SECondary aMENORRHOEA powerpoint presentation

Secondary amenorrhea

1. Seminar on Secondary AmenorrheA

2. A menorrhoea Definition: - A menorrhoea denotes absence of menstruation It’s symptom not a disease

3. AMENORRHEA PRIMARY SECONDARY

4. PRIMARY AMENORRHOEA Absence of menstruation by the age of 13 years when there is no visible development of secondary sexual characteristics. OR Absence of menstruation by the age of 15 years in presence of normal secondary sexual characteristics .

5. SECONDARY AMENORRHOEA Secondary absence of menstruation for six months or more in a women in whom normal menstruation has been established . BEREK $ NOVEK’S GYNECOLOGY

6. AETIOLOGY OF SECONDARY AMENORRHEA

7. 4 compartments • Compartment I Disorders of outflow tract or uterine target organ • Compartment II Disorders of ovary • Compartment III Disorders of the anterior pituitary • Compartment IV Disorders of CNS (hypothalamic) factors

8. 1. UTERINE FACTOR TUBERCULAR ENDOMETRITIS POST RADIATION SYNECHIAE SURGICAL REMOVAL

9. 2. OVARIAN FACTOR POLYCYSTIC OVARIAN SYNDROME PREMATURE OVARIAN FAILURE RESISTANT OVARIAN FAILURE HYPERESTROGENIC STATE GRANULOSA CELL TUMOUR HYPOESTROGENIC STATE PELVIC RADIATION

10. 3. PITUITARY FACTOR ADENOMA CUSHING’S DISEASE ACROMEGALY SHEEHAN SYNDRME SIMMOND’S DISEASE

11. 4.HYPOTHALAMIC FACTOR PSYCHOGENIC SHOCK STRESS ANOREXIA NERVOSA STRENUOUS EXERCISE TRAUMA INFECTION TUMOURS

12. 5. ADRENAL FACTOR ADRENAL HYPERPLASIA CUSHING SYNDROME 6.THYROID FACTORS HYPOTHYROID STATE

13. 7. GENERAL DISEASE MALNUTRITION TUBERCULOSIS DIABETES CHRONIC NEPHRITIS

14. 8. IATROGENIC OCP ANTIHYPERTENSIVE DRUGS reserpine or dopamine antagonist PSYCHOTROPHIC PHENOTHIAZINE DERIVATIVE

15. Secondary Physiologic Pregnancy Lactation Menopause Pathologic With features of androgen excess Polycystic ovarian syndrome Autonomous hyperandrogenism Adrenal or ovarian steroid-producing tumor Ovarian hyperthecosis Late-onset (nonclassic) congenital adrenal hyperplasia Without hyperandrogenism Hypergonadotropic hypogonadism Ovarian failure Hyperprolactinemia Hypothyroidism Other endocrine disease Organic hypogonadotropic hypogonadism Hypothalamic disease Pituitary disease Functional hypogonadotropic hypogonadism Hypothalamic amenorrhea Anatomic abnormalities

16. PATHOLOGICAL PHYSIOLOGICAL SECONDARY AMENORREA

17. Pathologic Without hyperandrogenism With features of androgen excess

18. With features of androgen exce ss Polycystic ovarian syndrome Autonomous hyperandrogenism Adrenal or ovarian steroid-producing tumor Ovarian hyperthecosis Late-onset (nonclassic) congenital adrenal hyperplasia Without hyperandrogenism Hypergonadotropic hypogonadism Ovarian failure Hyperprolactinemia Hypothyroidism Other endocrine disease Organic hypogonadotropic hypogonadism Hypothalamic disease Pituitary disease Functional hypogonadotropic hypogonadism Hypothalamic amenorrhea Anatomic abnormalities

19. Natural Treatment Interventions Overview Make an accurate diagnosis Understand underlying cause Methodical work-up: history / physical examination , our evaluation steps • Management : underlying cause, complications, disease prevention, general body support- organ specific , constitutional, mind/body

20. Investigation of secondary amenorrhoea Exclude pregnancy Estimation – S. TSH , Prolactin X-ray/CT/MRI- Sella tursica Normal TSH normal, PRL Abnormal stella Pituitary adenoma Progesterone challenge test Withdrawal bleeding + Withdrawal bleeding - Pcos Loss of progesterone receptor Diseased endometrium Estrogen - progesterone challenge test No bleeding Uterine synechiae Bleeding occurs Endometrium responsive E2 productoion – low ( <30 pg /dl ) Normal prolactin Abnormal TSH THYROID D/S

