Polikistik Over Sendromu’nda Bitkisel Tedavi

Paeonia lactiflora (2)

Bitkiler, tedavi ve hastalıklardan korunma amacıyla çok uzun zamandan beri yaygın olarak kullanılmaktadır(1,2,3,8,11,12,13,20,21,22,23). Günümüzde kullanılan ilaçların büyük çoğunluğu bitkilerden elde edilen doğal maddelerin taklit edilmesiyle suni (sentetik) olarak üretilmektedir(4,5,6). Fakat, ilaçların bir kısmı hâlâ bitkilerden elde edilen maddelerden yapılmaya devam etmektedir(4,5,6). Bitkiler, ilaç tedavisinin yerine tek başına veya sentetik ya da bitki kaynaklı ilaçlarla birlikte destek amacıyla kullanılmaktadır(7,8,9,10,11,12,13). Bitkisel tedavi çoğunlukla deneysel çalışmalara bağlı bilimsel verilerin yerine daha çok kuşaktan kuşağa aktarılan gözleme dayalı bilgilere dayanmaktadır. Fakat buna karşılık, özellikle son 50 yıl içinde bitkilerin tedavi amacıyla kullanılması ile ilgili yapılan bilimsel çalışmaların sayısı giderek artmıştır(14,15).

SAKINCALARI

Herba epimedii (2)

1-Hormon bozukluklarında bitkiler miktarı azalmış olan hormonun arttırılması ya da miktarı artmış olan hormonun da azaltılması amacıyla kullanılmaktadır. Bitkilerin gereğinden fazla miktarlarda kullanılması azalmış olan hormonun gereğinden fazla artmasına veya artmış olan hormonun da gereğinden fazla azalmasına neden olmaktadır(10).

2-Bitkilerin gereğinden fazla miktarlarda kullanılmasına bağlı bitkinin içindeki etken maddelerin vücutta birikmesine bağlı karaciğer hasarı görülebilmektedir(24). Zayıflama amacıyla kullanılan bazı bitkisel tedaviler böbrek nakli (transplantasyon) ile sonuçlanan böbrek hasarına (interstitial renal fibrosis) neden olmaktadır(25,26,27,28). Bitkilerin bir kısmı kalp ve damar sistemi üzerine toksik etki göstermektedir. Bu bitkileri kullananlarda kan basıncı düşüklüğü (hipotansiyon), hipertansiyon, çarpıntı, kalp krizi ve kalp yetmezliği ortaya çıkabilmektedir(29,30,31,32,33).

Soğan (Allium cepa) bitkisinin belirli bir miktarın üzerinde kullanılması, içinde bulunan bazı maddeler (thiols, disulfides) nedeniyle soğan zehirlenmesine (toxicity) neden olmaktadır(266). Bu miktar kişiden kişiye göre değişmektedir. Kırmızı kan hücrelerinde (eritrositler) bulunan oksijeni taşıyan maddenin (hemoglobin) içindeki demir (Fe), soğan içinde bulunan maddeler (thiols, disulfides) tarafından oksitlenerek kan hücrelerinin parçalanmasına neden olmaktadır(267,268). Bunun sonucunda bu kişilerde ani başlayan, şiddetli kansızlık (hemolytic anemia) ortaya çıkmaktadır. Kırmızı kan hücrelerini Glucose-6-phosphate dehydrogenase (G6PD) enzimi zararlı maddelere karşı korumaktadır. Türkiye’ de bazı bölgelerde sık görülen G6PD enziminin doğuştan (genetik) eksikliği çoğunlukla hiçbir belirti göstermezken, soğan tüketimi bu kişilerde ani başlayan şiddetli kansızlığa neden olabilmektedir(269,270,271).

Bu tür masum gibi görünen bitkilerin bilinçsizce kullanılması fayda sağlamayacağı gibi hayati tehlikeye de neden olabilmektedir. 

