenomyosis; teens: von Willebrand, ITP, Platelet dysfunction, and thrombocytopenia Hypomenorrhea Regularly timed menses but light flow – hypogonadotropic hypogonadism (anorexics and athletes), OCPs Depo-Provera, progestincontaining IUDs Metrorrhagia Any bleeding between normal menses, lighter (intermenstrual than normal menstrual bleeding bleeding) Cause: polyps, carcinoma menometrorrhagia Excessive or prolonged bleeding at irregular intervals Cause: uterine fibroids, adenomysois, endometrial polyps, hyperplasia, and cancer Oligomenorrhea Irregular cycles >35 days apart cause: thyroid disease, PCOS Polymenorrhea <21 days apart

Timing of Cycle Regular Regular

Flow amount Normal Heavy



Irregular Irregular

Normal-light Heavy

Irregular regular

Varies Normal

How do you evaluate abnormal menstrual bleeding?  Hx and physical— o Timing of bleeding o Quantity of bleeding o Menstrual hx with menarche and recent periods o Sx during menstruation  PE— o Rectal, urethral, vaginal and cervical causes should be ruled out o PCOS—hirsutism, acne, acanthosis nigricans, truncal obesity o Thyroid—thyromegaly, skin changes, diaphoresis, increased pulse o Bleeding disorder—bruising, petichiae o Pap smear—cervical dysplasia o Cervical cultures o Pregnancy test o TSH, PRL, FSH (PMOF)

o US—polyps, fibroids, hyperplasia, cancers, sonohysterogram, hysterosalpingogram, MRI, hysteroscopy Common causes: o Fibroids—causes heavy bleeding myomectomy o Adenomysosis— causes heavy bleeding hysterectomy, hormonal management o Cervical polyps—causes light bleeding polypectomy o Endometrial polyps—causes heavy bleeding, hysterectpy, polypectomy, D&C o Endometrial hyperplasia—varies, progestin therapy, hysterectomy o Endometrial cancer—heavy bleeding; hysterectomy, BSO, radiation o Pregnancy—varies, delivery o Miscarriage—heavy D&C o Ectopic—varies, methotrexate vs surgical removal o hypothydroidism—thyroid replacement o hyperprolactinemia—dopamine agonists o anovulation—cyclic OCPs or progestins

What happens if you can find no cause for uterin bleeding?  Dx—dysfunctional uterine bleeding  Most of these people are anovulatory  Ovary produces estrogen but no corpus luteum is formed and no progesterone is produced  Estrogen continues to cause proliferation of the endometrium until it outgrows its blood supply, breaks down and sloughs off (occurs in PMOF, hypothyroidism, hyperprolactinemia, hyperandrogenism)  Want to R/O other cuases of bleeding based on age group  Teens—usually related to hormonal problem  Reproductive yrs—perimenopausal, structural, should undergo an endometrial biopsy  Rx: o high-dose estrogen for patients who are hemodynamically stable but have excessive blood loss o OCP taper to stabilize the endometrial lining o NSAIDs o Combination estrogen and progesterone in the form of OCP o If predisposed to clots use progestin only dosing o Endometrial ablation o Hysterectomy What is menopause?  12 months of amenorrhea  postemenopausal bleeding is bad news  common cause—endometrial or vaginal atrophy due to lack of estrogen  endometrial cancer, polyps, and hyperplasia can cause postmenopausal bleeding  Dx: Labs—CBC, TSH, prolactin, FSH, CEA, LDH, inhibin, hCG, estradiol Biopsy—endometrial biopsy  Rx: vaginal atrophy—estrogen cream, HRT, ERT, hysteroscopic resection of polyps

Hirsutism and Virilism
What is vellus hair? Non-pigmented hair that covers the entire body and is soft What is terminal hair?  Pigmented, thick, covers the scalp, axilla, and pubic area

What is responsible for the conversion of vellus to terminal hair?  Androgens  Increased in androgens or 5alpha-reductase converts testosterone to more potent DHT is the main stimulant for terminal hair development What is hirsutism?  Increased hair growth on chin, face, chest, inner thighs, lower abdomen What is Virilization?  Development of male features such as deepending of the voice, frontal balding, increased muscle mass, clitoromegaly, breast atrophy, and male body habitus What are the components of the adrenal gland?  Cortex—makes glucocorticoids, mineralcorticoids, and androgens o Zona glomerulosa-- aldosterone o Zona fasciculata—cortisol and androgens o Zona reticularis-- androgens  Medulla—catecholamines (NE)  Androgens made from 17alpha-hydroxypregnenolone DHEA DHEAS testosterone  In ovaries—theca cells stimulated by LH to produce androstenedione and testosterone that is converted by granulose cells by FSH to aromatize to estrone and estradiol  CLINICAL—enzymatic blockade of cortisol or aldosterone can lead to increased androgen production (DHEAS used as a marker for adrenal production of androgens) What are some adrenal disorders?  Cushing—excess production of cortisol caused b pituitary adenoma or ectopic site of ACTH or tumor of the adrenal gland (adrenal gland tumours usually have decreased ACTH) dx’d with administration of dexamethasone suppression test  Congenital adrenal hyperplasia—accumualtion of DHEA due to deficiency of enzymes should measure 17-OHP (if elevated should confirm with cortrosyn test—see if marked increase in 17OHP) and 21alpha-hydroxylase What are other cause of hirsutism?  Non-neoplastic (Rx with OCPs that will increase SHBG and suppress LH and FSH or GnRH can suppress LH and FSH)—PCOS (LH: FSH 3:1), Theca Lutein Cysts , stromal hyperplasia and hyperthecosis  Neoplastic (rapid increased in virilization and testosterone >200) —sertoli-leydig cell tumours, granulosa-theca cell tumors What are some Rx?  Glucocorticoid administration  Finasteride – inhibits the peripheral conversion of testosterone to DHT

