Pharmaceutical Sciences 藥物科學荷爾蒙療法痤瘡用藥新觀點 義大醫院藥劑部藥師李旻芬 黃信裕 劉千慈 項怡平 摘要 (anti-androgens) cyproterone acetate spironolactone flutamide (low-dose glucocorticoids) (gonadotropin-releasing hormone agonists) spironolactone JAMA spironolactone 壹 前言 2009 10 1 81% 15% 30% isotretinoin (hyperandrogenism) 1 spironolactone cyproterone acetate lowdose oral corticosteroids flutamide and GnRH agonists 2 spironolactone (Food and Drug Administration, FDA) () FDA spironolacton spironolactone 2015 貳 各種藥物治療痤瘡有關的荷爾蒙 2 作用機轉 一 複方口服避孕藥 38 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016
FSH LH 5- - (5-alpha reductase) (sex hormone binding globulin, SHBG) (testosterone) () 2 2 表一各種藥物治療痤瘡有關的荷爾蒙作用機轉 Ethinylestradiol Cyproterone Low-dose GnRH Spironolactone Flutamide acetate corticosteroids agonists 5-alpha-reductase (SHBG, sex hormone binding globulin) 二 Cyproterone acetate (dehydrotestosterone, DHT) Cyproterone acetate (dehydroepiandrosterone, DHEA) 3-beta 17-betahydroxylase (androstenedione) LH/ FSH LH GnRH 5- - 四 Low-dose corticosteroids hydroxysteroid dehydrogenase (androstenedione) (linoleic acid) 21-hydroxylase 11-hydroxylase 三 Spironolactone 參 治療痤瘡荷爾蒙療法藥物之使用 與優 缺點 (sex hormone binding protein, SHBG) 322 Jun. 30 2016
Pharmaceutical Sciences 藥物科學 () benzoyl peroxide, azelaic acid retinoids 2,4 isotretinoin 2 () 2 () 4 表二治療痤瘡藥物療法 / (> 0.5-1 cm ) / retinoid + +/- benzoyl peroxide ( ) + retinoid Azelaic acid +/- benzoyl peroxide retinoid +/- benzoyl peroxide retinoid + + benzoyl peroxide + retinoid +/- benzoyl peroxide ( ) isotretinoin + retinoid +/- benzoyl peroxide ( ) + +/- retinoid benzoyl peroxide retinoid benzoyl peroxide Adapalene ( A ) tretinoin gel microsphere micronized tretinoin gel retinoid benzoyl peroxide adapalene benzoyl peroxide (Epiduo) 2 表三荷爾蒙治療痤瘡藥物優點和缺點 (combined oral contraceptives, COCs) Cyproterone acetate Spironolactone Low-dose corticosteroids prednisone (2.5-5 mg daily) or dexamethasone (0.25-0.75 mg daily) 1. 2. 1. 2. ( ) Flutamide () GnRH agonists (gonadotropin-releasing hormone) Buserelin, nafarelin and leuprolide 40 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016
Yaz 128 Cyproterone acetate Spironolactone Low-dose corticosteroids cyproterone acetate 2 mg and ethinylestradiol 0.035 mg (Diane-35) 121 50 200 mg 3 prednisone 2.5 5 mg dexamethasone 0.25 0.75 mg6 2 (IA) 3 50 mg spironolactone ( IB) spironolactone 100 mg 200 mg flutamide finasteride () 3 Metformin 2 表五治療多囊性卵巢症候群依實證醫學證據等級建議 (Acne) - (Level IV) Combined oral contraceptive pill containing low- or antiandrogenic progestins (Level IA) Addition of spironolactone (Level IB) 藥物科荷爾蒙治療痤瘡藥物使用劑量 學表四 Other antiandrogens: flutamide (Level IB) Metformin (Level III) Level of evidence () level IA evidence includes evidence from metaanalysis of randomized controlled trials; level IB evidence includes evidence from at least 1 randomized controlled trial; level IIB evidence includes evidence from at least 1 other type of experimental study; level III evidence includes evidence from nonexperimental descriptive studies; level IV evidence includes evidence from opinions or clinical experience of respected authorities. 一 複方口服避孕藥 FDA ethinyl estradiol 20/30/35 g/ norethindrone 1 mg (Estrostep), ethinyl estradiol 35 g/norgestimate 180/215/250 g (Ortho Tri-Cyclen), and ethinyl estradiol 20 g/drospirenone 3 mg (Yaz) 5 Yaz drospirenone progestin 17 -spironolactone antiandrogenic antimineralocorticoid antimineralocorticoid estrogen 23,000 estrogen progestin 100 g ethinyl estradiol 30-35 g 50 g ethinyl estradiol 20-25 g ethinyl estradiol FDA 35 g ethinyl estradiol 5 322 藥學雜誌 127 41 Jun. 30 2016
