26.2008 Reproductive Endocrinology


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26.2008 Reproductive Endocrinology

  1. 1. Zhang Huiying Normal and Abnormal Menstruation Reproductive Endocrinology
  2. 2. Main contents <ul><li>Normal manstruation </li></ul><ul><li>Abnormal uterine bleeding ★ </li></ul><ul><li>Amenorrhea ★ </li></ul><ul><li>Perimenopause and perimenopausal syndrome </li></ul><ul><li>polycystic ovarian syndrome(PCOS) </li></ul>
  3. 3. Normal menstruation <ul><li>Mean interval is 28 days +/- 7 days. </li></ul><ul><li>Mean duration is 2~7 days. </li></ul><ul><li>More than 7 days is abnormal. </li></ul><ul><li>Average blood loss with menstruation is 35-50 ml . More than 80 ml is abnormal </li></ul>
  4. 4. CNS-Hypothalamus-Pituitary Ovary-uterus Interaction Hypothalamus Gn-RH Ant. pituitary FSH, LH Ovaries Uterus Progesterone Estrogen Menses – ± ? CNS Not clear
  5. 5. <ul><li>The normal menstrual cycle is the result of complex interactions between the hypothalamic- pituitary-ovarian (HPO) endocrine axis. </li></ul><ul><li>Hypothalamus secrete gonadotropin-releasing hormone, </li></ul><ul><li>The anterior pituitary release the FSH and LH </li></ul><ul><li>Every cycle the ovary change from follicular development phase to the luteal phase secrete estrogen and progesterone </li></ul><ul><li>The endometrium change from proliferative phases to secretory phases. When progesterone and estrogen levels fall with the demise of the corpus luteum, vasoactive substances such as prostaglandins, histamine and bradykinin are produced by the endometrium. Prostaglandins cause spasm of the spiral arterioles which results in ischaemic necrosis and shedding of all but the basal layer of the endometrium. </li></ul>
  6. 6. The control of regular menstrual blood loss <ul><li>vasodilatation of spiral arterioles </li></ul><ul><li>fibrinolytic activity of menstrual blood </li></ul><ul><li>endometrial regeneration. </li></ul>
  7. 7. Abnormal uterine bleeding
  8. 8. Sorts of bleeding <ul><li>Abnormal menstrual bleeding </li></ul><ul><li>Other causes </li></ul><ul><li>pregnancy </li></ul><ul><li>Systemic disease </li></ul><ul><li>Cancer </li></ul>
  9. 9. Patterns of abnormal uterine bleeding <ul><li>Menorrhagia(hypermenorrhea) </li></ul><ul><li>Hypomenorrhea </li></ul><ul><li>Metrorrhagia(intermenstrual bleeding) </li></ul><ul><li>Polymenorrhea </li></ul><ul><li>Menometrorrhagia </li></ul><ul><li>Oligomenorrhea </li></ul><ul><li>Contact bleeding(postcoital bleeding) </li></ul>
  10. 10. Menorrhagia <ul><li>Menorrhagia is heavy or prolonged menstrual flow. It is defined as menstrual blood loss exceeding 80 ml per cycle. Submucous myomas , adenomyosis , IUDs , endometrial hyperplasias , malignant tumors , and dysfunctional bleeding are causes of menorrhagia. </li></ul>
  11. 11. Hypomenorrhea <ul><li>Hypomenorrhea is unusually light menstrual flow , sometimes only spotting. </li></ul><ul><li>cervical stenosis and Uterine synechiae ( Asherman's syndrome ) can be causative </li></ul>
  12. 12. Metrorrhagia <ul><li>Metrorrhagia is bleeding occurring at any time between menstrual periods. </li></ul><ul><li>Ovulatory bleeding occurs at midcycle as spotting </li></ul>
  13. 13. Polymenorrhea <ul><li>Polymenorrhea describes periods that occur too frequently, less than 21 days apart. This is usually associated with anovulation and rarely with a shortened luteal phase in the menstrual cycle. </li></ul>
  14. 14. Menometrorrhagia <ul><li>Menometrorrhagia is bleeding that occurs at irregular intervals. The amount and duration of bleeding also vary. </li></ul><ul><li>Sudden onset of irregular bleeding episodes may be an indication of malignant tumors or complications of pregnancy. </li></ul>
