Back to Basics: Gynecology Dr. Jessica Dy Assistant Professor Department of Obstetrics and Gynecology University of Ottawa March 29, 2010

Overview Normal Menstruation Menstrual Abnormalities Contraception Sexual development Menstrual cycle Menstrual Abnormalities Amenorrhea Abnormal uterine bleeding PCO Menopause Contraception Infertility Pelvic Pain Dysmenorrhea Endometriosis Pelvic Mass Ectopic pregnancy Pap smears Vaginal/pelvic infections

Female Sexual Development

A mother is concerned that her 12 yo daughter has not had her period yet (the other girls in her daughter’s class have already started their period). She thinks her daughter hasn’t shown signs of puberty yet. Knowing the usual first sign of the onset of puberty, you should ask which of the following questions? Has her daughter had any acne? Has her daughter started to develop breasts? Does her daughter have any axillary or pubic hair? Has her daughter started her growth spurt? Has her daughter had any vaginal spotting?

The usual events in normal pubertal development from first to last are: Peak growth, pubic hair, breast budding, menarche Breast budding, pubic hair, peak growth, menarche Breast budding, menarche, pubic hair, peak growth Pubic hair, breast budding, menarche, peak growth B- although accelerated growth is before breast Breast budding usually first recognized pubertal change Menarche usually occurs 2-3 yrs after onset of breast enlargement

Secondary Sexual Characteristics “Baby Has Gone Mad!” Breast Development (Thelarche) 10.5 yo Hair Development (Pubarche) 11.0 yo Growth (peak height velocity) 11.4 yo Menstruation (Menarche) 12.8 yo

Puberty Occurs between 8-13 years old in girls Decreased sensitivity to inhibitory effects of low levels of sex steroids Maturation of HPG axis: Hypothalamus (GnRH) Pituitary (FSH/LH) Gonads (Estradiol) Adrenals (Testosterone) 9-14 in boys

Hypothalamic-Pituitary-Ovarian Axis Hypothalamus GnRH Pituitary FSH, LH Ovary Estradiol Breast/Uterus/Vagina

Female Sexual Development In infancy and pre-puberty, FSH and LH levels are high or low ? Prior to onset of puberty, FSH and LH levels increase or decrease? This stimulates ovaries to produce In infancy and prepuberty – GnRH (gonadotropin releasing hormones) – (FSH and LH) levels are low Prior to onset of puberty: FSH and LH levels start to increase – stimulates gonads to produce sex steroids Estradiol levels increase – breast development occurs Soon enough estrogen available to initiate endometrial growth and menses (usually 2 years after breast budding) Menarche usually follows peak height velocity Adrenarche is a biologically unrelated event, increase in adrenal androgens – leads to pubic and axillary hair development temporally related to other pubertal changes Growth spurt is superimposed on pubertal process & begins prior to thelarche

Female Sexual Development In General: Low levels of FSH and LH found in infants and prepuberty Prior to onset of puberty: FSH and LH levels  Estradiol levels and breast development occurs Eventually sufficient estrogen available to initiate endometrial growth and menses Menarche usually 2 years following breast budding Adrenarche (pubarche) biologically unrelated event Temporally related to other pubertal changes Precedes gonadarche by 2-4 years Breast, hair, growth, menarche Menarche usually follows peak height velocity, - menarche is first menstrual period - usually anovulatory, regular ovulation occurs 1 year later Adrenarche – secretion of adrenal androgens, responsible for growth of axillary and pubic hair

Tanner Staging

Abnormal Sexual Maturation Accelerated Maturation Precocious puberty Dev’t of 2o sexual characteristics < 8 years Delayed Maturation Absence of thelarche by 13 years Absence of menarche by 15 years Onset of sexual maturation at any age 2.5SD earlier than the normal average age for that population

A 9 year old girl presents for evaluation of regular vaginal bleeding A 9 year old girl presents for evaluation of regular vaginal bleeding. History reveals thelarche at age 7 and adrenarche at age 8. Which of the following is the most common cause of this condition in girls? Idiopathic Gonadal tumors McCune-Albright syndrome Hypothyroidism CNS tumors

Precocious Puberty Isosexual: Heterosexual: puberty occurs in direction of expected body phenotype Estrogen mediated Heterosexual: Puberty occurs in direction opposite of expected body phenotype Mediated by androgens virilization

Precocious Puberty True (or Central) (GnRH dependent) Idiopathic (74%) CNS lesions (e.g., infections, tumors) Pseudo (or Peripheral) (GnRH Independent) Ovarian (e.g., granulosa cell tumor) McCune-Albright syndrome Adrenal Hypothyroidism Idiopathic (or constitutional) - Early activation of hypothalamic-pituitary-ovarian axis, seen more frequently in girls than boys CNS lesions – hamartoma, neurofibromas, gliomas Pseudo precocious – steroids produced for other non-central reasons, independent of pituitary gonadotropin release McCune-Albright syndrome – autonomous ovarian follicle estrogen production Triad of polyostotic fibrous dysplasia (cystic bony lesions & fractures), café au lait spots, autonomous endocrinopathy (most common GnRH hypersecretion)

Precocious Puberty: Investigations Initial: Height and weight Estradiol levels Androgens: DHEAS, testosterone FSH, LH, TSH levels Bone age Secondary: Imaging of pituitary/sella Ultrasound ovaries, uterus, adrenals Bone scan (McCune-Albright)

Precocious Puberty: Treatment Aimed at underlying process: Tumor: resection, radiation, chemo Idiopathic: GnRH agonist therapy suppresses GnRH when therapy stopped, appropriate chronologic changes resume McCune-Albright syndrome: Medroxyprogesterone acetate Aromatase inhibitors Longterm GNRH agonist, downregulation of GnRH receptors, stops pulsatile GnRH Continue until bone age matches chronologic age, or age 12

Abnormal Sexual Maturation Accelerated Maturation Precocious puberty Dev’t of 2o sexual characteristics < 8 years Delayed Maturation Absence of thelarche by 13 years Absence of menarche by 15 years

The most common cause of delayed puberty is: Turner’s syndrome Craniopharyngioma Constitutional delay Anorexia nervosa Primary hypothyroidism C -