21. Estimation of FSH/LH HIGH LOW/ NORMAL FSH > 40 mIU /ml LH<5 mIU /ml - Ovarian failure - Resistant ovarian failure Age <30 yrs karyotype Hypothalamic or pituitary lesion / dysfunction GnRH Dynamic test positive Negative Hypothalamic Pituitary

22. A diagnostic approach to secondary amenorrhea.

23. A menorrhea Evaluation • Menstrual history • Family history • Medication history • Review of systems • Other endocrine system problems • Chronic illness • Anorexia / bulemia • Chaotic/disordered eating; radical diets • Malnutrition • Excessive exercise

24. HISTORY MENTRUAL HISTORY- MODE OF ONSET OF AMENORRHEA –WHETHER SUDDEN OR GRADUAL MEDICAL HISTORY OF - TB , DIABETES , CHRONIC NEPHRITIS, HYPOTHYROID STATE FAMILY HISTORY -PREMATURE MANOPAUSE

25. SUDDEN CHANGE IN ENVIROMENT,STRESS PSYCOGENIC SHOCK, EMOTION, EATING DISORDER SUDDEN CHANGE IN WEIGHT INTAKE OF DRUGS INAPROPRIATE LACTATION

26. PHYSICAL EXAMINATION NUTRITIONAL STATUS EXTREME EMACIATION /OBESITY PRESENCE OF ACNE/ HIRSUTISM DISCHARGE OF MILK

27. ABDOMINAL EXAMINATION SRIAE ASSOCIATED WITH OBESITY-CUSHING DISEASE MASS IN ABDOMEN

28. PELVIC EXAMINATION ENLARGMENT OF CLITORIS ADENEXAL MASS-TUBERCULAR OVARIAN MASS,OVARIAN TUMOUR

29. Amenorrhea Evaluation Overview Tests : TSH, prolactin, pregnancy Progesterone challenge; E/P challenge Later considerations Imaging , FSH , LH

30. Step 1 • Pregnancy test, TSH, prolactin • If elevated TSH- then hypothyroid and treat • If positive pregnancy test- make decisions r.e. pregnancy • If elevated prolactin- determine if tumor : imaging (x-ray of sella turcica; MRI) • If all are normal- progestational challange test

31. Purpose :- asses the level of endogenous estrogene and outflow tract competence Methods MPA 20mg/dl -5day Omp 200-400mg -5-7 day Parentral progesterone in oil{200mg} Anovulation like pcos Lack of progesterone receptor Diseased endometrium Defect in hypothalamus/pitutary/ovary outcome Progesterone challenge test

32. Progesterone challenge test • Purpose: Asses the level of endogenous estrogen and outflow tract competence • 3 Methods 1. MPA 10 mg/day for 5 days 2. OMP 300-400 mg x 5-7 days 3. parenteral progesterone in oil (200 mg) Outcomes: 1. Progesterone withdrawal bleed- bleeds within 2-7 days of conclusion of progesterone challenge- then anovulation 2. No withdrawal bleed-need to clarify target outflow problem or lack of estrogen proliferation of endometrium

33. Estrogen/progesterone challenge test CEE 1.25mg0r estradial 2mg –daily for 21day and MPA 10mg – 5day RESULT – WITHDRAWAL BLEEDING DEFECT IN ESTROGEN PRODUCTION-OVARY /PITUITARY / HYPOTHALAMUS DEFECT IN ENDOMETRIUM/ OUTFLOW ASHERMAN’S SYNDOM /MULLERIAN ANOMALY

34. Step 2 • Estrogen/progesterone for 21 days Methods: 1. CEE 1.25 or estradiol 2 mg daily for 21 days + MPA 10 mg for the last 5 days 2. OCPs (use 30 mcg pill) Outcomes: No withdrawal bleed- defect in compartment I (endometrium, outflow tract) If bleeds-assume normal compartment I; if no infection or trauma- now determine if ovaries contain a normal follicular function and if sufficient pituitary gonadotropins

35. Step 3 Purpose: determine if ovaries contain a normal follicular function and if sufficient pituitary gonadotropins Methods: serum FSH, LH

36. Step 3 • Outcomes Elevated FSH/LH = (FSH> 20 IU/L) postmenopause/POF (< age 40) RARE: 1. FSH/LH elevated- lung cancer 2a. High of one and low of other 2b. FSH elevated, low LH a. rare-gonadotropin-secreting pitutary adenoma

