Female Reproductive Disorders.pdf

NPLEX II – REPRODUCTIVE SYSTEM Reproductive System Pathology 1 | Neoplasms Cervical Cancer Epidemiology • 3rd most common gynecological malignancy in the US after endometrial and ovarian cancer, and 3rd most common cause of death due to gynecological malignancy after endometrial and ovarian • Peak...

NPLEX II – REPRODUCTIVE SYSTEM Reproductive System Pathology 1 | Neoplasms Cervical Cancer Epidemiology • 3rd most common gynecological malignancy in the US after endometrial and ovarian cancer, and 3rd most common cause of death due to gynecological malignancy after endometrial and ovarian • Peak incidence: 35–44 years of age • Cervical intraepithelial neoplasia (CIN), a precursor of cervical cancer, typically occurs in young adults (25–35 years) Etiology • Human papillomavirus virus (HPV) infection with high risk strains HPV 16 & 18 is found in 70% of patients. • Risk factors • Associated with HPV infection: multiple sexual partners (strongest risk factor) early-onset of sexual activity, multiparity, immunosuppression (e.g., HIV infection, post-transplantation), history of sexually transmitted infections (e.g., herpes simplex, chlamydia) • Environmental risk factors: cigarette smoking, in-utero exposure to diethylstilbestrol (DES), use of OCPs (indirectly as they suppress folate levels) Clinical Features • Asymptomatic in early stages • Cervical discharge (initially watery, becoming brown or red) • Abnormal vaginal bleeding • • • Oligomenorrhea Post-coital or cervical bleeding Dyspareunia • • • Pelvic or back pain Bowel or bladder symptoms Friable, raised, reddened or ulcerated cervical lesions Diagnostics • Cervical exam: ulceration, induration or abnormalities seen on cervix • PAP smear: identifies abnormal cells on the cervix • Endocervical curettage: done when abnormalities noted, usually alongside colposcopy • Colposcopy shows cervical leukoplakia (collection of atypical cells that form white membrane on the cervix unable to be scraped off) Differential Diagnosis • Condyloma acuminata, cervical polyps, Nabothian cyst Treatment • Excision of lesion • Oncologist referral and naturopathic oncology support • Herbs: topical sanguinaria Monitoring & Follow Up • Repeat PAP 3-6 months following treatment Complications • Metastasis, complications from radiation or chemotherapy treatment 14 NPLEX II – REPRODUCTIVE SYSTEM Ovarian Cancer Epidemiology • Second most common gynecologic malignancy in the US (after endometrial cancer). • Median age at diagnosis: 63 years Etiology • Malignancy of the ovary • Risk factors: incidence of ovarian cancer increases with age, genetic predisposition (BRCA1/BRCA2 mutation, HNPCC syndrome, family history), hormonal factors (elevated number of lifetime ovulations, low fertility, early menarche; and late menopause, low number of pregnancies), endometriosis • Protective factors: surgical intervention (bilateral salpingo-oophorectomy), hormonal factors (oral contraceptives, breastfeeding, parity) Clinical Features • Post-menopausal bleeding • Adnexal mass • Increased abdominal girth • Vague, non-specific abdominal symptoms: nausea, vomiting, dyspepsia, anorexia, early satiety • • Constipation Urinary frequency Diagnostics • Bimanual exam • Liver function test • Imaging (transvaginal or pelvic ultrasound, CT) • CA-125 is elevated in 80% of malignant tumors (only used to monitor disease progression, not for diagnosis) Differential Diagnosis • Irritable bowel syndrome, colon cancer, gastric cancer, adenocarcinoma, colonic obstruction, adnexal tumors , ectopic pregnancy, ovarian cysts, ovarian torsion, uterine fibroids Treatment • Surgical excision • Oncologist referral and naturopathic support Complications • Metastasis Prostate Cancer Epidemiology • 2nd most common cancer in men in the US • Second leading cause of cancer deaths in the US after lung cancer Etiology • Risk factors: age >50, family history, African-American descent, genetic predisposition Clinical Features • Asymptomatic • Constitutional symptoms due to metastasis • Urinary retention • • • Hematuria Back pain Bony tenderness • • • Lower-extremity lymphedema, deep venous thrombosis Adenopathy Bladder distension due to outlet obstruction 15 NPLEX II – REPRODUCTIVE SYSTEM Diagnostics • Urinalysis • PSA levels: used in cases of suspected prostate cancer, monitoring for reoccurrence following treatment • DRE: should be performed in those with elevated PSA levels; may be normal in early disease or if located in area unpalpable. Features suggestive of prostate cancer = localized indurated nodules, prostate enlargement, aysymetry, obliteration of sulcus, hard, non-tender nodes • Uroflowmetry (decreased flow rates) • Digital rectal exam (asymmetric nodules) • Biopsy Differential Diagnosis • Prostatitis, prostatic abscess, benign prostatic hypertrophy, bladder cancer, urinary tract retention, Reiter’s syndrome Treatment • Alpha-adrenergic antagonist (tamsulosin, terazosin, doxazosin,alfuzosin) • 5-alpha reductase inhibitors (finasteride, dutasteride) • Prostatectomy • Radiation therapy • Herbs: cucurbita pepo, hydrangea arborescens, prunus africanum, serenoa repens, urtica dioica (root) Monitoring & Follow Up • Monitor PSA levels every 6 months for first 5 years Complications • Urinary retention, overflow incontinence, hydronephrosis