Fructus cnidii (2)

Bazı bitkilerin oluşturduğu allerjik reaksiyon akciğer hasarına (interstitial pneumonitis) neden olmaktadır(34,35). Bitkilerin bir kısmı kan pıhtılaşmasını (coagulation) azaltmaktadır(36,37). Bu bitkileri kullananlarda ameliyat sırasında kanama eğilimi ortaya çıkabilmektedir(36,37,38). Bitkilerin içinde bulunan maddelerin yan etkileri sonucunda bir çok kişi de hastanelerin acil servislerine zehirlenme (toxicity) nedeniyle başvurmak zorunda kalmaktadır(5,39,40,41,45).

3-Bitkisel tedavide bazen tek bir bitki veya bitkiden elde edilen (extraction) maddeler kullanılırken genellikle bu maddelerin karışımları kullanılmaktadır(2,7,8,10,11). Birden fazla bitkinin birlikte kullanılması bazen bitkilerin tek başına olan etkilerini arttırdığı (synergistic) gibi bazen de tek başına olan etkilerini (antagonistic) yok etmektedir(42,43,44). Bitkilerin birlikte kullanılması etkin maddenin kan dolaşımında bulunan miktarının artması sonucunda tek başına kullanıldıklarında görülmeyen beyin (neurotoxicity), karaciğer (hepatotoxicity) ve böbrek (nephrotoxicity) üzerinde toksik etkilerin ortaya çıkmasına neden olmaktadır(42,44).

Cyperus rotundus (2)

4-İlaçlarla birlikte kullanılan bitkiler ilacın emilerek kan dolaşımına geçmesini (absorption), kan dolaşımında taşınmasını ve parçalandıktan (metabolism) sonra da böbreklerden atılmasını (clearance) etkilemektedir(46,47,48).

Bitkilerin ilaçlarla birlikte kullanılması ilaçların etkinliğini değiştirebildiği gibi yan etkilere ve toksik etkilere de neden olabilmektedir(46,49,50). Bazı bitkiler kanama zamanını uzattıkları için kan sulandırıcı ilaçlar ile birlikte kullanıldıklarında morarma ve kanama eğilimine neden olabilmektedir(48,49,50,51). Bazı bitkiler karaciğer hasarı yapma ihtimali olan ilaçlarla birlikte kullanıldıklarında karaciğer hasarına (hepatotoxicity) neden olabilmektedir(46,49). Bitkilerin bir kısmı kalp ilaçlarının etkinliğini arttırarak toksik etkilere neden olurken, bir kısmı da azaltarak bu ilaçların işlevini engellemektedir(52,60). Kan şekerini etkileyen bazı bitkiler diyabet tedavisinde kullanılan insülin ve ilaçların etkinliğini değiştirmektedir(53,54,55).

Yaşlanma (Aging) ile birlikte sürekliliği olan iltihap (kronik inflamasyon) artışı görülmektedir(7,56,57). Yaşlılığa neden olan kronik inflamasyon (inflamm-aging) oksidatif stres (oxidative stress) karşısında antioksidan (antioxidant) sistemin zayıflaması sonucunda ortaya çıkmaktadır(56,57). Yaşlanmaya neden olan kronik inflamasyonu azaltmak amacıyla kullanılan bazı bitkiler astım ve romatolojik hastalıkların tedavisinde kullanılan anti-inflamatuar ilaçların etkilerini arttırarak yan etkilere ve toksik etkilere neden olabilmektedir(58,59).

Cuscuta chinensis (2)

Polikistik over sendromu olan kadınların büyük bir kısmı (%90) kullandıkları ilaçlardan memnun olmayıp, bu ilaçların dışında başka bir tedavi kullanmayı istemektedir. Bu kadınların çoğunluğu (%70) da bitkisel tedavi kullanmaktadır(16,17,18,19).

Nigella Sativa (2)

Polikistik over sendromu tedavisinde uzun zamandan beri kullanılan çok sayıda bitki vardır. Bu bitkilerin bir kısmının etkili olduğu bilimsel çalışmalar ile gösterilmiştir.