Elective Termination of Pregnancy
   50% of pregnancies are unwated and 44% end in elective abortion Most abortions are performed b/f 16 weeks Laws vary from state to state regarding when a termination can be performed up until, but usually up to 24 weeks (viability)

What is done before the termination?  Rh-negative women should received Rho-GAM

 

GA should be confirmed by LMP, US, physical exam 2-4 weeks following termination f/u to assess emotional and physical status of patient and counseled on reliable form of contraception, pap smear

What options exist for termination of pregnancy during the 1st and 2nd trimester?  First—  90% are performed b/f 12 weeks  < 6 weeks should try to locate the villi – serial hCG if persistent vaginal bleeding occurs o Evacuation of the uterus  Suction curettage D&C:  Uterosacral block or paracervical with local anesthetic  Mechanical dilation of the cervix and removal of POC and suction cannula  Sharp curettage may be performed to ensure the uterus is completely evacuated  Antibiotic prophylaxis—ceftriaxone, doxycycline, ofloxacin (prevents postabortion endometritis)  Manual vaccum aspiration:  Cannula dilates the cervical os and then extraction using self-locking vacuum syringe  Medical abortion: 2-weeks later confirm with US or serum B-hCG elvel  Mifepristone (MOA—progesterone antagonist that prevents the building of the endometrial lining causing an unsuitable environment to sustain the pregnancy Clinical Use—up to 49 days from LMP) + misoprostol  Methotrexate (dihydrofolate reductase inhibitor interferes with DNA synthesis and prevents placental villi proliferation) + misoprostol  SE—abdominal pain and cramps, N/V/D/prolonged uterine bleeding   Second— 14-24 weeks usually for congenital abnormalities, PPROM, hyperemesis, life-threatening maternal condition, undesired pregnancy o Surgical evacuation D&E:  Wider cervical dilation, suction cannula and forceps to extract uterine contents  SE: cerival laceration, hemorrhage, uterine perforation, infection, retained tissue o Medical induction of labor  Use cervical ripening agents (PGE2 and misoprostol), amniotomy, and high-dose IV oxytocin  High-dose oxytocin  Fetal-cidal agents—intraamniotic saline or digoxin, intracardiac potassium chloride  Intra-amniotic installation agents PG

Neoplastic Disease of the Vulva and Vagina
What are the types of preinvasive neoplastic disease of the vulva?  Squamous—vulvar intraepithelial neoplasia  Non-squamous—paget’s and melanoma in situ What are the sx of vulvar dyplasia and HPV-related conditions?  Vulvar itching, whitish discharge, no obvious lumps or sores  erythematous labia, thin white filmy discharge  multi-focal flat whitish lesions

 Cancer

NEXT STEP—colposcopy and directed biopsy of the vulva Pathogenesis
VINI—mild dysplasia VINII—moderate dysplasia (may present with multiple white, papules over the labial minora, majora, clitoral hood, and perineum—Rx with Co2 ablation) VINIII—severe dysplasia -correlated with HPV (16 and 18), cigarette smoking, immunocompromised state

-75% occur in premenopausal women (40)

- 50% asymptomatic; color changes, ulcerations, vulvar masses -Sx: vulvar pruritis or irritation; palpable abnormality, perineal, perianal burning, dysuria -PE: white lesions with or without punctations -Dx: biopsy

-risk of progression for women >40 can be 100% -excision, laser vaporization, and superficial skinning vulvectomy GOAL: dz free margin of 5-10mm -5FU and imiquimod to preserve vulvar anatomy 40-75% effective -1/3 will have recurrence of dz Note: w in past dx’d with candidasis but no response to antifungal meds

Vulvar intraepithelial neoplasia (VIN)

Paget’s Dz

-noninvasive melanoma and is very rare -coexistent adenocarcinoma occurs putting pt at high risk of mets

- pts > 60

Squamous cell carcinoma SCC

-most common type 90% of vulvar cancer; melanoma (occurs in postmenopausal women treated similarly to SCC –once it has metastasized the mortality rate is almost 100%) and basal cell are other types

chronic inflammatory changes – fiery red vulva with whitish hyper-keratotic lesions demarcated, thickened with areas of excoriation and induration; red velvety and then can become eczematous - accounts for 5% -lesions on the labia of gyn majora malignancies, risk -cauliflower-like factors include masses or indurated smoking, VIN, ulcers that spread via CIN, HPV, hx of the lymphatics cervical cancer Sx: vulvar pruritis, pain, bleeding Biopsy: radical local excision and inguinofemoral lymph node