  15. 15. Oligomenorrhea <ul><li>Oligomenorrhea describes menstrual periods that occur more than 35 days apart. </li></ul><ul><li>Bleeding is usually associated with anovulation </li></ul>
  16. 16. Contact bleeding(postcoital bleeding) <ul><li>Contact bleeding must be considered a sign of cervical cancer until proved otherwise. </li></ul>
  17. 17. Evaluation of abnormal uterine bleeding <ul><li>History </li></ul><ul><li>Physical examination </li></ul><ul><li>Cytologic examination </li></ul><ul><li>Endometrial biopsy </li></ul><ul><li>Saline hysterosonogram </li></ul><ul><li>Hysteroscopy </li></ul><ul><li>Dilatation and curettage(D & C) </li></ul><ul><li>Other diagnostic procedures(assay hCG,pelvic ultrasonography,laparoscopy) </li></ul>
  18. 18. History <ul><li>the amount of menstrual flow </li></ul><ul><li>the length of the menstrual cycle and menstrual period </li></ul><ul><li>the length and amount of episodes of intermenstrual bleeding </li></ul><ul><li>any episodes of contact bleeding. </li></ul><ul><li>the last menstrual period , the last normal menstrual period </li></ul><ul><li>age at menarche and menopause </li></ul><ul><li>any changes in general health. </li></ul>
  19. 19. Physical examination <ul><li>Abdominal masses and an enlarged , irregular uterus suggest myoma. </li></ul><ul><li>A symmetrically enlarged uterus is more typical of adenomyosis or endometrial carcinoma. </li></ul><ul><li>Atrophic and inflammatory vulvar and vaginal lesions can be visualized </li></ul><ul><li>cervical polyps and invasive lesions of cervical carcinoma can be seen. </li></ul><ul><li>Rectovaginal examination is especially important sometimes </li></ul>
  20. 20. Cytologic examination -cytologic smears A very useful method to screen the asymptomatic intraepithelial lesions.
  21. 21. Endometrial biopsy <ul><li>the Novak suction curet </li></ul><ul><li>the Duncan curet </li></ul><ul><li>the Kevorkisn curet </li></ul><ul><li>the pipelle. </li></ul>
  22. 22. Saline hysterosonogram <ul><li>Ultrasound following injection of saline into the uterus has been used to evaluate the endometrial cavity for polyps , fibroids , or other abnormalities. </li></ul>
  23. 23. Hysteroscopy <ul><li>Hysteroscopy Placing an endoscopic camera through the cervix into the endometrial cavity allows direct visualization of the cavity. </li></ul>
  24. 24. Dilatation and curettage(D & C) <ul><li>D & C is the gold standard for the diagnosis of abnormal uterine bleeding. </li></ul><ul><li>Curettage of the endocervix should be performed before sounding of the endometrial cavity or dilatation of the cervix is done. </li></ul>
  25. 25. Other diagnostic procedures <ul><li>assay hCG </li></ul><ul><li>pelvic ultrasonography </li></ul><ul><li>laparoscopy </li></ul>
  26. 26. abnormal uterine bleeding due to gynecologic diseases and disorders <ul><li>Vulva and vagina --atrophic vulvitis or vaginitis </li></ul><ul><li>Cervix – eversion, cervical polyps, cervical cancer </li></ul><ul><li>Uterus –endometritis, hyperplasias, cancer, submucous myomas,IUD </li></ul><ul><li>Ovaries—estrogen-producing tumor, other cancers </li></ul>
  27. 27. Abnormal bleeding due to nongynecologic diseases and disorders <ul><li>Severe hypothyroidism </li></ul><ul><li>Liver disease </li></ul><ul><li>Blood dyscrasias and coagulation abnormalities </li></ul><ul><li>Use anticoagulants or adrenal steroids </li></ul>
  28. 28. Dysfunctional uterine bleeding(DUB)