 Bu bitkiler kişide görülen belirtilere, muayene bulgularına, hormon düzeylerine ve hastalık geçmişine göre yardımcı tedavi amacıyla kullanılmaktadır. Herkese uygulanan standart bir tedavi reçetesi yoktur. Bilinçsizce ve rastgele kullanılmaları fayda sağlamak yerine tehlikeli olabilmektedir.  

Polikistik over sendromu tedavisinde kullanılan bitkileri laboratuvar deneyleri, hayvan çalışmaları ve insanlarda yapılan klinik çalışmalar sonucunda etki mekanizmalarına göre 3 gruba ayırabiliriz;

A-grubu İnsülin direncine karşı duyarlılığı arttırarak etki gösteren bitkiler (Tablo-1); Polikistik over sendromu’nda fazla kilolu ve şişman olan veya normal kilolu fakat bel çevresi kalın (erkek tipi yağlanma) olan kadınların büyük çoğunluğunda insülin direnci görülmektedir(61,62,63,64). İnsülin direncinin ilerlemesi, kötüye gitmesi sonucunda bozulmuş glukoz (şeker) toleransı ve şeker hastalığı (Diabetes mellitus) gelişmektedir. (65,66,67,68,69,70,71). Polikistik over sendromu olan kadınlarda genellikle insülin direnci daha hızlı bir şekilde ilerlediği, kötüye gittiği için bozulmuş şeker toleransı ve şeker hastalığı ergenlik (adolesan) döneminden itibaren daha genç yaşlarda ortaya çıkmaktadır(68,69,72).

Tablo-1

İnsülin direncine karşı duyarlılığı arttırarak etki gösteren bitkiler;

Gardeniae Jasminoides (2)

A1– İnsülin direnci nedeniyle kan dolaşımında fazla miktarda bulunan insülin hormonu polikistik over sendromu olan kadınların bir kısmında hem doğrudan yumurtalığa giderek hem de hipofiz bezinde LH (luteinizing hormon) üretimini arttırarak olgun folikül (preovulatory) (dominant) oluşumunu ve takiben yumurtlamayı (ovulation) engellemektedir(73,74). Bunun sonucunda adet kanamaları 35 gün ile 3 ay arasında değişen aralıklarla (oligomenorrhea) veya 3 aydan daha uzun aralıklarla (amenorrhea) olanlarda adet kanamaları 21 ila 35 günde bir (eumenorrhea) olanlara göre insülin direnci ve şeker hastalığı (diabetes mellitus ) daha sık görülmektedir(75,76,77,78,79).

A2- Kan dolaşımında fazla miktarda bulunan İnsülin hormonu doğrudan yumurtalığa giderek yumurtalıkta erkeklik hormonlarının üretimini arttırmaktadır (80,81,82,83,84,85). Erkeklik hormonlarının üretiminin artması (hiperandrogenism) nedeniyle bu kadınlarda tüylenme artışı, sivilce ve saç dökülmesi görülmektedir.

Salvia miltiorrhiza (2)

A3- Kan dolaşımında fazla miktarda bulunan insülin hormonu beyinde yer alan hipofiz bezinde erkeklik hormonlarının yumurtalıkta yapılmasını sağlayan LH (luteinizing hormon) üretimini arttırmaktadır(86,87,88,89). LH (luteinizing hormon) miktarının artması erkeklik hormonlarının yapımını arttırmaktadır (hiperandrogenism)(85,87,89,90).

A4- Karaciğerde üretilen sex hormone binding globulin (SHBG) erkeklik hormonlarına bağlanarak kan dolaşımında serbest bulunan etkin formların (serbest testosteron) miktarını azaltmaktadır(91,92). Kan dolaşımında fazla miktarda bulunan insülin hormonu sex hormone binding globulin (SHBG) üretimini azaltmaktadır(93).