- if no mets local excision can be curative - high recurrence rate -fatal if spreads to the lymph nodes

Complete pelvic exam: palpation of lymph nodes, cervical cytology, colposcopy of cervical vagina, vulva, and perianal area - wise radical local excision and lymph node dissection

dissection - associated with lichen sclerosus “itch-scratch-itch” cycle Vaginal intraepithelial neoplasia (VAIN) – preinvasive dz -VAIN I, II encompass the lower 1/3-2/3 of the epithelium and VAIN III occurs when > 2/3 of the epithelium are involved -associated with cervical cancer, condylomas, and HPV - mid to late 40s - 50-90% have patients with VAIN have coexisting neoplasia of vulva or cervix 1-2% of all gyn cancer - age 60 -associated with HPV but vagina is less susceptible to the effects of virus -DES exposure can predispose to clear cell carcinoma

-metastatic dz should have pelvic radiation -prognosis: depends on the # of + inguinal lymph nodes -asymptomatic -local excision or -abnormal pap smear laser ablation and no changes on - Rx with laser cervical iopsy vaporization - intravaginal 5FU

Squamous Cell Carcinoma

85% of vaginal cancer is SCC, 6% is adenocarcinoma -can spread via lymphatics, directly from rectum/bladder, hematogenously from liver, lungs, bone

-ulcerated, nodular, or exophytic involves the posterior wall and upper 1/3 of vagina - Sx: puritis, vaginal bleeding, postcoital bleeding, watery or bloody discharge, dysuria, hematuria, constipation -pt should undergo chest imaging, cystoscopy, proctosigmoidoscopy and pylogram to asses for dz spread

Stage I—surgical resection Stage III and IV – radiation only -overall survival time is about 45%-55%

Cervical Neoplasia and Cervical Cancer o endocervix: columnar epithelium that is o o o o
red and irregular with papillae and clefts (cervical os) ectocervix: squamous cells that are on the external ox columnar epithelium will mature into squamous epithelium transformation zone: area between the original squamous-columnar junction and current SCJ area where CIN and cervical cancer develop

When should women start cervical cancer screening? o No later than 3 years after having sex or age 21 o Should have one every year < 30 and every 2-3 years if age 30 and have had 3 negative cervical cytology screening tests and no hx of CIN2 or 3 When can women stop having pap smears? o Age >70 who have had 3 or more normal Pap tests in a row and a 20 year hx of normal pap smears o Hysterectomy and has 20 yr hx of normal pap smears but if intact cervix and supracervical hysterectomy still need pap smears What are potential changes seen on pap smears? o Normal, inflammation, infection, dysplasia, cancer o Classified as: o ASC-US – atypical squamous cell unknown significance o ASC-H—atypical sqamous cell high-grade squamous intraepithelial lesion o LSIL—low grade squamous intraepithelium lesion o HSIL—high-grade squmaous intraepithelium lesion o SCC—squamous cell carcinoma colposcopy, cervical biopsy and cold-knife conization o AGC—atypical glandular cell o ASC-H, LSIL or HSIL should proceed directly to colposcopy b/c of potential for both cervical and endometrial adenocarcinoma o AGC—colposcopy, cervical, and endometrial biopsy o ASC-US—should have reflex HPV testing if + for HPV should have colposcopy If a white plaque is found on the cervix what should be done?  Leukoplakia--biopsy the plaque under colposcopy  HPV testing would be done in the case of ASC-US—if high-risk HPV then do colpo + biopsy Is a pap smear a diagnostic test?  No it is a screening test What can present like menopause in a 48 y/o woman?  hyperthyroidism; thyroid stimulating hormone test and a pregnancy test would be the most appropriate choice  sx: thin, tachycardic with frequent irregular menses, temperature instability, and anxiety and sleep disturbance  pap smear-- active heavy vaginal bleeding, Pap smear should be rescheduled for a time when she is not bleeding  Pap is a screening test which samples exfoliated cells from the transformation zone, and has a high false negative rate

Obscuring blood, inflammation and drying artifact can hamper the cytopathologist’s ability to interpret the smear.