  29. 29. definition ★ <ul><li>Dysfunctional uterine bleeding(DUB) is irregular, abnormal uterine bleeding with no demonstrable organic causes. That is not caused by a tumor, infection, or pregnancy. It may be occur during postmenarchal and perimenopausal periods in a woman's reproductive life. </li></ul><ul><li>Exclusion of pathologic causes of abnormal bleeding establishes the diagnosis of DUB </li></ul>
  30. 30. <ul><li>DUB occur in </li></ul><ul><li>before the menopause(50%) </li></ul><ul><li>after menarche(20%) </li></ul><ul><li>reproductive times(30%) </li></ul>
  31. 31. <ul><li>Etiology of DUB: </li></ul><ul><li>1. disorders of </li></ul><ul><li>hypothalamus---pituitary ---ovary axis </li></ul><ul><li>immature of feedback regulation in young women </li></ul><ul><li>ovarian function failure in premenopause women </li></ul><ul><li>2.other Factors: </li></ul><ul><li>the effects of sex hormones </li></ul><ul><li>nervous </li></ul><ul><li>Circumstance change </li></ul><ul><li>PCOS,TSH ↑,PRL↑ </li></ul><ul><li>excessive physical exercise </li></ul>
  32. 32. Mechanisms <ul><li>have developing folliculi </li></ul><ul><li>no mature follicle </li></ul><ul><li>no corpus luteum </li></ul><ul><li>only have estrogen, but no progestin </li></ul><ul><li>breakthrough bleeding, spoting </li></ul>
  33. 33. pathologic Changes in the endometrium <ul><li>Endometrial hyperplasia </li></ul><ul><li>Simple hyperplasia </li></ul><ul><li>Complex hyperplasia </li></ul><ul><li>Atypical hyperplasia </li></ul><ul><li>Proliferative phase endometrium </li></ul><ul><li>Atrophic endometrium </li></ul>
  34. 35. Treatment <ul><li>Depends on the age of patient </li></ul><ul><li>Adolescent </li></ul><ul><li>Young woman </li></ul><ul><li>Premenopausal woman </li></ul>
  35. 36. Adolescent <ul><li>Acute hemorrhage :high-dose estrogen given intravenously or injection (25mg conjugated estrogen every 4h) </li></ul><ul><li>Hemodynamically stable patients: take oral conjugated estrogen (2.5mg every 4-6h) or take oral contraceptives 3-4 times the usual dose. </li></ul>
  36. 37. <ul><li>★ Lower the dose every 3 days for 1/3 dose after the bleeding stoped and when have lowered to an usual dose, give medroxyprogesterone acetate (MPA)10mg once or twice a day for 10-14d </li></ul>2.5mg / 6h 2.5mg / 8h 2.5mg / 12h 2.5mg / d Use to bleeding stoped 3d 3d 3d 1.25mg / d 10-14d medroxyprogesterone acetate 10-14d
  37. 38. <ul><li>Next 3-6 months give cycling theraphy </li></ul><ul><li>Sequential hormones </li></ul><ul><li>Oral contraceptive </li></ul>Adolescent
  38. 39. Young women <ul><li>Except the pathologic causes is necessary </li></ul><ul><li>Hormonal management is the same as for adolescents </li></ul><ul><li>Oral contraceptives may be used as normally prescribed if the patient don’t desire for childbearing </li></ul><ul><li>Induce ovulation if necessary </li></ul>
  39. 40. Premenopausal women <ul><li>More care should be given to excluding pathologic causes because of the possibility of endometrial cancer </li></ul><ul><li>Aspiration ,curettage,or both should clearly establish anovulatory or dyssynchronous cycles as the cause before hormonal therapy is started. </li></ul><ul><li>Recurrences of abnormal bleeding demand further evaluation </li></ul>
  40. 41. Surgical measures <ul><li>D & C:temporarily stop bleeding </li></ul><ul><li>Conservative surgery: endometrial ablation or resection using diathermy ,thermal (ballon, microwave..etc.)or laser. </li></ul><ul><li>Hysterectomy :whose lifestyle is compromised by persistence of irregular bleeding,coexistent endometriosis, myoma, other disorders of pelvic </li></ul>
  41. 42. polycystic ovarian syndrome(PCOS)