37. • Outcomes 3. Elevated FSH/normal LH Perimenopause follicles are the least sensitive;inadequate inhibin; could get pregnant 4. Elevated FSH/LH-Resistant or insensitive ovaryelevated gonadotropins despite ovarian follicles- either receptors absence or post receptor defect. 5. POF due to autoimmune diseasedeveloping follicles contain lymphocytes and plasma cells. Check thyroid antibodies; polyglandular syndrome? Other:

38. Step 3 • Outcomes 6. High FSH/LH normal ovarian follicles- galactosemia and 17 hydroxylase deficiency (affects both ovaries and adrenal glands) absent secondary sexual development; hypertensive

39. Step 3 • Outcomes Normal gonadotropins Most common: Hypothalamic amenorrhea Rare: abnormal gonadotropin molecules; inherited disorder of gonadotropin synthesis

40. Step 3: Low gonadotropins • Low FSH/LH (or normal) distinguish between pituitary compartment III) or CNS-hypothalamic (compartment IV) Imaging: if normal + normal prolactin

41. Autoimmune Testing • Fasting glucose • a.m. cortisol • Free T4 • TSH • Thyroid antibodies if thyroid function is abnormal • CBC/ESR • Total protein, albumin/globulin ratio • RF • Antinuclear antibody • Periodic adrenal surveillance

42. Chromosome Evaluation • Elevated FSH/LH Mosaicism + Y chromosome requires laparotomy and excision of gonadal areas Karyotype; could have a malignant tumor

43. Polycystic ovary syndrome

44. Polycystic ovary syndrome PCOS DESCRIBED BY STAIN $ LEVENTHAL -1935 PCOS AMENORRHOEA HIRSUTISM OBESITY

45. Mostly present with classical Stein-Leventhal syndrome (of oligomenorrhoea, obesity, hirsuitism, and infertility ) However a substantial group will have sec. amenorrhoea with no obesity or hirsuitism Diagnosis is made by finding  LH/FSH ratio Confirmation is made by laparoscopy . USG+

46. ROTTERDAM ESHRE/ASRM PCOS DIAGNOSTIC CRITERIA 2003 (2 out of 3) OLIGOMENORRHEA OR ANOVULATION CLINICAL /BIOCHEMICAL SIGN OF HYPERANDROGENISM USG-PCO > 12 FOLLICLE IN EITHER OVARY MEASURING 2-9mm diameter/.10ml VOLUME

47. Ultrasound : multiple small ovarian cysts enlarged ovary

48. CLINICAL FEATURES OBESITY BMI>30kg/cm Waist line.35” MENSTRUAL ABNORMALITIES- O LIGO/AMENORRHOEA INFERTILITY HIRSUTISM ACANTHOSIS NIGRA

49. CLINICAL FEATURES

50. PCOS-Treatment 1930’s— Ovarian Wedge Resection Traditional Treatment —aimed at the clinical features and dependent on the ones most bothersome to the patient. Response to therapy is slow, 6-9 months Rx of acne , hirsutism and menstrual irregulaties when fertility is not an issue requires a concentrated effort on many fronts

51. Nonpharmacologic measures are universally recommended. These measures include the following(Lifestyle Measures): A) Diet including seeing a dietician who is knowledgeable in PCOS B) Exercise C) Weight Reduction if the patient is obese or insulin-resistant.

52. Pharmacologic treatments include the following: oral contraceptives antiandrogen drugs (usually spironolactone) insulin sensitizers ?statins.

53. HYPOTHYROIDISM

54. Causes of HYPOTHYROIDISM PRIMARY (thyroid dysfunction) Hashimoto thyroiditis(mc) Iodine sufficient areas Autoimmune destruction of thyroid (thyroid peroxidase and thyroglobulin antibodies) Antithyroid antibodies are found in approximately 10% of women in second trimester. Endemic iodine deficiency Central Africa, South America, northern Asia History of ablative radioiodine therapy or thyroidectomy.

55. SECONDARY (pituitary dysfunction ) Sheehan’s syndrome Lymphocytic hypophysitis history of a hypophysectomy.

56. Diagram of the hypothalamic–pituitary–thyroid axis. The hypothalamus secretes TRH (green), which stimulates the production of TSH (red) by the pituitary gland. This in turn stimulates the production of thyroxine by the thyroid (blue). Thyroxine levels decrease TRH and TSH production by a negative feedback process

57. Fatigue Weakness Weight gain or increased difficulty losing weight Coarse, dry hair Dry, rough pale skin Hair loss Cold intolerance (you can't tolerate cold temperatures like those around you) Muscle cramps and frequent muscle aches Constipation Depression Irritability Memory loss Abnormal menstrual cycles Decreased libido Symptoms of Hypothyroidism

58. Diagnosis Serum TSH level If TSH level is found abnormal, measure fT3,fT4, Anti TPO antibodies. S.TSH and fT4 values are more significant because fT3 levels are normal in 25% of cases reflecting adaptive deiodinase responses to hypothyroidism.fT3 measurement is therefore not recommended.