Foeniculum vulgare (2)

B-grubu GnRH hormonu salgılayan jeneratörü (dinamo) etkileyerek LH (luteinizing hormon) miktarını azaltan bitkiler (Tablo-2); Beyinde hipotalamus bölgesinde GnRH (Gonadotropin-releasing hormone) salgılayan sinir hücreleri (neurons) bulunmaktadır(94,95). GnRH hormonunun belirli aralıklarla artışlar ve azalışlar gösterek salgılanmasına bağlı olarak hipofiz bezinde LH ve FSH hormonların üretim sıklığı ve miktarı belirlenmektedir(96,97,98).

Polikistik over sendromu olan kadınların bir kısmında erkeklik hormonlarının (testosteron, dihidrotestosteron) fazla miktarda üretilmesi ve insülin direncine bağlı insülin miktarının artması beyinde GnRH (Gonadotropin-releasing hormone) salgılayan hücrelerden daha üst seviyelerde bulunan sinir hücrelerinde üretilen GABA ve Kisspeptin (neurotransmitters) salgılanmasını etkileyerek GnRH hormonu salgılayan jeneratörün (dinamo) fazla çalışmasına neden olmaktadır. (96,99,100,101,102). GnRH hormonunun salgılanma sıklığının artması hipofiz bezinde üretilen LH hormonunun salgılanma sıklığının (frequency) ve kan dolaşımında bulunan miktarının artmasına neden olmaktadır. (96,98,103,104,105,106,107,108,109). LH (luteinizing hormon) miktarının artması erkeklik hormonlarının yumurtalıkta yapımını arttırmakta (hiperandrogenism) ve yumurtlama öncesi olgun folikül (dominant) gelişimini ve yumurtlamayı (ovulasyon) engellemektedir. (98,109,110,111,112,113,114,115,116,117,118).

Tablo-2

GnRH hormonu salgılayan jeneratörü (dinamo) etkileyerek LH (luteinizing hormon) miktarını azaltan bitkiler; 

Tribulus terrestris (2)

C-grubu Erkeklik hormonu (testosteron, dihidrotestosteron) üretimini azaltarak etki gösteren bitkiler (Tablo-3); Kadınlarda erkeklik hormonlarının (testosteron, dihidrotestosteron) büyük bir kısmı böbrek üstü bezinde üretilen DHEA (Dehydroepiandrosterone) ve Androstenedione hormonlarından deri, meme, ve yağ dokusunda üretilmektedir(119,120). Erkeklik hormonlarının küçük bir kısmı ise yumurtalık ve böbrek üstü bezinde üretilmektedir(120,121). Kan dolaşımında bulunan testosteron yumurtalık ve böbrek üstü bezinde üretilen miktarı göstermektedir. Testosteron hormonunun büyük kısmının üretildiği deri, yağ dokusu, meme gibi organlardan sadece küçük bir miktar (%10) testosteron kan dolaşımına girmektedir(121).

       Tablo-3

Erkeklik hormonu (testosteron, dihidrotestosteron) üretimini azaltarak etki gösteren bitkiler;

C1-Kan dolaşımında olmayan testosteron hormonunun büyük çoğunluğu 5- α reduktaz (reductase) enzimi tarafından üretildiği organda testosteron hormonundan 10 kat daha güçlü bir etkiye sahip olan dihidrotestosteron hormonuna dönüşmektedir(122,123,124,125). Dihidrotestosteron hormonunun etkili olabilmesi için erkeklik hormonu alıcısına (androgen receptor) tutunması gerekmektedir(126,127,128);

1-Erkeklik hormonu alıcıları deride en çok yağ bezlerinde (sebaceous glands), kıl köklerinde (dermal papilla) ve ter bezlerinde bulunmaktadır(129,130,131). Bu alıcılara tutunan dihidrotestosteron hormonu polikistik over sendromu olan kadınlarda tüylenme artışı, sivilce ve saç dökülmesine neden olmaktadır.

