停經荷爾蒙治療之回顧


  【24drs.com】April 8, 2010 — 根據發表於4月份婦產科(Obstetrics & Gynecology)期刊回顧停經前後之荷爾蒙治療角色的研究,必須告知婦女停經症候群之所有治療選項的可能利益與風險及顧慮,且應提供個人化的照護。
  
  波士頓哈佛醫學院與麻州綜合醫院的Jan L. Shifren醫師與Isaac Schiff醫師寫道,隨著Women's Health Initiative(WHI)試驗結果在2002年初次發表之後,荷爾蒙治療的使用急遽減少。停經婦女的主要健康考量包括血管舒縮症狀、泌尿生殖器萎縮、骨質疏鬆、心血管疾病、癌症、認知與情緒。根據最近的發現,有一特殊考量在於,開始荷爾蒙治療的時機對於冠狀動脈疾病的影響,最近對WHI再度分析之後,似乎應該再度評估醫師們對停經的處置方式。
  
  對於停經婦女的生活品質和健康,目前有許多治療選項,荷爾蒙治療的主要適應症為治療血管舒縮熱潮紅與相關症狀,依舊是這些症狀最有效的治療方式,且目前是美國食品藥物管理局唯一核准的選項。對於有血管舒縮症狀、在停經時開始荷爾蒙治療的健康婦女,荷爾蒙治療一般會利大於弊。
  
  不過,荷爾蒙治療與冠心症風險增加有關,根據最近的分析,主要是年長婦女以及已經停經數年之婦女的風險較高,根據這些分析,荷爾蒙治療不應用於預防心臟病,然而,這個證據再度確認荷爾蒙治療可以安全地用於其他方面健康的停經婦女,以處置其熱潮紅和夜間盜汗。
  
  雖然荷爾蒙治療有助於預防和治療骨質疏鬆,它很少單用於此適應症,特別是其他有效的方法耐受良好時。
  
  短期荷爾蒙治療優於長期治療,部分是因為延長使用時與乳癌風險增加有關,應給予最短期間、有效的最低雌激素劑量,因為荷爾蒙治療的風險隨著年紀、停經後期間、使用期間等增加。
  
  如果只有陰道症狀,建議使用低劑量、局部雌激素治療而非全身性荷爾蒙治療。
  
  對於有使用荷爾蒙治療禁忌症或風險增加的婦女,建議使用其他治療方式;這些禁忌症包括乳癌或子宮內膜癌、心血管疾病、血栓異常、活性期肝膽疾病。
  
  除了單用雌激素,單用黃體素或者併用雌激素與黃體素之外,有多種非荷爾蒙方式可用來治療血管舒縮症狀,生活型態介入包括減少體溫、維持健康體重、戒菸、執行放鬆反應技術、接受針灸等等。
  
  雖然並未證實效果大於安慰劑,非處方藥物如異黃酮補充品、大豆製品、黑升麻、維他命E,有時候可以用於治療血管舒縮症狀。
  
  有許多非荷爾蒙類處方藥物有時候被用來治療血管舒縮症狀,但是它們未獲食品藥物管理局核准此用途,屬於非適應症治療,這些藥物與其相關副作用包括:
  * Clonidine經皮貼片,每週0.1-mg,可能的副作用包括口乾、失眠與困倦。
  * Paroxetine (10 - 20 mg/天,控釋劑型為12.5 - 25 mg/天),可能會引起頭痛、噁心、失眠、困倦或性功能障礙。
  * Venlafaxine (緩釋劑型、37.5 - 75 mg/天),相關副作用包括口乾、噁心、便秘與失眠。
  * Gabapentin (每天300 mg - 300 mg、每天3次),可能的副作用包括嗜眠、疲勞、頭昏眼花以及週邊水腫。
  
  作者們寫道,婦女必須被告知所有治療選項的可能利益與風險,必須根據病史、需要與偏好,給予個人化照護,對於提早停經,特別是45歲前者,持續到自然停經的一般年紀之前,使用荷爾蒙治療的好處會超過風險。有關年輕婦女使用口服避孕藥之整體安全性的大量證據,應對那些提早停經者再做確認,特別是較低劑量之雌激素與黃體素的荷爾蒙處方。
  
  Shifren醫師擔任新英格蘭研究中心的科學顧問委員,她是Eli Lilly & Co與Boehringer Ingelheim藥廠的研究顧問,接受Proctor & Gamble Pharmaceuticals藥廠的研究支持。

Hormone Therapy for Menopause Reviewed

By Laurie Barclay, MD
Medscape Medical News

April 8, 2010 — Women must be informed of the potential benefits and risks of all treatment options for menopausal symptoms and concerns and should receive individualized care, according to a review of the role of perimenopausal hormone therapy published in the April issue of Obstetrics & Gynecology.