  42. 43. BACKGROUND <ul><li>In 1935, Stein and Leventhal published a paper on their findings in seven women with amenorrhea, hirsutism, obesity, and a characteristic polycystic appearance to their ovaries — one of the first descriptions of a complex phenotype today known as the polycystic ovary syndrome . The condition is now well recognized as having a major effect throughout life on the reproductive, metabolic, and cardiovascular health of affected women. </li></ul>
  43. 44. Clinical Manifestations <ul><li>Menstrual dysfunction- oligomenorrhea or amenorrhea </li></ul><ul><li>Hyperandrogenism -hirsutism, acne, male pattern balding or hair loss </li></ul><ul><li>Ovarian Morphology- Polycystic ovaries be seen on ultrasonography </li></ul><ul><li>Infertility </li></ul><ul><li>Obesity and insulin resistance -At least one-half of women with PCOS are obese and with insulin resistance </li></ul><ul><li>Biochemical Abnormalities-elevated serum androgen levels,LH/FSH≥2.5~3, hyperinsulinemia , Slightly elevated prolactin. </li></ul>
  44. 45. Hirsutism <ul><li>Excessive body hair. In women with PCOS dark, coarse hair will appear on the face, neck, chest, arms, and in between the legs. </li></ul>
  45. 46. Acne <ul><li>Because women with PCOS are producing more male hormone, that produces more sebum ( skin oils and old tissue) and causes blocked pores and more acne around the jawline, arms and chest. </li></ul>
  46. 47. Alopecia or Female Pattern Baldness <ul><li>This is caused by the increase of male hormone in the women's body. Thinning or loss of hair is usually contained to top of the scalp, but in severe cases loss of hair in front or on the hairline has been documented. </li></ul>
  47. 48. “ Dirty Skin” or Acanthosis Nigricans <ul><li>This condition causes light brown to black rough patches around the neck and under arms. </li></ul>
  48. 49. Clinical features <ul><li>Oligomenorrhoea 30-50% </li></ul><ul><li>Amenorrhoea 20-50% </li></ul><ul><li>Hirsutism 65-70% </li></ul><ul><li>Acne 27-35% </li></ul><ul><li>Alopecia 3-5% </li></ul><ul><li>Infertility 20-75% </li></ul><ul><li>Overweight 40% </li></ul><ul><ul><li>but obesity increases severity therefore those worst affected are likely to be obese </li></ul></ul>
  49. 51. Diagnostic Criteria of PCOS <ul><li>after the exclusion of related disorders, by two of the following three features: </li></ul><ul><li>1) oligo- or anovulation; </li></ul><ul><li>2) clinical and/or biochemical signs of hyperandrogenism; </li></ul><ul><li>3) polycystic ovaries. </li></ul><ul><li>expert conference held in </li></ul><ul><li>Rotterdam in May 2003 </li></ul><ul><li>defined PCOS </li></ul>
  50. 52. Long term risks of PCOS <ul><li>Type 2 diabetes </li></ul><ul><li>Cardiovascular disease </li></ul><ul><li>Infertility </li></ul><ul><li>Miscarriage </li></ul><ul><li>Gestational DM </li></ul><ul><li>Endometrial cancer </li></ul>
  51. 53. Mechanism of PCOS <ul><li>Complicated and unclearly knowed </li></ul>
  52. 54. Treatment <ul><li>If pregnancy is desired ------ induce ovulation </li></ul><ul><li>anti-estrogens(clomiphene) </li></ul><ul><li>Gonadotropins </li></ul><ul><li>insulin-lowering agents </li></ul><ul><li>anti-androgens (agents that lower </li></ul><ul><li>androgen levels) </li></ul><ul><li>gonadotropin releasing hormone </li></ul><ul><li>agonists (GnRHa) </li></ul>
  53. 55. <ul><li>If pregnancy is not desired </li></ul><ul><li>to reduce the risk of endometrial cancer ( birth control pills) </li></ul><ul><li>anti-androgens. </li></ul><ul><li>cyclical progesterone (MPA, Provera) </li></ul><ul><li>insulin-lowering agents (metformin ,Glucophage) </li></ul>Treatment