Ibuprofen txo qib Testosterone hauv cov poj niam uas muaj Polycystic Ovary Syndrome

Abstract

Cov ntsiab lus: Hyperandrogenism yog ib qho tseem ceeb ntawm polycystic zes qe menyuam syndrome (PCOS). Hauv vitro, cov kev tshawb fawb tau pom tias inflammatory stimuli txhawb thaum ibuprofen inhibits androgen ntau lawm los ntawm zes qe menyuam theca-interstitial hlwb.

Lub Hom Phiaj: Txoj haujlwm no yog txhawm rau txiav txim siab qhov cuam tshuam ntawm cov tshuaj tiv thaiv tsis zoo ntawm cyclooxygenases COX-1 thiab COX-2 ntawm qib testosterone.

Cov txheej txheem: Kev tshawb nrhiav yav tom ntej tau tshwm sim hauv tsev kho mob kev kawm ntawm cov poj niam nrog PCOS tau teev tseg raws li Rotterdam cov qauv (N=20). Kev ntsuam xyuas tau raug coj los ntawm qhov pib thiab tom qab 3 lub lis piam ntawm kev tswj hwm ibuprofen (400 mg ob zaug ib hnub lossis 400 mg 3 zaug hauv ib hnub, raws li, hauv cov poj niam uas hnyav < thiab ntau dua lossis sib npaug li 70 kg). Qhov txiaj ntsig tseem ceeb ntsuas yog tag nrho cov ntshav ntshav testosterone.

Cov txiaj ntsig: Ibuprofen kev tswj hwm tau cuam tshuam nrog kev poob ntawm tag nrho cov testosterone los ntawm {{0}}.75 ± 0.06 ng / mL rau 0.59 ± 0.05 ng / mL (P { {8}} .008). Tsis muaj kev hloov pauv tseem ceeb hauv cov qib ntawm lwm cov tshuaj hormones xws li dehydroepiandrosterone sulfate, gonadotropins, thiab insulin. Kev soj ntsuam ntau qhov kev rov qab pom tau tias qhov kev poob qis tshaj plaws hauv testosterone tau kwv yees ntawm nws tus kheej los ntawm theem pib testosterone theem (P=.004) thiab los ntawm lub hauv paus insulin rhiab heev Performance index (P=.03).

Xaus: Nonselective inhibition of COX-1 thiab COX-2 ua rau kev xaiv txo qis ntawm testosterone raws li kev cuam tshuam ncaj qha rau ntawm zes qe menyuam steroidogenesis.

Nyem rau cistanche herba rau testosterone

Polycystic ovary Syndrome (PCOS), feem ntau cov kab mob endocrine ntawm cov poj niam uas muaj hnub nyoog yug me nyuam, yog txuam nrog hyperandrogenism, ovulatory dysfunction, thiab polycystic zes qe menyuam morphology [1-4]. Thaum lub pathophysiology ntawm tus mob no tseem tsis tau to taub, lub hauv paus ntawm PCOS yog qhov ntau lawm ntawm androgens los ntawm zes qe menyuam theca hlwb [5]. Hauv 2 xyoo dhau los, cov ntaub ntawv pov thawj tau pom tau tias PCOS cuam tshuam nrog cov kab mob qis qis uas ua rau muaj kev nce ntxiv ntawm leukocytes, C-reactive protein, thiab ntau yam proinflammatory cytokines [6-10].

Peb cov kev tshawb fawb tsis ntev los no tau qhia tias cov poj niam uas muaj PCOS tau nce cov cim ntawm endotoxemia: lipopolysaccharides (LPS) thiab LPS-binding protein [11], tejzaum nws yog vim lub plab phab ntsa permeability thiab / lossis hloov plab microbiome [12]. Nyob rau hauv vitro thwmsim qhia tau hais tias proinflammatory stimuli yuav ua rau kom muaj zog synthesis ntawm androgens; Tseeb tiag, hauv kev tshawb fawb ntawm cov nas sib cais theca-interstitial hlwb, peb pom tias LPS thiab interleukin 1 ncaj qha txhawb kev tsim cov androgen los ntawm kev nthuav tawm ntawm cov noob tseem ceeb tswj kev sib txuas ntawm androgen: Cyp17a1 [13].