and renal compromise, renal colic, calculi, metastasis Seminoma Epidemiology • Peak incidence: 20-35 years of age Etiology • Germ cell tumor of the testicle that originates in the germinal epithelium of the seminiferous tubules. • Risk factors: cryptorchidism, contralateral testicular cancer Clinical Features • Painless testicular nodule or swelling • Negative transillumination test • • Dull lower abdominal or scrotal discomfort Gynecomastia • In metastatic disease: cough, shortness of breath, chest pain, low back or bone pain Diagnostics • Ultrasound: hypoechoic, homogenous, sharp margins • Macroscopic findings: uniform white cut section • Microscopy: fried egg cell appearance, cells have an abundance of watery cytoplasm, fibrous septae divide the tumor into lobules Differential Diagnosis • Hydrocele, varicocele, spermatocele, scrotal hernia 16 NPLEX II – REPRODUCTIVE SYSTEM Treatment • Radiotherapy and chemotherapy Monitoring & Follow Up • Overall prognosis is excellent, 5-year survival rate >95% Leiomyoma Etiology • Benign smooth muscle tumors of the uterus • Fibroids in a post-menopausal woman should prompt consideration of malignancy). Pathophysiology • Estrogen stimulates monoclonal smooth muscle proliferation and progesterone à inhibition of apoptosis. Clinical Features • Abnormal uterine bleeding, menorrhagia • Dysmenorrhea • • • Acute pelvic pain Dyspareunia Pelvic mass, pressure or heaviness • • Increased abdominal girth Bladder symptoms: frequency, urgency, retention Diagnostics • Bimanual exam: symmetrically enlarged uterus • Imaging: transvaginal or transabdominal ultrasound • Endometrial biopsy: rule out uterine cancer Differential Diagnosis • Dysmenorrhea, endometrial polyps, endometriosis, endometrial hyperplasia, endometrial, uterine or ovarian cancer, pelvic inflammatory disease Treatment • Prostaglandin synthetase inhibitors (Anaprox) • Oral contraceptive pills (suppress ovulation and reduce menstrual flow) • Surgical (uterine artery embolization, myomectomy, endometrial resection) • Herbs: Mitchella repens Complications • Infertility and pregnancy complications Endometrial Cancer Epidemiology • Most common gynecological malignancy and the 4th most common cancer in women. Etiology • Risk factors: unopposed estrogens, postmenopausal women most affected, white race, nulliparous, early menarche, late menopause, irregular menses of significant duration, obesity, diabetes, hypertension, infertility • Prevention: avoid use of unopposed estrogens unless uterus has been removed 17 NPLEX II – REPRODUCTIVE SYSTEM Clinical Features • Tends to be asymptomatic • Post-menopausal bleeding • Pelvic pressure Abnormal uterine bleeding (menorrhagia, spotting) in premenopausal women • • • Bloating Bowel dysfunction Diagnostics • Endometrial sampling and biopsy • Pelvic ultrasound (increase thickness) Differential Diagnosis • Hormone imbalance, endometriosis, fibroids, leiomyoma, uterine polyps, adenomyosis, copper IUD Treatment • Hysterectomy • Bilateral salpingo-oophorectomy • Chemotherapy Monitoring & Follow Up • Repeat Pap every 3 months for 2 years, then every 6 months for 3 years, yearly chest films and clinical exams to check for malignancy Complications • Metastasis, complications from radiation or chemotherapy treatment Vulvar Cancer Epidemiology • Rare (0.7% of female cancers) • Squamous cell carcinoma in 80% of cases Etiology • Risk factors: HPV infection (strains 16, 18, 31, and 33), vulvar dystrophy or cervical intraepithelial neoplasia, smoking, precancerous lesions (e.g., lichen sclerosus), immunosuppression Clinical Features • Asymptomatic • Local pruritus, possible burning sensation and pain • • Reddish, black, or white patches of discoloration Wart-like lesions or ulcers • • • Vulvar bleeding or discharge Dysuria, dyspareunia Lymphadenopathy in groin Diagnostics • Pelvic exam and colposcopy, biopsy Differential Diagnosis • Lichen sclerosus, vulvar intraepithelial neoplasia Treatment • Surgery, radiotherapy, chemotherapy Complications • Metastasis, death 18 NPLEX II – REPRODUCTIVE SYSTEM 2 | Infections O Pelvic Inflammatory Disease Epidemiology • PID is one of the most common causes of infertility Etiology • Inflammation of the upper genital tract (above the cervix), including the endometrium, fallopian tubes, ovaries, pelvic peritoneum and contiguous structures • Commonly associated with gonorrhea and chlamydia. Clinical Features • Constitutional symptoms (fever) • Lower abdominal pain • • • Dyspareunia Uterine, adnexal tenderness Menorrhagia, metrorrhagia • • Cervical motion tenderness Mucopurulent cervical discharge Diagnostics • Pregnancy test: to rule out ectopic pregnancy • Speculum and bimanual exam, vaginal swab (gonorrhea, chlamydia) • Urinalysis (leukocytosis) • Cervical motion tenderness: severe cervical pain elicited by pelvic examination. • Ultrasound: free fluid, abscesses Differential Diagnosis • Ectopic pregnancy, endometriosis, complications of ovarian cysts (rupture, hemorrhagic), acute appendicitis Treatment • Antibiotics (cefoxitin and doxycycline) Complications • Infertility, abscess, chronic pelvic pain, ectopic pregnancy, peritonitis, intestinal obstruction, disseminated infection (septicemia, septic, arthritis, endocarditis, meningitis) O Toxic Shock Syndrome Etiology • Risk factors: high absorbency