When is cervical conization indicated?  Unsatisfactory colposcopy  Biopsy shoes severe dysplasia  CIS  Inability to visual the SCJ  + endocervical curretage (ECC)  pap smear showing endocervical cancer in situ  discrepancy between pap smear and biopsy results – example discrepancy between HSIL pap smear result and the normal reading biopsy What do the following findings mean: mosacism, punctuations, aceto-white epithelium, disorderly, ectropion?  Mosacism and punctuations—new blood vessels on sides  Aceto-white epithelium— can represent dysplasia  Disorderly— may signify cancer  Ectropion—area of columnar cells that have not yet undergone squamous cell metaplasia If a woman has a lesion that is biopsied and negative but cannot be completely visualized by endocervical speculation what should be done?  Cold knife cone biopsy-- cervical conization What are the greatest risk factors for cervical cancer?  HPV exposure  Early sexual activity, multiple sex partners, hx HPV or other STIs What are women with HIV at greater risk of having?  Cervical dysplasia and invasive carcinoma  Dz severity corresponds to CD4 count  Should have 2 pap smears/yr in first yr after dx  After this yearly pap smears can resume  If ASC-H, LSIC, HSIC colposcopy and biopsy  Yeast infection should be treated with anti-fungal – lmidazole What are the 2 methods of evaluating the epithelium? o Cytologically with pap smear o Histologically with colposcopy or with biopsy o Colposcopy—looking a cervix stained with acetic acid under microscope What defines CIN3 and CIS?  Abnormal cells that extend to the full length of the squamous cell surface to the basement membrane but not beyond the membrane  Microinvasive  <3mm beyond the basement membrane  Paget’s disease is vulvar condition What are various findings on colposcopy? Cancer Pathogenesis Epidemiology
Cervical intraepithelial - refers to premalignanct changes -most commonly occurs during

- pap smear – scrape cells from the external

CIN I--repeat pap every 6mos for 1 yr

neoplasia (CIN) of the cervical epithelium - determined by the amount of epithelium showing dysplasia (changes start from the basal cell layer and progress into the epithelium) -CINI- mild dysplasia CINII- moderate dysplasia where 2/3 of epithelium is involved -CINIII expands the full thickness of the epithelium (carcinoma in situ)

menarche or after pregnancy— estrogen stimulates metaplasia in TZ of cervix from columnar to squamous cell -RISK FACTORS: infection with HPV (6,11 low risk; 16, 18, 31, 45 high risk); early age of sex, lots of sex partners, high-risk partners, low SES, STIs, cigarette smoking, immunodeficiency -dx’d in their 20s

os in the TZ and with cytobrush from the endocervix

or high-risk HPV screen in 1 yr x 2 if persistent CINII—LEEP CINIII—LEEP

Paget’s Dz

-noninvasive - pts > 60 melanoma and is very rare -coexistent adenocarcinoma occurs putting pt at high risk of mets

Squamous cell carcinoma SCC

chronic inflammatory changes – demarcated, thickened with areas of excoriation and induration; red velvety and then can become eczematous - 80% of cervical -Sx: post-coital cancer bleeding, pelvic - 20% pressure/pain, adenocarcinoma— watery discharge, at risk if exposed rectal urinary sx, to DES vaginal bleeding - median age of dx -PE: mas in the 52 and avg is 45 cervix, upper vagina, -RISK FACTORS: cul-de-sac cigarette smoking, - biopsy is the only HIV, high number way to dx cervical sex partners, eary cancer—if mass is age of onset of sex, found should US, CT high-risk HPV (16, (MRI and CT can tell 18, 31, 45) the extent of dz but not stage it) only gyn cancer that is staged clinically and not surgically—evaluate structures nearby with x-ray, cystoscopy, proctoscopy, peylography, colonoscopy, and barium enema

- if no mets local excision can be curative - high recurrence rate -fatal if spreads to the lymph nodes -preinvasive carcinoma and microcarcinoma = hysterectomy and cold-knife cone for maintaining fertility - early dz: radiation or rad hys + pelvic lymph node dissection -late dz: dz spread to pelvic sidewall so chemoradiation therapy – radiation and intracavitary radiation are used in combo with cisplatin-based chemo

What is a LEEP? o Loop electrosurgical excision procedure: removing a cone-shaped piece of the cervix with a cauterized fine-wire loop or laser (less blood loss than CKC—cold knife conization) o If endocervix is involved—CKC or a 2-stage LEEP where first remove the ectocervix and then a small portion of the endocervix o Complications: cervical stenosis, cervical insufficiency, bleeding, infection What is a rad hys? o Removal of uterus + parametria, upper vaginal cuff, uterosacral/cardinal ligament complex and local vascular and lymphatic supplies What is pelvic exenteration? o Removal of all the pelvic organs—uterus, vagina, ovaries, tubes, ureters, bladder, rectum, sigmoid colon, muscles of the pelvic floor

Endometrial Cancer
Pathogenesis— o 2 types: o pathogenic TYPE I—80% o more common in younger perimenopausal women with hx of chronic unopposed estrogen exposure o ESTROGEN-DEPENDENT o tend to be well-differentiated and more favorable prognosis o pathogenic TYPE II—20% o Post-menopausal and thin; AA or Asian o Depth of invasion is important— o 4 ways for it to spread: direct invasion, transtubally, lymphatically, hematogenously, o Most common histologic type—endometriod adenocarcinoma 75-85%; other types are mucinous, clear cell, papillary serous, and squamous o Most important prognostic indicator is the grade—well-differentiated better prognosis and poorly-differentiated worse prognosis Epidemiology— o Most common gynecologic cancer but has best survival rates b/c the sx present early and there are accurate dx modalities o Number 4 cancer in women o Age 61 Risk Factors-o Obesity—peripheral conversion of androgens to estradiol and estrone o Chronic anovulation—unopposed exposure to estrogen and not progesterone o Exogenous estrogen exposure—use of ERT or tamoxifen (partial agonist in the endometrium) o PCOS—chronic anovulation more central obesity and more peripheral conversion of androgens, lack of progesterone due to anovulatory cycles o Nulliparous—infertility and subfertility secondary to anovulation o Early menarche and late menopause—prolonged estrogen stimulation without progesterone exposure o DM—hyperinsulinemia may lead to abnormal proliferation of the endometrial lining o Fam Hx—Lynch syndrome HNPCC, breast cancer o Endometrial hyperplasia—without atypia 1% risk, with atypia 29% risk Protective factors-o OCPs o High parity

