LITERATURE REVIEW

ALTERNATIVE THERAPIES EOR BACTERIAL VAGINOSIS: A LITERATURE REVIEW AND ACCEPTABILITY SURVEY
Elizabeth K. Boskey. PhD, MPH, Objective This article reviews current research into non-antibiotic treatments tor bacterial vaginosis and assesses interest in the use of alternative therapies for women's health in a non-representative sample of women. Design Literature re\iew and online survey. Subjects A convenience sample of 192 women was selected from an online community devoted to the discussion of women's health. Results " Data on altemative treatments for bacterial vaginosis are mixed. Studies have shown both positive and null effects for probiotic- and lactic acid-based treatments. The results of antiseptic studies were more uniformly positive, but the studies were generally not placebo-controlled. Women in the survey population were both interested in and experienced with alternative and complementary therapies for reproductive health problems 44% of them had used home or natural remedies to treat vaginal infections or menstrual problems, and only 20% indicated that antibiotics and antiflingals would be their treatment of choice. Conclusions Women are interested in alternative treatments for women's health problems such as yeast infections and bacterial vaginosis. Although such treatments have been investigated, further researchparticularly in the form of high-quality, randomized, controlled trialsi.s strongly indicated. {Altern Ther Health Med. 2005;U(5):38-43.)

Elizabeth R. Boskey, PhD, MPH, CHES, is an adjunct professor in the Department of Preventative Medicine and Community Health at the State University of New York Health Science Center in Brooklyn, NY.

acterial vaginosis is characterized by an increase in the vaginal pM from a healthy, acidic pH of ~4 to a more neutral pH of >4.5. This change is due to an overgrowth of anaerobic bacteria and a concomitant decrease in the number of acid and ll^O^-producing lactohacilli. which are the microbial guards for vaginal health.' This understanding of bacterial vaginosis as a disruption in the normal vaginal ecosystem, as well as recent media coverage of antibiotic resistance and a growing movement toward "natural" therapies.' have led to increasing interest in non-antibiotic treatments for bacterial vaginosis. Most proposed non-antibiotic therapies for bacterial vaginosis fall into two categoriesprobiotic therapies, which aim to provide the bacteria to directly supplement or restore a woman's healthy lactohacillus-dommated flora (eg, lactobacillus capsules and yogurt-based treatments'"), and acid-restoring therapies such as BufferGel (Reprotect. Inc. Baltimore, Md) and lactic acid gels and creams, which aim to make the vagina a hostile environment to the acid-sensitive bacterial vaginosis organisms, thereby promoting native lactobacillus regrowth.'"'"' Natural antibiotics.

such as tea tree oil. are being studied for use in treating bacterial vaginosis and are frequently recommended by word of mouth in women's communities.'" This article reviews current research into non-antibiotic treatments for bacterial vaginosis. Additionally, to assess the potential for interest in non-antibiotic therapies, a survey was developed for web-based administration to a convenience sample of women with an expre.ssed interest in vaginal health. A sample of 192 women was acquired by posting a time-limited invitation to participate in the survey to an online community focusing on women's reproductive health. MATERIALS AND METHODS Literature Review A search of the literature for all articles containing the keywords "bacterial vaginosis" and "treatment" was conducted. Wherever possible, articles that discussed only antibiotic treatment of bacterial vaginosis were eliminated and all other articles were retrieved and individually reviewed for inclusion. Inclusion criteria were 1) the article must describe a treatment trial for bacterial vaginosisa decision was made to include trials of any size since alternative therapy trials are frequently small. 2) the article must include at least one treatment that is not one of the standard antibiotic therapies for bacterial vaginosis (eg, metronidazole. clindamycin), 3) trials of natural antibiotics (eg, tea tree oil) were acceptable because they are not part of standard pre-

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Altemative Therapies for Bacterial Vaginosis

scription regimens. Articles that met the inclu.sion criteria were also drawn from the reference sections of the selected literature. Data Abstraction The following data were systematically abstracted from each study: number of subjects, type of study design, tested compounds, whether a placebo was used, whether the compound was administered orally or vaginally, study duration, and results. Survey Design The survey was designed using a paid online survey tool Survey Monkey (SurveyMonkey.com, Portland, Ore)which allows for an unlimited number of respondents, the use of response-specific skip patterns, and many options for survey structure. The Institutional Review Board (IRB) approved survey consists of 4 sections: 1) an active consent section that requires 4 confirmatory an.swers before the participant can proceed to the main survey; 2) questions about the demographics of study participants and ascertainment ot where the)' were recruited into the survey: '') questions about experience with vaginal infections or problems and experience with prescribed, over-the-counter, and natural or home remedies; and 4) questions about provider choice for reproductive health problems and general use of complementary and alternative medical systems. Participants taking the survey could only go forwardthey could not go back to change previous survey answersand could opt out of the survey at any time. Skip patterns were used to end the survey early for those who did not consent or who were not eligible {ie. people who have taken the survey before and male respondents) and to skip questions that were not relevant to them based on earlier responses. Answers were not required for reproductive health questions but were required for the demographic and consent sections. The investigator's contact information was provided at the end of the survey in case participants had concerns or questions.

