Hirsutizm de Kombine Tedavi
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Hirsutizm de Kombine Tedavi

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Problemi Tanimla Hirsutism derecesini saptaPatofizyolojiyi tanimla Akut veya kronik problemi d?zeltHastayla tedavide basariyi tanimla Takip et. Hirsutism Tedavisi. Tedavi. 1-Genel prensipler - Varsa altta yatan hastaligin tani ve tedavisi - Obezite tedavisi2-Ila? tedavisi -
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Hirsutizm de Kombine Tedavi

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1. Hirsutizm de Kombine Tedavi Dr. Fatih Durmusoglu

2. Problemi Tanimla Hirsutism derecesini sapta Patofizyolojiyi tanimla Akut veya kronik problemi d?zelt Hastayla tedavide basariyi tanimla Takip et Hirsutism Tedavisi

5. Tedavi Overin baskilanmasi OK GnRH analoglari Adrenalin baskilanmasi Glukokortikoidler OK ? DHEA-S s?presyonu Antiandrojenler Spironolakton - Drospirenone Siproteron asetat Flutamid Finasterid

7. Kombine OK Over androgen seviyelerini LH sekresyonunu baskilayici etkisi ile azaltmaktadir. Serum SHBG d?zeylerini arttirmakta ve serbest androgen oranlarini azaltmaktadir. Adrenal kaynakli DHEA-S sekresyonu OK baskisi ile azalmaktadir. OK i?eriginde bulunan progestinler 5 alfa red?ktaz aktivitesini ciltte baskilamakta ve Testosteronun daha g??l? bir androgen olan DHT d?n?s?m?n? engellemektedir. Yeni, d?s?k androjen ve antiandrogenik etkisi olan progestinleri i?eren OK?lar kil follik?l?nde androgenlerle yarisarak periferik androgen bioaktivitesini d?s?rmektedir. Eski ?alismalarda, OK?larin insulin duyarliligini bozdugu bildirilmesine ragmen yeni OK?larla yapilan son ?alismalarda negatif bir etki g?zlenmemistir (ACOG b?lteni no:41). Clinical Endocrinology and Infertility , L Speroff -2011-8th edition

9. Kombine OK

10. Efficacy of a new oral contraceptive containing drospirenone and ethinyl estradiol in the long-term treatment of hirsutism Objective: This study represents long term clinical and biochemical results and the response of different body parts to medical therapy with oral ethinyl estradiol/drospirenone combination in hirsute patients with or without polycystic ovary syndrom (PCOS). Design: Prospective, open, controlled clinical study. Setting: Outpatients at Erciyes University Medical School. Patient(s): Fifty women with moderate to severe hirsutism were recruited. Two women were lost to follow-up. Intervention(s): Women were treated with 3 mg of drospirenone and 30 g of ethinyl estradiol for 12 cycles. Main Outcome Measure(s): Hirsutism was assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system. Serum FSH, LH, total and free testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), and sex-hormone binding globulin (SHBG) levels at 6 and 12 months of therapy were compared with baseline values. Result(s): Total mean FG score declined by 67% and 78% after 6 and 12 months, respectively. Improvement was most prominent on the chest and abdomen, followed by the upper lip and chin. The lowest effect was observed on the back and arms. Serum levels of total and free T and A decreased, whereas SHBG levels increased significantly after 6 and 12 months when compared with baseline levels. Conclusion(s): Drospirenone/ethinyl estradiol combination exerts significant antiandrogenic activity and is effective in improving facial hirsutism. The beneficial effect is most obvious after six cycles and continues thereafter at a slower rate. (Objective: This study represents long term clinical and biochemical results and the response of different body parts to medical therapy with oral ethinyl estradiol/drospirenone combination in hirsute patients with or without polycystic ovary syndrom (PCOS). Design: Prospective, open, controlled clinical study. Setting: Outpatients at Erciyes University Medical School. Patient(s): Fifty women with moderate to severe hirsutism were recruited. Two women were lost to follow-up. Intervention(s): Women were treated with 3 mg of drospirenone and 30 g of ethinyl estradiol for 12 cycles. Main Outcome Measure(s): Hirsutism was assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system. Serum FSH, LH, total and free testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), and sex-hormone binding globulin (SHBG) levels at 6 and 12 months of therapy were compared with baseline values. Result(s): Total mean FG score declined by 67% and 78% after 6 and 12 months, respectively. Improvement was most prominent on the chest and abdomen, followed by the upper lip and chin. The lowest effect was observed on the back and arms. Serum levels of total and free T and A decreased, whereas SHBG levels increased significantly after 6 and 12 months when compared with baseline levels. Conclusion(s): Drospirenone/ethinyl estradiol combination exerts significant antiandrogenic activity and is effective in improving facial hirsutism. The beneficial effect is most obvious after six cycles and continues thereafter at a slower rate. (