59. Management Hormone replacement Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long-acting form of thyroxine, known as levothyroxine ( L-thyroxine)

60. PREMATURE OVARIAN FAILURE

61. PREMATURE OVARIAN FAILURE DEFINATION :-Amenorrhea for 4months or more accompanied by two serum FHS level in the menopausal range for a women who is less then 40 year of age. BEREK & NOVEK’S GYNECOLOGY

62. CAUSE CHROMOSOMAL IATROGENIC CAUSES

63. Symptoms Premature aging Irregular or skipped periods (amenorrhea ) Hot flashes Night sweats Vaginal dryness Irritability or difficulty concentrating Decreased sexual desire

64. DIAGNOSIS H/O AMENORRHOEA >35 year SERUMFHS >40IU/ML SERUM E2 <20PG/ML KARYOTYPE AUTOANTIBODY OVARIAN BIOPSY

65. Pregnancy test. This test checks for the possibility of an unexpected pregnancy in a woman of childbearing age who has missed a period. Follicle-stimulating hormone (FSH) test. FSH is a hormone released by the pituitary gland that stimulates the growth of follicles in your ovaries. Women with premature ovarian failure often have abnormally high levels of FSH in the blood. Estradiol test. The blood level of estradiol, a type of estrogen, is usually low in women with premature ovarian failure. Prolactin test. High levels of prolactin — the hormone that stimulates breast milk production — in your blood can lead to problems with ovulation. Karyotype. This is a test that examines all 46 of your chromosomes for abnormalities. Some women with premature ovarian failure may have only one X chromosome instead of two or may have other chromosomal defects. FMR1 gene testing. The FMR1 gene is the gene associated with fragile X syndrome — an inherited disorder that causes intellectual problems. The FMR1 test looks at both of your X chromosomes to make sure they appear to be normal.

66. Treatments HRT BHRT- E3 2 mg/E2 0.5 mg/OMP 100 mg OCP Calcium and vitamin D supplements.

67. ASHERMAN’S SYNDROME Asherman’s syndrome , also known as intrauterine adhesions, is a condition where the cavity of the uterus develops scar tissue (adhesions).

68. CAUSES Secondary amenorrhoea following destruction of the endometrium by overzealous curettage. Mainly postpartum , DUB POSTABORTAL TUBERCULAR ENDOMETRITIS

69. S ymptoms Can be asymptomatic (without symptoms). Symptoms that women may have with intrauterine adhesions include: Infertility Recurrent pregnancy loss (miscarriage) Menstrual irregularities such as very light periods ( hypomenorrhea ) or absence of periods (amenorrhea). This can occur if scar tissue replaces the normal endometrium, so there is less endometrium shed during menses. It also can occur if scar tissue blocks the outflow of the menstrual blood. Cyclic pelvic pain can occur if scar tissue blocks the outflow of the menstrual blood, causing uterine cramping and pelvic discomfort or pain. 

70. DIAGNOSIS PROGESTERONE CHALLENGE TEST- NAGATIVE HYSTEROSALPINGOGRAPHY-HONEYCOMB APPEARANCE HYSTEROSCOPY

71. C lassification of intrauterine adhesions.  American Fertility Society/American Society for Reproductive Medicine classification of intrauterine adhesions.   T hree stages of disease: Stage I (mild ), Stage II (moderate ) Stage III (severe).  The stage of disease is determined by the extent of the endometrial cavity involved (adhesions throughout the uterus or just in a small area), the type of adhesions (filmy or dense) and the menstrual pattern.  Mild disease can involve just a few bands of scar tissue in a woman with normal periods .  Severe disease can be characterized by complete obliteration and occlusion (obstruction) of the endometrial cavity and no menstrual bleeding. 

