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1 발기부전환자에서홍삼농축분말의유효성및안전성 : 다기관, 무작위배정, 이중맹검, 위약대조임상연구 Efficacy and Safety of Red Ginseng Extract Powder in Patients with Erectile Dysfunction: Multicenter, Randomized, Double-Blind, -Controlled Study Won Sik Ham, Won Tae Kim, Jin Sun Lee, Hee Jeong Ju, Shin Jyung Kang 1, Jin Hwan Oh 1, Youl Her 1, Jae Yong Chung 2, Kwangsung Park 3, Young Deuk Choi From the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, 1 Industry Academy Cooperation Foundation, Joongbu University, Geumsan, 2 MECOX CureMed, Seongnam, 3 Department of Urology, Chonnam National University Medical School, Gwangju, Korea Purpose: To evaluate the safety and efficacy of red ginseng extract powder () for treating erectile dysfunction. Materials and Methods: Sixty-nine adult patients with mild to moderate erectile dysfunction of various etiologies were randomized to receive placebo or red ginseng extract powder. The red ginseng extract powder used in the present study was named. The primary efficacy parameter was response to the International Index of Erectile Function (IIEF) erectile function domain at baseline and week 8. Other IIEF domain scores were evaluated as secondary parameters. For safety evaluation, we performed history taking, physical examination, clinical laboratory tests, and hormonal tests at baseline and week 8. Results: There were no significant differences in the patients characteristics between the 2 groups. After 8 weeks of administration, primary efficacy (erectile function domain) and all secondary efficacy domains were significantly improved in the group compared with the placebo group (p<.5). Notably, even the domain related to sexual desire, frequency and degree of sexual desire, was also improved in the group (p<.1). There were no significant adverse reactions with administration, and there were also no significant differences in the results of laboratory tests between the 2 groups after administration. Conclusions: Our data show that red ginseng extract powder can be used as an alternative remedy for Korean men suffering from mild to moderate erectile dysfunction. (Korean J Urol 29;5: ) Key Words: Ginseng, Erectile dysfunction, Treatment efficacy Korean Journal of Urology Vol. 5, No. 2: , February 29 DOI: /kju 연세대학교의과대학비뇨기과학교실, 비뇨의과학연구소, 1 중부대학교산학협력단, 2 메콕스큐어메드, 3 전남대학교의과대학비뇨기과학교실 함원식ㆍ김원태ㆍ이진선ㆍ주희정강신정 1 ㆍ오진환 1 ㆍ허율 1 정재용 2 ㆍ박광성 3 ㆍ최영득 Received:October 1, 28 Accepted:December 15, 28 Correspondence to: Young Deuk Choi Department of Urology, and Urological Science Institute, Yonsei University College of Medicine, 25, Seongsan-ro, Seodaemun-gu, Seoul , Korea TEL: FAX: youngd74@yuhs.ac This study was supported by BT gin, Inc. ( ) and a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A8412). C The Korean Urological Association, 29 서론발기부전은전세계적으로약 1.5억명의남성이겪고있는흔한질환이다. 