Disorders of menstrual function. Neuroendocrine syndromes in gynecology

1. Disorders of menstrual function.Neuroendocrine syndromes in gynecology By I. Korda .

2. The menstrual cycle is a cycle of physiological changes that occurs in fertile females. The female menstrual cycle is determined by a complex interaction of hormones.

4. puberty is the process of physical changes by which a child's “body becomes an adult body capable of reproduction. • menarche- A woman's first menstruation is termed, and occurs typically around age 12.The menarche is one of the later stages of puberty in girls. • menopause - the end of a woman's reproductive phase, which commonly occurs somewhere between the ages of 45 and 55. Climacteric: 47-55 years Menopause Postmenopause starts 1 year after menopause Premenopause: 5 years before Perimenopause: transitional phase between pre- and postmenopause: 2 years before and 1 year after

5. Menstrual cycle: Days 1-5: Estrogen Falls, FSH Rises. Menstrual bleeding begins on Day 1 of the cycle and lasts approximately 5 days. During the last few days prior to Day 1, a sharp fall in the levels of estrogen and progesterone signals the uterus that pregnancy has not occurred during this cycle. This signal results in a shedding of the endometrial lining of the uterus.

6. Since high levels of estrogen suppress the secretion of FSH, the drop in estrogen now permits the level of follicle stimulating hormone (FSH) to rise. • FSH stimulates follicle development. • By Day 5 to 7 of the cycle, one of these follicles responds to FSH stimulation more than the others and becomes dominant. As it does so, it begins secreting large amounts of estrogen.

7. Days 6-14: Estrogen Is Secreted, FSH Falls. • Estrogen is secreted by the follicle during this phase of the menstrual cycle. It • stimulates the endometrial lining of the uterus • suppresses the further secretion of FSH. • At about mid-cycle (Day 14), the estrogen helps stimulate a large and sudden release of luteinizing hormone (LH). • This LH surge, which is accompanied by a transient rise in body temperature, is a sign that ovulation is about to happen. • The LH surge causes the follicle to rupture and expel the egg into the Fallopian tube.

8. Days 14-28: Estrogen And Progesterone Secretion First Rise, then Fall. • After rupture of the follicle, it is transformed into the corpus luteum and produces progesterone. • P supports to prepare the endometrial lining for implantation of the fertilized egg. (If the egg is fertilized, a small amount of human chorionic gonadotrophin (hCG) is released that stimulates further progesterone production.)

9. After implantation, the trophoblast will secrete human Chorionic Gonadotropin (hCG) into the maternal circulation. • HCG keeps the corpus luteum viable.The corpus luteum continues to produce estrogen and progesterone, which keep the endometrial lining intact. • By about week 6 to 8 of gestation, the newly formed placenta takes over the secretion of progesterone.

10. If the egg is not fertilized, the corpus luteum shrinks, and the levels of estrogen and progesterone drop, the uterus sheds its lining, and menstruation begins. Normal Menses: • Flow lasts 2-7 days • Cycle 21-35 days in length • Total menstrual blood loss 20-60 mL • The menstruation must be regular, painless. • In addition, with no estrogen to suppress it, FSH levels again start to rise. Thus, one cycle ends and another begins.

11. Estrogens • Estrogens stand for a group of hormones: • Estradiol (approximately 10-20% of circulating estrogens) • Estrone (approximately 10-20% of circulating estrogens) • Estriol (approximately 60-80% of circulating estrogens) • Estradiol is produced by the ovaries. It is the primary circulating estrogen before menopause. It is also the strongest estrogen and is responsible to the monthly ovulation and normal menstrual cycles. • Estrone is produced by the fatty tissues. It is less potent than estradiol, but more important after the menopause • Estriol is an estrogen that is prominent mostly during pregnancy.

13. Progesterone • Progesterone is made by the adrenal glands in both sexes and by the testes in males. It is a precursor of testosterone and of all the important adrenal cortical hormones. • Progesterone is made from the sterol pregnenolone that derives from cholesterol, • Progesterone stimulates the growth of a endometrial lining, prepares breast tissue for the secretion of breast milk, and generally maintains the advancement of pregnancy.

14. Androgens • Androgens stands for a group of primarily male hormones: • testosterone • androstenedione • dehydroepiandrosterone). • Androgens are also produced in the ovaries.