Tsis tas li ntawd, cov tshuaj molecules nrog cov lus hais tawm los tiv thaiv kab mob, xws li statins thiab resveratrol, inhibit qhov kev qhia ntawm Cyp17a1 thiab txo cov androgen ntau lawm hauv theca-interstitial hlwb [14, 15]. Hauv kev sim tshuaj, statins thiab resveratrol txo qis testosterone qib hauv cov poj niam nrog PCOS [16-20].

Tsis ntev los no peb pom tias cov tshuaj nonsteroidal anti-inflammatory, ibuprofen, inhibited androgen ntau lawm los ntawm nas theca-interstitial hlwb abrogating stimulatory ua ntawm LPS thiab interleukin 1 [21]. Cov teebmeem no tau pom nyob rau ntawm cov tshuaj pharmacological ntawm ibuprofen (0.1 mM; tib neeg kev tshawb fawb ntawm cov tib neeg noj 600 mg ntawm ibuprofen ob zaug ib hnub rau 6 lub lis piam [22, 23]). Raws li cov kev soj ntsuam uas tau hais los saum no, peb tau ua qhov kev sim sim rau cov poj niam nrog PCOS ntsuas qhov cuam tshuam ntawm ibuprofen ntawm cov ntshav testosterone thiab lwm yam tshuaj hormones.

Cov ntaub ntawv thiab cov txheej txheem

Cov neeg koom nrog Txoj kev tshawb no tau ua tiav ntawm Kev Kho Mob Kev Kho Mob Endocrinology & Infertility Clinical Services ntawm Poznan University of Medical Sciences hauv tebchaws Poland. Txhua tus neeg koom ua tiav cov txheej txheem PCOS raws li tau hais tseg los ntawm Rotterdam kev pom zoo [24] thiab muaj tsawg kawg yog 2 ntawm cov hauv qab no: 1) cov ntaub ntawv kuaj mob lossis kuaj cov pov thawj ntawm hyperandrogenism; 2) oligomenorrhea los yog amenorrhea; thiab/los yog 3) polycystic zes qe menyuam raws li txiav txim los ntawm transvaginal ultrasound [25].

Cov tib neeg uas muaj cov qog adrenal hyperplasia, hyperprolactinemia, thyroid kab mob, kab mob Cushing, thiab ntshav qab zib mellitus raug cais tawm. Thaum lub sij hawm 2 lub hlis ua ntej txoj kev tshawb fawb, tsis muaj leej twg ntawm cov neeg koom nrog kev tshawb fawb siv ib hom tshuaj hormonal xws li tshuaj tiv thaiv kab mob. Sau ntawv tso cai tau txais los ntawm txhua tus neeg koom. Kev pom zoo ntawm txoj kev tshawb no tau txais los ntawm lub koom haum tshuaj xyuas pawg thawj coj ntawm Poznan University of Medical Sciences.

Cov txheej txheem

Daim duab qhia kev ntawm txoj kev tshawb no tau piav qhia nyob rau hauv daim duab 1. Txhua tus neeg koom tau raug soj ntsuam ntawm lub hauv paus thiab tom qab 3 lub lis piam ntawm ibuprofen kev tswj hwm (400 mg ob zaug hauv ib hnub rau cov poj niam uas hnyav <70 kg thiab 400 mg 3 zaug hauv ib hnub hauv cov poj niam uas hnyav dua. tshaj los yog sib npaug li 70 kg). Qhov kev hloov kho ntawm cov koob tshuaj txhua hnub raws li qhov hnyav yog raws li cov pov thawj uas cov neeg hnyav pom tau tias muaj kev tshem tawm ntawm ibuprofen ntau dua thiab xav tau ntau dua kom tau txais cov ntshav plasma txaus [26].

Kev soj ntsuam kev soj ntsuam suav nrog kev txiav txim siab ntawm lub cev qhov ntsuas (BMI), lub duav-rau-hip piv (WHR), thiab hirsutism (siv cov qhab nia Ferriman-Gallwey). Kev ntsuam xyuas transvaginal ultrasound tau ua tiav siv Voluson S8 Kov (General Electric Co). Qhov ntim ntawm zes qe menyuam tau suav nrog cov mis prolate ellipsoid. Cov ntshav venous tau sau tom qab ib hmos ceev ceev. Cov khoom kuaj ntshav tau khaws cia ntawm -70 degree kom txog thaum kev soj ntsuam tau ua tiav.