tampons, prolonged placement of tampons, menstrual and vaginal sponges Pathophysiology • Very small amounts of superantigens can rapidly activate excessive numbers of T cells, triggering a massive release of proinflammatory cytokines Clinical Features • Prodrome: high fever, dermal rash (transient, erythematous macular rash commonly involving the palms and soles, typically desquamates 1-2 weeks after onset) • Shock and end organ dysfunction: tachycardia, tachypnea, high fever, altered mental status • Late symptoms: hypotension, delayed capillary refill, worsening altered mental state, evidence of organ failure Diagnostics • CBC: thrombocytopenia • Liver chemistries: ↑ ALT/AST, ↑ total bilirubin 19 NPLEX II – REPRODUCTIVE SYSTEM Treatment • Antibiotics, ICU admission Complications • End organ damage, death 3 | Uterine & Pelvic Disorders Endometrial Hyperplasia Etiology • Increased estrogen stimulation à excessive proliferation of the endometrium • Due to follicle persistence in anovulatory cycles (e.g., perimenopause, PCOS), granulosa cell tumors, HRT without progestin administration, obesity, tamoxifen therapy in post-menopausal women Clinical Features • Post-menopausal bleeding, vaginal bleeding (intermenstrual or constant) Diagnostics • Pelvic exam & cytologic smear • Imaging (transvaginal sonography): can assess endometrial thickening Differential Diagnosis • Endometrial cancer, cervical cancer, adenomyosis, leiomyoma (uterine fibroids), blood dyscrasias (myelosuppression, bone marrow hypoplasia, leukopenia, thrombocytopenia, pancytopenia, aplastic anemia) Treatment • Hormone therapy Complications • Cancer potential, complications from radiation or chemotherapy treatment Endometritis Etiology • Infection and inflammation of the endometrium, which can be acute or chronic. Clinical Features • Constitutional symptoms: fever, malaise, anorexia • Abnormal vaginal bleeding • • • Vaginal discharge Abdominal pain Dyspareunia • • • Uterine tenderness Vaginal discharge Infertility Diagnostics • Hormone panel: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Imaging: laparoscopy showing mulberry spots, “chocolate” ovarian cysts Differential Diagnosis • Urinary tract infection, pyelonephritis, vaginitis, appendicitis, sexually transmitted infection, pelvic abscess 20 NPLEX II – REPRODUCTIVE SYSTEM Treatment • Prostaglandin synthetase inhibitors • Oral contraceptive pills to suppress ovulation and reduce menstrual flow • Surgical: ablation or resection, lysis of adhesions, bilateral salpingo-oophorectomy, hysterectomy Complications • Infertility Endometriosis Epidemiology • Age of onset: 20–40 years • Incidence: 2–10% of all women Etiology • Presence of endometrial tissue outside of the uterine cavity, causing cyclic symptoms due to growth and bleeding of the ectopic endometrium. • Risk factors: nulliparity, prolonged exposure to endogenous estrogen (early menarche, late menopause), short menstrual cycles (<27 days), menorrhagia (> 1 week), family history Pathophysiology • Endometrial tissue occurs outside of the uterus à reacts to the hormone cycle; proliferates under the influence of estrogen • Endometriotic implants result in: ↑ Production of inflammatory and pain mediators, anatomical changes (e.g., pelvic adhesions) → infertility Clinical Features • Chronic or cyclic pelvic pain • Dysmenorrhea • Dyspareunia • Sacral backache • Characteristic sharp, firm, exquisitely tender nodular “barb” on the uterosacral ligament • • Bowel and bladder symptoms: frequent, dysuria, hematuria, diarrhea, constipation Rectovaginal tenderness and palpable adnexal mass Diagnostics • Hormone panel: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Imaging: transvaginal ultrasound, laparoscopy showing mulberry spots, “chocolate” ovarian cysts Differential Diagnosis • Dysmenorrhea, adenomyosis, leiomyoma (uterine fibroids), hemorrhagic corpus luteum, ectopic pregnancy, ovarian cysts, neoplasm, pelvic inflammatory disease Treatment • Prostaglandin synthetase inhibitors • Oral contraceptive pills to suppress ovulation and reduce menstrual flow • Surgical: ablation or resection, lysis of adhesions, bilateral salpingo-oophorectomy, hysterectomy • Herbs: angelica sinensis, dioscorea villosa, leonurus cardiaca, medicago sativa, pulsatilla vulgaris, viburnum opulus Complications • Adhesion formation, infertility 21 NPLEX II – REPRODUCTIVE SYSTEM Uterine Polyps Epidemiology • Most common in post-menopausal women Etiology • Focal overgrowth of localized benign endometrial tissue • Risk factors: hypertension, obesity, tamoxifen, HRT Pathophysiology • Localized within the uterine wall, extends into the uterine cavity • Can be pedunculated or sessile, single or multiple, and can express both estrogen and progesterone receptors (estrogen stimulates growth) Clinical Features • Menorrhagia spotting • Visible polyps protruding from cervix • Infertility Diagnostics • Imaging: transvaginal ultrasound • Endometrial biopsy to rule out other conditions Differential Diagnosis • Endometrial cancer, hormonal imbalance, fibroids, leiomyoma, adenomyosis, copper IUD Treatment • Electrocautery and excision Complications • Infection, obstruction of menstrual flow, obstetric complications Uterine Prolapse Epidemiology • Common in older women Etiology • Insufficiency of pelvic floor muscles