o Pregnancy o Physical activity History-o Vaginal bleeding—menorrhagia, post-coital spotting, intermenstrual bleeding o Non-bloody watery discharge, pelvic pain, pelvic mass, and weight loss o PE—obesity, HTN, acanthosis nigricans (evidence of metastisis – pleural effusion, ascites, hepatosplenomegal, lyphadenopathy, abdominal masses) DDx: o Fibroids, polyps, adenomyosis, endometrial hyperplasia, thyroid dysfunction, ovarian cysst Dx: o Endometrial biopsy o TSh, prolactin levels (if oligomenorrheic), FSH, (to check and see if pt really menopausal), CBC (R/O amenorrhea), CA-125 o Pap smear – 30-40% of pts with endometrial cancer have abnormal pap smear o Pelvic US to R/O fibroids, polyps, endometrial hyperplasia o Biopsy if woman has HNPCC Rx: o surgical staging for a pathologic confirmation b/c Rx differs based on STAGE o Stage I and II—TAHBSO and uterus should be opened to see defree of myometrial invasion o If patient has poor prognosis they may have large tumor mass >2cm, grade 3 tumor type, papillary serous, clear cell, enlarge lymph nodes they need dissection and radiation therapy o Stage III o Means the dz spread to the serosa and beyond and need arotic and pelvic lymph nodes sampling o Recurring Dz: high dose progestins, chemo Prognosis: o Overall survival 5 year 65% o 75% of recurrences in the first 2 years o 1st line Rx for recurrences—chemo or high-dose progestin (provera or megace)

FIGO GRADE II—TAHBSO, b/c pelvic and para-aortic lymphadenectomy and pelvic washings  A patient presents with vaginal bleeding and multiple risk factors for endometrial cancer: obesity, HTN, DM, nullparity, irregular menses (anovulatory cycle)—next step should be endometrial biopsy and then D&C as biopsy sample is critical.

Why is ovarian cancer so bad? o Third most common type of cancer of female genital tract after endometrial and cervical o Fifth most common cause of cancer death o Lack of screening tools o Overall survival is 25-45% Where does ovarian cancer come from? o Epithelium, stroma, germ cell, 5-10% are from mets from other parts of the body known as Krukenberg tumours How is it spread?

o Direct exfoliation of malignant cells from the ovaries o It follows the flow of peritoneal fluid flow o Lymphatic spread to retroperitoneal pelvic and para-aortic lymph nodes, hematogenous spread What causes ovarian cancer? o Malignant transformation of the ovarian tissue after prolonged periods of uninterrupted ovulation What are risk factors for ovarian cancer? o 10-15% of women have familial cancer syndrome HNPCC, BRCAI have an 85% risk of breast cancer and 30-50% risk of ovarian cancer; BRCA II 25% increased risk of breast cancer o family history of ovarian cancer o mother, sister or daughter or personal history of breast cancer have 2x increase of ovarian cancer o early menarche, nulliparity, infertility, delayed child bearing, late-onset menopause o protective factors: OCPs, breastfeeding, multiparity, chronic anovulation, tubal ligation and hysterectomy What are sx of ovarian cancer? o Abdominal distention, early satiety, vague lower abdominal pain, bloating o Later sx: back pain, urinary frequency, constipation, fatigue, dyspareunia, menstrual changes How do we dx ovarian cancer? o Pelvic US—adnexal mass o CT, MRI—can spread via peritoneal fluid so paracentisis and cyst aspiration should be avoided o Barium enema o IV pyelography
Origin % ovarian cancer Age group affected Surface epithelium 65-70% 20+ years mean age is 61 Germ Cell 15-20% 0-25+ years most common in women less than 20 yrs (blacks and Asians) Below for each tumor Yolk Sac— endodermal sinus tumor Marker: AFP PlacentalChoriocarcinoma Marker: AFP Sex cord-stroma 5-10% All ages Metastasis 5% Variable

Markers Types

CA-125 – elevated in 80% of epithelial cancer Brenner



Granulosa-theca Marker: estrogen and inhibin A Microscopically—coffee bean nuclei and Cal-exner body Sertoli-Leydig-testosterone