Ib qho 2-teev qhov ncauj qhov ncauj qhov siab ntsuas (OGTT) tau ua nrog kev txiav txim siab ntawm cov piam thaj thiab insulin hauv lub xeev yoo mov, nrog rau tom qab 75-g qabzib load ntawm 60 thiab 120 feeb. Glucose tau txiav txim siab los ntawm txoj kev hexokinase siv Roche Cobas e6001 immune analyzer (Roche Polska sp z oo). Insulin, tag nrho cov testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), kev sib deev hormone-binding globulin, 17-hydroxyprogesterone, thiab dehydroepiandrosterone sulfate, tau txiav txim siab siv cov tshuaj electrochemiluminescence tshwj xeeb (Roche Cobas e6001 immune analyzer; Roche Polska sp z oo).

Cov tshuaj insulin rhiab heev (ISI) tau suav nrog cov piam thaj thiab cov tshuaj insulin tau txais thaum lub sijhawm OGTT raws li tau piav qhia los ntawm Matsuda thiab DeFronzo [27]: ISI=(10 000}/square cag ntawm [(fasting qabzib × yoo mov. insulin) × (lub ntsiab lus qabzib × txhais tau tias insulin thaum OGTT)].

Kev txheeb cais

Kev tshuaj xyuas tau ua tiav siv JMP Pro 15 statistical software (SAS Institute). P qhov tseem ceeb tsawg dua .05 tau suav tias yog qhov tseem ceeb. Kev sib piv ntawm cov hauv paus ntsiab lus thiab cov txiaj ntsig rov qab tau ua los ntawm kev sib tw t-test. Thaum tsis muaj kev faib tawm ib txwm muaj (kuaj los ntawm AndersonDarling test), Wilcoxon tau kos npe rau kev xeem qib.

Kev sib raug zoo ntawm cov kev hloov pauv tau ua tiav siv Spearman qeb xeem. Ntau tus qauv regression tau ua tiav siv txoj hauv kev rov qab mus. Kev soj ntsuam fais fab tau qhia tias qhov kev ntsuam xyuas ntawm 20 tus neeg koom yuav muaj ntau dua 90 feem pua ​​​​lub zog los kuaj xyuas qhov txo qis ntawm 20 feem pua ​​​​ntawm tag nrho cov testosterone nrog cov coefficient ntawm kev sib txawv ntawm 100 feem pua, thiab qhov yuam kev ntawm .05.

Cov txiaj ntsig

Daim duab CONSORT flow diagram ntawm txoj kev tshawb no (saib daim duab 1) qhia tias 20 cov tib neeg tau ua tiav 3- lub lim tiam sim, raws li tau npaj thaum lub sijhawm sau npe ntawm txoj kev tshawb fawb ntawm kev sim tshuaj. gov. Qhov nruab nrab hnub nyoog thiab BMI ntawm cov neeg koom nrog, feem, 26.7 ± 0.8 xyoo thiab 27.3 ± 1.1 (txhais tau tias ± SEM).

Ua ntej pib kho ibuprofen, 95 feem pua ​​(19/20) ntawm cov neeg koom nrog tom qab ua tiav qhov kev sim muaj pov thawj ntawm kev kho mob lossis biochemical hyperandrogenism: Tag nrho ntawm 90 feem pua ​​(18/20) muaj tag nrho cov testosterone ntau dua. 0.5 ng / mL, thiab 80 feem pua ​​(16/20) muaj hirsutism (FerrimanGallwey qhab nia Ntau dua lossis sib npaug rau 8).

Cov teebmeem ntawm Kev Kho Mob

Table 1 nthuav qhia cov theem ntawm cov kev sim hloov pauv ntawm lub hauv paus thiab qhov kawg ntawm 3-kev kho mob lub lis piam nrog ibuprofen. Cov txiaj ntsig tseem ceeb, qib testosterone, poob los ntawm 21 ± 7 feem pua ​​(P=.008) nyob rau hauv parallel nrog 28 ± 11 feem pua ​​​​ntawm cov testosterone dawb (P=.01). Hauv qhov sib piv, tsis muaj kev hloov pauv tseem ceeb hauv qib ntawm lwm cov tshuaj hormones, suav nrog dehydroepiandrosterone sulfate, gonadotropins, thiab kev ntsuas ntawm insulin rhiab heev.