Delayed Puberty Delayed Menarche + 2o Sexual Dev’t Anatomic genital abnormalities Androgen insensitivity syndromes (complete forms) Delayed Puberty + Inadequate/Absent 2o Sexual Dev’t Hypothalamic-pituitary dysfunction (low FSH) Reversible: Constitutional delay, weight loss due to extreme dieting, protein deficiency, fat loss without muscle loss, drug abuse Irreversible: Kallmann's syndrome, pituitary destruction Gonadal failure (high FSH) Abnormal chromosomal complement (eg, Turner's syndrome) Normal chromosomal complement: chemotherapy, irradiation, infection, infiltrative or autoimmune disease, resistant ovary syndrome

Delayed Puberty Anatomic genital abnormalities Androgen Insensitivity Syndrome Central Cause (low FSH) Gonadal Disorders (high FSH) Each one can be congenital or acquired usually less than 13 yo, Inadequate or Absent 2o Sexual Dev’t reversible HP dysfunction – constitutional delay, anorexia, weight loss, extreme stress irreversible HP dysfunction – Kallmann’s syndrome (hypogonadotropic hypogonadism + anosmia) Gonadal failure – most common is Turner’s syndrome, gonadal dysgenesis 3&4, Usually primary amenorrhea (and normal secondary sex characteristics), in mid teens

…and other menstrual abnormalities The Menstrual Cycle …and other menstrual abnormalities

Normal Menstrual Cycle Follicular phase and secretory phase Proliferative/follicular – begins day 1 of menses, until ovulation, variable length Rise in FSH recruits ovarian follicular growth, single dominant follicle ovulates Rise in estrogen from the granulosa cells of enlarging dominant follicle – proliferation of endometrium Estrogen peak causes LH surge, ovulation occurs 38-48 hours after LH surge Secretory phase – ovulation to menses Menses occurs 14 days after ovulation (fixed) Corpus luteum produces progesterone and estrogen Progesterone – rise in basal body temperature by 0.5 to 1, prepares endometrium for embryo implantation If no pregnancy, hormone levels decrease, withdrawal of E and P causes constriction of spiral arteries, ischemia, endometrial shedding

Normal Menstrual Cycle Follicular Phase Proliferative Phase Granulosa Cells (dominant follicle) Estrogen Luteal Phase Secretory Phase Corpus Luteum Progesterone

Amenorrhea Primary Amenorrhea Secondary Amenorrhea No menses by age 13 in the absence of development of secondary sexual characteristics or No menses by age 15 regardless of presence of normal growth and development Secondary Amenorrhea No menses for a length of time equivalent to a total of at least 3 of the previous cycle intervals > 6 months of amenorrhea Old notes say age 14 and 16. Traditionally, investigations are initiated at age16, but secular trends toward earlier menarche, evaluation should begin by age 15 (97% of girls should have experienced menarche

Hypothalamic-Pituitary-Ovarian Axis Hypothalamus Pituitary Ovary Uterus/vagina

Amenorrhea: Etiology Pregnancy – always rule out! Hypothalamic-pituitary-gonadal axis anorexia nervosa, stress, tumor End organ (failure, abnormality, absence) genetic, idiopathic, menopause, radiation, chemotherapy Outflow tract defects Septum, Asherman’s syndrome Endocrine disorders Prolactin, PCOS, Thyroid Other Drugs: metoclopramide, neuroleptics, danazol

Amenorrhea - Etiology PREGNANCY Hypothalamus Pituitary Ovary ALWAYS NEED TO RULE OUT!! PREGNANCY Extreme Stress, Anorexia nervosa, Tumors, Infection, Congenital (Kallman’s syndrome) Hypothalamus (35%) Prolactin adenomas, 1o hypopituitarism, Sheehan syndrome, (Thyroid) Pituitary (20%) Congenital, Premature Ovarian Failure, Anovulation (PCO, tumors) Ovary (20%) Congenital Absence, Imperforate hymen, Vaginal septum, Asherman’s syndrome Uterus/vagina (5%) Drugs (Metoclopramide, neuroleptics) Others

Amenorrhea - Hypothalamic Extreme stress/systemic illness/nutritional deprivation Anorexia Nervosa Calorie restriction +/- exercise induced Loss of pulsatile GnRH secretion Critical body fat threshold Hypothalamic tumor, infiltrative disorder Congenital GnRH deficiency Kallmann’s syndrome

Amenorrhea - Pituitary Pituitary Adenomas: Non-functioning – most common (30-40% of all pituitary lesions) Prolactinoma Growth Hormone secreting - Acromegaly ACTH secreting - Cushing’s Disease Primary Hypopituitarism Sheehan syndrome Postpartum hemorrhage & ischemic necrosis of anterior pituitary (portal system) Failure of lactation

Amenorrhea – Pituitary Lesions Any mass lesion may cause stalk compression ↓ dopamine suppression ↑ prolactin levels ↓ GnRH secretion ↓ FSH/LH levels amenorrhea

Amenorrhea – Pituitary Lesions  levels of prolactin cause  secretion of GnRH from hypothalamus  FSH/LH = amenorrhea Any mass lesion may cause stalk compression  dopamine suppression with  prolactin Infiltrative: sarcoidosis, tuberculosis, lymphocytic hypophysitis Tumour: teratomas, craniopharyngioma

Amenorrhea - Ovary Anovulatory: PCOS Ovarian failure Premature exhaustion of follicles “menopause” occurs < 40 years Genetic, idiopathic, surgical, radiation, chemotherapy, immunological

Premature ovarian failure may be due to any of the following except: Turner’s syndrome Autoimmune dysfunction Hyperandrogenism Radiation exposure C – Hyperandrogenism usually occurs with PCOS, causes anovulation, but not atresia of follicles

Ovarian Abnormal Development Gonadal Dysgenesis Pure gonadal dysgenesis : 46 XX Turner’s Syndrome: 45 XO, +/- mosiacisms Swyer’s syndrome: 46 XY Androgen insensitivity I (testicular feminization) Absent receptor for testosterone 46 XY, development of female habitus, breast development, diminished pubic/axillary hair, absent uterus, blind vagina, gonads are testes Androgen insensitivity II 5a-reductase enzyme deficiency (T → DHT) 46 XY, born with female external genitalia, but male pubertal development Turners: short stature, neck, shield chest, low set ears, congenital heart defects (coarctation of aorta) 45 XO – may present as primary, mosaic, may be secondary Accelerated atresia of ovarian follicles Swyer’s syndrome – no testosterone, default female (infantile) phenotype, usually no secondary sexual dev’t Testicular feminization – live as normal females, with infertility, peripheral conversion of testosterone to estrogen DHT needed in fetal development of male external genitalia, closure of cloaca, phallic urethra, formation of prostate