and ligaments causing protrusion of the pelvic organs into or out of the vagina • Includes uterine prolapse (protrusion of the cervix and uterus into the vagina), cystocele (protrusion of the bladder into the anterior vaginal wall) and enterocele (protrusion of the small bowel into the upper posterior vaginal wall). • Risk factors: multiple vaginal deliveries or traumatic births, low estrogen levels (during menopause), increased intraabdominal pressure (e.g., obesity), previous pelvic surgery Clinical Features • Vaginal protrusion, bulge • Sensation of pressure • Urinary symptoms: frequency, incontinence, incomplete voiding • • Rectal fullness, constipation, or incomplete rectal emptying Lower back and pelvic pain • • Anterior prolapse is more common than prolapse to posterior vaginal wall Weakened pelvic floor muscle and anal sphincter tone Diagnostics • Speculum and bimanual exam 22 NPLEX II – REPRODUCTIVE SYSTEM Differential Diagnosis • Cystocele, rectocele, enterocele, pelvic floor dysfunction Treatment • Kegel exercises and pelvic floor physiotherapy • Local vaginal estrogen therapy • Vaginal pessary • Herbs: chamaelirium luteum, caulophyllum thalictroides Complications • Ureter obstruction, ulcerations 4 | Vaginal Disorders Bartholin Cyst Epidemiology • Peak incidence: women in the reproductive age group Etiology • Bacterial infection of the Bartholin’s gland, often due to blockage of the duct. Pathophysiology • Blockage of the duct by inflammation or trauma → accumulation of secretions from gland → cyst formation Clinical Features • Vulvar or perineal mass • Often asymptomatic • Unilateral swelling and pain in the inferior lateral opening of the vagina • • Dyspareunia Painful sitting and walking Diagnostics • Clinical exam: unilateral, palpable mass in the posterior introitus Differential Diagnosis • Urethritis, vaginitis, cystitis, vulvar lesions (hematoma, fibroma, lipoma), malignant lesion of Bartholin’s gland Treatment • Antibiotics • Incision and drainage • Hydrotherapy (sitz bath, warm compress) Complications • Bartholin-rectal fistula, infection of deeper tissue or other reproductive organs 23 NPLEX II – REPRODUCTIVE SYSTEM Colpocele Epidemiology • Common disorder in older women Etiology • Vaginal hernia or prolapse: insufficiency of the pelvic floor muscles and the ligamentous supportive structure of the uterus and vagina • Risk factors: multiple vaginal deliveries and/or traumatic births (greatest risk factor), low estrogen levels (e.g., during menopause), increased intraabdominal pressure (due to, e.g., obesity, previous pelvic surgery Clinical Features • Feeling of pressure on or discomfort around the perineum (“sensation of vaginal fullness”) • Lower back and pelvic pain • • Diagnostics • Clinical exam Rectal fullness, constipation, incomplete rectal emptying Prolapse of the anterior (most common) or the posterior vaginal wall • • Possibly with excessive vaginal discharge on inspection Weakened pelvic floor muscle and anal sphincter tone Treatment • Pelvic floor exercises, pessary, surgical repair if indicated Cystocele Epidemiology • Common disorder in older women Etiology • Anterior vaginal prolapse, or prolapsed bladder (bladder drops from usual position and pushes on wall of vagina) • Risk factors: multiple vaginal deliveries and/or traumatic births (greatest risk factor), low estrogen levels (e.g., during menopause), increased intraabdominal pressure (due to, e.g., obesity, previous pelvic surgery Clinical Features • Feeling of pressure on or discomfort around the perineum (“sensation of vaginal fullness”) • Lower back and pelvic pain • • Rectal fullness, constipation, incomplete rectal emptying Prolapse of the anterior (most common) or the posterior vaginal wall • • Possibly with excessive vaginal discharge on inspection Weakened pelvic floor muscle and anal sphincter tone Diagnostics • Clinical exam • Postvoid residual urine measurement • Voiding cystourethrogram Differential Diagnosis • Cystocele, rectocele, enterocele, pelvic floor dysfunction Treatment • Pelvic floor exercises, pessary, surgical repair if indicated 24 NPLEX II – REPRODUCTIVE SYSTEM Dyspareunia Etiology • Pain that occurs during or after sexual intercourse and is due to organic and/or psychogenic factors • Psychogenic factors: severe relationship stress, intimate partner violence, lack of desire/arousal • Superficial dyspareunia (organic): pain limited to the vulvar or vaginal entrance (vulvodynia, vaginal dryness , vulvovaginal atrophy, vulvovaginitis, genital lichen planus, lichen sclerosus, perineal laceration, episiotomy, and/or perineal repair, congenital anomalies (e.g., hymenal variants), urethral diverticulum • Deep dyspareunia (organic): pain in deeper parts of the vagina or the lower pelvis (pelvic inflammatory disease, urinary tract infections, endometriosis, interstitial cystitis) Clinical Features • Superficial or deep pain before, during, or after sexual intercourse • Pain is often reproducible e.g., during any sexual activity involving the genitals, gynecologic exams (e.g., speculum insertion), insertion of a tampon or menstrual cup • Chronic vulvar pain, burning, and irritation may indicate an underlying vulvovaginal condition e.g., vulvodynia, vulvovaginal atrophy Diagnostics • Complete patient history and physical exam • Gynecologic