Mucinous Serous

Fetal- teratoma AFP & hCG Dysgerminoma Marker- LDH


Endometriod Clear Cell Early satiety, bloating, abdominal pain, pelvic pain, ascites, lower back pain, menstrual changes, fatigue, constipation, urinary frequency/urgency, dyspareunia

Grow fast and limited to one ovary; hemorrhage and necrosis and pelvic pain, pressure sx on the bladder or rectum or pain from torsion or rupture of the tumor—considered curable

Granulosa-theca— precocious puberty, postmenopausal bleeding, secondary amenorrhea, mentrual irregularities, endometrial hyperplasia Sertoli-Leydig—produce androgens, virilizing effects—breast atrophy, hirsutism, deepened voice, acne, clitoromegaly, receding hairline Fibroma—Meigs syndrome: triad of pleural effusion, fibroma, ascites Unilateral SO > childbearing yrs— TAH/BSO



Surgical-TAHBSO, omentectomy, cytoreduction or “debulking” with goal of trying to have mass of < 1cm left behind Medical— Carboplatin (MOA: crosslinks DNA SE: CN8 nerve damage and nephrotoxicity)/ paclitaxel (Taxol: inhibits microtubule disassembly) or docetaxel (Taxotere: stabilizes microtubules) SE: myelosuppresion 5-year survival 20%

unilateral SO BEP— Bleomycin Etoposide Platinol (cisplatin)

5-year survival 85%


What is the most common tumor found in women of all ages? o Dermoid—can contain teeth, hari, sweat and sebaceous glands, cartilage, bones, fat o 80% occur during the median age of occurrence of 30 yrs What is the pathogenesis of fallopian tube cancer? o Arise from the mucosa of the tube o Spreads peritoneally and ascites accumulation occurs What are the sx and Rx of fallopian tube tumors? o Profuse watery discharge, pelvic pain, pelvic mass—hydrops tubae profluens o US and CA-125 o TAHBSO, omentectomy, cytoreduction, and pelvic lymph node sampling followed by combo chemotherapy and carboplatin/taxol

Infertility and Assisted Reproductive Technologies
What is infertility?  Inability to conceive after 12 mos of unprotected sex

What is fecundability?  Ability to achieve pregnancy in one menstrual cycle  Avg: 20-25% in the first 3 months, 15% during the next 9 months – by 12 months 80-90% of couples can spontaneously conceive  45-55% due to female factors  35% due to male factors What are female factors for infertility?  Ovulatory abnormalities o Most common PCOS and AMA o Caused by disruption of the HPA WHO defines them as the following  Hypogonadotropic hypogonadal anovulation – hypothalamic anovulation  Rx: GnRH therapy—Lutrepulse Factrel  MOA: pulsatile GnRH/gonadorelin is a GnRH agonist that stimulates release of FSH/LH from pituitary  Normogonadotropic normoestrogenic anovulation (PCOS)  Hypergonadotropic hypoestrogenic anovulation (premature ovarian failure, AMA)  No treatment for ovarian failure b/c they lack viable eggs and can be offered edgg donation, gestational surrogacy, or adoption  Hyperprolactinemic anovulation o Central: pituitary insufficiency (tumor, trauma, congenital), hypothalamic insufficiency, hyperprolactinemia, luteal phase defect o Peripheral: gonadal dysgenesis, premature ovarian failure, ovarian tumor, ovarian resistance o Metabolic: PCOS, thyroid disease, liver disease, obesity, androgen excess  Fallopian tube abnormalities o PID causes adhesions that prevent sperm from flowing through the tube o Gonorrhea and Chlamydia increase risk o Endometriosis, ectopic pregnancy, and previous surgery or nongynecologic infection such as appendicitis or diverticulitis  Endometriosis o Rx:  no Rx for infertility—may try surgical ligation of periadnexal adhesions during laparoscopy and laparotomy with excision, coagulation, vaporization or fulguration of endometrial implants (tissue destruction), but can use progestin Rx for sx  Danazol, Lupron, oral medroxyprogesterone (provera)  Uterine and cervical factors: o Uterine conditions—fibroids, polyps, intrauterine synechiae (adhesions)—caused by infection, D&C, PID--, congenital malformations o Endometrial abnormalities—hyperplasia, carcinoma o Cervical problems—abnormal mucous production cervical stenosis  Rx: cervical dilators or bypassing the cervix via IUI  Other factors: o Luteal phase defect—caused by reduced production of progesterone from the corpus luteum that causes insufficient endometrial lining and impaired implantation o Genetic defects—turner syndrome What is PCOS?  Polycycstic ovarian syndrome—hyperandrogenism  Mechanism—hyperinsulinemia  increased GnRH pulsatility increasing LH: FSH ratio  increased androgen production and decreased follicular development and decreased SHBG

    