Amenorrhea – Uterus/Vagina Blockage (Mullerian abnormalities) transverse vaginal septum imperforate hymen non-communicating cavities Cervical stenosis Congenital mullerian agenesis (MRKH syndrome) Endometrial Failure (Asherman’s syndrome) 2o vigorous D&C, usually postpartum ++ adhesions in uterine cavity MRKH –Mayer Rokitansky-Kuster-hauser syndrome

Amenorrhea - Endocrine Hyperprolactinoma Hyper/hypothyroidism Hyperandrogenism: e.g. PCOS, ovarian/adrenal tumor, testosterone injection Cushing’s disease

Assessment of estrogen status The initial work-up for a patient with 2o sexual characteristics and amenorrhea include all of the following except: Pregnancy test Pelvic ultrasound Prolactin level Thyrotropin level Assessment of estrogen status Pregnancy always need to be ruled out. Need to assess prolactin, TSH, and estrogen level. With sexual dev’t, there is evidence of some estrogen production at some point, but current E status need to be confirmed eitherThrough progesterone withdrawal test or Estradiol levels. A pelvic ultrasound should be considered if anatomic defect is suspected, but not necessarily as initial work-up

Approach to Amenorrhea yes Stop investigating no E+P challenge History: menstrual history (LMP), sexual activity, secondary sexual characteristics dev’t, CNS symptoms (h/a, visual changes) Exercise, dieting, psychiatric history Thyroid symptoms (hypo or hyper) Symptoms of estrogen deficiency, of virilization (hirsutism, voice changes) Family history or delayed/absent puberty Hx of chemo/radiation Physical Exam: tanner staging Height, weight Palpate thyroid, assess hair distribution Examinations of external genitalia, vagina, bimanual exam no bleed *Need to do Karyotype

Polycystic Ovarian Syndrome (PCOS)

PCOS Syndrome resulting from chronic anovulation and/or chronic ovarian androgenism Can be associated with  insulin levels Diagnosis is made clinically +/- biochemical support Wide spectrum seen in clinical practice

PCOS - pathophysiology insulin ↑estrogen ↓FSH + ↑LH anovulation ↑peripheral estrogen ↑androgens from ovary oligomenorrhea HAIR-AN syndrome – hirsutism, anovulation/amenorrhea/infertility, insulin resistance, acanthosis nigricans (darkening of skin folds in intertriginous zones) obesity HIRSUTISM INFERTILITY

PCOS Clinical features: Biochemistry: Ultrasound: Average age 15-35 years Hirsutism, anovulation/amenorrhea, infertility, insulin resistance, obesity, acanthosis nigricans (HAIR-AN) Biochemistry:  testosterone and DHEAS, LH:FSH ratio > 2:1 Fasting glucose:insulin ratio < 4.5 => insulin resistance Ultrasound: multiple follicles peripherally arranged (“string of pearls”) Diagnosis (need 2 out of 3 to make Dx): Oligomenorrhea/irregular menses Clinical or lab evidence of hyperandrogenism Polycystic ovaries on US US string of pearls is non-specific, may also be seen in normal cycling women and if on OCP

Clinical Significance of PCOS Infertility Menstrual bleeding problems Oligo/amenorrhea & DUB Androgen effects: hirsutism, acne and alopecia  risk of endometrial cancer  risk of CAD  risk of type 2 diabetes if insulin resistant

Treatment of PCOS Cycle Control Infertility Weight loss: diet and exercise Cyclic progesterone or OCP to prevent endometrial hyperplasia/ cancer Metformin to  insulin levels & ? reduce risk of progression to type 2 diabetes Infertility Ovulation induction: Clomiphene, FSH, LHRH, etc. Metformin to sensitize to ovulation induction Ovarian drilling *Treatment will depend on patient’s immediate concerns and risk factors

Treatment of PCOS Hirsutism OCP or specifically Diane 35: antiandrogenic Mechanical removal of hair + spironolactone (inhibits steroid receptor) Finasteride (5alpha reductase inhibitor) Flutamide (androgen reuptake inhibitor)

Abnormal Uterine Bleeding

Abnormal Uterine Bleeding Abnormal bleeding at unexpected time (pre-menarche or post-menopausal) Change in pattern of menstrual flow Frequency (interval < 24 days) Duration (> 7 days) Amount (> 80 cc per cycle/clots) Need to rule out organic causes

Abnormal Uterine Bleeding Menorrhagia: Cyclic menstrual bleeding occurring at regular intervals but excessive in amount (>80 cc/cycle) and/or duration (>7 days) Metrorrhagia (intermenstrual bleeding): Uterine bleeding occurring at irregular intervals Polymenorrhea Cycles occurring too frequently, < 24 days Menometrorrhagia: Excessive amount of bleeding at irregular intervals Less frequently encountered problems: Hypomenorrhea – very light flow (usually secondary to IUD, OCP, Asherman’s) Oligomenorrhea – very infrequent bleeding (cycles > 35 days) – spectrum leading to amenorrhea Post-coital bleeding

Causes of Abnormal Uterine Bleeding Ovarian anovulatory cycles Ovarian cancer Uterine polyps, fibroids PID, endometritis IUD exogenous hormones endometrial hyperplasia endometrial cancer Cervical Polyps Infection cervical cancer External Genitalia Vulvovaginitis trauma Vaginal or vulvar cancer Others Coagulation disorders Thyroid disease

Anovulatory, dysfunctional bleeding Coagulopathy Pregnancy A 15 yo female is brought to the ED because of very heavy vaginal bleeding. Her Hb level is 90 g/L. Each of the following diagnoses should be considered except: Anovulatory, dysfunctional bleeding Coagulopathy Pregnancy Endometrial polyps Thyroid dysfunction D – endometrial polyps are rare in adolescents

