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Reproductive Pathology Dr. Gary Mumaugh – UNW St. PaulAlterations of Sexual MaturationDelayed pubertySecondary sex characteristics have not appeared in girls by age 13Secondary sex characteristics have not appeared in boys by age 1495% of cases are simply a constitutional delay5% are caused by some type of disruption of the hypothalamic-pituitary-gonadal axisPrecocious pubertySexual maturation before age 6 in black girls and age 7 in white girlsSexual maturation before age 9 in boysFemale Reproductive PathologyHormonal AlterationsPrimary dysmenorrheaPainful menstruation associated with prostaglandin release in ovulatory cyclesRelated to the duration and amount of menstrual flowSecondary dysmenorrheaPainful menstruation related to pelvic pathologyCan occur any time in the menstrual cycleDysmenorrheaMost common of all gynecologic complaintsAffects over 50% of womenThe leading cause of absenteeismCharacterized by lower abdominal cramps and pain from mild to debilitatingOften associated with nausea, vomiting, diarrhea, headaches, vertigo, back painPrimary DysmenorrheaPain without pelvic pathologyUsually starts before age of 20 With nausea 50% of timeWith vomiting 25% of timeWith stool frequency 35% of timePain usually starts a few hours before mensesUsually lasts a few hours to a few daysSecondary DysmenorrheaPain with pelvic pathology and lesions Endometriosis, P.I.D., Surgical AdhesionsAlso caused by I.U.D.Usually lateralized to one side and later in lifeBegins a few days before mensesLasts several daysDysmenorrhea EtiologyLike all chronic pain problems, the etiology is often multi-factoral.On the biochemical level, Prostogladins (PGS) account for most of the symptoms.Stimulation of the uterus by estrogen and progesterone increases the endometrial stores of Arachidonic Acid, which is the main PGS causing pain and symptoms.Arachidonic AcidHas been found to cause significant symptoms, especially in teenagersDietary ConsiderationsBeef - red meats, Chicken and turkey, Dairy products, Whole milkDysmenorrheaDiagnosisDiagnosis of primary is self-apparentDiagnosis of secondary with ultrasound for fibroids, CT for endometriosis, cervical culture for PIDTreatmentPrimary – NSAIDs and oral contraceptivesSecondary – treat the primary causeRemove IUD, remove fibroidsPrimary AmenorrheaAbsence of menstruation by age 14 Causes:Congenital defects of gonadotropin production, Genetic disordersCongenital central nervous system defects, Congenital anatomic malformations, Acquired CNS lesionsSecondary AmenorrheaAbsence of menstruation for a time equivalent to three or more cycles or 6 months in women who have previously menstruatedCauses:Pregnancy, Dramatic weight loss, Malnutrition or excessive exerciseAnovulation, Hyperprolactinemia, Hirsutism Abnormal BleedingNormal – 2-3 ounces per cycle (4 days)Amenorrhea – absencePrimary – period never beginsPituitary, genetic, thyroidSecondary – period began normally then stoppedMalnutrition, tumors, endocrine, anorexia nervosa, PTSD, excessive exerciseHypomenorrhagia – light or scanty periodsPolymenorrhea - frequent periodsCaused by oral contraceptives, endocrine, thyroid, pituitary, diabetesDiagnosis with US and laporoscapyMenorrhagia – long and heavy periodsCaused by uterine fibroids, oral contraceptives, IUD, thyroid disordersS & SSoaking through pads or tampons every hour or twoNeeding double protection on frequent basisProlonged heavy periods more than one weekPassing large clotsConstant crampingPossible anemia symptomsMetrorrhagiaDysfunctional irregular uterine bleedingCommonly caused by fibroidsPolycystic ovarian syndromeOligo-ovulation or anovulationElevated levels of androgens or clinical signs of hyperandrogenism and polycystic ovariesLeading cause of infertility in the United StatesMultifactorialHyperinsulinism, Hypertension, DyslipidemiaDysfunction of follicle developmentPremenstrual Syndrome (PMS)Cyclic physical, psychological, or behavioral changes that impair interpersonal relationships