Sx: hirutism, acne, male pattern balding, elevated serum androgen concentration Most common cause of anovulation RISK FACTORS: obesity, insulin resistence, DM, infertility, premature andrenarche, hx of PCOS Hyperinsulinemia produces high levels of androgens by the ovary and decreased circulating levels of SHBG leading to disruption of HPGA Rx: o Weight loss  MOA—small amounts of weight loss can reduce the fasting insulin levels, testosterone, and androstenedione o Metformin  MOA—inhibition of gluconeogenesis and increased peripheral glucose uptake through insulin sensitization which causes decreased androgen production and helps produce ovulation  Clinical use—non-insulin dependent DM o Ovulation induction with Clomid or letrozole (Femora)  Clomid or clomiphene citrate—  MOA—antiestrogen stimulates follicular development for ovulation induction  Letrozole (Femora)—  Aromatase inhibitor, reduces androgen conversion to estrogen and stimulates follicular development for ovulatory induction o

What is endometriosis?  15% of infertile women have endometriosis  endometrial cells outside of the uterine cavity that invades local tissues and causes inflammation and adhesions  can interfere with tubal mobility and obstruction; create inflammation that impairs ovulation, fertilization or implantation How do we do a workup for someone with infertility?  Good menstrual hx—ask about ovulatory dysfunction (amenorrhea, oligomenorrhea, menorrhagia, thyroid dysfunction, PCOS, weight changes  PE—look for signs of PCOS—hirtuism, acne, acanthosis nigricans, central obesity, premature ovarian failure (vaginal atrophy), look for cervical stenosis, endometriosis, pelvic adhesions, leimyoma  Dx: o Tracking the menstrual cycle with basal body temperature o Monitoring cervical mucous o Measuring mid-luteal progesterone o CCCT—clomiphene citrate challenge test  Assess for decreased ovarian reserve: the basis of these tests is that women with good ovarian reserve have sufficient production of ovarian hormones from small follicles early in the menstrual cycle to maintain FSH at a low level. Women with a reduced pool of follicles and oocytes have insufficient production of ovarian hormones to provide normal inhibition of pituitary secretion of FSH, so FSH rises early in the cycle  Administration of clomiphene on day 5-9 of the cycle  FSH levels are measured on day 3 and 10 and increased FSH correlated to decreased fecundity o Progestin Challenge Test

Give progesterone for 5-10 days to build up the endometrium and then withdraw—see if have bleeding within 1 week o Endocrine  FSH, LH, prolactin, TFTs, and thyroid antibodies  Cushing’s (an increase in cortisol and androgens due to an increase in ACTH) – DHEAS, cortisol, testosteroine, overnight dexamethasone suppression test (Dexamethasome: based on the ability of DEX (a synthetic glucocorticoid) to inhibit ACTH secretion. In normal persons low-dose DEX will suppress the ACTH and cause low cortisol. In someone with an ACTH-secreting tumor low dose dex does not inhibit cortisol but high-doses will or someone with an adrenal corticol secreting tumor neither high or low doses with inhibit cortisol secretion.  CT or MRI if suspect tumor  Laparoscopy or laparotomy—endometriosis or pelvic adhesions suspected  Pelvic US if suspect tumours  HSG—anatomic abnormalities  Pap smear—gonorrhea and Chlamydia testing  What is the Rx for infertility?  Etiology specific  Uncorrected cases—ovulation induction with fertility drugs, IUI with sperm, IVF with placement of the embryo into the uterus What are causes of male infertility?  Endocrine disorders—hypogonadotropic hypogonadism, thyroid disease  Abnormal semen—cryptorchidism, mumps orchitis, antisperm antibodies, motility  Anatomic defects—varicocele, testicular torsion, vasectomy  Sexual dysfunction—erectile dysfunction, ejaculation failure, retrograde ejaculation  Genetic—cystic fibrosis, kleinfelters syndrome, immobile cilia syndrome What are the risk factors for infertility in men?  35% of infertility is due to the man  Occupational or environmental exposure to chemicals, radiation, or excessive heat  Medications can depress semen quality, quantity, ejaculation, erectile dysfunction o Cimetidine, Sulfasalazine, Spironolactone, Antidepressants o Heroine, cocaine, mj, anabolic steroids How do we do a workup for male infertility?  Semen analysis – sperm count, pH, motility, WBC count  endocrine—FSH, TFTs, serum testosterone, prolactin  postcoital test – look at interaction between sperm and cervical mucus – if abnormal may be due to presence of antisperm antibodies  Rx: depends on etiology o Vaicoceles can be repaired by liation o Hypothalamic-pituitary failure—treated with injections of human menopausal gonadotropins o Low semen volume, low sperm density and low sperm motility can all be treated by washed sperm for IUI o Intracytoplasmic sperm injection ICSI—injecting a sperm directly into an egg and placing it in the uterus cavity for IVF What are methods of assisted reproductive technologies?