11. GnRH agonistleri Serum androgen seviyeleri kastrasyon seviyelerine kadar d?smektedir. OK kombinasyonu ?strojen eksikligi ve osteoporozis semptomlarinda yararli olmaktadir. OK ilavesi ile SHBG de artis ve serbest androgen seviyelerinde azalma saglanmaktadir OK + Antiandrogen tedavisinden daha az etkindir. GnRH analog tedavisinin yan etkilerinin azaltilmasi ve hasta ila? uyumlulugu a?isindan etkin Tek basina GnRH tedavisinden Hirsutizm anlaminda daha etkin degildir. * Antiandrogenlere ?st?nl?g? yok * Daha pahali Pazos F, et all. Fertil Steril 1999; 71: 122-8.

13. Spironolakton * Sentetik steroid * Aldosteron ve androgen antagonisti * DHT resept?rlerini tutar * Androgen sentezi inhibisyonu

14. Spironolakton Aldosteron antagonisti AR afinitesi DHT afinetisinin %67?si Zayif bir progestin, T sentez inhibit?r? ve 5a reduktaz inhibit?r? Rx 2 x 25-100 mg/g?n OK ile beraber kullanilmali. Yan etkileri (adet d?zensizlikleri, poli?ri, bulanti, kusma) y?ksek dozlarda ortaya ?ikmakta. G?venli ve ucuz

15. Spironolakton Yan etkiler 1- Diurezis 2- Gastrointestinal yan etkiler (20%) - Bulanti - Kusma - Diare - Abdominal rahatsizlik 3- N?rolojik yan etkiler (%20) - Somnolans - Mental konf?zyon - Basagrisi - Vertigo 4- Memelerde gerginlik (high dose % 40) 5- Irreg?lar menses (polimenore: %70) 6- Hiperkalemi

16. Spironolakton

18. spironolactone-oral contraceptive vs cyproterone acetate-estrogen Erenus M, Y?celten D, G?rb?z O, Durmusoglu F, Pekin S. Fertil Steril 1996; 66: 216-9. Spironolactone 100 mg/g?n + OC (n:21) CPA 50 mg/d (10 g?n) + EE2 (n: 21), 9 aylik tedavi Benzer etki

19. Cyproterone acetate for severe hirsutism: results of a double-blind dose-ranging study Barth JH, et all. Clin Endocrinol 1991; 35: 5 Dianette + placebo Dianette + 20 mg CPA Dianette + 100 mg CPA CPA: day 1-10 FG ve Hair shaft diameter Dozlar benzer iyilesme sagladi CPA 2 mg y?ksek dozlar kadar etkili

20. Cyproterone acetate or drospirenone containing combined oral contraceptives plus spironolactone or cyproterone acetate for hirsutism: Randomized comparison of three regimens Objective: To compare the effectiveness of three different combinations of combined oral contraceptives (COCs) and antiandrogens in the treatment of hirsutism. Methods: A total of 134 women with moderate and severe hirsutism were randomly assigned to three treatment regimens: Group I received 30 mg of ethinyl estradiol (EE)/3 mg of drospirenone (DRSP) plus 100 mg of cyproterone acetate (CPA) (n = 45); group II received 30 mg of EE/3 mg of DRSP plus 100 mg of spironolactone (n = 44); and group III received 35 mg of EE/2 mg of CPA plus 100 mg of CPA (n = 45), daily for 6 months. The decrease in the modified Ferriman?Gallwey hirsutism score (mFGS) was the main outcome measure. Results: The mean decrease in mFGS after 3 and 6 months of the treatment course was 26% and 49% in group I (both p < 0.01), 27% and 49% in group II (both p < 0.01), and 25% and 45% in group III (both p < 0.01), respectively, when compared with baseline. Although the mFGS was significantly decreased in all groups, there was no significant difference between groups. Conclusion: CPA or DRSP containing COCs in combination with CPA or spironolactone have similar effects for the treatment of hirsutismObjective: To compare the effectiveness of three different combinations of combined oral contraceptives (COCs) and antiandrogens in the treatment of hirsutism. Methods: A total of 134 women with moderate and severe hirsutism were randomly assigned to three treatment regimens: Group I received 30 mg of ethinyl estradiol (EE)/3 mg of drospirenone (DRSP) plus 100 mg of cyproterone acetate (CPA) (n = 45); group II received 30 mg of EE/3 mg of DRSP plus 100 mg of spironolactone (n = 44); and group III received 35 mg of EE/2 mg of CPA plus 100 mg of CPA (n = 45), daily for 6 months. The decrease in the modified Ferriman?Gallwey hirsutism score (mFGS) was the main outcome measure. Results: The mean decrease in mFGS after 3 and 6 months of the treatment course was 26% and 49% in group I (both p < 0.01), 27% and 49% in group II (both p < 0.01), and 25% and 45% in group III (both p < 0.01), respectively, when compared with baseline. Although the mFGS was significantly decreased in all groups, there was no significant difference between groups. Conclusion: CPA or DRSP containing COCs in combination with CPA or spironolactone have similar effects for the treatment of hirsutism