or interfere with usual activitiesPremenstrual dysphoric disorder (PMDD) in 3% to 8% of womenGreater than 200 physical, emotional, and behavioral signs and symptomsPMS PathophysiologyRecurrent, cyclical set of physical and behavioral symptoms occurring 7-14 days before the cycleTroublesome enough to interfere with daily lifeOccurs up to 40% of womenMost severe cases 5% of 25-35 year oldsProposed Etiologies of PMSHormonalEstrogen deficiency or excess, progesterone deficiency or excessProlactin excessBeta-endorphin deficiencyAltered estrogen : progesterone ratioFluids and ElectrolytesVasopressin excessAldosterone excessSodium : Potassium ratio Na : KPremenstrual Syndrome (PMS)Proposed Etiologies of PMSNeurotransmittersSerotonin deficiency, cortisol excess, adrenal insufficiencyThyroid abnormalities, hypoglycemia or decreased glucose toleranceProstaglandinsExcess or deficiency, essential fatty acid deficienciesHeredityVitamins and MineralsPyridoxine deficiency, Vitamin A and E deficiencyMagnesium deficiency, calcium deficiency or excessPotassium deficiency, zinc deficiency, dopamine deficiencyTrace mineral deficiencyPsychological factorsBeliefs around menses, coping skillsSelf esteem, psychiatric problemsSocial FactorsStress and social network, marital and sexual relationships Psychosexual experiences, attitudes of PMSSymptoms of PMSNervousness, fatigue, mood swings, tender breastsBack pain, diarrhea, clumsiness, social isolationAnxiety, lethargy, water retention, headache, acneDecreased libido, dizziness, insomnia, irritabilityDepression, abdominal bloating, appetite changeSugar cravings, constipation, low self esteem, joint painClassifications of PMSPMS – A Anxiety - Caused by increased estrogenPMS – CCarbohydrate craving - Caused by increased binding of insulinPMS – DDepression - Caused by decreased estrogenPMS – HHyper hydration - Caused by increased aldosteroneConsider other medical conditionsIt is important to address any underlying medical conditions that may be masked by PMS.One study found that 75% of women receiving care for PMS actually had another diagnosis that accounted for many of the major symptoms of depression and mood swings.394335-22606000Infection and InflammationPelvic inflammatory disease (PID)Acute inflammatory disease caused by infectionMay involve any organ of the reproductive tractSalpingitisOophoritisSexually transmitted diseases migrate from the vagina to the upper genital tractPolymicrobial infection16319521590000VaginitisInfection of the vaginaSexually transmitted pathogens, bacterial vaginosis, and Candida albicansAcidic nature of the vagina provides some protectionMaintained by cervical secretions, normal flora, and lactobacillus acidophilusCervicitisInflammation or infection of the cervixMucopurulent cervicitis (MPC)Infection and InflammationVulvitisInflammation of the female external genitaliaCauses:Contact with soaps, detergents, lotions, hygienic sprays, shaving, menstrual pads, perfumed toilet paper, or nonabsorbing or tight-fitting clothingVaginal infections that spread to the labiaBartholinitisInflammation of one or both ducts that lead from the vaginal opening to the Bartholin glandsCaused by microorganisms that infect the lower female reproductive tractInflammation narrows the distal portion of the ductsLeads to obstruction and stasis of glandular secretions2387600-59309000Pelvic Relaxation DisordersThe bladder, urethra, and rectum are supported by the endopelvic fascia and perineal musclesThe muscular and fascial tissue loses tone and strength with agingFails to maintain organs in proper position416560018288000Pelvic Relaxation DisordersCystocele and rectoceleUrethroceleCystourethroceleEnteroceleVaginal prolapseUterine prolapseBenign Growths Benign ovarian cysts - Unilateral Produced when a follicle or number of follicles are stimulated but no dominant follicle develops and reaches maturityFollicular cysts, corpus luteum cystsDermoid cystsCysts can cause ovarian torsion290639511874500Benign Growths Endometrial polypsBenign