Anovulatory, dysfunctional bleeding Coagulopathy Pregnancy A 45 yo female is brought to the ED because of very heavy vaginal bleeding. Her Hb level is 90 g/L. What is the least likely diagnosis? Anovulatory, dysfunctional bleeding Coagulopathy Pregnancy Endometrial polyps Thyroid dysfunction D – endometrial polyps are rare in adolescents

Approach to AUB

Abnormal Bleeding Investigations:

Dysfunctional Uterine Bleeding (DUB) Uterine bleeding without any evidence of organic disease i.e., no polyps, malignancy, pregnancy, etc. Diagnosis of exclusion Anovulatory DUB (90%) no ovulation = no progesterone secretion Prolonged, high, unopposed estrogen exposure Fragile endometrium, areas of shedding and re-growth Ovulatory DUB (10%) Luteal phase progesterone unable to maintain endometrium endometrium is exposed to prolonged & unopposed estrogen resulting in estrogen breakthrough bleeding fragile, non-uniform growth of endometrium: areas of shedding and re-growth

Acute DUB Treatment Severe: Mild: OCP Cyclic Medroxy Progesterone Acetate (Provera) Severe: Stabilize patient as required (ABC’s) Premarin IV 25 mg q4-6h or high dose OCP + Add OCP or Provera for maintenance D&C if severely ill or unresponsive to medical therapy

DUB Longterm Treatment Hormonal Manipulation of Cycle Combined Contraceptives Progesterone only Progesterone IUD (Mirena) GnRH analogue Control of Menorrhagia NSAIDS for menorrhagia Anti-fibrinolytic agents (Cyklokapron) Surgical endometrial ablation hysterectomy

Coffee Break !!!

PMS

Premenstrual Syndrome Regular monthly experience of at least one of affective (depression, anger, irritability, anxiety) somatic (breast tenderness, bloating, headaches) Occurs 5 days before onset of menses Relieved within 4 days of menses Interferes with social/economic function Multifactorial: genetics, neurotransmitters, hormones Serotonergic dysregulation Premenstrual Dysphoric Disorder (PMDD) More severe form of PMS Specific diagnostic criteria DSM-IV PM SYMPTOMS Usually precedes menses 1-2 weeks

PMS - Treatment Diet/supplements Avoid Na, sugars, caffeine, alcohol Ca, Mg, Vit E, Vit B6 Psychological support, cognitive behavioral therapy Regular aerobic exercise Medications NSAIDS SSRI (luteal phase) Spironolactone (luteal phase) OCP, progesterone, Danazol, GnRH agonists

MENOPAUSE

The following statements are true except: Menopause occurs at ~51 years of age as a result of a genetically determined depletion of ovarian follicles responsive to gonadotropins. Menopause occurs earlier in smokers. Loss of ovarian function results in absolute estrogen deficiency. Hormone replacement therapy should not be used for prevention of cardiovascular disease or dementia C – there is still peripheral (adrenal) source of estrogen

Menopause Physiologic Artificial average age 50-51 in North America 1-2M oocytes at birth, 500,000 in puberty, only 400-500 ovulate, the rest vanish by atresia Few remaining oocytes not responsive to gonadotropins Artificial Surgery radiation

Menopause Perimenopause Menopause Postmenopause 2-8 years preceding and 1 year after last menses Elevated FSH in follicular phase Irregular menses Menopause Final menstruation Postmenopause 6-12 months of amenorrhea Premature menopause/ovarian failure – spontaneous cessation of menses < 40 yo

Menopause

Clinical Conditions In Menopause Vasomotor symptoms 75% of women > 1 year in 80% of women Major indication for ERT/HRT SSRI, clonidine, gabapentin, black cohosh Urogenital atrophy Lubricants, local estrogen therapy Osteoporosis Ca, Vit D, smoking cessation, exercise Bisphosphonates, ERT/HRT, SERMs (raloxifene) Hot flushes – heat/burning in the face, neck, chest, followed by outbreak of sweating Results from “defect” in central thermoregulatory function Clonidine central alpha agonist

HRT Good Bad relief of vasomotor and GU symptoms Increases BMD, decreases fracture risk Bad Increases VTE, CAD, stroke ? Increased risk of breast cancer, dementia No increased risk of endometrial cancer

CONTRACEPTION

Contraception Permanent Reversible Vasectomy, tubal ligation Barrier methods Hormonal Contraceptives (pill, patch, ring), progesterone only Intrauterine devices Post-coital Abstinence, rhythm, withdrawal, lactation

Barrier Contraception Male condom Protects against STIs Failure rate 10-30% in typical use Female barriers Female condom, diaphragm, cervical cap Need to fit properly, more inconvenient Failure rate higher than male condom Spermicidal preparations 30% failure rate when used alone (typical use)

Combined hormonal contraceptives: Decrease the risk of stroke and VTE Should only be started on the first day of a menstrual period Suppress ovulation mainly through an estrogen dominant effect Is contraindicated in women >35 years old Decrease dysmenorrhea, menorrhagia and acne

Hormonal Contraception Combined Contraceptives Pill, patch, ring Most contain low dose (20-35 mg) ethinyl estradiol + progestin Mechanism of action (mainly from progestin): Ovulatory suppression by FSH/LH inhibition Decidualization of endometrium Thickening of cervical mucous Non-contraceptive benefits Multiple, but mild side effects Does not protect against STI’s Risk of ovarian and endometrial cancer is reduced Less PID, PMS, benign breast disease, acne Less ovarian cysts

Hormonal Contraception Absolute contraindications Pregnancy Undiagnosed vaginal bleeding Thromboembolic disease Estrogen dependent tumors Coronary/cerebrovascular disease Impaired liver function Uncontrolled hypertension Migraines with neurological symptoms Smoker, age >35 Relative contraindication Migraines (non-focal) Controlled hypertension Hyperlipidemia Sickle cell anemia Gallbladder disease SLE

Hormonal Contraception Progestin Only Methods Suitable for lactating women or women with contraindications to combined OCP “Minipill” (Micronor) Higher failure rate Taken daily, no pill free interval Depot-medroxyprogesterone acetate Injectable, q 3 mos Common irregular bleeding to complete amenorrhea Highly effective Return to fertility may take up to 1-2 yrs Risk of osteoporosis