Kev soj ntsuam ntawm cov pab pawg ntawm cov poj niam uas tau txais koob tshuaj qis dua ntawm ibuprofen (400 mg ob zaug ib hnub) vs cov koob tshuaj ntau dua (400 mg 3 zaug hauv ib hnub) qhia ib qho tsis tseem ceeb rau kev txo qis hauv qib testosterone ntau dua hauv cov neeg tau txais cov tshuaj qis dua (–{15}}.25 ± 0.09 ng / mL; 29 ± 10 feem pua ​​​​) vs cov koob tshuaj ntau dua (–0.10 ± 0.07 ng / mL ; 15 ± 10.0 feem pua ​​) (P=.17). Cov poj niam uas tau txais ib koob tshuaj ibuprofen qis dua tau txheeb xyuas qhov BMI qis dua (P=.008).

Table 2 qhia tau hais tias qhov poob ntawm testosterone correlated nrog WHR, theem pib ntawm tag nrho cov testosterone, thiab dawb testosterone. Qhov tseem ceeb, txij li qhov sib txawv ntawm qhov sib txawv tau txhais tau tias yog "tsawg," tus nqi tsis zoo tshaj plaws, uas yog, qhov poob qis tshaj plaws ntawm testosterone, cuam tshuam nrog qis WHR, siab dua tag nrho testosterone, thiab siab dua testosterone dawb. Kev txheeb xyuas ntau qhov kev thim rov qab tau qhia txog qhov poob qis tshaj plaws ntawm testosterone correlated ntawm nws tus kheej nrog theem pib testosterone theem thiab hauv paus ISI; 2 qhov sib txawv no tau piav qhia 50 feem pua ​​​​ntawm qhov sib txawv (hloov R2) hauv cov qauv no (Table 3).

Kev sib tham

Txoj kev tshawb fawb tam sim no qhia tau hais tias luv luv 3-ib lub lim tiam ntawm cov tshuaj uas tsis yog tshuaj tiv thaiv kab mob, ibuprofen, ua rau txo qis ntawm cov qib testosterone hauv cov poj niam nrog PCOS. Qhov kev soj ntsuam no ua rau pom lub teeb tshiab ntawm kev nkag siab ntawm cov txheej txheem tswj hwm androgen ntau lawm thiab tuaj yeem muab lub hauv paus rau kev tshawb nrhiav cov kev kho tshiab uas tswj hwm ntawm hyperandrogenism. Peb tsis paub txog cov ntawv tshaj tawm yav dhau los piav txog qhov cuam tshuam ntawm nonsteroidal anti-inflammatories ntawm kev ua me nyuam ntawm poj niam physiology; Txawm li cas los xij, kev tshawb fawb yav dhau los hauv cov txiv neej tau qhia tias kev tswj hwm ibuprofen tau coj mus rau "compensated hypogonadism" [22].

Hauv txoj kev tshawb no, LH thiab ibuprofen plasma qib tau zoo sib raug zoo thiab qhov piv ntawm testosterone rau LH raug txo. Cov ntsiab lus tam sim no piav qhia txog kev tswj hwm ntawm zes qe menyuam androgen ntau lawm tsom rau kev ncaj qha ntawm LH ntawm zes qe menyuam theca hlwb uas ua rau muaj kev cuam tshuam ntawm cov enzymes tseem ceeb, suav nrog Cyp11a1 thiab Cyp17a1 [28-30]. Lwm qhov pom zoo ntawm endocrine stimulator ntawm androgen synthesis yog insulin ua ib leeg lossis hauv kev sib koom ua ke nrog LH [31, 32].

Hauv txoj kev tshawb fawb tam sim no, kev poob qis hauv qib testosterone tom qab kev kho ibuprofen tsis cuam tshuam nrog kev hloov pauv tseem ceeb hauv LH lossis qib insulin, qhia tias kev ua ibuprofen tsis kho los ntawm cov tshuaj hormones thiab tej zaum yuav yog vim kev ua ncaj qha ntawm theem ntawm zes qe menyuam. Tseeb tiag, hauv peb qhov kev sim dhau los ntawm nas theca-interstitial hlwb, peb pom tias ibuprofen ua rau txo qis androgen ntau lawm thiab inhibits RNA qhia ntawm Cyp11a1 thiab Cyp17a1 [21].

Ibuprofen yog ib tug tsis xaiv inhibitor ntawm cyclooxygenases COX1 thiab COX 2, cov enzymes lub luag hauj lwm rau kev hloov ntawm arachidonic acid rau active prostaglandins, xws li proinflammatory prostaglandin E2 (PGE2), ib qho tseem ceeb paracrine mediator nyob rau hauv lub zes qe menyuam. Tseeb tiag, granulosa hlwb ntawm cov poj niam nrog PCOS tsim thiab tso tawm ntau dua ntawm PGE2 dua li cov hlwb los ntawm cov poj niam tsis muaj PCOS [33]. Hauv kev tshawb fawb tsiaj, PGE2 tau pom tias txhawb kev tsim cov testosterone [28].