er and the survey URL from the web browser's History file. The survey was available for 3 weeks, and a second post referring people to the initial recruitment message was placed 4 days before the study closed. Analysis The survey was analyzed by simple descriptive statistics becau.se of the non-random nature of the sampling procedure. The survey was intended to demonstrate only whether there is an interest in alternative therapies for vaginal infections among a non-representative sample of women with an avowed interest in women's health. RESULTS Literature Review Results Eighteen studies that examined treatments for bacterial vaginosis with medications other than commercial antibiotics were identified. The treatments could largely be broken down into the 3 categories of antiseptics, probiotics, and acidification devices, but one trial also examined the spermicide nono\ynol-9 as a treatment regimen. Studies varied in quality, witb more than half of them having no control group or nonrandomized controls (Table 1). Most studies were small, and they varied considerably in design. Not surprisingly, because negative studies are rarely published, most of the available studies showed a positive effect for the alternative therapies. Only 3 of the studies bad ambivalent or negative results.'""' Although design quality was problematic in many of the studies, the results suggest that all 3 main methodsprobiotics, antiseptics, and acidification agents-^are potentially useful non-antibiotic therapies for bacteria! vaginosis. Survey Results The women who cbose to participate in the survey were primarily white, college-educated women in their late tetns and 20s (Table 2), as would be expected based on the recruitment method. The majority of these women (74%) have worried about their vaginal health at one time or another, but more of them sought advice from a non-healthcare professional than went to a doctor for care. Slightly more than one-third of the population (39%) had been diagnosed with a vaginal infection (eg, bacterial vaginosis, yeast infection) or sexually transmitted disease at some point in the past, and more than half (60%) of those diagnosed with a vaginal infection were prescribed antibiotics. Most women (56%) saw MDs for tbeir reproductive healthcare, although a similar number were seen by nurse practitioners, and a substantial minority (14%) were unwilling to seek care. Use of home remedies and alternative therapies in this population was high (Table 2). Almost half (45%) of the women have used home or alternative remedies for vaginal infections in the pasta slightly higher percentage than those who had used an over-the-counter yeast infection treatment without seeing a doctor (37%). When asked what their first choice for a

Recruitment Survey recruitment was through a post to a woman's health community on an online journal website (ie, www.livejournal.com). The community had approximately 1,300 members and was monitored by another 700 individuals who are part of the larger site where the community is located. The invitation included permission to forward a link to the survey website to friends. The survey recruitment post had a disclaimer section written written by the 1KB. with detailed disclosure on possible issues with anonymity. This was necessary because although the survey collected no identifying data, it did collect the computer's Internet protocal (IP) address to prevent people from taking the survey multiple times, and it also left a "cookie" on the participant's computer. The disclosure included detailed instructions on how to remove the cookie file from the comput-

Alternative Therapies for R.icterial Vaginosis

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TABLE 1 Review of ihe Literature on Ndu-Aiitibiotic Treatments for Bacterial Vaginosis Study Number of Study Type Participants 10 Feasibility' Tested Compounds Treatment Placebo- Oral/ Length of Category Controlled Vaginal Foiiowup Probiotic No Oral Result.s

Reid etal 2001'

L rhaimwsus CR-1 + Ljcrmcntum RC-14 suspension in milk /. rtmmihmis CR-l + i.fcwwitum W-\A or L rlhimmms C,C, Bio-Three

4 weeks. OgaiiismsrecoveredfhiiT! thevn^giias ] 2 ueeks of most women. Six women v\ith abiior(3 women) malflorahad resolution within 1 week 42 days One treatment group with from treat- tiR-l/RC-14 had good resolution ment of B\' bi' Nugent .scortall women were i-linicall\' heaitliv Significant decreases in vaginal discharge, redness, and pi I as well as a 44% rnicrobiologic cure rate Gynoflor was effective in treatingBV

Reid etal 2001'

42

Feasibilit)' study

Probiotic

Inactive

Oral

Chimura 1998''*

16

Trial

Probiotic

No

Vaginal 3 days

Parent etal 1996" Shalev et al 1996'

