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

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1 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 % 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

(hyperandrogenism) 1 spironolactone cyproterone acetate lowdose oral corticosteroids flutamide and GnRH agonists 2 spironolactone (Food and

2 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

Cyproterone acetate (dehydroepiandrosterone, DHEA) 3-beta 17-betahydroxylase (androstenedione) LH/ FSH LH GnRH 5- - 四 Low-dose corticosteroids hydroxysteroid

3 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 / (> 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 ( mg daily) ( ) Flutamide () GnRH agonists (gonadotropin-releasing hormone) Buserelin, nafarelin and leuprolide 40 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun

isotretinoin + retinoid +/- benzoyl peroxide ( ) + +/- retinoid benzoyl peroxide retinoid benzoyl peroxide Adapalene ( A ) tretinoin gel microsphere micronized tretinoin gel retinoid benzoyl peroxide

4 Yaz 128 Cyproterone acetate Spironolactone Low-dose corticosteroids cyproterone acetate 2 mg and ethinylestradiol mg (Diane-35) mg 3 prednisone mg dexamethasone 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 g 50 g ethinyl estradiol g ethinyl estradiol FDA 35 g ethinyl estradiol 藥學雜誌 Jun

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

5 Pharmaceutical Sciences 藥物科學 dehydroepiandrosterone 35 2 二 Cyproterone acetate ( ) (Taiwan Food and Drug Administration TFDA) cyproterone acetate 2 mg and ethinylestradiol 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 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 meq/l < 5 meq/l 72 spironolactone JAMA spironolactone Brigham and Women's Hospital Massachusetts General Hospital ( ) reninangiotensin-aldosterone system angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, -blockers, amiloride hydrochloride, or triamterene (60 ml/ min) meq/l 42 THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun

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

6 7.0 meq/ L < spironolactone spironolactone (0.72%) ( meq/l) spironolactone Spironolactone (4.00) 2014 (clinical 藥物科學 meq/l meq/l laboratory fee schedule by the Centers for Medicare & Medicaid Services) spironolactone 伍結論 spironolactone flutamide FDA 3 spironolactone 6 spironolactone 藥學雜誌 Jun

7 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): Bettoli V, Zauli S, Virgili A: Is hormonal treatment still an option in acne today? Br J Dermatol ;172 Suppl 1: 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 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): Plovanich M, Weng QY, Mostaghimi A: Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne. JAMA Dermatol. 2015;151(9): THE JOURNAL OF TAIWAN PHARMACY Vol.32 No.2 Jun

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

Ferriman-Gallwey 資料來源 : 參考資料 ) testosterone 150 ng/dl (5.2 nmol/ L) free testosterone2 ng/dl (0.07 nmol/l) DHEA-S700 mcg/dl (13.6 µmol/l

Ferriman-Gallwey 資料來源 : 參考資料 ) testosterone 150 ng/dl (5.2 nmol/ L) free testosterone2 ng/dl (0.07 nmol/l) DHEA-S700 mcg/dl (13.6 µmol/l 家庭醫業前言及定義病態生理學 F e r r i m a n - G a l l w e y hirsutism scoring system 9 04 Ferriman-Gallwey score8 (hirsutism) hypertrichosis hypertrichosis hirsutism androgen t e s t o s t e r o n e d i h y d r o