Raws li cov lus hais saum toj no thiab cov kev tshawb pom tam sim no, peb xav tias ibuprofen ncaj qha inhibits zes qe menyuam PGE2 ntau lawm thiab yog li txo cov androgen synthesis. Muab cov kev mob tshwm sim ntawm ibuprofen, nws txoj kev siv mus sij hawm ntev hauv cov neeg mob hyperandrogenic tsis tuaj yeem pom zoo. Tsis tas li ntawd, txij li cov txheej txheem ntawm ovulation cuam tshuam nrog kev ua kom cov kab mob inflammatory [34], kev tswj hwm ntawm nonsteroidal anti-inflammatory tshuaj yuav tsum zam rau cov poj niam xav ovulation. Txawm li cas los xij, qhov kev tshawb pom tam sim no taw qhia txog qhov muaj peev xwm rau kev kho tshiab ntawm kev tsim cov androgen ntau dhau los ntawm kev txhim kho cov kev kho tshiab tsom rau qhov mob, lossis tejzaum nws xaiv inhibition ntawm ntau lawm thiab / lossis kev ua ntawm PGE2.

Lwm qhov kev soj ntsuam tseem ceeb hauv kev soj ntsuam yog kev sib raug zoo ntawm ISI nrog cov lus teb rau kev kho ibuprofen (saib Table 3), uas cov poj niam uas muaj cov tshuaj insulin loj tshaj plaws tau ntsib kev poob qis ntawm testosterone ntau dua. Hauv lwm lo lus, cov neeg uas muaj cov tshuaj insulin tsis kam, thiab yog li them nyiaj rau hyperinsulinemia, tsis tshua muaj peev xwm teb rau ibuprofen, qhia tias cov tshuaj insulin-mediated androgen synthesis tsis tshua nkag siab rau inhibition ntawm proinflammatory pathways.

Txoj kev tshawb fawb tam sim no, thaum nthuav tawm cov kev tshawb pom nthuav dav, muaj cov kev txwv tseem ceeb suav nrog qee tus neeg koom nrog cov tub ntxhais hluas nrog, qhov nruab nrab, tsuas yog nce siab BMI xwb. Yog li ntawd, kev sim tshuaj loj dua ntxiv rau ntau haiv neeg ntawm cov poj niam uas muaj PCOS raug lees paub. Hauv cov ntsiab lus, txoj kev tshawb fawb no txhawb nqa lub tswv yim tias hyperandrogenism tuaj yeem txo qis los ntawm kev tawm tsam ntawm txoj hauv kev proinflammatory.

Lub mechanism ntawm Cistanche boosts testosterone nyhuv

Cistanche tau pom los txhawb qib testosterone ntau ntau txoj hauv kev. Ua ntej, nws muaj cov tebchaw hu ua echinacoside thiab acteoside, uas tau pom tias txhim khu kev tsim cov tshuaj luteinizing hormone (LH) hauv pituitary caj pas. LH txhawb nqa Leydig hlwb hauv cov qe ntshav los tsim testosterone. Cistanche kuj tseem muaj cov polysaccharides thiab phenylethanoid glycosides, uas tau pom tias muaj cov tshuaj tua kab mob antioxidant thiab tiv thaiv kab mob. Qhov no tuaj yeem pab txo qis oxidative kev nyuaj siab thiab mob hauv cov qog nqaij hlav, uas tuaj yeem cuam tshuam rau testosterone ntau lawm Tsis tas li ntawd, Cistanche tau pom tias yuav ua rau kom muaj kev qhia ntawm cov noob koom nrog hauv testosterone synthesis thiab txo cov haujlwm ntawm cov enzymes uas ua rau testosterone, xws li {{1} }alpha-reductase. Zuag qhia tag nrho, kev sib xyaw ua ke ntawm cov txheej txheem no tau xav tias yuav pab txhawb rau Cistanche's testosterone-boosting teebmeem.

Cov ntaub ntawv

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Beata Banaszewska, 1 Katarzyna Ozegowska, 1 Martyna Polska, 1 Leszek Pawelczyk, 1, R. Jeffrey Chang, 2 thiab Antoni J. Duleba2,

1 Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, 60-535 Poznan, Poland; thiab

2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, California 92093-0633, USA