examination: inspection, palpation of the external genitals with a cotton swab to elicit pain, careful palpation of the vaginal walls • Diagnostic criteria: persistent or recurrent difficulty with ≥ 1 of the following: vaginal penetration during sexual intercourse, severe vulvovaginal or pelvic pain during vaginal intercourse or attempted penetration, severe anticipatory anxiety related to vulvovaginal or pelvic pain during attempted vaginal intercourse or attempted penetration, severe tightening of pelvic floor muscles during attempted vaginal penetration Treatment • Treatment of the underlying cause (e.g., vaginal estrogen therapy for vulvovaginal atrophy) • Symptomatic management: topical analgesics, non-hormonal vaginal moisturizers and lubricants • Pelvic floor physical therapy: considered best initial treatment option ; consists of a combination of modalities, such as patient education, internal manual techniques, dilatation exercises, local tissue desensitization, and home exercises (e.g., Kegel exercises). • Psychotherapy • Local botox injections for refractory cases Rectocele Epidemiology • Common disorder in older women Etiology • Posterior vaginal prolapse, associated with descent of the rectum • Risk factors: multiple vaginal deliveries and/or traumatic births (greatest risk factor), low estrogen levels (e.g., during menopause), increased intraabdominal pressure (due to, e.g., obesity, previous pelvic surgery Clinical Features • Feeling of pressure on or discomfort around the perineum (“sensation of vaginal fullness”) • Lower back and pelvic pain • • Rectal fullness, constipation, incomplete rectal emptying Prolapse of the anterior (most common) or the posterior vaginal wall • • Possibly with excessive vaginal discharge on inspection Weakened pelvic floor muscle and anal sphincter tone 25 NPLEX II – REPRODUCTIVE SYSTEM Diagnostics • Clinical exam Differential Diagnosis • Cystocele, rectocele, enterocele, pelvic floor dysfunction Treatment • Pelvic floor exercises, pessary, surgical repair if indicated Vaginitis – Bacterial Epidemiology • Most common vaginal infection in women Etiology • Pathogen: Gardnerella vaginalis (a pleomorphic, gram-variable rod) • Risk factors: sexual intercourse (primary risk factor, but it is not considered an STD), intrauterine devices, vaginal douching, pregnancy Pathophysiology • Lower concentrations of Lactobacillus acidophilus lead to overgrowth of Gardnerella vaginalis and other anaerobes Clinical Features • Minimal vaginal irritation • Vulvodynia • Dyspareunia • • • Grey, diffuse discharge Fishy odor Pruritus/pain uncommon • • Dysuria Strawberry cervix Diagnostics • Whiff test • KOH wet mount (clue cells, positive whiff test, pH > 4.5) • Cervical swab (rule out gonorrhea, chlamydia) Differential Diagnosis • Gonorrhea, chlamydia, candidiasis, trichomoniasis, pinworms, polyps, lichen planus, condyloma acuminata Treatment • Antibiotics (metronidazole, clindamycin) • Herbs: Echinacea spp., Commiphora myrrha, Melaleuca alternifolia Complications • Pelvic inflammatory disease Vaginitis - Candida Epidemiology • Second most common cause of vulvovaginitis Etiology • Overgrowth of C. albicans • Can be precipitated by the following risk factors: pregnancy, immunodeficiency, both systemic (e.g., diabetes mellitus, HIV, immunosuppression) and local (e.g., topical corticosteroids), antimicrobial treatment 26 NPLEX II – REPRODUCTIVE SYSTEM Clinical Features • Intense pruritus • Swollen, inflamed genitals • Vulvodynia, vulvar burning • Vaginal burning sensation, strong pruritus, dysuria, dyspareunia • • Diagnostics • KOH wet mount (pseudohyphae, spores, pH < 4.5) • Cervical swab (rule out gonorrhea, chlamydia) White, crumbly, and sticky vaginal discharge that may appear like cottage cheese and is typically odorless Erythematous vulva and vagina Differential Diagnosis • Bacterial vaginosis, trichomoniasis, STIs (gonorrhea, chlamydia), cervicitis, polyps, lichen sclerosis, condyloma acuminata Treatment • Topical treatment • Fluconazole • Herbs: Melaleuca alternifolia Complications • Dyspareunia, disseminated fungal infection Vaginitis – Trichomonas Etiology • Pathogen: Trichomonas vaginalis (anaerobic, motile protozoan with flagella, does not encyst and, therefore, does not survive well outside the human body) • Transmission: sexual Clinical Features • Vaginal and cervical petechiae • Irritated, tender vulva • • Dysuria Urinary frequency • Yellow-green malodorous, diffuse discharge Diagnostics • KOH wet mound (motile, flagellated organisms, WBC, PMN) • Cervical swab (rule out gonorrhea, chlamydia) Differential Diagnosis • Bacterial vaginosis, candidiasis, pinworms, polyps, lichen sclerosus, condyloma acuminata Treatment • Antibiotics (metronidazole) Complications • Pelvic inflammatory disease 27 NPLEX II – REPRODUCTIVE SYSTEM 5 | Ovarian Disorders Mittelschmerz Epidemiology • Occurs in approx. 