mass of endometrial tissueIntermenstrual; excessive bleeding can occurLeiomyomasCommonly called uterine fibroidsBenign tumors of smooth muscle cells in the myometriumCause abnormal uterine bleeding, pain, and symptoms related to pressure on nearby structuresUterine FibroidsNoncancerous tumors of smooth muscle cells and fibrous tissueAlso called leiomyomas, fibromas, fibromyomasStarts off microscopic and grows over the yearsThe most common pelvic tumorIncidence 25% to 50% of women from 25-45Up to ? in white women and ? in black womenAutopsy results consistent with 75%AdenomyosisIslands of endometrial glands surrounded by benign endometrial stroma within the myometriumAsymptomatic, or abnormal bleeding, dysmenorrhea, uterine enlargement, and tendernessProliferative ConditionsEndometriosisPresence of functioning endometrial tissue or implants outside the uterusResponds to hormone fluctuations of the menstrual cyclePossible causes:Retrograde menstruation37084008445500Spread through vascular or lymphatic systemsStimulation of multipotential epithelial cells on reproductive organsGenetic predispositionFemale Reproductive CancerCervical cancerCervical dysplasia (CIN)Cervical carcinoma in situInvasive carcinoma of the cervixRisk factors:HPV and HIVMultiple sexual partnersVaginal cancerVulvar cancerEndometrial cancerOvarian cancer590555842000Impaired FertilityInfertilityInability to conceive after 1 year of unprotected intercourse with the same partnerFertility can be impaired by factors in the man, woman, or bothFertility tests: Structural and HormonalMale Reproductive PathologyDisorders of the Penis:Phimosis Inability to retract foreskin from the glans of the penis (distal to proximal)Paraphimosis Inability to replace or cover the glans with the foreskin (proximal to distal)Frequently caused by poor hygiene or chronic infectionsPeyronie disease“Bent nail syndrome”Slow development of fibrous plaques (thickening) in the erectile tissue of the corpus cavernosa, causing a lateral curvature of the penis during erectionOccurs in middle-aged men and causes painful erections and intercoursePriapismCondition of prolonged penile erectionUrologic emergencyPenile cancerCarcinoma of the penis is rareMostly squamous cell carcinomasRequires surgery, radiation, or chemotherapy5-year survival rate 50%Balanitis - Inflammation of the glans penisUsually associated with foreskin inflammation (posthitis)Accumulation under the foreskin (smegma) causes irritation of the glansDisorders of the ScrotumVaricoceleInflammation/dilation of veins in the spermatic cordCaused by inadequate or absent valves in the spermatic veinsHydroceleScrotal swelling caused by collection of fluid within the tunica vaginalisImbalance between fluid secretion and reabsorptionSpermatocelePainless diverticulum of the epididymis located between the head of the epididymis and the testisContains milky fluid that contains sperm and does not cover the entire anterior scrotal surfaceDisorders of the TestisCryptorchidismFailure of one or more of the testes to descend from the abdominal cavity into the scrotumTreatment - Hormone therapy or surgery (orchiopexy)OrchitisAcute inflammation of the testisComplication of a systemic disease or related to epididymitisMumps most common causeTorsion of the testisRotation of the testisThe rotation causes the twisting of the blood vessels in the spermatic cordPainful and swollen testisCondition may be spontaneous or follow physical exertion or traumaSurgical emergencyCancer of the testisAmong the most curable of cancersCommon in men between ages 15 and 35Causes painless testicular enlargementImpairment of Sperm Production and QualityHormone and growth factorsFSH, LH, and testosteroneAndrogen-binding protein, inhibin B, and other peptidesAdequate spermatogonia - Sperm count >20 million/mLSperm motilityAntisperm antibodiesDrugs and toxins in the semenDisorders of the EpididymisEpididymitisInflammation of the epididymisCommon in sexually active young menThe pathogenic microorganism reaches the epididymis