2016年12月29日 星期四

更年期女性服用荷爾蒙,小心引發或加重耳鳴!

陽明大學腦科學博士/國軍桃園總醫院耳鼻喉科主任  郭錦龍醫師

更年期症候群


更年期症候群
女性過了40歲以後,開始進入更年期,卵巢濾泡功能逐漸衰退,不再分泌女性荷爾蒙(包括雌激素estrogen及黃體素progesterone)。一開始月經不一定會立刻停止,但月經週期會變得不規律,可能過期不來或形成亂經,最後就停經了。由於卵巢不再分泌雌激素,身體開始出現許多不適症狀,包括熱潮紅、盜汗、心悸、失眠、憂慮、易怒、失眠、性慾減退等,這些症狀合稱為「更年期症候群」。為了改善更年期症候群,臨床醫師會給予更年期女性「荷爾蒙補充療法(Hormone Replacement TherapyMenopause Hormone Therapy)」,包括單獨使用雌激素或合併使用黃體素[1-3]


荷爾蒙補充療法的後遺症
美國國家衛生研究院(National Institutes of Health)所屬之女性健康促進會(Women's Health Initiative)研究約二萬七千位停經後女性發現(平均年紀63)使用荷爾蒙補充療法會導致許多嚴重後遺症,包括乳癌、冠狀動脈心臟病、中風及靜脈栓塞[4-6]。有鑑於此,美國內分泌醫學會於2015年發表最新的更年期症候群治療指引[3]。專家們一致認為只有針對小於60歲或停經後10年內的女性,使用荷爾蒙補充療法才會利大於弊;反之,荷爾蒙療法後遺症風險過高,不建議使用。因此,臨床醫師必須依照個別風險考量及病人意願提供病患個別化的治療選擇,尤其如果病人本身是乳癌或心血管高風險族群,不建議荷爾蒙補充療法[3]。荷爾蒙補充療法可能出現的後遺症經過數十年的大型研究已經廣為人知,包括乳癌[7]、冠狀動脈心臟病[8]、中風[9]及靜脈栓塞[10]等,但一項鮮少被臨床醫師注意到的後遺症就是可能會傷害聽覺系統,造成聽力受損並引發耳鳴[11-13]


英國案例
一位45歲的英國女性在切除子宮後,開始荷爾蒙補充療法(oestradiol,商品名Climaval)。然而,荷爾蒙治療不到兩天後,她的左耳出現耳鳴的情形,緊接著左耳聽力也開始惡化。她的醫師隨即停止荷爾蒙補充療法,並給予口服類固醇。三天後聽力恢復正常,耳鳴也不再出現。由於病患子宮摘除後,仍有補充雌激素的需要,6週後醫師建議重新補充荷爾蒙,為了避免耳鳴及聽損等後遺症,改服用另一種雌激素(conjugated estrogen,商品名Premarin)。結果服用後,再度出現耳鳴及聽力受損的情形[11]


荷爾蒙補充療法導致耳鳴之機轉
荷爾蒙補充療法造成聽覺系統受損併引發耳鳴的機轉十分複雜。根據研究發現,雌激素及黃體素會改變體內組織電解質的平衡,破壞內耳淋巴液的恆定,內耳聽覺受器也受到破壞,導致聽神經受損、引發耳鳴[11, 13]。在豚鼠的研究發現雌激素和黃體素皆會造成耳蝸持續性的發炎反應,導致聽覺系統的損害[14]。此外,雌激素對神經組織活化有負面的影響,干擾聽覺神經傳導,最終導致聽力受損及耳鳴[11, 15, 16]


慎用荷爾蒙補充療法
更年期會使女性出現許多不適的症狀,適度地使用荷爾蒙補充療法可以改善更年期症候群。然而,臨床醫師必須依照風險高低及病人意願提供病患個別化的治療選擇。對於更年期症候群不明顯的女性,醫師開立荷爾蒙給病患服用的臨床效益不大,還可能因此造成聽覺系統受損、引發耳鳴;對於更年期症候群不明顯、但飽受耳鳴之苦的女性,給予病患服用荷爾蒙可能導致耳鳴情形更加惡化,不可不慎!


參考文獻
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[2] North American Menopause S. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause 2012;19:257-71.
[3] Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. The Journal of clinical endocrinology and metabolism 2015;100:3975-4011.
[4] Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Jama 2002;288:321-33.
[5] Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. Jama 2004;291:1701-12.
[6] Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. Jama 2013;310:1353-68.
[7] Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. Jama 2003;289:3243-53.
[8] Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, et al. Estrogen plus progestin and the risk of coronary heart disease. The New England journal of medicine 2003;349:523-34.
[9] Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. Jama 2003;289:2673-84.
[10] Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. Estrogen plus progestin and risk of venous thrombosis. Jama 2004;292:1573-80.
[11] Strachan D. Sudden sensorineural deafness and hormone replacement therapy. The Journal of laryngology and otology 1996;110:1148-50.
[12] Guimaraes P, Frisina ST, Mapes F, Tadros SF, Frisina DR, Frisina RD. Progestin negatively affects hearing in aged women. Proceedings of the National Academy of Sciences of the United States of America 2006;103:14246-9.
[13] Price K, Zhu X, Guimaraes PF, Vasilyeva ON, Frisina RD. Hormone replacement therapy diminishes hearing in peri-menopausal mice. Hearing research 2009;252:29-36.
[14] Bittar RS, Cruz OL, Lorenzi MC, Marone SA, Miniti A. Morphological and functional study of the cochlea after administration of estrogen and progesterone in the guinea pig. The international tinnitus journal 2001;7:41-5.
[15] Kelly MJ, Moss RL, Dudley CA. Differential sensitivity of preoptic-septal neurons to microelectrophoresed estrogen during the estrous cycle. Brain research 1976;114:152-7.
[16] Silva NL, Boulant JA. Effects of testosterone, estradiol, and temperature on neurons in preoptic tissue slices. The American journal of physiology 1986;250:R625-32.

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