32

Multicenter. randomized

n.J].Jactobacilli and Estriol (Gynoflor) yogurt ivif b L luidophilux

Probiotic plus estriol Probiotic Pasteurized yogurt

Vaginal 4 weeks Oral

20-BV. Crosso\'er 18-Canditia trial 8 - Both

6 months. Increase in L aeidopbinlus isolated in women in treatment group. Significant decrease in B\' in treatment group Treatment led to significant decreases in vaginal discharge, redness, and pH as well as a 54% microbiologic cure rate Potentially effective for reducing recurrent B\' if used with metronidazole Both treatments effective at treating B\'. but yogurt substantially more so The alternative treatments were only rarel)' effecti\'e. All were substantially less effective than metronidazole Prevalence of BV declined significantly in study population

Chimura et al 1995**

11

Trial

Intravaginal yogurt

Probiotic

No

Vaginal 3 days

Pattman et al 1994' Neri et al 1993'" Fredricsson et al 1987" 84 pregnant 61

Audit

Gynatren vaccine (/. aclihpliihis lysate) 1) Yogurt douche 2) Acetic add tampon 1) Acetic acid ielly 2) Dinoestrol creme 3) ComETiercial yogurt 4} Metronidazole BufferGel 1) Oral metronidazole 2) Vaginal lactic acid Ijctal gel

Probiotic vaccine

No

Neitber - 6 mo

Open randomized randomized

Probiotic, Treatment Vaginal 2 months and tampon refusals Probiotic. acid gel, hormone Acid gel Acid suppositor\' Acid gel Acid gel No Vaginal 1 month

van deWijgertetal 2001'^ Boeke et al 1993'' Hoist et al 1990'* Anderschetal 1986'"' Wewalka et al 2002'" Petersen et al 2002" Blackwell 1991'" Ison et al 1987-"

98 125 10 pregnant 114-62 withBV 70

Drug safety trial Randomized clinical trial Pilot study

No Yes No No No

Vaginal 14 days Both

3 months Lactic add ineffective in treating BV Lactal effective in treating BV Lactate gel as effective as metroTiidazole in treating BV. Patients in botli groups improved both clinically and subjectively. Betadine had a stronger long-tenn ertkt Both treatments effective in treating BV Vaginal flora and pH resolved to normal after self-treatment Clorhexidine as effective as metronidazole in treating BV No difference in B\' incidence between treatment and placebo groups

Vaginal 8 weeks Both 8 da\'s

Randomized 1) Oral metronidazole trial 2} Vaginal lactate gel

Randomized 1) Betadine suppositories Antiseptic, trial 2)/.ij/j.wm capsules. probiotic Randomized, 1) Dequaliiiium chloride Antiseptic double-blind 2) Povidone iodine Case study Tea tree oil. vaginal pessaries Antiseptic Antiseptic Spermicide

Vaginal 10 days

180 - 73 with BV 1 79

No No No Yes

Vaginal 4 weeks \'aginal 1 montb Botli 28davs

Randomized, I) X'aginal ClorhexidiTie single-blind 2) Oral Metronidazole

Richardson et al 278 CSWs Randomized, Nonoxynol-9 2001'' U2BV double-blind

Vaginal Median 50 weeks

Artitic in Japanese. B\'-lla(lcrJa! vaginosis; CSVV=tommercial sra workers

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Alteniiitive Therapies for Bacterial Vaginosis

TABLE 2 Survey Responses

Demographic Questions }Ustor\ of Vitjiimil Problems ami Remedies (Continued)

Age (years) <17 18-19 20-24 25-29 30-39 40 or older Skipped Race White (non-Hispanic) Black (non-Hispanic) Hispanic Asian/Pacific Islander ,\merican Indian/Alaskan Native Olher Skipped Educational Level less than high scluHil High school diploma or GED Some college Associates degree Bachelor's degree Graduate or Postgraduate Skipped
History of Vaginal Pmhiems ami Experieme With Remedies

n 19 43 83 29 13 2 3 167 1 2 5 2 12 3 19 16 91 10 4o 7 3

% 9,9 22,4 43.2 15,1 6,8 1.0 1.6 870 0.5 1.0 2.6 1.0 6.i 1.6 9,9 8,3 474 5,2
')A l\

n If diagnosed, prescribed antibiotics? {n=68) 41 Yes 27 No If antibiotics prescribed, were the\' taken? (n=41) 2 No 38 Yes 1 [lon't Remember Providers seen for reproducti\e health care (all that apply) 107 MDOB/GYN specialist 50 Ml")Other 7 Nurse Midwite or Midwife 50 Nurse practitioner 2 Osteopath 6 CAM Provider 8 No practitioner-uninsured 7 No practitioneruncomfortable 11 No practitionerother 15 Other Practitioner/L'nknown Type 14 Skipped
Home ami Aiternative Remediesfor Vaginal Problems