   

Ovulation induction—clomiphene citrate (clomid) antiestrogen that competitively binds estrogen receptors in the hypothalamus to increased pulsatile GnRH increases FSH and LH leading to follicular growth and ovulation (day 3 or 5 of the follicular phase of the menstrual cycle for 5 days) o 80% can ovulate and 36% become pregnant o SE: antiestrogen—hot flashes, abdominal distention, bloating, emotional lability, depression, visual changes, multiple gestation pregnancy 8% o Ovarian hyperstimulation syndrome—life-threatening condition caused by overstimulation of the ovaries occurring 1% to 3% of patients undergoing ovulation – ovarian enlargement, minimal sx to significant ovarian enlargement, torsion, or rupture—complicated by ascites, pleural effusions, hypercoaguability Letrozole—aromatase inhibitor that decreased the conversion of androgens to estrogen, lower estrogen causes decreased neg feedback on the hypothalamus and increased FSH and follicular developemtn hMGs – human menopausal gonadotropins—pituitary fails to secrete FSH and LH to stimulate follicular maturation and ovulation used for severe hypothalamic dysfunction 80-90% ovulation success rate and 10-40% pregnancy success rate higher rate of multiples gestation 20% o come in FSH and LH or FSH alone preps o monitor estrogen levels and pelvic ultrasounds o once ovulation occurs fertilization may be attempted by intercourse or IUI o eggs can be retrieved with transvaginal aspiration o remaining eggs preserved with cryopreservation and uterus is prepped with endometrial receptivity

What is IVF?  Oocytes mature briefly in vitro before washed sperm are added  Fertilization is verified 14-18 hours later  Coneptuses are placed into the uterus through the cervix using a catheter What is ICSI?  Intracytoplasmic sperm induction—spermatozoon is directly injected into the cytoplasm of a harvested oocyte and then implanted into the uterus What is PGD?  Preimplantation genetic diagnosis—evaluate the embryo for genetic abnormalities prior to transfer during an IVF cycle

Gestational Trophoblastic Disease
What is GTD?  Group of diseases that result from abnormal proliferation of trophoblastic (placental) tissue What are the types of GTP?  Benign-80%-- 90% are complete moles  Malignant—20% pervasive/invasive mole, choriocarcinoma, placental site trophoblastic tumor PSTT Who get molar pregnancies?  Asian women—japan have highest incidence 1:500  Decreased rate of GTD in blacks  Extremes in age >35 and prior hx of GTD get molar pregnancy

 

Nulliparity—70% of molar pregnancies have never given birth High incidence in regions where low beta-carotene, folic acid, and animal fat

What are complete moles?  Empty ovum is fertilized by 1 sperm and then divides – 46 XX all parentally derived  No associated fetus  Presentation: irregular vaginal bleeding, enlarged uterus, passage of vesicles (grape-like uterus)  PE: uterine size is greater than GA, theca lutein cysts, absence of fetal heart sounds no associated fetus in complete molar pregnancy  LABS: VERY HIGH hCG-- > 100,000  US—snowstorm pattern, theca lutein cysts  Rx: D&C and ocytocin for hemostasis; Rh status to prepare for heavy vaginal bleeding, antihypertensives to prevent stroke, beta blockers like propranolol to prevent thyroid storm and trophoblastic embolism  Follow up—measure within 48 hrs and then weekly until negative for 3 consecutive weeks (14 weeks until normal hCG)-- NEED CONTRACEPTION  Recurrence—can be malignant dz 15% of time, recurrence 1%, but after 2 is 16-28% What sx do the high levels of hCG cause in complete molar pregnancy?  hCG has 2 subunits beta and alpha; alpha subunit is similar to LH, FSH, and TSH and can result in theca lutein cysts 6cm and hyperthyroidism  Hyperemesis gravidarum (severe nausea and vomiting), preeclampia b/f 20 weeks gestation (irritability, dizziness, photophobia), hyperthyroidism (nervousness, anorexia, tremors), thec lutein cysts  ** in the absence of chronic hypertension preeclampsia b/f 20 weeks is diagnostic of molar pregnancy What are partial moles?  10% of molar pregnancies are partial moles and result from fertilization of normal ovum by 2 sperm 69, XXY  presentation: vaginal bleeding from spontaneous or incomplete abortion associated with presence of fetus and can have amniotic fluid and fetal heart rate present – syndactyly or hydrocephalus and growth restriction – may be confused with a missed abortion or spontaneous abortion  don’t usually see hyperemesis, hyperthyroidism, preeclampsia  LABS: hCG levels only slightly elevated  Pelvic US – swiss cheese appearance  Rx: D&C  Follow up: serial hCG What is pervasive/invasive mole?  Type of malignant GTD  Pervasive/invasive moles – make up 75% of malignant GTD and are usually dx’d by plateauing or rising hCG levels after molar evacuation  Dx: hCG levels and pelvic US  Rx: since confined to the uterus single-agent chemotherapy 95-100% cure rate What is choriocarcinoma?  Malignant necrotizing tumor that occurs weeks to years after any type of gestation  Presentation—mets!!! Lungs, vagina, liver, brain, kidneys  Dx: pelvic US, hCG levels, should not be biopsied b/c very vascular lesions

Rx: single or multi-agent chemo

What is PSTTs?  Arises from placental implantation site  No villi and have proliferation of cytotrophoblasts—chronic low levels of hCG<100  Invades into the myometrium and blood vessels and patients can have vaginal bleeding and low levels of hCG  Rx: hysterectomy or multiagent chemo

Sign up to vote on this title
UsefulNot useful