21. Flutamid ? Yan etkiler 1- Kuru cilt 2- Libido azalmasi 3- Bulanti - kusma 4- Karaciger toksisitesi - Anormal transaminaz seviyesi - Kolestatik sarilik - Hepatik nekroz - Hepatik ensefalopati

22. Finasterid * 5 ?-red?ktaz inhibit?r? * Testosteronun DHT?a konversiyonunu inhibe eder * Testosteron sekresyonuna etkisi yoktur

23. Finasterid Tip I.....ciltte Tip II.... prostat ve reprod?ktif dokularda, Erkek fetusun mask?linizasyonundan sorumlu bu nedenle OK kombinasyonu ?nerilmektedir. Rx 1 x 5 mg/g?n Ciddi bir yan etkisi bulunmamakta, sadece minimal hepatik ve renal toksisite.

24. Finasterid

25. Finasteride treatment for one year in 35 hirsute patients Bayram F, M?derris II, Sahin Y, Kelestimur F. Exp Clin Endocrinol Diabetes 1999; 107: 195-7 FG skoru %45 d?st? Iyi tolere edilir, ?nemli yan etkisi yok

27. 42 hasta, 9 ay tedavi * Diane 35 finasteridden daha etkili * Diane ayni zamanda cost effective

28. Metformin Table 2. The effects of metformin on hirsutism score ? Duration Dose N Hirsutism score p value ? (Month) (mg/d) (before treatment) (after treatment) ? Kolodziejczyk et al. 3 1500 35 8.11?0.73* 7.86?0.7 ? .05 ? Kelly et. al. 6 1500 10 17.7?1.4** 15.8?1.4 ? .002 ? Ibanez et al. 6 1275 10 16.6?1.4** 10.7?1.3 ? .001 ? Morin-Papunen et al. 6 1000-2000 8 10.3?1.9*** 10.0?1.9 NS ? Pasquali et al. 6 1700 10 14.8?7.5** 12.9?7.6 ? .05 Harborne et al. 12 1500 18 20.3 (cl, 17.8-22.9) ** < .01 ? Sahin Y, Kelestimur F. Medical Treatment Regimens of Hirsutism. RBM Onlinee 2004

29. Sonu?lar Ins?lin sensitizanlar: metformin, rosiglitazon * ?alismalar yetersiz. * Obez ve ins?lin rezistansi olanlarda etkili olabilir. * Antiandrojenlerle kombinasyonu: ? Sahin Y, Kelestimur F. Reproductive BioMedicine Onlinee 2004 *** 9 Plasebo kontroll? yapilan ?alismada Hirsutizm tedavisinde Metformin t?r? ila?larin etkinligi g?sterilememistir. *** Leon Speroff 2011 Clinical Gynecologic Endocrinology and Infertility

30. Tedavi sonrasi n?ks oranlari

31. Anahtar noktalar ve sonu? Medikal tedaviye yanit yavas olmakta ve 6 aylik zamana gerek vardir.Bu s?re kil folik?l?n?n yasam siklusu ile de baglantilidir. Hirsutizm tedavisinde ilk basamak tedavi kombine OK haplaridir. Kombine OK tedavisine yetersiz yanitta antiandrojen ve tercihan Spironalactone ilavesi uygundur. Tedaviye rezistan olgularda GnRH uygundur fakat OK ile add-back yapilmasi tercih nedenidir. Hormonal s?presyonu takiben mekanik y?ntemler uygulamasi uygun olacaktir. Leon Speroff 2011 Clinical Gynecologic Endocrinology and Infertility

33. Tedavi maliyetleri


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