40% of female individuals of reproductive age Etiology • Physiological preovulatory pain in female individuals of reproductive age • Also referred to as ovulatory or midcycle pain • Enlargement and rupture of the follicular cyst and contraction of Fallopian tubes during midcycle ovulation lead to transient peritoneal irritation from follicular fluid. Clinical Features • Recurrent unilateral lower abdominal pain (can mimic appendicitis) • Can last up to 3 days • • Pain occurs during midcycle in individuals with regular menses. Dull and achy pain which can become cramp-like • Physical examination: lower abdominal pain on palpation, enlarged adnexa Diagnostics • Pelvic ultrasound shows simple follicular cyst and small amount of intraperitoneal fluid Differential Diagnosis • Appendicitis, pelvic inflammatory disease, premenstrual syndrome Treatment • Reassurance; NSAIDs Ovarian Cysts Etiology • Fluid-filled sacs within the ovary, common types are functional follicular cysts, corpus luteum cysts, and theca lutein cysts, which all develop as part of the menstrual cycle and are usually harmless and resolve on their own. Overview • Functional ovarian cysts: result from a disruption in the development of follicles or the corpus luteum and often resolve on their own. o Follicular cyst of the ovary (most common ovarian mass in young women): develops when a Graafian follicle does not rupture and release the egg (ovulation) but continues to grow à eventually develops into a large cyst (∼ 7 cm) lined with granulosa cells; associated with hyperestrogenism and endometrial hyperplasia o Corpus luteum cyst: enlargement and buildup of fluid in the corpus luteum after failed regression following the release of an ovum, produces progesterone, which may delay menses o Theca lutein cysts: often multiple cysts that typically develop bilaterally; result from exaggerated stimulation of the theca interna cells of the ovarian follicles due to excessive amounts of circulating gonadotropins such as βhCG; strongly associated with gestational trophoblastic disease and multiple gestations and usually resolve once β-hCG levels have normalized • Nonfunctional ovarian cysts: chocolate cysts, dermoid cysts, cystadenoma, malignant cysts (form of ovarian cancer) Clinical Features • Usually asymptomatic (incidental finding) • Can depend on type • • Adnexal mass that is sometimes palpable Possibly signs of the underlying cause, such as menorrhagia in endometriosis • • Hirsutism, acne, and infertility in polycystic ovary syndrome Can cause lower abdominal pain and lead to complications 28 NPLEX II – REPRODUCTIVE SYSTEM Diagnostics • Pelvic ultrasound: simple cysts will have smooth lining on all sides o Single: e.g., follicular cyst of the ovary, corpus luteum cyst o Multiple: e.g., polycystic ovary syndrome, multilocular theca lutein cysts Treatment • Functional cysts: watchful waiting with repeat ultrasound • Complications, large cysts, persistent painful cysts consider surgery Complications • Ovarian torsion, ruptured ovarian cyst 6 | Cervical Disorders Cervical Dysplasia Etiology • Precursor lesion characterized by epithelial dysplasia that begins at the basal layer of the squamocolumnar junction and extends outward • May progress to invasive carcinoma if left untreated Classification • CIN I: mild dysplasia, involves ∼ ⅓ of the basal epithelium, koilocytes may be present (epithelial cells with perinuclear halos - pathognomonic for HPV infection) • CIN II: moderate dysplasia • CIN III: severe, irreversible dysplasia or carcinoma in situ Clinical Features • Usually asymptomatic Diagnostics • Cervical biopsy Treatment • Repeat PAP • Excision via LEEP or ablation via cryotherapy Monitoring & Follow Up • PAP should be repeated every 12 months until normal result is obtained Complications • Can progress to cervical cancer Nabothian Cysts Etiology • A benign cyst that can form on the surface of the cervix when squamous epithelium grows over glandular columnar epithelium (retention cysts that form in the transformation zone) Clinical Features • Typically asymptomatic • May cause pain or feeling of vaginal fullness 29 NPLEX II – REPRODUCTIVE SYSTEM Diagnostics • Colposcopy Treatment • Ablation with electrocautery 7 | Vulvar Disorders Lichen Sclerosus Epidemiology • Sex: most commonly affects (perimenopausal and postmenopausal) women • Mean age of onset: prepubertal girls Etiology • Unknown • Factors such as genetic predisposition, autoimmunity, hormonal changes are thought to play a role Clinical Features • Papules and plaques that are white, polygonal, well-demarcated, and potentially surrounded by a red inflammatory halo • Dominant symptom: severe pruritus • Most commonly affects the anogenital area • • Women: figure-eight appearance involving the vulva and perianal area, may be associated with dyspareunia and dysuria Men: lesions on the glans penis potentially associated with phimosis and dysuria • • Both: anal lesions may be associated with anal fissure and/or painful defecation Advanced disease: ulceration, hemorrhage, lichenification, skin thinning/fragility, and erosive scarring Diagnostics • Punch biopsy is recommended to confirm diagnosis and rules out squamous cell carcinoma, shows epidermal atrophy with hyperkeratosis and/or dermal fibrosis and sclerosis Differential Diagnosis • Vaginal infections, lichen planus, atrophic vaginitis, psoriasis, chronic cutaneous lupus erythematosus, lichen simplex chronicus, pityriasis rosea, tinea, candidiasis Treatment • First-line: topical steroids (clobetasol, sometimes betamethasone) • Second-line: topical calcineurin inhibitors (e.g., tacrolimus) • If necessary, surgical excision Complications • Benign condition • Increased risk of squamous cell