Intrauterine Device (IUD) Device that sits in the uterine cavity Nova-T (copper containing) foreign body reaction in endometrium Mirena (levonorgestrel releasing) decidualization of endometrium + thickening of cervical mucous One time insertion, lasts up to 5 years Very effective, failure rate 1% Reversible

IUD Absolute contraindications Pregnancy Undiagnosed vaginal bleeding Acute or chronic PID Lifestyle risk for PID Allergy to copper Wilson’s disease (for copper) Immunosuppressed individuals Relative contraindication Valvular heart disease Past Hx of PID Past Hx of ectopic pregnancy Abnormalities of the uterine cavity, fibroids Severe dysmenorrhea or menorrhagia (for copper) Cervical stenosis

Contraception Case 27 yo nulligravid student was “celebrating” with her male partner after successfully passing her exams. Immediately after intercourse she noticed that the condom is broken. Her LMP was 12 days ago and she has regular 28 day cycles with molimina. She normally takes Alesse but has stopped taking this about 6 months ago. She paged you at 2 am. She does not want to get pregnant. What would be the appropriate management(s) to offer this couple? (You may chose up to three answers)

Contraception Urgent pregnancy test (serum) Suggest expectant management and wait to see if she misses a period If she still has her Alesse tablets, take 5 of these now, and another 5 in 12 hours Insertion of copper containing IUD 0.75 mg Levonorgestrel po now and again in 12 hours Suggest doing a handstand q hourly x 48 hours to prevent implantation

Emergency Contraception Yuzpe Method within 72 hours of intercourse 2 Ovral tablets q12h x 2 doses (often with Gravol) 6% chance of pregnancy decreases to 2% with Yuzpe ‘Plan B’ 0.75 mg levonorgestrel every 12h x 2 doses (less nausea) similar efficacy to Yuzpe Copper IUD Insertion within 5 days of intercourse 1% failure rate Hormonal methods – delay or inhibit ovulation Yuzpe = 100mcg estradiol + 500-600 mcg levonorgestrel

Contraceptive Efficacy Typical use Perfect use Pearl Index (%preg/y) (%preg/y) Chance 85 85 Withdrawal 19 4 Condom 12 3 Condom + spermicide 5 Female condom 21 5 Diaphragm 18 6 IUD 0.8-2.0 1.5-0.6

Contraceptive Efficacy Method Typical use Perfect use (%preg/y) (%preg/y) OCP ~3 0.1 Nuva-ring ~3 0.1 Ortho Evra ~3 0.1 Depo Provera 0.3 0.3 Norplant 0.3 0.3 Female Sterilization 0.4 0.4 Male Sterilization 0.15 0.1

INFERTILITY

Infertility Definition: one year of ‘frequent’ unprotected intercourse without conception Primary: no prior pregnancies Secondary: previous conception 10-15% of couples in the reproductive age group must investigate both partners

Infertility - Epidemiology Time Required for Conception in Couples Who Will Attain Pregnancy Duration of Exposure % Pregnant 3 months 57% 6 months 72% 12 months 85% 24 months 93% Guttmacher 1956

Preliminary Diagnosis Fertility Requirements 1) Oocyte: regular ovulation, good quality oocytes 2) Normal Female Genital Tract: patent tubes, ‘relatively’ normal uterus, cervix and vagina 3) Sperm: sufficient quantity and quality 4) Implantation: appropriate endometrial/embryo interaction e.g. ‘luteal phase deficiency’, “septa”, ‘polyps’ 5) Immunological Factors: appropriate immunological environment e.g. ‘endometriosis’, ‘antisperm antibodies’, Antiphospholipid Syndrome, ‘Blocking antibodies’

Infertility - Etiology Ovarian Problems (15%) Tubal/Pelvic Pathology (35%) Sperm Problems (35%) Unexplained (10-15%)

Etiology Ovulatory dysfunction (15-20%) Hypothalamic (functional amenorrhea) Pituitary: prolactinoma, hypopituitarism Ovarian PCOS POF Luteal phase defect (poor follicle production, premature corpus luteum failure, failed uterine lining response to progesterone) Systemic diseases (thyroid, Cushing, renal/hepatic failure) Congenital (Turner, gonadal dysgenesis, gonadotropin deficiency)

Infertility: Ovulatory Dysfunction Overall Primary Investigations: Day 3 FSH Day ‘21’ progesterone TSH Prolactin Basal Body Temperature

Etiology Outflow tract abnormality Tubal obstruction (~35%) PID Adhesions (previous surgery, peritonitis, endometriosis) Ligation/occlusion (e.g., previous ectopic) Uterine factors (<5%) Congenital anomalies (DES exposure), bicornuate uterus, uterine septum Intrauterine adhesions (e.g. Asherman’s) Infection (endometritis, pelvic TB) Fibroids/polyps Endometrial ablation Cervical factors (5%) Hostile, or acidic cervical mucous Anti-sperm antibodies

Infertility: Tubal Factor Overall Primary Investigations: Hysterosalpingogram or Sonohysterogram/saline infusion scan or Laparoscopy In early proliferative phase of cycle after cessation of menses for evaluation of structural defects diagnostic and therapeutic (may open tubes)

Hysterosalpingogram (HSG)

Hysterosalpingogram (HSG)

Sonohysterogram with Echovist®

Laparoscopy

Laparoscopy

Etiology Pre testicular Testicular Post testicular (normal FSH,LH,T) 3. Male factor (~40%) Pre testicular Hypothalamic, pituitary (low LH, FSH, T) Testicular Testicular failure (sometimes high FSH, low T) Genetic Acquired Insult (infectious, varicocele) Post testicular (normal FSH,LH,T) Obstruction

Infertility: Sperm/Male Factor Semen analysis WHO Criteria: volume > 2.0 ml concentration > 20 million sperm/ml motility > 50% morphology > 30% normal forms

Semen Variability

Infertility: Sperm/Male Factor Overall Primary Investigations: semen analysis x 2 Other investigations: karyotype TSH, Testosterone, PRL, FSH postcoital (sperm/cervical mucus interaction)

Infertility Investigations Ovarian Function Day 3 FSH Day 21 progesterone TSH, Prolactin Basal Body Temperature Female Genital Tract HSG/SHG/SIS Laparoscopy Male Factor Semen analysis x 2

