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PATHOPHYSILOGY OF CLIMACTERIUM

PATHOPHYSILOGY OF CLIMACTERIUM. Definition s. Menopause Premenopause Postmenopause Perimenopause. LAST MENSTRUAL PERIOD -4 -3 -2 -1 0 1 2 3 4 5 6. PREMENOPAUSE. POSTMENOPAUSE. PERIMENOPAUSE. Premenopause. beginning - 45,1 years (39-51 )

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PATHOPHYSILOGY OF CLIMACTERIUM

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  1. PATHOPHYSILOGY OF CLIMACTERIUM

  2. Definitions • Menopause • Premenopause • Postmenopause • Perimenopause

  3. LAST MENSTRUAL PERIOD • -4 -3 -2 -1 0 1 2 3 4 5 6 PREMENOPAUSE POSTMENOPAUSE PERIMENOPAUSE

  4. Premenopause • beginning - 45,1 years (39-51 ) • mean time of duration 4 years (2-8 ) Treolar i wsp. ( study of 2700 patients)

  5. Massachussets Women’s Health Study • median of the premenopausal period began 47,5 years • 10% had no irregular bleeding

  6. Mean age of the menopause occuring 50,2 +/- 3,9 years

  7. FACTORS FLOWING IN ACCELERATE OF MENOPAUSE OCCURING • Social and economical factors • Mountainlife • Smoking !!! • Lost of one ovary in reproductive age • Multiple hyperstimulations • Genetic factors

  8. FACTORS RETARDING OF MENOPAUSE OCCURING • Early menarche • Oral contraceptive • Genetic factors

  9. HORMONAL CHANGESpremenopausal period • FSH growth • Absence of LH pulsation • Decrease level of inhibin • Normal or even sometimes increase level of E2 solidification • Decrease of progesteron

  10. Decline number of oocytesdecrease of inhibin productionFSHgrowthfirst small increase of E2 and then decrease level of E2

  11. HORMONAL CHANGESpostmenopausal period • High levels of FSH i LH • Low level of E2 • Comparatively growth E1 • Less androgen levels • Anrostendion • Testosteron • DHEA i DHEAS

  12. 70 - 80% of womenhave symptoms because of hypoestrogenism

  13. Symptoms • Early • vasomotor • somatic • psychical • atrophic • urinary incontinance • Late • CVD • osteoporosis • changes in central nervous system

  14. Symptoms • Vasomotor symptoms • Hot flushes • Drenching sweat • Nocturnal sweat • Somatic symptoms • Headache , dizzinesses • Hard palpitating • Weight gain • Sleep disorder • Constipations • Psychical symptoms • Irritability • Depression • Attempts of weeping

  15. Hot flushes • They are the subjective sensation of intense warmth of the upper body and range duration from 30 seconds to 5 minutes. • They frequently follow a prodrome of palpations or sensation of presure within the head • They usually end in sweating and cold senasation • The frequency varies from several per year to many per day

  16. Hot flushes • Are result of withdrawal of estrogens in postmenopause , not from hypoestrogenism per se • The loss of estrogen may cause a hypothalamic thermoregulatory instabilisation • They accompanynatural, surgical and „medical” menopause

  17. Other reasons for hot flushes • Carcinoid tumor • Leukaemia • Pheochromocytoma • Thyroid diseases (thyreotoxicosis) • Stress • Psychosomatic disorders • Drugs (nitroglicerine, nifedipine, vancomycin, corticotropin - releasing hormone)

  18. Atrophic symptoms • Atrophic vaginitis • Atrophic changes at external genitals • Urinary stress incontinence • Detrusor overactivity • Atrophic urethritis and trigonitis

  19. Cardiovascular system and estradiol influencing • E2 has beneficial action on lipoprotein levels • There is evidence that estrogens act directly to promote vasodilatation ( the binding of estrogens to endothelial estrogen receptors could stimulate the release of nitric oxide) • Estrogens increasing levels of prostacyclin and decreasing the levels of thromboxane

  20. Lipid metabolism disorders • LDL cholesterol and TG levels growth • Not big decrease of HDL cholesterol levels

  21. Carbohydrate metabolism disorders • We oftener observed • Hyperinsulinemia • Cellular insulin resistance • Diabetes II

  22. ESTROGENS CAN ACT AS ANTIOXIDANT FACTORS

  23. CARDIOVASCULAR DISEASES PREMENOPAUSAL WOMEN APPEAR TO BE PROTECTED AGAINST CVD BY THEIR TYPICALLY LOWER LDL LEVELS AND HIGHER HDL LEVELS, COMPARED WITH MEN IN THE SAME AGE

  24. SYNDROM X • Symptoms of coronary disease • Positive exercise test • Normal coronarogram Kemp 1973 rok

  25. Postmenopausal osteoporosis • Progressive reduction in bone mass in the first years after menopause • Most frequent fractures • Distal radius 55 years • Vertebral bodies 65 years • Famoral neck 75 years

