Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Menopausal Transition 彰化基督教醫院 主治醫師黃志成 Definitions zMenopause {A point in time that follows 1 year after the cessation of menstruation zPostmenopause • Those years following this point zPremature ovarian failure {Cessation of menses before age 40 {Associated with an elevated follicle-stimulating hormone (FSH) level 1 Definitions zPerimenopause or climacteric {The time period in the late reproductive years {Usually late 40s to early 50s zBegins with menstrual cycle irregularity zExtends to 1 year after permanent cessation of menses {The more correct terminology for this time is menopausal transition zTypically develops over a span of 4 to 7 years zAverage age at its onset is 47 years Symptoms associated with menopausal transition zChanges in menstrual patterns {Shorter cycles are typical (by 2-7 days) {Longer cycles are possible zVasomotor symptoms {Hot flushes {Night sweats {Sleep disturbances 2 Symptoms associated with menopausal transition zPsychological and mental disturbances {Worsening premenstrual syndrome {Depression {Irritability {Mood swings {Loss of concentration {Poor memory zSexual dysfunction {Vaginal dryness {Decreased libido Symptoms associated with menopausal transition zSomatic symptoms {Headache {Dizziness {Palpitations {Breast pain and enlargement {Joint aches and back pain zOther symptoms {Urinary symptoms {Dry, itchy skin {Weight gain 3 Evaluation of abnormal bleeding zSonography {In postmenopausal women with abnormal bleeding zEndometrial biopsy is not required • If the endometrial thickness is less than 5 mm Evaluation of abnormal bleeding zEndometrial biopsy is indicated in {A premenopausal patient zIf a clinical history suggests long-term unopposed estrogen exposure, even if the endometrial thickness is "normal" (5 to 12 mm) 4 Evaluation of abnormal bleeding zHysteroscopy {Evaluation of focal intrauterine lesions {Targeted biopsy of specific lesions such as zSubmucous leiomyomas zEndometrial polyps zFocal areas of endometrial hyperplasia zEndometrial cancer Vasomotor symptoms zHot flashes, hot flushes, and night sweats zThe incidence of hot flushes {10 percent during the premenopausal period {Approximately 50 percent after cessation of menses 5 Vasomotor symptoms zHot flushes {Begin an average of 2 years before the FMP {85 percent of women who experience them will continue to experience them for more than 1 year {Of these women z25 to 50 percent will have hot flushes for 5 years z15 percent may experience them for >15 years Vasomotor symptoms z Hot flush {Generally lasts 1 to 5 minutes {Skin temperatures rise because of peripheral vasodilation z This change is particularly marked in the fingers and toes • Where skin temperature can increase 10 to 15°C {Most women sense a sudden wave of heat z Spreads over the body • Particularly on the upper body and face z Sweating begins primarily on the upper body z Sweating has been observed in women during 90 percent of hot flushes 6 Vasomotor symptoms zIncreases in both awake and sleep systolic blood pressure are noted with hot flushes zHeart rate increases 7 to 15 beats per minute {At approximately the same time as peripheral vasodilatation and sweating zHeart rate and skin blood flow {Usually peak within 3 minutes of the onset of the hot flush Vasomotor symptoms zSimultaneously with sweating and peripheral vasodilation {The metabolic rate also significantly rises zHot flushes may also be accompanied by {Palpitations, anxiety, irritability, and panic 7 Vasomotor symptoms zFive to 9 minutes after a hot flush begins, {Core temperature decreases 0.1 to 0.9°C zDue to heat loss from perspiration and increased peripheral vasodilation zIf the heat loss and sweating is significant {May experience chills zSkin temperature gradually returns to normal {Sometimes taking 30 minutes or longer Pathophysiology of vasomoter symptoms zThe medial preoptic area of the hypothalamus {Contains the thermoregulatory nucleus {Responsible for regulating perspiration and vasodilatation zIf exposed to temperature changes {This nucleus activates these heat dissipation mechanisms zThese maintain core body temperature in a regulated normal range 8 Pathophysiology of vasomoter symptoms zEstrogens play a vital role in the development of hot flushes zWomen with gonadal dysgenesis (Turner syndrome) {Who lack normal estrogen levels {Do not experience hot flushes zUnless first exposed to estrogen • Then withdrawn from treatment Pathophysiology of vasomoter symptoms zNeurotransmitter {Altered neurotransmitter concentrations zMay create • A narrow thermoregulatory zone and a lowered sweating threshold y Even subtle changes in core body temperature may trigger heat loss mechanisms 9 Pathophysiology of vasomoter symptoms zNorepinephrine {The primary neurotransmitter zResponsible for • Lowering the thermoregulatory setpoint zTriggering the • Heat loss mechanisms associated with hot flushes {Plasma levels of norepinephrine metabolites zIncreased before and during hot flushes Pathophysiology of vasomoter symptoms zThat norepinephrine injections {Can increase core body temperature zInduce a heat loss response zConversely {Medications that decrease norepinephrine levels zMay reduce vasomotor symptoms 10 Pathophysiology of vasomoter symptoms z Estrogens {Are known to modulate adrenergic receptors in many tissues z Freedman and colleagues (2001) suggested {Hypothalamic 2-adrenergic receptors are decreased z By menopause-related decreases in estrogen levels {A decline in presynaptic 2-adrenergic receptors z Leads to increased norepinephrine levels • Thereby causing vasomotor symptoms. Pathophysiology of vasomoter symptoms zSerotonin {Estrogen withdrawal is associated with a decreased blood serotonin level zUpregulation of serotonin receptors in the hypothalamus 11 Pathophysiology of vasomoter symptoms zThat reductions and significant fluctuations in estradiol levels {A decline in inhibitory presynaptic 2-adrenergic receptors {An increase in hypothalamic norepinephrine and serotonin release zNorepinephrine and serotonin lower the setpoint in the thermoregulatory nucleus • Allows heat loss mechanisms to be triggered by subtle changes in core body temperature Sleep Dysfunction and Fatigue zWomen may awake several times during the night {May be drenched in sweat zDisturbed sleep can lead to {Fatigue, irritability, depressive symptoms, cognitive dysfunction, and impairment in daily functioning 12 Fatigue prevention instructions z Obtain adequate sleep every night z Exercise regularly to reduce stress z Avoid long work hours and maintain your personal schedule z If stress is environmental, take vacations, switch jobs, or approach your company or family to help resolve sources of your stress z Limit intake of alcohol, drugs, and nicotine z Eat a healthy and well-balanced diet z Drink adequate amounts water (8 to 10 glasses) during the early part of the day z Consider seeing a specialist in menopausal medicine Hormone treatment 彰化基督教醫院 主治醫師黃志成 13 The mature woman zThe typical "mature woman" is {Aged 40 years or older and has completed childbearing {During their late 40s zMost women enter menopausal transition zThis period of physiologic change is usually completed between ages 51 and 56 Current Approach to Hormone Replacement Administration zSummary of Risks and Benefits {Suggest that zOnce coronary heart disease is established • Hormone therapy (HT) has no effect in reversing disease progression {The incidence of cardiovascular events zCan potentially increase in older groups due to an increased risk for blood clots {Benefits are noted with HT zIncreased bone mineral density and decreased rates of fracture and colorectal cancer 14 Summary of Current Use Indications zHT is indicated today only for treatment of {Vasomotor symptoms {Vaginal atrophy {Osteoporosis prevention or treatment zShould be prescribed {In the lowest effective dose {For the shortest period of time Estrogen should not be used in the following conditions z z z z z z z z Undiagnosed abnormal genital bleeding Known, suspected, or history of breast cancer Known or suspected estrogen-dependent neoplasia Active deep vein thrombosis, pulmonary embolism, or history of these conditions Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke or myocardial infarction) Liver dysfunction or disease Known hypersensitivity to the ingredients of the estrogen preparation Known or suspected pregnancy 15 Estrogen should be used with caution in women with the following conditons z Dementia z Gallbladder disease z Hypertriglyceridemia z Prior cholestatic jaundice z Hypothyroidism z Fluid retention plus cardiac or renal dysfunction z Severe hypocalcemia z Prior endometriosis z Hepatic hemangiomas "Bioidentical" Hormones zThe FDA pronounced: {"Other doses of CEE and MPA, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials, and in the absence of comparable data, these risks should be assumed to be similar". zThus, these hormones cannot be assumed to be safer than conventional pharmaceutical estrogen or progestins 16 Nonhormonal agents used as therapy for vasomotor symptoms z Prescriptions (brand name) z SSRI { Venlafaxine (effexor) { Fluoxetine (prozac, sarafem) { Paroxetine (paxil) z z z z Clonidine (catapres) Gabapentin (neurontin) Mirtazapine (remeron) Trazodone (desyrel) z z z z Nonprescription Black cohosh Dong quai Red clover { Isoflavones z Soy isoflavones z Vitamin E SSRI = selective serotonin reuptake inhibitor Complementary and Alternative Medicine zPhytoestrogens (isoflavones) {Plant-derived compounds {Bind to estrogen receptors zHave both estrogen agonist and antagonist properties {They are found in soy products and red clover (苜蓿) {Small studies evaluating their effectiveness for the treatment of vasomotor symptoms zNo efficacy or mixed results 17 Complementary and Alternative Medicine zSoy products {The effects of soy protein found in various food preparations are not bioequivalent {For example zThe alcohol processing • Often used in the manufacture of tofu and soymilk • Removes the biologically active forms y The aglyconic isoflavones Complementary and Alternative Medicine zFlaxseed(亞麻籽) or flaxseed oil (Linum usitatissimum) {Rich in -linolenic acid, a form of omega-3 fatty acid {Also known as linseed, flaxseed is touted(招徠) to reduce zInflammation, bone