Pharmaceutical Sciences 藥物科學 dehydroepiandrosterone 35 2 二 Cyproterone acetate ( ) (Taiwan Food and Drug Administration TFDA) cyproterone acetate 2 mg and ethinylestradiol 0.035 mg (Diane-35) FDA cyproterone acetate EMA (Pharmacovigilance Risk Assessment Committee, PRAC) cyproterone acetate ethinylestradiol 3 mg drospirenone 1 mg cyproterone acetate 3 三 Spironolactone spironolactone 3 3 mg drospirenone 25 mg spironolactone Yaz spironolactone 4 6 5 eplerenone Addison's disease 四 Low-dose corticosteroids 17-hydroxyprogesterone, DHEA androstenedione ACTH 2 肆 對年輕健康女性治療痤瘡具優勢 6 的藥物 Spironolactone (Aldosterone) 2013 / (American College of Cardiology Foundation and American Heart Association, ACCF/AHA) creatinine spironolactone 33 5.5 meq/l < 5 meq/l 72 spironolactone JAMA spironolactone Brigham and Women's Hospital Massachusetts General Hospital ( ) 2000 12 12014 3 31 reninangiotensin-aldosterone system angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, -blockers, amiloride hydrochloride, or triamterene (60 ml/ min) 3.5-5.0 meq/l 42 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016
7.0 meq/ L 1559 18 45 3941165 191 < 2 974 spironolactone 676 298 spironolactone 141802 13 (0.72%) (5.1-6.0 meq/l) spironolactone 6 1 3 7 Spironolactone (4.00) 2014 (clinical 藥物科學5.1-6.0 meq/l 6.1-6.9 meq/l laboratory fee schedule by the Centers for Medicare & Medicaid Services) 6.27 43.51 78405.02 spironolactone 伍 結論 spironolactone flutamide FDA 3 spironolactone 6 spironolactone 藥學雜誌 127 43 322 Jun. 30 2016
Hormonal Therapy Drugs for Acne New View Min-Fen Li, Hsin-Yu Huang, Chien-Tzu Liu, Yi-Ping Hsiang Department of Pharmacy, E-Da Hospital Pharmaceutical Sciences 藥物科學參考資料 : Abstract Hormonal therapy of endocrine disorders involves acne, polycystic ovary syndrome, hirsutism, alopecia and male hyperandrogenism. Hormonal therapy drugs of acne include combined oral contraceptives, anti-androgen drugs (anti-androgens) such as cyproterone acetate, spironolactone, flutamide, low-dose corticosteroids (low-dose glucocorticoids) and gonadotropin-releasing hormone agents (gonadotropin-releasing hormone agonists). Spironolactone and combined oral contraceptive were common used in hormonal therapy of acne, but the combined oral contraceptive was the preferred. However, a dermatology study published that spironolactone be used for ance of healthy young woman was inexpensive, safe and effective drug in JAMA. 1. Ebede TL, Arch EL, Berson D: Hormonal treatment of acne in women. J Clin Aesthet Dermatol. 2009;2(12):16-22. 2. Bettoli V, Zauli S, Virgili A: Is hormonal treatment still an option in acne today? Br J Dermatol. 2015 ;172 Suppl 1:37-46. 3. Buzney E, Sheu J, Buzney C, et al: Polycystic ovary syndrome: a review for dermatologists: Part II. Treatment. J Am Acad Dermatol. 2014;71(5):859.e1-859.e15; quiz 873-4. 4. Gollnick H, Cunliffe W, Berson D, et al: Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003; 49:S1. 5. Lam C, Zaenglein AL: Contraceptive use in acne. Clin Dermatol. 2014;32(4):502-15. 6. Plovanich M, Weng QY, Mostaghimi A: Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne. JAMA Dermatol. 2015;151(9):941-4. 44 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun. 30 2016