Back to Basics: Gynecology

1. Back to Basics:Gynecology Dr. Jessica Dy Assistant Professor Department of Obstetrics and Gynecology University of Ottawa

2. Normal Menstruation 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 Overview

3. Female Sexual Development

4. 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?

5. 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

6. 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

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

8. 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

9. Tanner Staging

10. 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

11. 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

12. 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

13. 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)

14. 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

15. 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

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

17. 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

18. Delayed Puberty • Anatomic genital abnormalities • Androgen Insensitivity Syndrome • Central Cause (low FSH) • Gonadal Disorders (high FSH)

19. The Menstrual Cycle …and other menstrual abnormalities

20. Normal Menstrual Cycle

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

22. Amenorrhea Primary Amenorrhea • No menses by age 13 in theabsence 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 or • > 6 months of amenorrhea

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

24. Amenorrhea - Etiology 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

25. 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

26. 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

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

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

29. Premature ovarian failure may be due to any of the following except: • Turner’s syndrome • Autoimmune dysfunction • Hyperandrogenism • Radiation exposure

30. 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

31. 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

32. 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

33. Approach to Amenorrhea yes Stop investigating no E+P challenge no bleed *Need to do Karyotype

34. Polycystic Ovarian Syndrome (PCOS)

35. 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

36. PCOS - pathophysiology insulin ↑estrogen ↓FSH + ↑LH anovulation ↑peripheral estrogen ↑androgens from ovary oligomenorrhea obesity HIRSUTISM INFERTILITY

37. PCOS • Clinical features: • 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

38. 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

39. Treatment of PCOS Cycle Control • Weight loss: diet and exercise • Cyclic progesteroneor 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

40. 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)

41. Abnormal Uterine Bleeding

42. 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

43. 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

44. 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 Causes of Abnormal Uterine Bleeding

45. 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

46. 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

47. Approach to AUB

48. Abnormal Bleeding Investigations:

49. 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

50. Acute DUB Treatment • 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