발기부전의유병률과정도는연령의증가및비만, 당뇨, 고혈압그리고우울증과같은내과적또는정신과적질환들이동반되었을때더높아진다. 1 국내 보고에서도 3세이상남성의절반이상에서발기부전이나타나며, 이는연령의증가뿐만아니라성인병의발생증가와도밀접한연관성이있다고보고되고있다. 2-4 우리나라에서는예로부터발기부전치료에대한민간요법으로인삼, 홍삼, 녹용, 구기자, 산수유, 복분자, 토사자및오미자등다양한약제가이용되어왔고, 외국의경우에도 Lepidium meyenii 추출물 5 이나 Ferula hermonis의뿌리추출 159

2 16 Korean Journal of Urology vol. 5, , February 29 물 6 등의생약제제가성기능개선약물로이용되고있다. 특히인삼은오래전부터한방치료에서여러질병의예방과치료에사용되고있는대표적인약제로서인삼이나홍삼은동물실험뿐만아니라임상적으로도효과가있다는보고도있다. 7,8 하지만이런약제들의발기부전에대한치료효과와안전성에대한임상연구는부족한상태로, 본저자들은홍삼농축분말이실제임상적용에있어서유용성과안전성이있는지조사하였다. 대상및방법 1. 연구대상및평가 27년 6월부터 1월까지 2개대학교병원비뇨기과에최소 3개월이상지속된발기부전을주소로내원한환자들중 6개월이상 1명의여성파트너와성관계를유지하며, 본임상시험의목적을이해하고자의로참여를결정한후서면동의한성인남성 73명을대상으로하였다. 발기부전의정의는만족스러운성관계에충분한음경발기의유발혹은유지하지못하는경우로하였고, 발기부전의정도는 International Index of Erectile Function (IIEF) 설문지의조사항목중발기능영역점수에따라 17점이상은경도, 11-16점은중등도, 그리고 -1점은고도로분류하였고, 고도발기부전환자는시험대상에서제외하였다. 또한지난 6개월이내에뇌졸중, 심근경색증, 불안정형협심증과같은심혈관계질환을진단받았거나, 시험개시전 2주이내에발기부전치료를위해 phosphodiesterase-5 (PDE-5) 억제제또는혈관확장제의자가주사요법을사용한경우도시험대상에서제외하였다. 발기부전의원인은환자의과거력, 신체검사및검사실결과그리고, 기존의진단적검사법에의해결정되었다. 자세한병력청취및상담을통해발기부전의원인이정신적이유나인간관계에서비롯되었다고판단된경우심인성발기부전으로정의하였고기질적인원인이동반된경우는복합성발기부전으로정의하였다. 선정된피험자를무작위, 이중맹검법으로홍삼농축분말 (2 mg/1캡슐, 1일 2회, 하루 4캡슐 ) 투여군과위약투여군으로선정하였다. 피험자는투여전과 8주간투여후병원을방문하여안전성과유효성에대한평가와검사를시행하였다. 약제의유효성은 IIEF 설문조사로평가하였다. IIEF의발기능영역에대한결과를일차유효성평가변수로하였고, IIEF의나머지영역인절정감, 성적욕구, 성교만족도, 그리고전반적성생활만족도영역에대한결과를이차유효성평가변수로하였다. 안전성에대한평가로약물투여전과투여 8주후에각 각병력조사, 활력증후, 심전도를검사하였고, 임상실험실검사로는혈액학및혈액응고검사, 혈액화학검사, 요검사, HbA1C, 총테스토스테론및전립선특이항원 (prostatespecific antigen; PSA) 검사를시행하였다. 약물을복용하는동안, 혹은복용후에발생하는이상반응에대해서도보고하도록교육하였다. 임상시험의전과정은각병원임상시험심사위원회의심의와감독하에시행되었다. 2. 약물제조방법본연구에사용한홍삼농축분말은유효성분강화를위해다음의정제과정을거쳐제조하였으며, 이를 로명명하기로하였다. 건조삼 1 kg을 9% 에탄올로 6 C에서 3시간추출하여농축하고, 이를다시 95% 에탄올로 6 C에서 3시간추출하는과정을 2회반복하여추출물약 1 g을수득하였다. 이를물에녹여 DIAION HP-2 이온교환수지 (Mitsubishi Chemicals Corp., Tokyo, Japan) 가충진된 column에통과시켜흡착시킨후 95% 에탄올로탈착시켜 Rb1, Rb2, Rc, Rd, Re, Rg1, Rf 그외미량의기타 ginsenoside 혼합물로구성된순도 9% 이상의복합 ginsenoside 3 g을얻었다. 복합 ginsenoside 12 g을 Bacillus sp. 유래베타글루코시다제와반응시켜 (75 C, 12시간, ph 6.) ginsenoside Rd의함량이 4% 이상이되도록제조하였고, 이과정을통해얻은복합 ginsenoside 1 g을 1% 초산용액 2 l에반응시켰다 (8 C, 12시간 ). 이반응물을 DIAION HP-2 이온교환수지가충진된 column에통과시켜흡착시킨후 95% 에탄올로탈착시켜 Rg2 15 mg, F4 11 mg, Rg6 12 mg, Rg g, Rg5.84 g, Rk g, Rh g, Rh4 1.1 g, Rk3.73 g, Rh2 8 mg, Rh3 2 mg, Rk2 2 mg, PPT 4 mg 및기타 51 mg을함유한순도 9% 이상의 ginsenoside 혼합물을얻었다. 시험약 는최종적으로얻은복합 ginsenoside 1 mg과 4-5 년근홍삼농축분말 1 mg을무게비 1:1로균질하게혼합하여제조하였고, 시험약 와동일한향과맛을가진위약 2 mg에는결정셀룰로스 2 mg이함유되었다. 본실험에사용한 와위약은 ( 주 ) 비티진에서제공받아사용하였다. 3. 통계분석방법임상시험과관련된모든피험자의자료를각군별로평가하였고, 연속형자료는평균과표준편차로나타냈으며범주형자료는빈도와비율을구하였다. 두군간의차이는연속형변수는 Student's t-test로비교하였으며, 범주형변수는 Fisher's exact를이용하여비교하였다. 치료전후호전여부분석에는선형대선형결합분석 (linear by linear association) 을이용하였고, 유효성의평가분