72. MANAGEMENT: Hysteroscopic lysis of adhesions (removal of scar tissue) Under G.A. breakdown intraut. Adhesions through hysteroscopeinsert an IUCD to deter reformation hormone therapy (E2 + P) THIN FRAGID SYNECHIAE – dIvided with tip of rigid diagnostic hysteroscope T HICKER -divided opretive resectoscope Radiofrequency electrode,Nd:YAG laser

73. Hyperprolactinemia

74. Prolactin Human prolactin is a 198 amino acid polypeptide Primary function is to enhance breast development during pregnancy and to induce lactation Normal plasma level – 1-20 ng /ml Prolactin also binds to specific receptors in the gonads, lymphoid cells, and liver Secretion is pulsatile; it increases with sleep, stress, pregnancy, and chest wall stimulation or trauma

75. Secretion of prolactin is under tonic inhibitory control by dopamine, which acts via D2-type receptors located on lactotrophs Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP)

76. Hyperprolactinemia Pathologic conditions Hypothalamic lesions Craniopharyngioma Glioma Granuloma Stalk transection Irradiation damage Pseudocysts Pituitary tumors Cushing disease Acromegaly Prolactinoma Reflex causes Chest wall injury herpes zoster neuritis Upper abdominal op Hypothyroidism Renal failure Ectopic pdoduction Bronchogenic carcinoma Hypernephroma

77. Hyperprolactinemia Pharmacologic conditions Estrogen therapy Anesthesia DA receptor blocking agents Phenothiazones Haloperidol Inhibition of DA turnover Opiates DA re-uptake blocker Nomifensine CNS-DA depleting agents Reserpine -methyldopa MAO inhibitor Stimulation of serotoninergic system Amphetamines Hallucinogens Histamine H2-receptor antagonists

78. Hyperprolactinemia Physiologic conditions Sleep Feeding Exercise Coitus Menstrual cycle Amniotic fluid Pregnancy Puerperium Nursing Fetus Neonate

79. Clinical Manifestation Galactorrhea indicates elevated PRL in 10% of women Amenorrhea: indicates elevated PRL in 15% of women Galactorrhea plus amenorrhea: indicates elevated PRL in 75%of women Infertility: indicates elevated PRL in up to 33% of women Osteoporosis: increased with elevated PRL--due to estrogen lack. If normal menses are present, osteoporosis does not occur.

80. Work up of Patient with Hyperprolactinemia P regnancy must always be ruled out Get a TSH- hypothyroidism is another common cause of elevated prolactin: Obtain detailed drug history- rule out medication effects Rule out other common causes including: Nonfasting sample Nipple stimulation or sex Excessive exercise History of chest wall surgery or trauma Renal failure Cirrhosis If no cause determined or tumor suspected, consider MRI, especially if high prolactin levels (> 100 ng/mL)

81. Investigation Slight to moderate elevation Repeat the test, if still high, screen for gross abnormality by lateral skull X-ray. If it shows enlargement of the pituitary fossa or erosion of the clinoid process … . CT scan to detect macro-adenoma. Marked elevation … repeat the test + arrange CT scan ASAP. Specially urgent when headache or visual field defect present.

82. MRI scanning offers better resolution for small micro-adenomas An abnormal pituitary fossa may be due to the empty sella syndrome where there is congenital incompleteness of the roof of the fossa and the sub-arachnoid

83. Treatment Micro-adenomas tend to grow slowly if at all. In up to 30% of patients spontaneous regression of micro-adenoma will occur The treatment of choice is Dopamine agonist ( e.g. bromocriptine, or cabergoline). This will suppress prolactin secretion, correct estrogen deficiency, permits ovulation and reduce the size of most prolactinomas.

84. Dopamine Agonists Bromocriptine start low dose at 1.25- 2.5 mg day at night before increasing to 2.5 – 10 mg per day in divided doses. Take with food to reduce side effects.

85. Cabergoline- more effective and with less side effects than Bromocriptine also more expensive- given once or twice a week with a starting dose of 0.25 mg 2 x week

86. Surgery and radiotherapy are usually reserved for patients with very large tumours with extrasellar manifestations (e.g. pressure on the optic chiasma). If pregnancy happens check visual field every 2 months and prescribe a dopamine agonist

87. SHEEHAN’S SYNDROME

88. SHEEHAN’S SYNDROME Sheehan syndrome (SS) or post-partum pituitary necrosis is an adeno-pituitary insufficiency from hypovolemia secondary to excessive blood losses during of after the delivery. I t was first described by Sheehan in 1937. H/O SEVER POSTPARTUM HAEEMORRHAGE COMMON MANIFESTATION- Failing lactation ,loss of pubic &axillary hair lethargy, hypotention secondary amenorrhoea atrophy of breast $ genitalia

89. M/M REPLACEMENT THERAPY -CORTICOSTEROID AND THYROXINE FERTILITY CAN ACHIEVED WITH hMG AND hCG

90. Thank You