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MENOPAUSAL TRANSITION

MENOPAUSAL TRANSITION. William ’ Gynecology 21th edition. Thanks for listening Q and A. What ’ s the definition of menopausal transition and -5~-1 of reproductive stage for a women? What ’ are risk factors for hot flush? How to D.D. abnormal uterine bleeding?

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MENOPAUSAL TRANSITION

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  1. MENOPAUSAL TRANSITION William’ Gynecology 21th edition

  2. Thanks for listeningQ and A • What’s the definition of menopausal transition and -5~-1 of reproductive stage for a women? • What’ are risk factors for hot flush? • How to D.D. abnormal uterine bleeding? • How to prevent osteoporotic fracture? • … Dr. Bi-Hua Cheng

  3. Dr. Bi-Hua Cheng

  4. Symptoms Associated with Menopausal Transition Dr. Bi-Hua Cheng

  5. Dr. Bi-Hua Cheng

  6. PHYSIOLOGICAL CHANGES 1.Hypothalamus-Pituitary-Ovarian Axis Changes 2.Ovarian Changes 3.Adrenal Steroid Level Changes 4.Sex Hormone-Binding Globulin Level Changes 5.Endometrial Changes Dr. Bi-Hua Cheng

  7. premenopausal ovaries have greater volume and contain follicles, which are seen as multiple, small, anechoic smooth-walled cysts postmenopausal ovaries have smaller volume and are characteristically devoid of follicular structures Dr. Bi-Hua Cheng

  8. 2.Ovarian Changes • Ovarian senescence is a process from birth，primordial follicles are continuously being activated, mature partially, and then regress. 400 ovulatory 40s 700,000 oocytes A more rapid depletion of ovarian follicles Dr. Bi-Hua Cheng

  9. 3.Adrenal Steroid Level Changes 6.2 micromoles • DHEAS concentrations peaked at ages 20 to 30 years, and then decreased steadily. ,and then decreases to 74 percent at aged 70 to 80 years. • Androstenedione peaks at ages 20 to 30 years and then decreases to 62 percent of this peak level in women aged 50 to 60 years. • Pregnenolone diminishes by 45 percent from reproductive life to menopause 1.6 micromoles Dr. Bi-Hua Cheng

  10. Because the ovary contributes to the production of these hormones during the reproductive years, but after menopause, only the adrenal gland continues this hormone synthesis Dr. Bi-Hua Cheng

  11. 5.Endometrial Changes Microscopic changes in the endometrium directly reflect the level of systemic estrogen and progesterone In a proliferative endometrium, the glands are rounded and closely packed and have tall columnar epithelium with mitosis Secretory endometrium shows tortuous glands lined by cells with cytoplasmic and luminal secretions Dr. Bi-Hua Cheng

  12. In pregnancy, these changes become more pronounced with a hypersecretory effect demonstrated by cell clearing and cytoplasmic blebs Inactive endometrial tissue shows only scattered, inactive nonproliferating glands in the basalis. With endometrial atrophy, cystic changes can occur Dr. Bi-Hua Cheng

  13. EVALUATION OF ABNORMAL BLEEDING • Sonography • Endometrial Biopsy: D & C • Hysteroscopy • targeted biopsy: • submucousleiomyomas, • endometrial polyps, or • focal areas of endometrial hyperplasia or • endometrial cancer • with misoprostol 100 mg orally the night before and the morning of scheduled hysteroscopy, to ease cervical dilation. Dr. Bi-Hua Cheng

  14. Central Thermoregulation Changes 1.INCIDENCE 2.VASOMOTOR SYMPTOMS 3.PATHOPHYSIOLOGY OF VASOMOTOR SYMPTOMS 4.Estrogens Dr. Bi-Hua Cheng

  15. Hot Flush- frequently with palpitations, anxiety, irritability, and panic. A. Core body temperature. B. Respiratory exchange ratio. C. Skin temperature. D. Sternal skin conductance. Dr. Bi-Hua Cheng

  16. Interaction between sex steroid hormones and serotonin in the central nervous system (CNS) response • What’s the effects on thermoregulatory in thermoregulatory zone ? • Neurotransmitters besides estrogen • Norepinephrine • Serotonin Dr. Bi-Hua Cheng

  17. 1.Hypothalamus-Pituitary-Ovarian Axis Changes Dr. Bi-Hua Cheng

  18. This hypothesis is supported by the fact that women with gonadal dysgenesis (Turner syndrome), do not experience hot flushes • Estrogen stabilizes the CNS thermoregulatory set point and leads to a normal response. Dr. Bi-Hua Cheng