carcinomas, e.g., vulvar carcinoma Vulvodynia Etiology • A condition of chronic vulvar pain (e.g., persistent burning or soreness) without a clearly identifiable underlying cause. May be associated with nerve injury or irritation. • Vulvodynia is an idiopathic, non cyclic vulvar pain. 30 NPLEX II – REPRODUCTIVE SYSTEM Clinical Features • Dyspareunia • • Diagnostics • Clinical exam Itching Stinging • Vulvar pain during intercourse Differential Diagnosis • Vestibulitis, candidiasis, lichen planus, vulvar carcinoma Treatment • Symptomatic relief (sexual lubricant, avoid irritants) Complications • Impaired social and occupational functioning 8 | Menstrual Disorders Amenorrhea Definitions • Primary amenorrhea: the absence of menarche at 15 years of age despite normal development of secondary sexual characteristics, or absence of menses at 13 years of age in female individuals with no secondary sexual characteristics • Secondary amenorrhea: the absence of menses for more than 3 months in individuals with previously regular cycles, or 6 months in individuals with previously irregular cycles Etiology • Primary amenorrhea: constitutional growth delay, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, anatomic anomalies, receptor and enzyme abnormalities • Secondary amenorrhea: pregnancy, medications (antipsychotics, ovarian disorders, hypothyroidism, hyperthyroidism, hyperprolactinemia, Sheehan syndrome, Cushing syndrome, adrenal insufficiency, obesity, hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, functional hypothalamic amenorrhea Clinical Features • No menses by 14 years of age • No menses for > 6 months or 3 cycles after documented menarche Diagnostics • Pregnancy test • Hormone pane: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Progesterone challenge: withdrawal bleed indicates anovulation, no withdrawal bleed indicates uterine or vaginal defect • Imaging: transvaginal or transabdominal ultrasound Differential Diagnosis • Functional (pregnancy, prolonged/ intense exercise, excessive dieting) • Endocrine abnormalities (hypo- or hyperthyroidism, hypothalamic dysfunction, prolactinoma) • Ovarian dysfunction (menopause, premature ovarian failure, polycystic ovarian syndrome, gonadal dysgenesis) • Structural defect (atrophy, imperforate hymen, mullerian agenesis) Treatment • Treat underlying cause • Herbs: Angelica sinensis, chamaelirium luteum, caulophyllum thalictroides, verbena officinalis, vitex agnus-castus 31 NPLEX II – REPRODUCTIVE SYSTEM Complications • Infertility Dysmenorrhea Epidemiology • Prevalence up to 90% (most common gynecologic condition) • Manifests during adolescence (typically within three years of menarche) Etiology • The etiology of primary dysmenorrhea is not completely understood. • Associated with some risk factors (e.g., early menarche, nulliparity, smoking, obesity, positive family history) Pathophysiology • Increased endometrial prostaglandin (PGF2 alpha) production leads to vasoconstriction/ischemia and stronger, sustained uterine contractions (to prevent blood loss). Clinical Features • Colicky pain in the abdomen, radiating to the lower back, labia, and inner thighs • • Pain beginning hours before onset of bleeding and persisting for hours or days Fatigue • • • Nausea and vomiting Altered bowel habits Headaches Diagnostics • Pregnancy test (rule out) • Hormone panel: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Progesterone challenge: withdrawal bleed indicates anovulation, no withdrawal bleed indicates uterine or vaginal defect • Imaging: transvaginal or transabdominal ultrasound Differential Diagnosis • Endometriosis, pelvic inflammatory disease, hemorrhagic corpus luteum, ectopic pregnancy, ovarian neoplasm Treatment • Prostaglandin synthetase inhibitors • Oral contraceptives pills to suppress ovulation and reduce menstrual flow • Herbs: Angelica sinensis, Chamaelirium luteum, Caulophyllum thalictroides, Cimicifuga racemosa, Dioscorea villosa, Mitchella repens, Pulsatilla vulgaris, Viburnum opulus Complications • Impaired social and occupational functioning Menorrhagia Etiology • A condition of abnormally high flow of bleeding (> 80 mL of bleeding volume) or prolonged duration of bleeding (> 8 days of menstruation) during menstrual periods. • Seen in conditions including endometriosis, endometrial hyperplasia, and endometrial cancer. • Associated with obesity, anovulation, hormonal disturbances (estrogen dominance, PCOS, prolonged progestin or OCP administration), ovarian tumor, endometrial growths, IUD and coagulation disorders. Clinical Features • Regular cycle with prolonged bleeding (>7 days) or excessive amount 32 NPLEX II – REPRODUCTIVE SYSTEM Diagnostics • Pregnancy test • CBC • Coagulation studies: INR, PT, PTT • Hormone panel: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Imaging: transvaginal or transabdominal ultrasound Differential Diagnosis • Endometrial pathology (endometritis, endometrial polyps or growths, endometrial hyperplasia or carcinoma), fibroids, uterine polyps, adenomyosis, endocrine imbalance (thyroid dysfunction, PCOS, estrogen producing tumor), coagulation disorders, pelvic inflammatory disease, copper IUD Treatment • Herbs: Achillea millefolium, Capsella bursa-pastoris, Chamaelirium luteum, Caulophyllum thalictroides, Cinnamomum glabra, Mitchella repens