Lecture 28 Female Reproductive Disorders 2023 McGriff.pdf

Female Reproductive Disorders WIL MCGRIFF, MPH, OD CHRISTOPHER WALKEN, OD, FAAO ASSOCIATE PROFESSOR MORE COWBELL [email protected] [email protected] Lecture Learning Objectives u Understand types of common menstrual disorders u Differentiate between physiologic and pathologic changes during...

Female Reproductive Disorders WIL MCGRIFF, MPH, OD CHRISTOPHER WALKEN, OD, FAAO ASSOCIATE PROFESSOR MORE COWBELL [email protected] [email protected] Lecture Learning Objectives u Understand types of common menstrual disorders u Differentiate between physiologic and pathologic changes during pregnancy u Recognize systemic and ocular effects of menopause u Understand epidemiology and pathology of breast, cervical, and ovarian cancer NBEO Outline L. Reproductive System (NBEO 36 R 1-6) 1. Epidemiology 2. Pregnancy a. Normal physiological changes b. Pathological changes 3. Complications of pregnancy (e.g., pre-eclampsia, eclampsia) 4. Implication of breast feeding 5. Diagnostic testing and imaging 6. Diseases/Disorders a. Neoplasms (including breast cancer) b. Disorders of the menstrual cycle Menarche to Menopause Menstrual Cycle u Rhythmic synthesis and release of ovarian hormones u Menarche to menopause u u u ~13 yoa to ~51yoa Cycle usually lasts 28 days 3 main phases u Menstrual phase (Days 1-4) u Follicular phase (Days 5-14) u u Ovulation (usually Day 14) Luteal phase (Days 14-28) Hormones of the Menstrual Cycle u Controlled by anterior pituitary gland u FSH begins cycle u u u Ripens ovum in a Graafian follicle Follicle secrets estrogen u u u Hormone prepares endometrium for egg LH (luteinizing hormone) u u Triggers ovulation and conversion of follicle to corpus lutem Ovulation occurs about day 14 u Corpus lutem u Remains in ovary u Secretes progesterone and estrogen If no fertilization: u Estrogen and progesterone levels drop u Endometrium is released in menstruation u Cycle begins again If fertilization occurs: u Estrogen and progesterone remain high u Endometrium remains u FSH and LH decline u HCG (Human Chorionic Gonadotropin)starts to rise Oral Contraceptives u 97-99% effective in preventing pregnancy if used properly u Often taken for reasons other than pregnancy prevention u Process of negative feedback u Estrogens suppress production of FSH u u Prevents ovulation Progestins suppress luteinizing hormone (LH), u Block ovulation u Thicken the cervical mucus u Reduce ovum movement u Thin the endometrium Oral Contraceptives u Reduce risk of: u Increase risk of: u Endometrial cancer by 50% u Venous thromboembolism (3X)* u Ovarian cancer by 40% u Myocardial infarction (3X)* u Benign breast disease u Stroke u Ectopic pregnancy u Smoking u Fibroids u HTN u Anemia u Dysmenorrhea u PID u Smokers > 35 yoa u Acne u Liver disorder u Osteoporosis u Coronary heart disease u Breast cancer u u Gallstones Contraindications Menstrual Disorders u u Dysfunctional uterine bleeding u Oligomenorrhea (too light flow) u Menorrhagia (too heavy flow) u Dysmenorrhea (painful, difficult menstruation) u Amenorrhea (absence of monthly flow) Caused by: u Hormone imbalances u Systemic disorders u Uterine problems Premenstrual Syndrome (PMS) u u Affects 80% of women u Symptoms u Emotional or physical changes u Emotional changes u 2nd half of cycle u Fatigue u 3% - 8% severe cases u Bloating u Headaches Treatment u Lifestyle modifications u Appetite changes u Diuretics u Painful and swollen breasts u Analgesics u Swelling of hands and feet u Anxiolytics Endometriosis u Ectopic endometrial tissue u Risk factors u u Nulliparous u >30-40 years of age Signs and symptoms: u u Effects u Periodic hemorrhage of ectopic tissue u Peritoneal irritation u Adhesion formation Treatment u Dysmenorrhea u Excessive menstrual bleeding u Analgesia u Pain u Hormone therapy u Dyspareunia u Surgery u Pain with defecation Ovarian Cysts u u u Ovarian follicle >2cm u Very common u 95% benign Sign and symptoms: u Usually asymptomatic u Pain u Urinary retention u Menstrual irregularity Treatment: u Hormonal contraceptives u Analgesics u Surgery (>5cm) Polycystic