3 Won Sik Ham, et al:efficacy and Safety of Red Ginseng Extract Powder with ED 161 석을위해서치료전평균점수의영향을통제하기위해공분산분석 (analysis of covariance; ANCOVA) 을시행하여양군간에치료후의평균점수를비교분석하였다. p값이.5 미만인경우통계적으로유의한것으로판단하였고, 통계프로그램은 SPSS 12 (SPSS Inc, Chicago, USA) 를이용하였다. 1. 임상적특성 Table 1. Characteristics of patients Characteristics 결 발기부전환자 73명을대상으로무작위로두군으로나누었으며, 37명은 를투여받고나머지 36명은위약을각각투여받았다. 이들중 8주간투약후에약물효능및안전성평가를완료한 69명을대상으로하였다 (군 35 명, 위약군 34명 ). 중도탈락한피험자 4명의탈락사유는모두동의철회였다. 대상환자의연령, 결혼여부및기간, 배우자의연령은두군간의유의한차이가없었다 (p>.5). 음주력은두군간에유의한차이가없었으나, 흡연력에있어 군에서는과거흡연력이있는경우가많았고, 위약군에서는현재흡연자가많아두군간에차이를보였다 (p=.12). 발기부 Mean age (years) a Marital status Mean duration (years) a Mean age of spouse (years) a Smoking history (%) Smokers Ex-smokers Never smoked Alcohol history (%) Drinker Past drinker No drinker Diabetes mellitus (%) Hypertension (%) Etiology of erectile dysfunction (%) Psychogenic Organic Mixed Testosterone (ng/ml) a PSA (ng/ml) a (n=35) 53.2± ±1 5.2±8.9 4 (11.4) 23 (65.7) 27 (77.1) 4 (11.4) 4 (11.4) 1 (28.6) 16 (45.7) 17 (48.6) 2 (5.7) 4.5±2 1.4±1.4 (n=34) 5.8± ± ± (41.2) 12 (35.3) 8 (23.5) 22 (64.7) 9 (26.5) 9 (26.5) 15 (44.1) 18 (52.9) 4.7±1.8 1.±.7 p-value.256 b.169 b.362 b.12 c.296 c.244 c.785 c 1. c.695 b.215 b : red ginseng extract powder, PSA: prostate-specific antigen, a : mean±sd, b : Student s t-test, c : Fisher s exact test 과 전의원인에따른분류는두군간에차이가없었으며 Table 2. Change from baseline in IIEF erectile score IIEF questionnaire Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q1 Q11 Q12 Q13 Q14 Q15 Change from baseline in IIEF score (%) No increase 11 (31.4) 18 (51.4) 17 (48.6) 1 (28.6) 12 (34.3) 26 (76.5) 2 (57.1) 14 (4.) 14 (4.) 25 (73.5) 29 (85.3) 12 (34.3) 23 (67.6) (34.3) 5 (13.9) 1 (28.6) 4 (11.8) 7 (2.6) 18 (51.4) 7 (2.6) 16 (45.7) 14 (4.) 14 (4.) 1 (29.4) 1 (28.6) 11 (31.4) 1 (28.6) (.) (.) 11 (31.4) 7 (2.) (.) 1 (28.6) 6 (17.1) 4 (11.8) p-value <.1 a <.1 a.16 a.16 a <.1 a <.1 a.16 a <.1 a.6 a.1 a <.1 a.1 a.33 a.1 a.2 a IIEF: International Index of Erectile Function, : red ginseng extract powder, a : Linear by linear association test