Complications • Anemia Metrorrhagia Etiology • Menstrual bleeding at inappropriate times in cycle, occurrence of abnormal bleeding between menstrual periods. • Common causes include ovarian insufficiency, endometrial cancer or hyperplasia, cervical cancer, and oral contraceptive use. Clinical Features • Irregular cycle • Spotting • Full mental bleeding in middle of cycle Diagnostics • Pregnancy test • Hormone pane: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Imaging: transvaginal or transabdominal ultrasound Differential Diagnosis • Benign spotting, pregnancy (implantation bleeding), endometritis, endometriosis, endometrial polyps or growths, endometrial hyperplasia or carcinoma, cervicitis, cervical dysplasia), ovarian cysts, vaginitis, fibroids, uterine polyps, adenomyosis, endocrine imbalance (thyroid dysfunction, PCOS, estrogen producing tumor), pelvic inflammatory disease, newly initiated IUD or OCP use, trauma, foreign objects Treatment • Treat underlying cause • Herbs: Achillea millefolium, Capsella bursa-pastoris, Cinnamomum zeylanicum Complications • Infertility 33 NPLEX II – REPRODUCTIVE SYSTEM Oligomenorrhea Etiology • Infrequent menstruation: cycles > 38 days • Associated with pregnancy (including ectopic pregnancy), PCOS, insufficient caloric intake (e.g., due to anorexia nervosa), hyperthyroidism, perimenopause Clinical Features • Decreased or abnormal menstrual flow Diagnostics • Pregnancy test • Hormone panel: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Progesterone challenge: withdrawal bleed indicates anovulation, no withdrawal bleed indicates uterine or vaginal defect • Imaging: transvaginal or transabdominal ultrasound Differential Diagnosis • Pregnancy, stress, weight loss, thyroid dysfunction, PCOS, Cushing’s syndrome, hyperprolactinemia, antipsychotics, narcotics, anti-hypertensives Treatment • Treat underlying cause • Herbs: Verbena officinalis, Vitex angus-castus Complications • Infertility Premenstrual Syndrome Epidemiology • Occurs in up to 12% of female individuals • Age of onset: 20–30 years of age Etiology • Thought to be a CNS- mediated neurotransmitter interaction with sex steroids (progestone, estrogen and testosterone) causing serotonergic dysregulation. Clinical Features • Affective symptoms: depression, anger, irritability, anxiety, social withdrawal • Somatic symptoms: breast tenderness, abdominal bloating, headache or migraine • Symptom onset – 5 days before menses and abating within 4 days of menses onset Diagnostics • Diagnosis is based on history and self-assessment (e.g., using a PMS diary) • Pre-existing endocrine and psychiatric disorders should be ruled out • Hormone pane: LH, FSH, prolactin, TSH, DHEA, testosterone, estradiol, androstenedione • Imaging Differential Diagnosis • Hypothyroidism, perimenopause, major mood or anxiety disorders 34 NPLEX II – REPRODUCTIVE SYSTEM Treatment • Analgesics (NSAIDs) • Spironolactone (for fluid retention) • SSRI antidepressants • Dietary: avoid sodium, simple sugars, caffeine, alcohol • Herbs: evening primrose oil, Black cohosh, St. John’s wart, Kava kava, Ginkgo biloba Complications • Impaired social and occupational functioning 9 | Female Fertility Disorders Epidemiology • Risk of infertility increases with age Etiology • Ovulatory disorders such as hypogonadotropic hypogonadal anovulation (i.e., hypothalamic amenorrhea), normogonadotropic normoestrogenic anovulation (i.e., polycystic ovarian syndrome (PCOS)), hypergonadotropic hypoestrogenic anovulation (i.e., premature ovarian failure), and hyperprolactinemic anovulation (i.e., pituitary adenoma) • Endometriosis • Pelvic adhesions and tubal blockages such as pelvic inflammatory disease (PID). • Other tubal/uterine abnormalities such as space-occupying lesions or reduced endometrial receptivity (i.e., fibroids, congenital uterine abnormalities, uterine septums) • Hyperprolactinemia Clinical Features • Failing to achieve pregnancy within 12 months of unprotected intercourse Diagnostics • Medical history: duration of infertility, obstetrical history, menstrual history, medical, surgical, and gynecological history to include a history of sexually transmitted infections, sexual history to include coital frequency and timing, male partner (erection and ejaculation), social and lifestyle history (cigarettes, alcohol, and illicit drug use, exercise, and diet, occupation), family history, screening for genetic issues, history of venous thrombotic events, recurrent pregnancy loss, and infertility • Physical exam: vital signs and BMI, thyroid evaluation, breast exam for galactorrhea, signs of androgen excess (dermatological and external genitalia exam), appearance of abnormal vaginal or cervical anatomy, pelvic masses or tenderness, uterine enlargement or irregularity, transvaginal ultrasonography is often done at the bedside as part of the initial physical exam • Semen analysis from male partner • Assessment of ovarian function and reserve (menstrual cycle history, LH tests, progesterone, AMH) • Assessment of the uterine cavity (hysteroscopy) • Assessment of the fallopian tubes (laproscopy) • Endocrinological serum studies (prolactin, TSH) Treatment • IUI or IVF • Lifestyle changes: smoking cessation, reducing alcohol intake, increased exercise, weight loss, stress reduction, avoidance of toxins 35