Ovary Syndrome u ~5M women affected u Risk factors u u PCOS increases risk of: u T2DM u Obesity u Gestational diabetes u Young age u Hyperlipidemia u CVD Signs and Symptoms u Hirsutism u HTN (stroke!) u Androgen excess u Sleep apnea u Infertility u Depression and anxiety u Obesity u Acne u Ocular manifestations u Dry eye u Papilledema (?) Fibroids u u u Uterine Leiomyomas u Benign u Smooth muscle tumors u ~20% women >35 years u Blacks>Whites (3:1) Signs and symptoms u Pain u Bleeding u Local compression Treatment u Observation u Medication u Surgery Age-related Changes u u u Ovarian Changes u Follicles are depleted u Decreasing estrogen and progesterone levels u Degenerative changes in uterus and vagina Premature ovarian failure u Onset of menopause before the age of 40 u Affects 1% of women Menopause u Cessation of the menstrual cycle x 1 yr u Generally occurring in the late 40s or early 50s u Remaining follicles become unresponsive to FSH and LH u Production of FSH and LH rises sharply Menopause Symptoms and Tx u u Hot flashes u Anatomical changes u Sweating u Uterus and breast size reduction u Flushing of chest and face u Vaginal glandular atrophy u Palpitations u Urethral and vaginal epithelia thinning u Reduction in bone deposition Emotional changes u Depression u Fat redistribution u Irritability u Skin and hair changes u Headaches u Insomnia u Treatment u Hormone Replacement Therapy* u Healthy living (exercise, diet, not smoking) Postmenopausal Health u Long-term estrogen deprivation u Long-term Hormone Replacement Therapy (HRT) Decreases risk of: u Osteoporosis u Accelerated atherosclerosis* u Osteoporosis u Macular degeneration u Colorectal cancer u Cognitive impairment u u Increases risk of: u Breast cancer u Stroke u Myocardial infarctions Pregnancy and Related Disorders Pregnancy u u Hormonal Changes u Estrogen* u Progesterone* u Thyroxine u Adrenocortical Physiological Changes u Laxity or loosening of ligaments and joints u Enlargement and alteration of uterus u Altered nutritional requirements u Increased fluid volume (~45% increase in blood volume) u Enlargement of the breasts Pregnancy Changes & Complications u Gallstone formation u Coagulopathies u Transient hypotension u Morning sickness u Frequent urination u Immunosuppression u Sinus congestion u Gingivitis u Decreased gastrointestinal motility u Peripheral edema Benefits of Breastfeeding u Reduced risk in children of: u Reduced risk in mothers of: u Asthma u Hyperlipidemia u Childhood leukemia u HTN u Childhood obesity u T2DM u Ear infections u CVD u Eczema (atopic dermatitis) u Breast cancer (certain types) u Diarrhea and vomiting u Ovarian cancer u Lower respiratory infections u Necrotizing enterocolitis u Sudden infant death syndrome (SIDS) Benefits of Breastfeeding in Visual Development u Visual evoked potential (VEP) & visual acuity @ 4mo u Stereopsis and letter matching at 36 months Ocular Changes during Pregnancy u u Common u Decreased corneal sensitivity u Increased corneal curvature u Decreased IOP u Decreased tear production Uncommon u Transient loss of accommodation u Krukenberg spindles u Increased pigmentation around the eyes and cheeks u Visual field loss u Ptosis Krukenberg spindle Bitemporal hemianopia Ectopic Pregnancies u A fertilized egg implants outside of uterus (1-2/100 pregnancies) u u u 90% occur in a fallopian tube Risk factors u Prior ectopic pregnancy u Prior pelvic or abdominal sx u STI u Endometriosis u Cigarette smoking u >35 yoa u Hx of infertility u u Symptoms u Abdominal pain (often one-sided) u Abnormal vaginal bleeding u Weakness, dizziness, fainting Possible outcomes u Rupture of the fallopian u Internal bleeding u Death Treatment u Methotrexate u Surgery Molar Pregnancy/Hydatidiform mole u u u Defect of fertilization u Occurs in 1 in 1200 pregnancies u Partial: abnormal placenta and some fetal development u Complete: abnormal placenta and no fetal development Signs and symptoms u Bleeding in early pregnancy u HTN in early pregnancy u Severe nausea and vomiting u Elevated hCG Normal ultrasound Treatment u Suction curettage Abnormal