Amenorrhoea PCOD

AMENORRHOEA FOR UNDERGRADUATE
PCOD

1. DR SALINI MANDAL B.G. ASST P ROFESSOR DEPT OF OBG FMHMC

2. PRIMARY AMENORRHOEA

3. HYPOGONADOTROPIC HYPOGONADISM

4. DELAYED PUBERTY : DELAYED GnRH pulse reactivation

5. HYPOTHALAMIC AND PITUITARY DYSFUNCTION: Gonadotropin deficiency due to stress, weight loss, excessive exercise, c/c d’se .

6. KALLMANN’S SYNDROME : Inadequate GnRH pulse secretion Kallmann syndrome  is a condition characterized by delayed or absent puberty and an impaired sense of smell. This  disorder  is a condition affecting the production of hormones that direct sexual development. ( GnRh neurons are absent due to partial or complete agenesis of olfactory bulb)

7. CNS TUMOURS: Craniopharyngioma  reduced GnRH secretion

8. HYPERGONADOTROPIC HYPOGONADISM

9. Primary ovarian faliure (sex chromatin nil) Resistant ovarian syndrome (functional disturbance of the gonadotrophin receptors in the ovarian follicles)

10. ABNORMAL CHROMOSOMAL PATTERN

11. Turner’s syndrome Pure gonadal dysgenesis Androgen insensitivity syndrome (Testicular feminization syndrome) Partial deletions of the X chromosome.

12. DEVELOPMENTAL DEFECT OF GENITAL TRACT

13. Absence of uterus Atresia of upper third of vagina and cervix.

14. INVESTIGATIONS ???

15. MANAGEMENT

16. Complete agenesis of vagina – vaginal reconstruction. Chromosomal abnormalities: hormonal therapy atleast for development of breast Androgen insensitivity syndrome: extra gonad removed. Hypothalomopituitary ovarian axis defect:

17. Metabolic and Nutritional: DM, Tb treated. Correction of anemia. Correction of malabsorption , weight loss stress. Unresponsive endometrium : no known treatment.

18. SECONDARY AMENORRHOEA

19. UTERINE SYNECHIAE OR ASHERMAN’S SYNDROME

20. There is formation of adhesions following post- abortal and puerperal curettage and also following diagnostic curettage in dysfunctional uterine bleeding. Menstrual abnormalities include hypomenorrhea , oligomenorrhea or amenorrhea . Hysterosalpingography shows honeycomb appearance.

21. Clinical features: The patient complains of increasing obesity (abdominal – 50%), menstrual abnormalities (70%) in the form of oligomenorrhea , amenorrhea or DUB and infertility. Presence of hirsutism and acne are the important features Virilism is rare.

22. HAIR-AN syndrome in patients with PCOS is characterized by hyperandrogenism , insulin resistance and acanthosis nigricans . Internal examination reveals bilateral enlarged cystic ovaries which may not be revealed due to obesity.

23. Investigations…

24. Sonography — Transvaginal sonography is specially useful in obese patient. Ovaries are enlarged in volume (> 10 cm3 ). Increased number (> 12) of peripherally arranged cysts (2–9 mm) are seen

25. PATHOPHYSIOLOGY

26. HYPOTHALAMIC- PITuITARY COMPARTMENT

27. Ovary produces excess androgens due to — ( i ) stimulation of theca cells by high LH ( ii) P450 C17 enzyme hyperfunction (iii) stimulation of theca cells by IGF-1 (insulin growth factor-1)

28. B. Adrenals are stimulated to produce excess androgens by stress P450 C17 enzyme hyperfunction

29. C. Systemic metabolic alteration Hyperinsulinemia causes: Stimulation of theca cells to produce more androgens. Insulin results in more free IGF-1. By autocrine action, IGF-1 stimulates theca cells to produce more androgens. Insulin inhibits hepatic synthesis of SHBG, resulting in more free level of androgens.

30. (ii) Hyperprolactinemia: In about 20% cases, there may be mild elevation of prolactin level due to increased pulsitivity of GnRH or due to dopamine deficiency or both. The prolactin further stimulates adrenal androgen production.

31. Anovulation: Because of low FSH level, follicular growth is arrested at different phases of maturation (2–10 mm diameter). The net effect is diminished estradiol and increased inhibin production.

32. Due to elevated LH, there is hypertrophy of theca cells and more androgens are produced either from theca cells or stroma. There is defective FSH induced aromatization of androgens to estrogens . Follicular microenvironment is therefore more androgenic rather than estrogenic.

33. OBESITY AND INSULIN RESISTANCE

34. O besity is also associated with reduced SHBG . It also induces insulin resistance and hyper- insulinemia which in turn increases the gonadal androgen production.

35. Etiology of insulin resistance is unknown. Mutations of the insulin receptor gene in the peripheral target tissues and reduced tyrosine autophosphorylation of the insulin receptor, is currently thought to be an important cause. Increased central body fat leads to android obesity.

36. PREMATURE OVARIAN INSUFFICIENCY

37. Premature ovarian insufficiency (failure) is defined when ovarian failure occurs before the age of forty . It occurs in about 1% of the female population.

38. During intrauterine life either there is failure of germ cell migration or there may be normal germ cell migration but an accelerated rate of germ cell depletion (apoptosis) due to various reasons. This results in either no follicle or only few follicles left behind in the ovary by the time they reach puberty

39. History of amenorrhea in less than 35 years of age. Karyotype abnormality Ovarian biopsy ( afollicular , follicular and autoimmune variety) In autoimmune variety, there is perifollicular lymphocyte infiltration. In resistant ovarian syndrome, follicles are present. FSH receptor is either absent or defective. Diagnosis/Investigations

40. Patient presents with amenorrhea — primary (25%) or secondary (75%). Features of hypoestrogenic state like hot flushes, vaginal dryness, dyspareunia and psychological symptoms are there. The possibility of autoimmune disorders should be considered below the age of 35. For this, antithyroid antibodies, rheumatoid factor and antinuclear antibodies should be measured. In younger patients (age below 30) karyotype is to be done to rule out chromosomal abnormality.

41. PITUITARY ADENOMA (PROLACTINOMA)

42. A . Physiological stress and exercise Pregnancy Stimulation of nipples CAUSES OF HYPERPROLACTINEMIA

43. Prolactin level is more than 100 ng/mL is often associated with prolactinoma . (normal: 1-20ng/ml) DIAGNOSIS OF PITUITARY ADENOMAS

44. SHEEHAN’S SYNDROME

45. There is history of severe postpartum hemorrhage , shock or severe infection. Depending upon the degree of anterior pituitary necrosis, the features vary.

46. The common manifestations are failing lactation, loss of pubic and axillary hair , lethargy, hypotension , secondary amenorrhea and atrophy of the breasts and genitalia.

47. Gonadotropin level is low, so also T3, T4 and cortisol. The hormones affected in order of frequency are, growth hormone (GH), prolactin, gonadotropins (FSH and LH), TSH and ACTH. Hyponatremia may be present (30%). The syndrome may develop slowly over 8–10 years time.