4 162 Korean Journal of Urology vol. 5, , February 29 Table 3. Results for primary efficacy (erectile function domain) analysis Group Baseline Last observ. p-value (n=35) a (n=34) a 17.2± ± ± ±8.3.3 b IIEF: International Index of Erectile Function, Last observ.: last observation after 8 weeks, : red ginseng extract powder, a : mean±sd, b : analysis of covariance (ANCOVA) test Table 4. Results of the secondary efficacy (IIEF domain except erectile function) analysis Domain Group Baseline Last observ. p-value Intercourse satisfaction a Orgasmic function a Sexual desire a Overall satisfaction a (n=35) (n=34) (n=35) (n=34) (n=35) (n=34) (n=35) (n=34) 6.5± ± ± ±3. 4.9± ± ± ± ± ± ± ±3. 6.9± ± ± ±2.1.9 b.21 b <.1 b.24 b IIEF: International Index of Erectile Function, Last observ: last observation after 8 weeks, : red ginseng extract powder, a : mean±sd, b : analysis of covariance (ANCOVA) test Table 5. Results for adverse events in overall cases Adverse events Respiratory system disorder (%) Acute nasopharyngitis Rhinitis Skin and appendages disorder Eczema Skin disease Gastrointestinal system disorder Diarrhea Anal bleeding Central and peripheral nervous system disorder Voice disorders Visual system disorder Ophthalmalgia Genital system disorder Perineal pain Generalized disorder Chest pain Urologic system disorder Renal stone (n=35) (n=34) Total (%) 8 (23.2%) 5 (14.5) : red ginseng extract powder (p=1.), 대상환자의혈청총테스토스테론치와전립선특이항원수치는모두정상범주로서두군간에유의한차이는없었다 (p>.5)(table 1). 2. 치료전후호전례분석치료전 IIEF 증상점수에비해치료후 IIEF 증상점수의증가여부를분석한결과, IIEF 모든항목에서 군에서위약군에비해서는유의하게 IIEF 증상점수가증가하였다. (p<.5)(table 2). 하지만 3번문항과 9번문항에서는 5% 미만의환자에서 치료후 IIEF 증상점수가증가하였다. 3. 일차유효성평가변수 : 발기능영역치료전점수의영향을통제하기위해시행한공분산분석결과에서 군이위약군에비해치료후발기능영역의평균점수가유의하게높았다 (p=.3)(table 3). 4. 이차유효성평가변수 : 성교만족도, 절정감, 성적욕구, 전반적성생활만족도영역성교만족도, 절정감, 성적욕구및전반적성생활만족도영역에대한이차유효성평가에서도공분산분석결과모든영 역에서 군이위약군에비해치료후의평균점수가유의하게높았다 ( 각각, p=.9,.21, <.1,.24)(Table 4). 5. 약물안전성 8주간 와위약을투여하는과정에서모두 11명에서 14건의이상반응이발현되었는데, 군에서 8건 (23.2%) 발생하였고, 위약군에서 5건 (14.5%) 발생하였다. 모두시험약과연관성이없었으며중대한이상반응은없었다 (Table 5). 8주방문시점에실시한실험실검사결과를양군간에비교한결과, 일반혈액검사의 WBC를제외하고는다른검사실검사는양군간차이를보이는항목은없었다. 고찰최근산업화와평균수명의연장에의한성인병의증가와발기부전의노출을꺼려하던사회적인식의변화로성기능장애를주소로병원에내원하는환자들이점차많아지고있다. 현재대부분의발기부전의 1차치료제인경구용 PDE-5 억제제는음경해면체내평활근의 PDE-5를억제하여 cgmp의분해를방지함으로써평활근의이완과음경혈관의확장이지속되도록한다. 9 그러나이러한경구용발기

5 Won Sik Ham, et al:efficacy and Safety of Red Ginseng Extract Powder with ED 163 부전치료제의경우, 소화불량, 두통, 얼굴화끈거림, 비염등의약물부작용이있고, 간혹드물게심각한시각장애나, 심혈관계부작용을나타내기도한다 이에반해발기부전치료에대한민간요법으로이용되어온다양한약제들은비교적좋은치료효과와함께적은부작용을나타낸다는장점으로인해전통적으로많이사용되고있다. 최근 Kam 등 16 에의해산수유복합추출분말이위약에비해혈액학이나혈액화학검사에서이상을초래하지않으면서, 유의하게성기능을개선시킨다고보고되었다. 산수유복합추출분말의성기능개선효과는성기능장애가심한집단일수록개선의정도가더욱뚜렷하였고, 별다른치료없이해소되는경미한부작용만을나타내어, 산수유복합추출분말의복용이안전하며유의한성기능개선효과가있다고하였다. 