turnover, heart disease, cancer, diabetes, and cholesterol levels zFor perimenopausal women, it also is purported(傳說 的) to protect against breast cancer, hot flushes, and mood disturbances 18 Complementary and Alternative Medicine zRed Clover {It contains at least four estrogenic isoflavones zMarketed as a source of phytoestrogens {A randomized controlled trial of 252 women studied hot flush frequency in women given red clover isoflavone extracts and placebo over 12 weeks zNo significant change in hot flush frequency was reported between groups receiving isoflavones and those given placebo Complementary and Alternative Medicine zDong Quai {Within traditional Chinese medicine (TCM) practice zDong quai is suggested to • Regulate and balance the menstrual cycle, strengthen the uterus, and enrich the blood zIt is also said to exert estrogenic activity {However, its benefit cannot be substantiated based on available evidence. 19 Complementary and Alternative Medicine zBlack Cohosh(升麻) {The root of the herb Cimifuga racemosa is also thought to have estrogenic properties zThe mechanism of action is unknown {In a randomized placebo-controlled trial in 85 women zIt did not decrease the frequency of vasomotor symptoms compared with placebo Complementary and Alternative Medicine zPhytoprogestins {Extracts, tablets, and creams derived from yams(山芋類植物;山藥;馬鈴薯) zTo be progesterone substitutes zA natural source of dehydroepiandrosterone (DHEA) {Based on the lack of bioavailability zThe hormones in wild and Mexican yam would not be expected to have efficacy {No published reports demonstrating the effectiveness of wild yam cream for postmenopausal symptoms 20 Complementary and Alternative Medicine zVitamin E {In 125 women with a history of breast cancer zVitamin E produced a 25-percent reduction in hot flushes compared with a 22-percent reduction with placebo zA decrease of one hot flush per person per day The end IMS updated recommendations on postmenopausal hormone therapy IMS: international menopause society Climateric 2007;10:181-194 彰化基督教醫院 主治醫師黃志成 21 Introduction zThese recommendations were reviewed and discussed by representatives of more than 60 National and Regional Menopause Socoieties from all continents Governing principles zA spontaneous or iatrogenic menopause {Before the age of 45 years and particularly before 40 zAre at higher risk for cardiovascular disease and osteoporosis zHormone replacement should be given at least until the normal age of menopause 22 Governing principles zDosage should be titrated to the lowest effective dose zLower doses of HT {Can maintain quality of life in a large proportion of users {Long-term data regarding fracture risk and cardiovascular implications zStill lacking Governing principles zLow-dose vaginal estrogens {Do not require progestogen co-medication zAndrogen replacement {Reserved for women with clinical signs and symptoms of androgen insufficiency {Bilateral oophorectmy or adrenal failure 23 Benefits of hormone therapy zEffective in preventing the bone loss zEven lower than standard-dose preprarations {Maintain a positive influence on bone indices zStandard-dose HT {Not recommended for the sole purpose of the prevention of fractures after the age of 60 years Postmenopausal osteoporosis Benefits of hormone therapy zThe initiation of HT dose not cause early harm and in fact reduces cardiovascular morbidity and mortality in {Women less than 60 year old {Recently menopausal {Without prevalent cardiovasular disease Cardiovascular disease 24 Benefits of hormone therapy zContinuation of HT beyond the age of 60 {Should be decided as a part of the overall riskbenefit analysis Cardiovascular disease Benefits of hormone therapy zBenefits for connective tissue, skin, joints and intervertebral disks zReduce the risk of colon cancer zInitiated around the time of menopause or by younger postmenopausal women {Reduced risk of Alzheimer’s disease Other benefits 25 Potential serious adverse effects of hormone therapy zMillion Women Study {Risk was increased as early as the first year zWomen’s Health Initiative(WHI) study {No increased risk zIn women initiating HT, for up to 7 years Breast cancer Potential serious adverse effects of hormone therapy zWHI and Nurses’ Health Study suggest {Long-term estrogen-only for 7 and 15 years, respectively zDoes not increase the risk of breast cancer in American women zRecent European observational studies {Risk may increase after 5 years Breast cancer 26 Potential serious adverse effects of hormone therapy zUnopposed estrogen administration {Dose-related stimulation of the endometrium zContinuous combined estrogenprogestogen regimens {A lower incidence of endometrial hyperplasia and cancer than normal population Endometrial cancer Potential serious adverse effects of hormone therapy zIncreases with age, obesity and thrombophilia zStandard-dose HT {Transient slightly increased risk of coronary events zRiks of stroke {Correlated with age zIncrease the risk after age of 60 Thromboembolism, Cardiovascular events 27 Conclusion zThe safety of HT {Depends on age zYounger than 60 years old • Should not be concerned about the safety profile of HT The end 28