"With the first publication of the results of the Women's Health Initiative (WHI) trial in 2002, the use of HT [hormone therapy] declined dramatically," write Jan L. Shifren, MD, and Isaac Schiff, MD, from Harvard Medical School and Massachusetts General Hospital in Boston. "Major health concerns of menopausal women include vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, cognition, and mood.... Given recent findings, specifically regarding the effect of the timing of HT initiation on coronary heart disease [CHD] risk, it seems appropriate to reassess the clinician's approach to menopause in the wake of the recent reanalysis of the WHI."

Many therapeutic options are currently available for management of quality of life and health concerns in menopausal women. Treatment of vasomotor hot flushes and associated symptoms is the main indication for hormone therapy, which is still the most effective treatment of these symptoms and is currently the only US Food and Drug Administration–approved option. For healthy women with troublesome vasomotor symptoms who begin hormone therapy at the time of menopause, the benefits of hormone therapy generally outweigh the risks.

However, hormone therapy is associated with a heightened risk for coronary heart disease. Based on recent analyses, this higher risk is attributable primarily to older women and to those who reached menopause several years previously. Hormone therapy should not be used to prevent heart disease, based on these analyses. However, this evidence does offer reassurance that hormone therapy can be used safely in otherwise healthy women at the menopausal transition to manage hot flushes and night sweats.

Although hormone therapy may help prevent and treat osteoporosis, it is seldom used solely for this indication alone, particularly if other effective options are well tolerated.

Short-term treatment with hormone therapy is preferred to long-term treatment, in part because of the increased risk for breast cancer associated with extended use. The lowest effective estrogen dose should be given for the shortest duration required because risks for hormone therapy increase with advancing age, time since menopause, and duration of use.

Low-dose, local estrogen therapy is recommended vs systemic hormone therapy when only vaginal symptoms are present.

Alternatives to hormone therapy should be recommended for women with or at increased risk for disorders that are contraindications to hormone therapy use. These include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active hepatic or gallbladder disease.

In addition to estrogen therapy, progestin alone, and combination estrogen-progestin therapy, there are several nonhormonal options for the treatment of vasomotor symptoms. Lifestyle interventions include reducing body temperature, maintaining a healthy weight, stopping smoking, practicing relaxation response techniques, and receiving acupuncture.

Although efficacy greater than placebo is unproven, nonprescription medications that are sometimes used for treatment of vasomotor symptoms include isoflavone supplements, soy products, black cohosh, and vitamin E.

There are several nonhormonal prescription medications sometimes used off-label for treatment of vasomotor symptoms, but they are not approved by the Food and Drug Administration for this purpose. These drugs, and their accompanying potential adverse effects, include the following:

  • Clonidine, 0.1-mg weekly transdermal patch, with potential adverse effects including dry mouth, insomnia, and drowsiness.
  • Paroxetine (10 - 20 mg/day, controlled release 12.5 - 25 mg/day), which may cause headache, nausea, insomnia, drowsiness, or sexual dysfunction.
  • Venlafaxine (extended release 37.5 - 75 mg/day), which is associated with dry mouth, nausea, constipation, and sleeplessness.
  • Gabapentin (300 mg/day to 300 mg 3 times daily), with possible adverse effects of somnolence, fatigue, dizziness, rash, palpitations, and peripheral edema.

"Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences," the review authors write. "For women experiencing an early menopause, especially before the age of 45 years, the benefits of using HT until the average age of natural menopause likely will significantly outweigh risks. The large body of evidence on the overall safety of oral contraceptives in younger women should be reassuring for those experiencing an early menopause, especially given the much lower estrogen and progestin doses provided by HT formulations."

Dr. Shifren serves as a scientific advisory board member for the New England Research Institutes. She has been a research study consultant for Eli Lilly & Co and Boehringer Ingelheim and has received research support from Proctor & Gamble Pharmaceuticals.

Obstet Gynecol. 2010;115:839-855.

    
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