Ginseng (2)

2-Erkeklik hormonları yumurtalıklarda alıcılara tutunarak folikül seçimi aşaması öncesinde bulunan ve daha küçük (< 2 mm) foliküllerin sayısını arttırırken folikül seçimi aşamasındaki (5-10 mm) foliküllerden bir tanesinin seçilerek daha ileri aşamaya ulaşmasını da engellemektedir (arrested follicles) (132,133,134,135,136,137,138,139). Yumurtlama öncesi olgunluğuna ulaşmış bir folikül oluşmadığı için polikistik over sendromu olan kadınlarda adet düzensizliği ortaya çıkmaktadır(111,112,113,141). Bu kadınlarda çoğunlukla 35 gün ile 3 ay arasında değişen aralıklarla (oligomenorrhea) adet kanamaları olmaktadır(141,142,144,145,146,147). Bir kısmında ise 3 aydan daha uzun aralıklarla (amenorrhea) adet kanamaları görülmektedir(141,143,144,145,146,147).

C2-Yumurtalıklarda erkeklik hormonları teka hücrelerinde üretilmektedir(87,148). İnsülin ve LH’ nın teka hücrelerinde erkeklik hormonlarının üretimini arttırmasının yanında polikistik over sendromu olan kadınların bir kısmında hem teka hücrelerinin sayısı fazla olduğu için hem de her bir teka hücresinde erkeklik hormonu üreten enzimin (CYP17 ) üretim kapasitesi yüksek olduğu için fazla miktarda erkeklik hormonu üretilmektedir(86,87,126,127,148,149,150).

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173-Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens. Marks LS, Hess DL, Dorey FJ, Luz Macairan M, Cruz Santos PB, Tyler VE. Urology. 2001 May;57(5):999-1005.

174-Herbal preperations for the treatment of hair loss. Zgonc Škulj A, Poljšak N, Kočevar Glavač N, Kreft S. Arch Dermatol Res. 2019 Nov 3.

175-Effect of green tea on metabolic and hormonal aspect of polycystic ovarian syndrome in overweight and obese women suffering from polycystic ovarian syndrome: A clinical trial. Tehrani HG, Allahdadian M, Zarre F, Ranjbar H, Allahdadian F. J Educ Health Promot. 2017 May 5;6:36.

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177-Green Tea: A magical herb with miraculous outcomes. Jigisha A, Nishant R, Navin K, Pankaj G. IRJP. 2012;3(5):139-148.

178-The effects of tea polyphenolic compounds on hair loss among rodents. Esfandiari A, Kelly AP. J Natl Med Assoc.2005 Aug;97(8):1165-9.

179-Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols. Hiipakka RA, Zhang HZ, Dai W, Dai Q, Liao S. Biochem Pharmacol. 2002 Mar 15;63(6):1165-76.

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181-Effect of pumpkin seed oil on hair growth in men with androgenetic alopecia: a randomized, double-blind, placebo-controlled trial. Cho YH, Lee SY, Jeong DW, Choi EJ, Kim YJ, Lee JG, Yi YH, Cha HS. Evid Based Complement Alternat Med. 2014;2014:549721.

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235-Comparison of potential preventive effects of pomegranate  flower, peel and seed oil on insülin resistance and inflammation in high-fat and high-sucrose diet-induced obesity mice model. Harzallah A, Hammami M, Kępczyńska MA, Hislop DC, Arch JR, Cawthorne MA, Zaibi MS. Arch Physiol Biochem. 2016 ;122(2):75-87.

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237-Supplementation with viti vinifera L.  skin extract improves  insülin resistanceand prevents hepa tic lipid accumulation and steatosis in high-fat diet-fed mice. Santos IB, de Bem GF, Cordeiro VSC, da Costa CA, de Carvalho LCRM, da Rocha APM, da Costa GF, Ognibene DT, de Moura RS, Resende AC. Nutr Res. 2017 Jul;43:69-81.

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