ultrasound Placental Abruption u u Premature separation of the placenta u Etiology u ~1% of pregnancies u Idiopathic* u A leading cause of bleeding in 2nd half of pregnancy u Blunt abdominal trauma u Acceleration/deceleration injury Risk factors u Older women u Multiparous women u Smoking u Drug abuse u Hypertension u Effects u Pain u Vaginal bleeding u Pre-term birth u Maternal mortality u Perinatal mortality Placenta Previa u u u Growth of the placenta over the cervical opening u May be total or partial u Increases risk of bleeding during labor and delivery u Occurs in ~1/200 pregnancies Risk factors u Older women u Multiparous women u Smoking u Previous cesarean delivery u Previous placenta previa Treatment u Delivery by cesarean section Preeclampsia u u Pregnancy-induced HTN u Risk factors u ~5% incidence u First pregnancy u HTN >140/90 after 20 wk u Multiple pregnancy u Obesity Signs and symptoms u Edema of the hands/face/eyes u >35 years of age u Sudden weight gain u Hx of diabetes, HTN, kidney disease u Proteinuria* u Oliguria u Blur* u Nausea and vomiting u Preeclampsia retinopathy u Ocular manifestations Retinopathy of Preeclampsia http://www.nejm.org/doi/full/10.1056/NEJMicm1306891#t=article Preeclampsia and Eclampsia u u u Treatment and Prevention u Delivery u Bed rest u HTN management ~0.8% of women with preeclampsia develop eclampsia u Seizures* u Loss of consciousness u Potentially fatal Potential pregnancy complications u Placental abruption u Premature delivery u Disseminated Intravascular Coagulation (DIC) Pituitary Adenomas u May enlarge during pregnancy u u u Pituitary apoplexy Presenting symptoms u Headache u Visual field change u Visual acuity loss Treatment u Radiation u Surgical intervention Breast Health Fibrocystic Breast Changes u ~50% of women u Palpable breast mass that fluctuates with menstrual cycle u u >30-50 years Signs and symptoms u u Diagnosis u Ultrasound u Needle aspiration Treatment u Analgesia u Tenderness or pain in one or both breasts u Heat or cold for swelling u Firm, regular in shape, mobile on palpation u Well-fitting bra u Located in upper outer quadrant of breasts u Oral contraceptive u Size fluctuates throughout menstrual cycle u Danazol Breast Cancer Incidence and Mortality over Time Breast Cancer Epidemiology u u Most common form of cancer in women (~268K cases in 2019) u 13% lifetime risk of developing breast cancer u ~85% of breast cancer cases have NO family history u Only 5-10% inherited (BRCA1 and BRCA2 genes) u White>Black incidence, after 40 yoa 2nd leading cause of cancer-related death in women (~42K deaths) u u Blacks>Whites Leading cause of cancer-related death in Hispanic women Breast Cancer Risk Factors u Sex* u Sedentary lifestyle u Age* u Alcohol use u Personal history of cancer u Obesity after menopause u Genetics (BRCA1 or BRCA2 mutation) u Reproductive history u Hormonal medication use u Radiation exposure u Family history of breast cancer u Race u Breast tissue density u Menstrual history Breast Cancer Cases and Risk by Age Surveillance, Epidemiology, and End Results Program (SEER). BRCA1 & BRCA2-Associated Breast Cancers u Associated w/ 5% to 10% of breast cancer cases u Individuals w/ BRCA1 or BRCA2 mutations have 50-80% lifetime chance of cancer u Also associated w/ increased risk of ovarian and prostate cancer u May choose to treat w/ prophylactic surgery or medications Breast Cancer Signs and Symptoms u Persistent lump / thickening* u Dimpling of the skin u Nipple retraction u Changes in breast contour u Redness on breast or nipple u Bloody discharge from nipple Breast Cancer Diagnosis u Mammogram* u MRI u Biopsy Credit: Bartron Medical Imaging Mammography Recommendations Organization Onset Frequency Until American College of 40 yoa Radiology Annually Life expectancy <7 years American College of 40 yoa Ob-Gyns Every other year until 50, then annually Maybe 75 American Cancer Society 45 yoa Annually until 55, then every other year Life expectancy <10 years USPSTF 50 yoa Every other year 75 70-80% of breast cancers are invasive ductal carcinoma Key Breast Cancer Subtypes HR-positive “Triple-negative” Inflammatory 66% of cases 10-15% of cases 1-5% of breast cancer cases Estrogen and progesterone receptors present on cancer cells No hormone or HER2 receptors Highly aggressive Usually dx before 40 Usually dx after 50 Most likely to recur More aggressive More common in Black women More responsive to therapy Less responsive to treatment Lower associated mortality Higher mortality 2x more likely in Black women than white women Breast Cancer Prognosis u 5-year survival rate is 98% with no lymph involvement u 5-year survival rate is 26% with metastasis Breast Cancer Treatment Options u Prevention if possible u Mainstays of treatment u u Surgery* u Chemotherapy u Drug therapy* u Radiation therapy Emerging treatment u Immunotherapy u Targeted molecular therapies u u Ex. Interferons, interleukins, monoclonal antibodies Stem cell transplantation Breast Cancer And The Eye u Breast cancer causes ~72% of ocular cancer metastases u u ~12% of all cancer cases metastasize to the eye 89% of ocular metastases occur in the uvea The eye is not a common site for breast cancer metastases Source % of cases Breast 71.8 Lung 8.9 GU 3.2 GI 2.4 GYN 1.6 Sarcoma 1.6 Other 10 Ocular Symptoms Of Breast Cancer u Flashes u Floaters u Reduced acuity u Visual field defects u Diplopia u Loss of vision u Ptosis u Proptosis u Pain Treatment Of Ocular Metastases u Observation u Chemotherapy u Photocoagulation u Cryosurgery u Surgical resection u Localized plaque therapy u External beam radiation Gold brachytherapy plaque Ocular Effects Of Cancer Treatment u Dry eyes* u Cataract u Conjunctivitis u Radiation retinopathy u Diplopia u Optic neuropathy u Floaters u Exposure keratopathy u Reduced acuity u Retinal detachment u Reduced color vision u Epiretinal membrane u Visual field defects Tamoxifen u Selective, estrogen receptor modulator (SERM) u Potential side effects include: u u Dryness* u Cataract (possibly) u Optic neuritis u Vortex keratopathy Retinopathy associated with higher dose and longer treatment (>2 years) u 1-12% occurrence u Refractile crystals around the macula u Macular edema Managing Ocular Effects: Make Them Comfortable & Help Them See u Artificial tears u Prism u Warm compresses u Bangerter filter u Discontinue contact lenses u Tinted lenses u Moisture goggles u Topical immunosuppressants u Autologous serum Cervical Cancer u ~12K cases / ~4K deaths annually u Causes u u HPV (16 & 18) Risk factors u High parity (4X) u Smoking (3X) u Oral contraceptive use (4X) u Unprotected sex u HSV 2 co-infection Cervical Cancer u u u Signs and symptoms u Abnormal vaginal bleeding u Persistent vaginal discharge u Pain and bleeding after intercourse Treatment u Surgery u Radiation u Chemotherapy Prevention u Vaccine: Gardasil, Gardasil 9, Cervarix u Regular pap smears Ovarian Cancer u u u ~22K cases / ~15.5K deaths annually High mortality u No effective screening test u CA-125 used for diagnosis u 45% 5-year survival rate Signs and symptoms u Asymptomatic until late u Increased abdominal girth u Weight loss u Abdominal pain u Dysuria or urinary frequency u Constipation Ovarian Cancer u u Risk factors u Family history of cancer* u Personal history of cancer u >55 years of age u Nulliparous Treatment u Oophorectomy u Radiation therapy u Chemotherapy u Prophylactic oophorectomy or salpingo-oophorectomy Cancer Comparison Type Cases/Deaths Risk Factors Screening Prevention Breast ~247K cases ~40K deaths Various 1st-degree relative 5-10% genetic Mammogram Self exam Mastectomy Cervical ~12K cases ~4K deaths HPV High Parity Smoking OC use Pap smear Vaccine Ovarian ~22K cases ~15.5 K deaths Family history >55 yoa Nulliparous None Oophorectomy Lecture Learning Objectives u Understand types of common menstrual disorders u Differentiate between physiologic and pathologic changes during pregnancy u Recognize systemic and ocular effects of menopause u Understand epidemiology and pathology of breast, cervical, and ovarian cancer Female Reproductive Disorders WIL MCGRIFF, MPH, OD CHRISTOPHER WALKEN, OD, FAAO ASSOCIATE PROFESSOR MORE COWBELL [email protected] [email protected]