Infertility - Treatments Approach based on fertility requirements: 1) Oocytes 2) Abnormal Female Genital Tract 3) Sperm use these categories to organize treatment options for each particular couple

Treatment Options Ovarian problems: Tubal factors: Male factors: - Treat any hypothyroidism/hyperprolactinemia If PCOS, weight loss, metformin, ovarian drilling Induce ovulation (clomiphene, letrozole, etc) + IUI/IVF donor oocytes/embryos, adoption Tubal factors: Tuboplasty In-Vitro Fertilization (IVF) Male factors: Artificial Insemination (washed or donor sperm) IVF + ICSI Varicocele repair, surgical repair of obstruction IVF was initially used as a treatment for tubal obstruction where tubal surgery is not possible Now, indication have expanded to include most forms of infertility, and is the treatment of choice for severe tubal disease and severe sperm defects

ICSI Intracytoplasmic Sperm Injection: requires very few moving sperm can combine with testicular sperm retrieval requires IVF (female risks & discomfort)

Pelvic Pain

Pelvic Pain 26 yo G0P0 woman presents to the office with 8 years of constant pelvic pain. She has had 3 previous diagnostic laparoscopies (2 months, 2 years, and 6 years ago). All demonstrated a normal pelvis. She has recently been seen by specialists in General Surgery, GI, Urology, Orthopedics, and Gynecology. All investigations have been normal and no cause for the pain has been found.

Differential Diagnosis Gynecologic - CHRONIC: Endometriosis/adenomyosis dysmenorrhea (cyclic pain) Ovarian cysts Chronic PID adhesions Uterine prolapse Cancer invasive (late) Fibroids Pelvic congestion syndrome ** RULE OUT PREGNANCY!!! Gynecologic - ACUTE: Adnexal: Mittelschmerz ovarian cysts, rupture, torsion Hemorrhage into ovarian cyst or neoplasm Uterine: Degenerating fibroids Torsion of pedunculated fibroid Pyometra/hematometra Infectious Acute PID Endometritis

Differential Diagnosis Non-Gynecologic: Urinary tract: infection, stones, retention interstitial cystitis GI: appendicitis, diverticulitis, obstruction, infarct constipation, hernia, IBD, IBS MSK: nerve entrapment, referred pain, abdominal wall, MS Psychological trauma: Depression, anxiety, somatization ~20% of chronic pelvic pain patients have a history of sexual abuse/assault

Diagnostic laparoscopy for pelvic pain should be performed to: Evaluate women with cyclic pain who respond to NSAIDs or OCP Initially evaluate women with chronic noncyclic pelvic pain Biopsy and treat endometriotic lesions Lyse all adhesions C

Pelvic Pain - Investigations Gynecology related: CBC, bhCG vaginal/cervical cultures pelvic U/S or MRI Laparoscopy GI related: stool cultures abdominal U/S, CT/MRI endoscopy Urologic: urine cultures, urinalysis IVP, U/S, CT Musculoskeletal: xray, CT, MRI Dependent on symptoms and findings at presentation

Endometriosis Abnormal growth of endometrial tissue outside the uterine cavity Pathogenesis is unknown Infertility dysmenorrhea, dyspareunia, dyschezia On pelvic exam: Tender nodules, fixed uterus May also be normal Retrograde menstruation Metaplasia of coelomic epithelium Hematogenous or lymphatic spread Genetics

Which of the following statements are true? Women with endometriosis always have dysmenorrhea or chronic pelvic pain. Minimal or mild endometriosis should never be treated surgically, only medically. The degree of pelvic pain correlates with laparoscopic findings. Medical treatment of endometriosis includes OCP, progestins, GnRH analogues, Danazol. Medical treatment of endometriosis results in long term disease suppression and pain relief after cessation of therapy. A-false B-false C-false D-true E-false

Case 31 y.o. woman complains of sudden onset of RLQ pain. The pain is constant and worse with movements. There is no nausea/vomitting. Bowel movements are normal. Her LMP is 7 weeks ago, and she has been actively trying to get pregnant. Past medical history is positive for PID requiring hospitalization for IV antibiotics for 4 days. Her vitals are stable, and she is afebrile. She is having mild vaginal bleeding (<1pad) that started today. What is your differential diagnosis???

Case What 3 initial investigations would be most appropriate? A) CBC B) pelvic ultrasound (endovaginal and transabdominal) C) flat plate (x-ray) of abdomen D) Quantitative bhCG E) sigmoidoscopy with possible colonoscopy F) IVP with delayed films A,B,D

Ectopic Pregnancy

Ectopic Pregnancy Definition Epidemiology embryo implants outside of the endometrial cavity Epidemiology 1-2% of all pregnancies ~14% if previous ectopic pregnancy ~1/30,000 pregnancies is heterotopic (1 IUP + 1 ectopic) 4th leading cause of maternal mortality

Location of Ectopic Pregnancy

Ectopic Pregnancy

Ectopic Pregnancy

Ectopic Pregnancy Risk Factors Relative Risk Tubal surgery 20 Previous ectopic 10 Previous salpingitis 4 Assisted Reproduction 4 Age < 25 3 Previous pelvic infection 3 Infertility 2.5 Cigarettes 2.5 * ~50% of patients have no risk factors * IUD use does not increase the risk of ectopic pregnancy But with an IUD, if you do get pregnant, 3-4% will be ectopic

Ectopic Pregnancy Clinical Presentation amenorrhea abdominal pain (90%) + rebound (45%) vaginal bleeding bimanual exam: - CMT and adnexal tenderness (usually unilateral) - palpable adnexal mass (50%) ruptured ectopic pregnancy: - acute abdomen with  pain - hypovolemic shock Usually just spotting (vaginal bleeding not from direct blood loss from tubal bleeding - hormonal event from estrogen breakthrough bleeding)

Investigations Hx & Px bHCG quantitative, CBC, blood T&S Pelvic ultrasound an intrauterine pregnancy should be seen if bhCG > 1200-1500, definitely by 2,000 Serial bhCG: - normal doubling time is about 2 days inadequate doubling suggests abnormal pregnancy Laparoscopy: definitive diagnosis

In order to distinguish an IUP from an ectopic pregnancy, the change in bHCG levels over 48 hours is observed. What percentage rise in bHCG represents the lower limit of normal values for viable IUP? 33% 50% 66% 100% 66%

Treatment Medical (Methotrexate): 50 mg/m2 (1/5 chemo dose) serial bhCG weekly f/u 10-15% failure rate, 25% require 2nd dose criteria: - patient clinically stable - <3.5cm unruptured ectopic pregnancy - no FHR - bhCG <5000 - no hepatic/renal/heme disease - compliance and f/u essential Surgical Laparoscopy vs laparotomy Salphingectomy vs salphingotomy Goal: conservative, preservej tube if possible

Tea Break!!!