  19. During menopausal transition, decreased estrogen levels lead to instability of the set point and an altered response to externalthermal stimuli. Dr. Bi-Hua Cheng

  20. Gradually over time, the set point becomes stable again. Alternatively, pharmacologic intervention with exogenous estrogen or selective serotonin reuptake inhibitors (SSRIs) may also stabilize the set point Dr. Bi-Hua Cheng

  21. Take home message -1Norepinephrine & Serotonin • Significant fluctuations in estradiol levels lead to a decline in inhibitory presynaptic 2-adrenergic receptors and an increase in hypothalamic norepinephrine and serotonin release • Norepinephrine and serotonin lowerthe set-point in the thermoregulatory nucleus and allows heat loss mechanisms to be triggered by subtle changes in core body temperature. Dr. Bi-Hua Cheng

  22. Sleep Dysfunction and Fatigue • fatigue, irritability, • depressive symptoms, • cognitive dysfunction, and • impairment in daily functioning. Dr. Bi-Hua Cheng

  23. Insomnia by Severity of Hot Flushes and Menopausal Symptoms Ohayon (2006) Dr. Bi-Hua Cheng

  24. Fatigue Prevention Instructions • Obtain adequate sleep every night • Exercise regularlyto reduce stress • Avoid long work hours and maintain your personal schedule • If stress isenvironmental, take vacations, switch jobs, or approach your company or family to help resolve sources of your stress • Limit intake of alcohol, drugs, and nicotine • Eat a healthy and well-balanced diet • Drink adequate amounts water (8 to 10 glasses) during the early part of the day • Consider seeing a specialist in menopausal medicine Dr. Bi-Hua Cheng

  25. Osteoporosis 1. Osteoporosis sequel 2. Pathophysiology 3. Diagnosis 4. Prevention 5. Treatment Dr. Bi-Hua Cheng

  26. 1. Osteoporosis sequelae • Mortality：the risk of dying following a clinical fracture (especially hip fracture) is twofold higher than for persons without fractures Dr. Bi-Hua Cheng

  27. 2. Pathophysiology • Both aging and menopausal estrogen deficiency lead to a significant increase in osteoclastic activity. Dr. Bi-Hua Cheng

  28. Dr. Bi-Hua Cheng

  29. A. DEXA report describing normal hip density. • B. DEXA report describing osteopenia of the hip Dr. Bi-Hua Cheng

  30. A.DEXA report describing normal vertebral body density. B.DEXA report describing vertebral body osteoporosis. Dr. Bi-Hua Cheng

  31. For each standard deviation of BMD below a baseline level,the fracture risk approximately doubles 。 (National Osteoporosis Foundation, 2003). Dr. Bi-Hua Cheng

  32. 4. Prevention Dr. Bi-Hua Cheng

  33. Having trouble with the FRAX tool? Dr. Bi-Hua Cheng

  34. 吸菸、喝酒及類固醇 • 每日飲用酒精3單位或以上 若患者每日飲用酒精3單位或以上選擇為是1單位的酒精含量因不同國家而有些微差別介於8-10克之間相當於1杯標準杯啤酒（285毫升）、1小杯烈酒（30毫升）、1中杯葡萄酒（120毫升）或1杯開胃酒（60毫升） • 這些危險因子會因攝入劑量有所差異。例如，攝入量越大，危險性越大。攝入量未被考量在內，預測是以假設平均劑量去計算。攝入量的低或高應透過臨床判斷。 Dr. Bi-Hua Cheng

  35. Teriparatide 衛生署核准之適應症 在健保給付規範方面 ，自94年5月1日起修正施行之給付規定為： 用於因嚴重骨質疏鬆症而造成二個（含）以上脊椎或一個髖骨骨折之患者、 使用期限不得逾18個月、 以X光或DXA形態測定時，應將壓迫性程度記錄於報告中、 不得併用biphosphonates、calcitonin、 raloxifene及活性維生素D3等藥物 • 主要是停經後婦女骨質疏鬆症具高度骨折風險者， • 以及男性原發性或次發性的腺功能低下之骨質疏鬆症且具高度骨折風險者。 Dr. Bi-Hua Cheng