  26. Postmenopausal osteoporosis • Additional risk factors • Cigarettes, coffee, alcohol • Low calcium and vit. D3 consumption • Low body mass index • Sedentary • High protein or phosphate diets • Family history

  27. Postmenopausal osteoporosis • Diagnostic • Method of choice: QDR (quantitive digital radiography) • Excellent precision ( 1-2%) • Lower radiation exposure than tomography • More precision method than ultrasound densitometry

  28. Estrogens and CNS • Facilitate to build the synapses • Antioxidant peculiarities • Accelerate the blood flow in CNS • Escalate metabolism in CNS • Have positive influence on protein metabolism witch are connected with Alzheimer Disease (b-amyloid)

  29. Alzheimer disease • more frequent at women than men • symptoms at women are more severe • hypoestrogenism is one of the most important factors involve in pathogenesis • estrogen treatment relieving symptoms of these disease

  30. Fertility in premenopausal period • FSH > 20 IU/L oraz LH > 30 IU/L • IUD • oral contraceptives with the lowest estrogen solidification

  31. Benefits of OC use in the premenopausal period • frequency of endometrial cancer • frequency of ovarian cancer • mineral bone mass • better control of bleeding

  32. PRACTICAL RECOMENDATIONS FOR HRT IN THE PRE AND POSTEMENOPAUSE. Expert Workshop, February 2004

  33. Teatment in the climacterium period ONLY WHEN THERE ARE INDICATIONS TO THE TREATMENT

  34. Indications for HRT • menopausal symptoms (autonomic disturbances such as hot flushes, sweating, insomia, palpitations etc) • atrophic changes in the urogenital tract and their consequences (EG vaginal dryness, dyspareunia , urinary friquency )

  35. Indications for HRT • Prevention and treatment of postmenopausal osteoporosis • estrogens prevent postmenopausal bone loss and reduce fracture risk • in symptomatic women treated with HRT , the effect of bone mass is major additional benefit • Premature menopause ( is associated with ana accelerated risk of osteoporosis and probably coronary heart disease)

  36. Teatment in the climacterium period • estrogens with progestogens ( in women in the intact uterus ) • only after total or subtotal hysterectomy estrogens alone

  37. Initiation of treatment • Perimenopause • progestogens, if menstrual disturbances are the main symptoms • HRT , if vasomotor symptoms have begun or cycle regulation is needed • OC (preferebly low dose) , if contraception is also needed • Postmenopause – early initiation of HRT in symptomatic patients is major importance

  38. PRINCIPLE OF USE THE LOWEST EFFECTIVE DOSE

  39. HRT DOSE RECOMENDATION • 0,5-1 mg 17B-estradiol • 0,3-45 mg conjugated equine estrogens • 25-37,5 ug transdermal estradiol • 0,5 estradiol gel • 150 ug intranasal estradiol ( only in about 10% of patients higher dose may be required)

  40. DURATION OF TREATMENT Indication, dose and type of HRT should be re-evaluated annually • To relieve menopausal symptoms 2-3 years • For the prevention or treatment osteoporosis only long-term therapy is effective ( HRT may be initial option and then could be followed by SERMs or biphosphonates • To relieve symptoms of urogenital atrophy –long-term topical treatment

  41. DURATION OF TREATMENT • individually • depend on symptoms • no longer then 5-6 years • exceptionally after 60

  42. ROUTES OF ADMINISRTRATION • Oral • Non-oral (lack of the first-pass effect on the liver ) ,may be preferable in women with • Hypertrigliceridemia • Liver diseases • Migraine headaches • Increased risk of venous thrombosis • Vaginal estrogens for women with urogenital symptoms alone

  43. MONITORING TREATMENT • Pretreatment assessment should include: • History and physical examination • Weight • Blood preasure • Mammography • Vaginal ultrasound • Bone mineral density

  44. CONTRAINDICATIONS • Current, pass or suspected breast cancer • Known or suspected estrogen-dependent malignant tumors • Undiagnosed genital bleeding • Untreated endometrial hyperplasia • Previous or current venous thromboembolism • Active or recent arterial thromboembolic disease • Untreated hypertension • Active liver disease • Porphyria • Known hypersensivity to the active substances or to any of the excipiens

  45. Estrogen-progestin therapy • Sequence ( with bleeding) • continuously • cyclically • Continuous without bleeding

  46. Sequence - continuously 28 days of estrogens 10-12 days progestins bleeding

  47. Sequence - cyclically 21 days of estrogens 10-12 days progestins bleeding

  48. Continuous 28 days of estrogens 28 days progestins

  49. HRT AND BREAST CANCER • There is small increase in the incidence of breast cancer in women on long-term HRT with estrogens or estrogen/progestogen combination • There is no definite evidence of any differences between the various estrogens and progestogens in terms of their effect on the risk of breast cancer • Tibolone also increased the risk • The increased risk returns to the never-user of HRT after 5 years of discontinuation of treatment • Breast cancer associated with HRT have better prognosis • Low-dose vaginal estrogen treatment has not been reported to increase breast cancer risk

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