Pelvic Mass

Differential Diagnosis Adnexal Ovarian cysts/tumors Ectopic pregnancy Tubo-ovarian abscess hydrosalpinx Uterine Pregnancy Fibroids Adenomyosis Endometrial cancer hematometra *And non-gynecologic causes: Pelvic kidney, GI masses, abscess, lymph nodes

A 60 year old woman presents with a pelvic mass A 60 year old woman presents with a pelvic mass. What percentage of ovarian neoplasms in post-menopausal women is malignant 5% 10% 30% 80% Compared to < 10% in premenopausal women.

Ovarian Cysts/Tumors Benign vs. malignant Benign Physiological (follicular cysts, corpus luteal cysts, hemorrhagic cysts) Endometrioma Benign adenomas Germ cell tumors (dermoid cysts)

Ovarian Tumors

Ovarian Tumors

Pelvic Mass 1) History: - weight loss/gain - increase in abdominal girth - fatigue - fevers/chills - abnormal vaginal discharge or bleeding - menstrual history - pregnancy symptoms (amenorrhea, molimina) - pain - bowel/bladder dysfunction - family history of gynecological/bowel cancers

Pelvic Mass 2) Physical Exam: - complete general survey (including nodes) - abdominal exam - pelvic: speculum, bimanual, pelvi-rectal 3) Investigations: - U/S: abdominal and endovaginal - + CT or MRI - pre-op investigations - + pregnancy test

Pelvic relaxation/prolapse

Definitions Cystocele: downward displacement of bladder Uterine Prolapse: descent of the uterus and cervix into vaginal canal towards the vaginal introitus Rectocele: protrusion of rectum into posterior vagina Enterocele: herniation of small bowel into vagina Vaginal Vault Prolapse: descent of vaginal apex into vaginal canal towards introitus after a hysterectomy

Pelvic relaxation

Predisposing Factors age pregnancy and vaginal childbirth menopause (↓ estrogen) changes in pelvic anatomy (surgery) obesity chronic cough chronic constipation connective tissue disorders

Symptoms Pelvic pressure, bulge, heaviness Low back ache Possibly relief with lying down worse symptoms at the end of the day Voiding difficulty, incomplete emptying, UTIs, stress incontinence Constipation (need to reduce the rectocele to have BM) dyspareunia

Treatment Conservative Surgical Pessary (not useful for rectocele) Kegels weight loss stool softeners HRT smoking cessation Surgical Vaginal Hysterectomy (for uterine prolapse) Vaginal Repair (anterior, enterocele, and/or posterior repair) Vault suspension Anti-incontinence procedure

Pap Smear Management

Screening Test Sampling of transformation zone (endo/exocervix) Detection of early pre-malignant lesions Multiple classification systems Bethesda vs CIN System

Bethesda vs CIN

2005 Ontario Cervical Screening Guidelines Note: These recommendations do not apply to those women who have had previous abnormal Pap tests. Screening initiated within 3 years of first vaginal sexual activity Done annually until 3 consecutive negative Pap tests Then every 2-3 years Cessation at age 70 if adequate negative screening (3-4 negatives in last 10 years)

PAP Smear Management Possible Results (Squamous) Within Normal Limits Atypical Squamous Cells of Undetermined Significance (ASCUS): may favour reactive or premalignant/malignant process Low Grade Squamous Intraepithelial Lesion (LSIL) High Grade Squamous Intraepithelial Lesion (HSIL) Squamous Cell Carcinoma

PAP Smear Management Possible Results (Glandular cells) Within Normal Limits Atypical Glandular Cells of Undetermined Significance (AGUS): may favour reactive or premalignant/malignant process Adenocarcinoma endocervical, endometrial, extra-uterine, NOS

Decision Making Chart

Decision Making Chart (If > 35yrs or abnormal bleeding) + ECC AIS With endocervical assessment (If > 35yrs or abnormal bleeding) + ECC AIS Cone biopsy

Gynecologic Infections

Case 19 year old G0 woman presents to the ER with lower abdo/pelvic pain for 2 days. She had developed a fever today and a vaginal discharge. She has recently become sexually active, and is not using contraception. A pregnancy test is negative.

Case What is the most likely diagnosis? A) early appendicitis B) chlamydial cervicitis C) disseminated herpes D) PID E) trichomonas vaginitis

Acute Pelvic Inflammatory Disease (PID) Clinical diagnosis implying patient has upper genital tract infection and inflammation Ascending infection to endometrium, tubes, peritoneum Most often an STD: chlamydia, gonorrhea Rarely endogenous vaginal bacteria, TB

PID – Risk factors Age < 30, sexually active Vaginal douching IUD (esp. 1st 10 days post insertion) Invasive gyne procedures: D&C, endometrial biopsy History of previous STI Multiple sexual partners No barrier contraception Contact with infected person

Presentation Spectrum of severity Up to 2/3 asymptomatic, many subtle or mild symptoms Common: Fever > 38.3 lower adbo pain and tenderness (adnexal) - Cervical motion tenderness on bimanual exam abnormal discharge: vaginal, cervical Uncommon: Nausea, vomiting Dysuria irregular vaginal bleeding RUQ pain (Fitz-Hugh-Curtis)

Investigations Bloodwork Speculum exam Ultrasound Laparoscopy BhCG (r/o ectopic), CBC, blood cultures if septic Speculum exam Vaginal swab Cervical cultures for GC and chlamydia Ultrasound May be normal Fluid in cul-de-sac Hydrosalpinx, tubo-ovarian abscess, pelvic abscess Laparoscopy For definitive diagnosis

What are the criteria that would require inpatient treatment of PID?