15. Menstrual cycle irregularities:1. abnormal frequency Kaltenbach chart: Duration: 28 d 5 Amount: 3-5 pads or tampons (35 mL) Normal cycle Abnormal frequency:oligomenorrhea Duration > 35 days Abnormal frequency:polymenorrhea Duration < 22 days

16. Menstrual cycle irregularities: 2. abnormal amount of duration Kaltenbach chart: Duration: 28 d 5 Amount: 3-5 pads or tampons35 mL) Normal cycle Hypomenorrhea Amount < 2 per day Hypermenorrhea Amount > 5 per day Menorhagia Duration 7-14 days at regular intervals

17. Menstrual cycle irregularities:3. others Spotting: bleeding unrelated to menses Ovulatory bleeding Metrorrhagia: > 14 days, no clear cycle Painful menses: • Algomenorrhea — pain during menses in genital organs region • Dysmenorrhea — general disturbances during menses (headache, nausea, anorexia, raised irritability) • Algodysmenorrhea — a combination of local pain and general state disturbance

18. Amenorrhea: absence of bleeding for more than 6 months • Primary amenorrhea is the absence of menstrual function from puberty age. • Secondary amenorrhea is the suppression of menstrual function in woman who has menstruated before.

19. Clinical Presentation • Physical examination • Height and Weight • Sign of thyroid disease • Secondary sexual characteristics • Thelarche • Adrenarche • Decrease in breast size or Vaginal dryness • Presence of Cervix and Uterus

20. Differential Diagnosis • Primary amenorrhea • Gonadal failure • Anorexia nervosa • Secondary amenorrhea • Hypothalamic disorders and PCOD 49-62 % • Pituitary 7-16 % • Ovarian disorder 10 % • Ascherman’s syndrome 7 %

21. Physiologic Amenorrhea • Pregnancy • Lactation • Menopause • Hormone: contraception etc.

22. Dysorder of Hypothalamus • Abnormalities Affecting Release of Gonadotropin-Releasing Hormone • Variable Estrogen Status • Anorexia nervosa • Exercise-induced • Stress-induced • Pseudocyesis • Malnutrition • Chronic diseases : DM, Renal, Lung, Liver, Chronic infection, Addison’s disease • Hyperprolactinemia • Thyroid dysfunction

23. Euestrogenic States • Obesity • Hyperandrogenism • PCOD • Cushing’s syndrome • Congenital adrenal hyperplasia • Androgen secreting adrenal tumor • Androgen secreting ovarian tumor • Granulosa cell tumor • idiopatic

24. Menstrual disorders • Irregular patterns of bleeding • Hypothalamic ovarian insufficiency:Psychogenic stress, anorexia nervosa • Pituitary causes:for instance: acromegaly – increased somatotropic hormones (STH) Cushings diseas: impaired cortisol rhythm • Ovary: polycystic ovary • Thyroid:  hypothyroidism: anovulatory cylces and dysfunctional bleeding  hyperthyroidism: hypomenorrhea/ oligomenorrhea • Adrenal: Cushings syndrome: impaired cortisol rhythm

25. Polycystic Ovary Syndrome (PCOS) • The ovaries contain many small follicles or cysts. Each has an egg, but they do not grow normally and shrink before ovulation. Each month, new follicles develop and shrink into cysts. • The fertility is reduced. • Most PCOS cases are unexplained. • The disorder may be inherited. • Deficiency in luteinizing hormone (LH) • Resistance to insulin. A similar effect on the ovaries can occur in women with eating disorders (anorexia or bulimia), or women whose bodies do not properly make estrogen and other steroids (for example, women with congenital adrenal hyperplasia).

26. Polycystic OvarySyndrome (PCOS) • Clinical consequences of • persistent anovulation • 1. Infertility • 2. Menstrual dysfunction • 3. Hirsutism, Alopecia, Acne • 4. Risk of endometrial cancer , breast cancer • 5. Risk of CVS disease • 6. Risk of DM in patients with insulin resistance

27. Disorder of Anterior Pituitary Infarction Surgical or Radiological ablation Sheehan’s syndrome Diabetic vasculitis • Pituitary Tumors • Non functioning adenomas • Hormone-secreting adenoma • Prolactinoma • Cushing’s disease • Acromegaly • Primary hyperthyroidism • Craniopharyngioma • Meningioma • Glioma

28. Prolactin Secreting Adenoma • Most common pituitary tumor • 50% identified at autopsy • Disruption of the reproductive mechanism • S/SPRL • Amenorrhea -Visual field defect • Galactorrhea -Headache • Treatment • Medical : dopamine agonist • Surgical

29. Sheehan’s syndrome • Postpartum hemorrhage • Acute infarction and necrosis • Hypopituitarism= early in the PP period • Failure of lactation • Loss of pubic and axillary hair • Deficiencies : • GH, Gn (FSH,LH), • ACTH, TSH (in frequency)