인삼은발기부전의주요원인인당뇨, 고혈압, 고콜레스테롤증및노화등의대사질환에대하여당을감소시키고, 혈압을떨어뜨리며, 콜레스테롤대사에개선효과가있음이밝혀졌고, 순환기계에서말초혈관의확장과말초저항을감소시켜서말초혈액순환을개선한다는보고가있어, 이런결과들을토대로인삼이음경발기에미치는영향에대하여많은연구가진행되었다. 17,18 인삼의발기부전에대한치료기전으로인삼이 nitric oxide (NO) 의생산을증가시켜혈관내피세포의이상을개선시키고, 말초혈관의확장및말초저항의감소로혈액순환을원활하게하는작용이있다. 또한인삼을증기등의방법으로쪄서익힌후말려제조하는홍삼의경우, 가공하지않은인삼에비해동양의학적인관점에서체질에따른부작용이적으며, 증숙및건조과정에서특정 ginsenoside 성분들이소멸되거나새로이발생하여치료효과가증가하는것으로알려져있다. 이러한홍삼은동물의생체외실험결과 NO나칼슘및칼륨통로에관여하여음경해면체평활근에대해이완작용을하며, 특히홍삼의 saponin 분획물은음경해면체평활근에대한이완작용과내압을높이는작용으로음경발기력을향상시키는효과가있고, 그효과는함유조성에따라차별성이있다는것이확인되었다 홍삼의음경해면체평활근에대한실험결과를바탕으로, 본연구에서는실제임상적용에서의 의효용성과안전성을 IIEF 설문지를이용하여 군과위약군간의치료효능의차이로평가하였다. 발기능영역에대한일차유효성평가에서위약군에비하여유의한치료효과가있었고, 나머지 4가지범주에대한이차유효성평가에서도모두 군에서위약군에비해통계학적인치료효과가있었으며, 약물의안정성평가에서약물관련특이반응이나특별한부작용이없었다. 특이할만한결과는성적욕구영역 의성욕의빈도및성욕의정도항목에서도위약군에비해 군에서유의한치료효과를나타냈다는것이다. 식용식물에서추출한 phytochemical을이용하는전통의학에서는질환을신체전반으로적절한기능이조절되지못하는상태로정의하고있으며, 이러한근본원인을치유하고자하는방향으로초점이맞춰져있다. 따라서발기부전도신체전반의장애의일부라는관점에서접근하고있다. 실제로 Tribulus terrestris L에서추출한 Protodioscin의경우성적욕구의향상에도움이된다는보고가있고, 22 인삼성분이포함된영양보충제가여성에서성적욕구가유의하게증가하였다는보고들도있는상태이다. 23,24 따라서이러한결과들은 군에서성적욕구가증가한다는본연구의결과와연관성이있을것으로생각되며이에대해보다많은환자를대상으로한추가적연구에서확인이필요할것이다. 본연구에서는고도발기부전환자가제외되었고, IIEF 일부항목에서는 치료후에도절반이상의환자가호전되지않았던경우도있어 가발기부전치료제로서한계는있다. 그러나 는경도및중등도의발기부전환자들에서안전하며유의한성기능개선효과가있는것으로판단된다. 결 홍삼농축분말은경도및중등도의증상을나타내는발기부전환자에서특별한독성이나부작용없이위약군에비해성기능전반에걸쳐유의한치료효과를나타냈으며, 특히성적욕구에대해서도향상효과를나타냈다. 고도발기부전환자를포함한더많은환자를대상으로한연구가필요하고성적욕구향상에대한기전을밝히는노력이필요하나, 경구용발기부전치료제에대한부작용이나거부감을보이는환자에서는대체약물의하나로사용가능할것으로생각한다. 론 REFERENCES 1. McKinlay JB. The worldwide prevalence and epidemiology of erectile dysfunction. Int J Impot Res 2;12(Suppl 4):S Kim TH, Chung TG, Ahn TY. Relation between lower urinary tract symptoms and erectile dysfunction: epidemiologic study in Jeong-Eup, Korea. Korean J Androl 1998;16: Ryu SB, Min KD, Park KS, Park YI, Rhee JA, Kweon SS. Epidemiologic study of the male erectile dysfunction with risk factors in rural area. Korean J Androl 21;19: Chun DC, Choi YD, Choi HK. The clinical characteristics of male patients complaining sexual dysfunction. Korean J Urol

6 164 Korean Journal of Urology vol. 5, , February ;39: Zheng BL, He K, Kim CH, Rogers L, Shao Y, Huang ZY, et al. Effect of a lipidic extract from lepidium meyenii on sexual behavior in mice and rats. Urology 2;55: Hadidi KA, Aburjai T, Battah AK. A comparative study of Ferula hermonis root extracts and sildenafil on copulatory behaviour of male rats. Fitoterapia 23;74: Kim DW, Kim DH, Choi DH, Kim DH, Jung GW. Effects of Ginseng alkaloid on the tension of rabbit corpus cavernosum. Korean J Androl 22;2: Kim SW, Paick SC. Clinical efficacy of Korean Ginseng on vasculogenic impotent patients. Korean J Androl 1999;17: Juilfs DM, Soderling S, Burns F, Beavo JA. Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs). Rev Physiol Biochem Pharmacol 1999;135: Hayreh SS. Erectile dysfunction drugs and non-arteritic anterior ischemic optic neuropathy: Is there a cause and effect relationship? J Neuroophthalmol 25;25: Danesh-Meyer HV, Levin LA. Erectile dysfunction drugs and risk of anterior ischaemic optic neuropathy: casual or causal association? Br J Ophthalmol 27;91: Kekilli M, Beyazit Y, Purnak T, Dogan S, Atalar E. Acute myocardial infarction after sildenafil citrate ingestion. Ann Pharmacother 25;39: Hayat S, Al-Mutairy M, Zubaid M, Suresh C. Acute myocardial infarction following sildenafil intake in a nitrate-free patient without previous history of coronary artery disease. Med Princ Pract 27;16: Lee U, Lee M, Kim SY, Ji YH, Hong JH, Ahn TY. Clinical efficacy and safety of sildenafil in the men with erectile dysfunction in Korea. Korean J Urol 21;42: Yoo C, Park J, Kim W, Hong B, Hong J, Ahn TY. Comparison of the efficacy, safety and patient preference of the phosphodiesterase type 5 inhibitors for the patients with erectile dysfunction. Korean J Urol 27;48: Kam SC, Choi SM, Jeh SU, Lee SH, Hwa JS, Jung KH, et al. Efficacy and safety of a herbal formula that mainly consist of cornus officinalis for erectile dysfunction: a double-blind, placebo-controlled study. Korean J Urol 27;48: Hah JS, Kang BS, Kang DH. Effect of Panax ginseng alcohol extract on cardiovascular system. Yonsei Med J 1978;19: Kim ND, Kang SY, Schini VB. Ginsenosides evoke endotheliumdependent vascular relaxation in rat aorta. Gen Pharmacol 1994;25: Choi YD, Park JA, Choi HK, Nam KY. Effects of composition of saponin fraction from Korean Red Ginseng in the relaxation of rabbit and rat corpus cavernosum. J Ginseng Res 1999;23: Choi YD, Xin ZC, Choi HK. Effect of Korean Ginseng on the isolated rabbit corpus cavernosal smooth muscle. J Ginseng Res 1996;2: Nam KY, Ko SR, Choi KJ. Relationship of saponin and non-saponin for the quality of Ginseng. J Ginseng Res 1998; 22: Adimoelja A. Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions. Int J Androl 2;23(Suppl 2): Ito TY, Polan ML, Whipple B, Trant AS. The enhancement of female sexual function with ArginMax, a nutritional supplement, among women differing in menopausal status. J Sex Marital Ther 26;32: Ito TY, Trant AS, Polan ML. A double-blind placebo-controlled study of ArginMax, a nutritional supplement for enhancement of female sexual function. J Sex Marital Ther 21;27:541-9

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