by ascending the vas deferens from an already infected bladder or urethraDisorders of the Prostate GlandBenign prostatic hyperplasiaEnlargement of the prostate glandSymptoms associated with urethral compressionRelationship to agingEvaluationDigital rectal examsProstate-specific antigen (PSA) monitoringAffects 50% of men 50-60At 75, most men experience decrease of force and caliber of urinary flowAt 80, 90% of men have BPHDespite being one of the most common diseases of the aging male, the etiology of BPH remains a mysteryThe condition seems to be due to aging and DHT – DihydrotestosteroneAfter 50, serum testosterone decreases and estrogen increasesEstrogen increases the number of receptors on the prostate and inhibits prostate metabolismThis ultimately causes urinary outflow obstruction336296054546500The muscles of the bladder try to compensate by increasing pressure to expel urine, which only leads to more instability and worse symptomsProstatitisInflammation of the prostateNormal protective barriers:Urethral lengthMicturitionEjaculationAntimicrobials in prostatic fluid (PAF)Similar symptoms to BPHAcute bacterialChronic bacterial NonbacterialProstatodyniaAcute ProstatitisBacterial prostate infectionRare, but can be caused by E. coli or pseudomonasS & SSupra-pubic pain, fever, severe dysuriaAcute ProstatitisDiagnosisUrine culture – initial and midstream (Initial culture will have more WBC) TreatmentHospitilization with IV antibiotics, hydration and pain medsChronic ProstatitisIt is the most common reason why men over 50 go to a UrologistAlthough it literally means “inflammation”, inflammation or infection is rarely presentOnly 5% of men have bacterial prostatitis 95% have non bacterial prostatitis which is often called male pelvic pain syndromeEtiology Genetics, hormonal imbalances, aging, chemical irritants, and fungal infectionsDifferential Diagnosis – bladder cancer, prostate cancer, cystitis (all have prostatic symptoms)Cancer of the ProstateAccounts for 29% of all cancers in malesProstatic cancer is asymptomatic until its advanced stagesSymptoms are similar to BPHRisk FactorsDietary factors, hormones, vasectomy, chronic inflammation, familial factorsIncidenceMost common cancer of men 190,000 new cases per year with 31,000 deathsAverage age of Diagnosis is 72Many pathologists believe that every man will eventually get prostate cancer, if they live long enoughS & SSame as BPH, but sometimes has hematuriaDiagnosisYearly PSA screeningShould be done before rectal examYearly rectal exams for all men over 55Bone scan if bone pain present or if PSA over 10ngTreatmentRadiation has good success ratesHormone replacementRadical prostatectomy with lymph node dissectionEpididymitisVery painful inflammation of epididymisUsually from E. coliCan also be caused by trauma, after catheterization, or after a vasectomyS & S - Extreme testicular pain and low grade feverTreatment - Antibiotics, heat packs, bed restHydroceleCommon, painless swelling around testis with fluidS & S - Usually unnoticed, but can be large enough for a feeling or heaviness or fullnessDiagnosis - transilluminates with a flashlight because of the cystic lesionTreatmentNo treatment as most spontaneously subsideNot usually drained because of the chance of introducing infectionSurgery only if largeVaricoceleVaricose veins of the testesVery common and harmlessS & S - Feels like a bag of worms in the top of the scrotumDiagnosis - Classic “bag of worms” palpation in testesTreatmentUsually no treatment usedIf varicocele is large enough, can cause sterilityMale Sexual DysfunctionVascular, endocrine, and neurologic disordersChronic diseasesRenal failure and diabetes mellitusPenile diseases and penile traumaIatrogenic factorsSurgery and pharmaceuticalsTreatment both medical and surgicalViagra Disorders of the Female BreastMastitisVery common during nursingUsually due to staphylococcusS & SUsually unilateral redness, tenderness & hardeningSevere inflammatory changes in a non-lactating breast is often inflammatory