  36. Dr. Bi-Hua Cheng

  37. Alendronate 作用機轉 / 適應症/副作用 作用機轉 副作用 頭痛 腹痛 便秘 消化不良 食道潰瘍 骨骼肌肉疼痛(骨頭、肌肉、關節) • 為bisphosphonate類藥物，可抑制蝕骨細胞所引起之骨再吸收作用。 適應症 • 停經婦女骨質疏鬆症 • 男性骨質疏鬆症

  38. Bisphosphonate 用法用量 • 使用方式為每週一次，每次口服一顆70mg錠劑

  39. Alendronate/Bisphosphonate禁忌症 • 低血鈣症 • 無法站立或坐直至少30分鐘者 • 對Alendronate、其他雙磷酸鹽藥物或任何成分過敏者 • 會延遲食道排空的食道疾病與某些狀況，如食道狹窄或弛緩不能

  40. Alendronate + 維生素D的討論要點 • 接受Alendronate治療的病患，必須攝取足夠的維生素D和鈣 • NOF於2010年強調 : • 年齡 • 鈣 • 維生素D • 所有現行的骨質疏鬆症治療準則皆建議使用Alendronate • 必須確定攝取足夠的鈣質及維生素D 美國國家骨質疏鬆症基金(NOF)

  41. Alendronate + 維生素D Alendronate與維生素D補充劑分開使用 • 靈活度較佳，可依目前攝取的維生素D來調整維生素D劑量 • 避免高劑量維生素D的不良反應 • 若給予Alendronate Sandoz處方，可搭配隨手可得的維生素D補充劑，費用更划算 • 自100年1月1日起，活性維生素D3製劑，被付於停經後婦女患有脊椎壓迫性骨折或髖骨骨折病患。 美國國家骨質疏鬆症基金(NOF)

  42. Dr. Bi-Hua Cheng

  43. Mean percentage change in Bone mneral density at Lumbar Spine (Panel A), Femoral Neck (B), Trochonter (C), Total Hip (D), Total body (E) and Urinary N-Telopeptides of type I Collagen (F) 10 mg alendronate 5 mg alendronate Discontinue Dr. Bi-Hua Cheng

  44. Height loss Women with non-vertebrae fractures No/100 subject-yr Dr. Bi-Hua Cheng

  45. Cardiovascular Changes CARDIOVASCULAR DISEASE RISK CARDIOVASCULAR DISEASE PREVENTION Physical activity -walking  central obesity Atherogenic lipid HDL ( ≥ 55~60 mg) Dietary modification Estrogen treatment Lipid-lowering medication • CVD history • Hypertension • Smoking • DM • Abnormal lipid profile • Obesity • Age • 2x~6X after menopause • 3x Cholesterol > 265 mg Dr. Bi-Hua Cheng

  46. Weight Gain and Fat Distribution - reduction of metabolic rate 45-54 y/o Since menopausal transition Insulin resistance Diabetes mellitus Genetic factors Neuropeptides Adrenergic nervous system activity Loss of muscle mass with aging • Significantly greater increase in weight and hip circumference than 55-65 y/o • Less physical activity • Less Work activity • HRT may decrease slightly the rate of age-related increases. Dr. Bi-Hua Cheng

  47. Central Nervous System) Sleep dysfunction (sleep fragmentation) : Cognitive dysfunction (during menopausal transition) depression, mood changes, poor concentration impaired memory commonly associated with • hot flushes, • nocturia, • urinary frequency, • urgency daytime fatigue, mood liability, irritability, and problems with short-term memory Dr. Bi-Hua Cheng

  48. Psychosocial Changes Well-being in midlife? Libido Changes recurrent depression hormonal fluctuations physical and mental health smoking marital satisfaction sexual desire and activity  Women reported loss of libido, dyspareunia, and orgasmic dysfunction, with 86 percent reporting no orgasms after menopause (Tungphaisal, 1991) • Dermatologic changes • Dental Changes • Breast Changes • interpersonal stress, • Psychosomatic S, premenstrual symptoms ? • attitude to menopause • current perceived health status • Psychosocial factors ? Dr. Bi-Hua Cheng

  49. Urogenital pathologyUrinary symptoms Etiology Thinning of urethral and bladder mucosa urethritis with dysuria, urge incontinence, and urinary frequency there are estrogen and progesterone receptors in • pelvic floor muscles • pelvic floor ligaments • vulva • Vagina mucosa • bladder mucosa Dr. Bi-Hua Cheng

  50. Prolapse of vaginal wall Dr. Bi-Hua Cheng

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