Treatment - Outpatient ORAL Regimen A: Ofloxacin 400 mg twice daily for 14 days OR Levofloxacin 500 mg once daily for 14 days WITH OR WITHOUT Metronidazole 500 mg twice daily for 14 days

Treatment - Outpatient ORAL Regimen B: Ceftriaxone 250 mg IM in a single dose OR Cefoxitin 2 g IM x 1 and Probenecid 1g PO PLUS Doxycycline 100 mg twice daily for 14 days WITH or WITHOUT Metronidazole 500 mg twice daily for 14 days

Treatment - Inpatient PARENTERAL Regimen A: Cefoxitin 2g OR Cefotetan 2g IV q6h (at least 48 h) PLUS Doxycycline 100mg IV/PO BID x 14 days PARENTERAL Regimen B: Clindamycin 900mg IV q8h (at least 48 h) Gentamicin 2mg/kg loading dose then 1.5mg/kg maintenance dose q8h (at least 48 h)

Treatment - Inpatient Alternative PARENTERAL Regimens: Ofloxacin 400 mg IV q 12 hours OR Levofloxacin 500 mg IV once daily WITH OR WITHOUT Metronidazole 500 mg IV q 8 hours Ampicillin/Sulbactam 3 g IV q 6 hrs PLUS Doxycycline 100 mg orally/IV q 12 hrs If no improvement within 48 h may need to drain abscess Precutaneously Laparoscopically Laparotomy

Chlamydial Cervicitis Etiology: Chlamydia trachomatis Intracelluar parasite Most common bacterial STI in Canada Often associated with N. Gonorrhea Reportable disease Risk Factors: sexually active < 25 y.o. history of previous STI new partner in last 3 months multiple partners no barrier contraception contact with infected person

Presentation Investigations: Asymptomatic (70%) mucopurulent endocervical discharge pelvic pain/discomfort to PID Urethral syndrome: dysuria, frequency, pyuria with no bacteria post coital spotting or intermenstrual bleed Investigations: Cervical cultures Rescreen women 3-4 months after treatment due to high prevalence of repeat infection

Treatment - Chlamydia Doxycycline 100mg PO BID x 7 days OR Azithromycin 1g PO x 1 Alternative treatments: Erythromycin base 500 mg qid for 7 days OR Erythromycin ethylsuccinate 800 mg qid for 7 days OR Ofloxacin 300 mg twice daily for 7 days OR Levofloxacin 500 mg for 7 days * if pregnant Erythromycin, Amoxicillin, Azithromycin **Screen and treat partners

Neisseria Gonorrhea Cervix, urethra, rectum: gram negative intracellular diplococci reportable disease Presentation and Risk Factors: same as chlamydia Investigations: cervical, rectal and throat culture

Gonorrhea - intracellular Gram negative diplococci

Treatment Ceftriaxone 125mg IM x 1 OR Cefixime 400mg PO x 1 OR Ciprofloxacin 500mg PO x 1 OR Ofloxacin 400 mg/Levofloxacin 250 mg AND Treatment for Chlamydia * If pregnant: cephalosporin regimen or 2g spectinomycin IM

Vulvovaginitis Organism Discharge Symptoms Wet Mount Ph Candida(Yeast) White thick -itching KOH <5 -satellite lesions -hyphae -edematous -red Bacterial Vaginosis Grey, thin, - fishy odour - clue cells 5-5.5 (anaerobes, diffuse - worse after KOH (+whiff test) Gardnerella, etc.) intercourse - no irritation/ inflammation Trichomonasis Yellow/green -strawberry -fagellated 5-6.5 (Trichomonas spots protozoa Vaginalis) Physiologic (high E2 states) Clear/white - no irritation/ -normal <4.5 inflammation epithelial cells

Vulvovaginitis Candida Vulvitis

Vulvovaginitis Candida - KOH prep Hyphea

Vulvovaginitis Clue cell - epithelial cell with bacteria clustered peripherally

Vulvovaginitis Trichomonas- strawberry spots

Vulvovaginitis Treatment Candida(Yeast) -clotrimazole, miconazole, terconazole -Diflucan 150 mg PO x 1(resistant cases) -lactobacillus acidophilus Bacterial Vaginosis Metronidazole 500mg PO BID x 7 days (or 2g PO x1) OR Clindamycin 300mg PO BID x 7 days OR topical above creams QHS x 7 days Trichomonas Metronidazole 500mg PO bid x 7days or 2g PO x 1

Vulvar Lesions Condylomata Acuminata (genital warts) human papilloma virus (HPV) strongly associated with cervical/vulvar intraepithelial neoplasia and cancer acetowhite lesions, wart-like projections Not preventable even if using condoms Treatment: podofilox solution or gel x 3 days than repeat x 4 wks Imiquimod (Aldara®) 3x/wk qhs x 16 wks liquid N repeat q1-2 wks TCA weekly laser, electro, excision intralesional interferon

Condylomata Acuminata

Condylomata Acuminata

Vulvar Lesions Molluscum Contagiosum Molluscipox virus mildy contagious nodule with umbilicated centre Treatment Curette TCA, silver nitrate, carbonic acid

Molluscum Contagiosum

Molluscum Contagiosum

Genital Ulcers Organism Description Diagnosis Herpes -prodromal viral culture (HSVII, I(10%)) -small vesicle progresses to shallow, painful, inflamed Syphilis -smooth, raised border dark field micro (Treponema -painless, smooth base -spirochetes pallidum) -VDRL etc. Chancroid -irregular border, deep culture Gram stain (Hemophilus undermined edges, painful -GNB in rows ducreyi) +/- buboe (tender lymphadenopathy)

Genital Herpes

Genital Herpes

Syphilis - Treponema pallidum

Darkfield Microscopy - Treponema pallidum

Genital Ulcers Organism Treatment Herpes 10 acyclovir 400mg PO TID x 7-10d (HSVII, I(10%)) 20 acyclovir 400mg PO TID x 5d daily suppressive: if 6-8 attacks/yr: acyclovir 400mg PO BID Syphilis benzathine penicillin G 2.4 million units IM (all stages) (Treponema -treat partners pallidum) -reportable illness Chancroid -erythromycin 500mg QID x 7 days (Hemophilus OR ceftriaxone 250mg IM x 1 ducreyi) OR azithromycin 1g PO x1 -treat partners

Questions?