carcinomaDiagnosisConfirmed by historyBlood tests and biopsy for more severe casesTreatmentDicloxacillin or cephalosporin 7-10 daysMay lead to abscess, which requires drainage and IVNipple DischargesClear or white – may be due to clothing irritation, manual stimulation, foreplayMilky - galactorrheaGreen – fibrous growthRed-tinged or bloody – tumorFoul-smelling – breast infectionUnilateral nipple discharge – benign or cancerous tumor or infectionBilateral nipple discharge – suggests a systemic problem such as hormonal tumor or drugsMedication side effectAntidepressants, antihypertensives, oral contraceptives, hormone replacement drugsGalactorrheaPersistent and sometimes excessive secretion of milky fluid from the breasts of a woman who is not pregnant or nursingGalactorrhea also can occur in men Usually due to pituitary tumorMay also cause amenorrhea and decreased libidoFibrocystic BreastsFibrocystic breast condition is lumpiness in one or both breasts Breast tenderness or pain are usually present in fibrocystic breast conditionFibrocystic breast condition is a very common and benign conditionNormal hormonal variation during the menstrual cycle is the primary contributing factor to fibrocystic breast conditionFibrocystic breast condition is a cumulative process that mainly affects women 30-50S & SThe lumps in fibrocystic breast condition can mimic and mask breast cancer. Multiple tender and painful lumps, tend to be fluid filled. Changes in size as the fluids increase or reabsorbFibrocystic BreastsDiagnosisNot an increased risk of breast cancerDiagnosis must be differentiated due to anxietyFirm persistent nodules should biopsy and mammographyFibroadenomasBenign breast tumors Significant anxieties for patientsDiagnosisFirm, rubbery masses in young women 20-30Movable mass, not fixedSeen more in African American womenTreatmentUS, needle biopsy and aspirationExcisional biopsy of suspicious lesionsBreast CancerIncidence211,000 new case per year and 40,000 deaths56,000 diagnosed as DCIS – ductal carcinoma in situ1 in 7 women will develop at one time in their lifePrognosisCure rate 75-90% if cancer is localized to the breast without metastases90% survival rate with small mamo detected and no lymph node involvement45% five year survival if in axillary nodes - 25% to ten year survival5-10% five year survival with distant metastasis - 2% ten year survivalBreast Cancer Risk FactorsAge - chances increase with age80 percent older than age 50In 30s, 1 in 233 chance of developing breast cancerBy age 85, chance is 1 in 7Most significant is family historyGenetic predispositionRadiation exposureEarly menarche and late menopauseFirst pregnancy after 30 or never pregnantExcess weight, excess alcohol, smokingBirth control pillsHormone replacement therapyEnvironmental factorsBreast Cancer DiagnosisShould have breast exam every two years between 20-40 and yearly over 40Yearly mammography over 40On palpation – present as single, firm hard mass, usually non tender with poor marginsPainless lump 70% of time90% of time – patient self discovered60% in upper outer breast quadrantOn mammography – appears as clustered lesionsStaging Breast CancerTumor Size Lymph Node Involvement Metastasis (Spread) I <2 cm NoNoII 2-5 cmNo or in same side of breastNoIII >5 cmYes, on same side of breastNoIV Not applicable Not applicable Yes Breast Cancer TreatmentFor Stage I & IIModified radical mastectomy alone orLumpectomy and axillary dissectionPost surgical radiation and chemotherapyBreast conservation therapy with radiation presents with 75% cure rateComplications of surgeryPost surgical complicationsUp to 30% have arm edemaDisorders of the Male BreastGynecomastiaOverdevelopment of the breast tissue in a maleResults from hormone alterationsIdiopathic and system disorders, drugs, or neoplasmsMale breast cancerMost commonly seen after age 60Tumors resemble carcinomas of the breast in womenCrusting and nipple discharge are common clinical manifestations ................
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