30. Disorders of the Ovary 4. Iatrogenic causes: effect of radiation and chemotherapy 5. Infections 6. Autoimmune disorders 7. Galactosemia 8. Cigarette smoking 9. Idiopathic 1. Chromosomal etiology • Turner’s Syndrome • Mosaicism • XY gonadal dysgenesis • Gonadal agenesis 2. Resistance ovarian syndrome (Savage syndrome) 3. Premature ovarian failure (the early depletion of ovarian follicles)

31. Turner’s Syndrome • Gonadal dysgenesis associated with 45,XO • Most common chromosomal abnormality in spontaneous abortion • Characteristics • Sexual infantilism -Less common • Short stature Autoimmune • Webbed neck CVS anomalies • cubitus valgus Renal anomalies • Mosaicism • Treatmant

32. Ovarian Causes • Premature ovarian failure • follicular depletion before age 40 • autoimmune diseases • genetics • infectious • physical insult : • Rad. • Chemo. • Investigation: • Laparotomy ? • Autoimmune disease • Ovarian Resistance Syndrome • Primordial follicles fail to progress • Despite elevated gonadotropins • Normal growth and developement

33. Disorders of the Outflow Tract or Uterus 1. Asherman’s syndrome 2. Mullerian anomalies 3. Androgen Insensitivity (Testicular Feminization) 4. Infection TB

34. 1. Asherman’s Syndrome • Cause : • Curettage, • Uterine surgery • Diagnosis : • HSG • Hysteroscope • S/S : • Miscarriage • Dysmenorrhea • Hypomenorrhea

35. 2. Mullerian anomalies • Lack of MullerianDevelopment • Ovaries : Normal • Associated anomalies • urinary • skeleton • Investigation : • U/S , MRI, Laparoscope ?

37. Mayer- Rokitansky-Kuster-Hauser syndromeMullerian Agenesis

38. ImperforateHymens

39. 3. Androgen Insensitivity (Testicular Feminization) • Male Pseudohermaphrodite • Gonadal Sex :46xy • Phenotype Female • Blind vaginal canal • Uterus absent • Absent or meager pubic and axillary hair • Malignancy, • Hormone : • T or slightly • LH

40. Premenstrual Syndrome

41. Case • 20 year old Jessica • Episodes of irritability and moodiness • Lead to huge arguments with her boyfriend. • Sleeps away the day and miss school or work • Her boyfriend jokes and makes off-the-wall remarks about PMS. She comes to you for advice. • Bloated, tired and hungry during the days just prior to menses.

42. Definitions • PMS = Recurrent psychological or physical symptoms during the luteal phase of menstrual cycle, resolves by the end of menstruation, and interferes with some aspect of function. • Premenstrual Dysphoric Disorder (PMDD) = more severe form of PMS meeting DSM-IV criteria. • About three per cent of women across all countries suffered the most severe type of PMS, called premenstrual dysphoric disorder (PMDD)

43. Symptoms Anger Outbursts

44. Symptoms Cravings

45. Irritability

46. Mood Lability

47. Symptoms of PMS • Psychological • Irritability (91) • Fatigue (92) • Anxiety/tension (89) • Depression (80) • Forgetfulness (56) • Poor concentration (47) • Physical • Fatigue (92) • Bloating (90) • Breast tenderness (85) • Acne (71) • Swelling (67) • Headache (60) • GI symptoms (48) • Hot flashes (18) • Heart palpitations (14) • Dizziness (14) • Behavioral • Mood lability (81) • Food cravings (78) • Increased appetite (70) • Oversensitivity (69) • Anger (67) • Crying easily (65) • Feeling isolated (65)

48. Diagnosing PMS • UCSD criteria: • >1 somatic and affective symptom 5 days prior to menses x 3 cycles • Somatic: Depression, anger, irritability, confusion, social withdrawal, fatigue • Affective: breast tenderness, bloating, headache, swelling • Resolve within 4 days onset of menses and symptom free until day 12 of cycle • Not due to medications, drugs or ETOH use • Causes Dysfunction • Marital, parenting, work/school attendance/performance, isolation, legal difficulties, suicidal ideation

49. Differential Diagnosis • Menstrual exacerbation of: • psychiatric disorder • Medical condition: • Dysmenorrhea • hyper- or hypo- thyroidism • Peri-menopause • Migraine • Chronic fatigue syndrome • Irritable bowel syndrome

50. Rx of mild to moderate PMS • Some evidence: • Vit B6 during luteal phase (1 system review) • neurotoxicity • Calcium (2 large RCTs ) • Benefits bones • Evening primrose oil (weak RCTs) • Magnesium (weak RCTs)