%
60.3 39.7

4.9
92,7

2,4
55.7 26,0

3,6
26.0

1.0 11 4.2 16 5,7 78 73

3,6 1,6

Ever worrietl might have a vaginal infection? \'es No Skipped If yes, what was done? (n=143) (all that apply) Went to the doctor Sought ad\ ice from family/friends Sought ad\ ice from the Internet Bought over the lounter remedy Used a home/natural remedy Waited for symptoms to go away Other/Skipped Ever tliagnosed with a vaginal infection/STD? Yesvaginal infection Yessexually transmitted disease \esboth (not concurrently) No Skipped

143 43 6 71 59 84 53 36 77 3 54 7 14 109 8

74.5 22.4 3,1 49,7 41.3 58.7 37,1 25.2 53,8 2.1 28,1 3,6 7.3 56,8 4,2

Ever treated a yeast infection with OTC medication? 70 \es 9 Yesonly afrer seeing a healthcare provider 105 No 8 Skipped Home/natural remedy ever used for women's health? 86 ^es 96 No 10 Skipped First choice treatment for treating a vaginal infection 39 An antibiotic or antihmgal pill or creme 12 An over-the-counter product that is not an antibiotic 15 ,\ probiotic product 47 A natural remed)' \'ou could prepare yourself 6G "1 don't care what I take as long as it works" 13 Skipped
Treatments interested in using (all that apply) An antibiotic or aotitiingal pill or creme An over-the-counter product that is not an antibiotic A probiotic product A natural remedy you could prepare yourself" "I don't care what 1 take as long as it wtirks" Skipped

36,5

4,7
54.7

4,2
44.8 50.0

5.2
20.3

6.3 7.8
24.5 34.4 (S.8 56.3 58.3 58.3 65.1 44.3

108 112 112 125 85 13

6.8

remedy for a vaginal infection would be, 39% chose a non-traditional therapy (ie. probiotic, non-antibiotic over-the-counter cemcdy. tiatiiral or home remedy), only 20% cbose an antibiotic or anti-fungal, and 34% said they would take anything as long as it worked. When asked whicb therapies tbey would be willing to use. approxitiiatcly (50% were willing to use any therapy on the list. The population, as a whole, was also reasonably experienced with alternative therapies in other aspects of their

tnedieal care (Table 3). Althougb ]^7% of the women stated tbat they used tio complementary or alternative tberapies, 31% used dietary supplements, and approximately 10% used aromatherapy, naturopathy, homeopathy. Reiki, therapeutic massage, and chiropractic services. Types of bome remedies for vaginal probletiis used by participants were diverse (Table 4). The most common therapy by far was yogurteither applied vaginally or ingested. Yogurt and

AltiTiiali\ e Therii|iit's for B:!( itrial Vaginosis

ALTERNATIVE THERAPIES, SEPT/OCT 2005, VOL, 11, N O , 5

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I/VBLE 3 Types of Complementary and Alternative Medicine (CAM) Providers and Practices L'sed by Survey Participants CAM providers or products used (all tbat apply) None Acupuncture Osteopathic medicine Cbiropractic medicine Homeopathy Naturopatbic medicine Aromatherapy Therapeutic massage Ayurvedic tberapy Qigong Reiki Therapeutic touch Dietary supplements (not prescribed by an Mi)) Other oriental medicine system Other CAM practice not listed Skipped

TABLE 4 Types of Home or Natural Remedies Used by Survey Participants for Vaginal or Menstrual Problems* Either eaten or applied vaginally (n=48) Eaten or inserted (n=4) Acid vaginal suppositories (n-2) When specified, as a rinse or douche (n=6) Juice or pills (n= Hi) Either eaten or inserted (n=13) Pads, packs, hot baths, and compresses (n-10) Herbal teas: ttickiding parsleyteinmenagogue), thyme, tansy (pregnanc) teniiination/emmenagogue), raspberr)', ginger, chamomile, molasses, and peppermint (n=23) Herbs and essential oils: Including black cohosh, blue cohosh, pennyroyal, evening primrose oil, dong quai, Chinese herbs, yarroiv. calendula oil. tea tree oil (n=9) Intoxicants: Alcohoi, marijuana (n=2) Epsom sa!t, oatmeal, baking soda, Special baths and rinses; peroxide (n=8) Lysine (for 1ISV-1 outbreaks), calcium, magSupplements: nesium, vitamin C (emmenagogue) (n=5) Massage, acupuncture (n=2) Therapies: "Number of women mentioning the llierapy is in parenthesis. Most common reasons for use of therapies, when given, were cramps, yeast infections, and urinary tract iiifectiDiis, When a specific use, olher than the above, was meiilioiied for a therapy, it is listed in paremhests. Yogurt: Acidophilus tablets: Boric: Vinegar: Cranberry: Garlic: Heating:

n
71 8 3 20 24 22 29 19 1 1 15 2 60 4 11 30

% 37.0 4.2 1.6 L0.4 12.5 11,5 15,1 9.9 0.5 0.5 7.8 1.0 31.3 2.1 5.7 15.6

acidophilus tablets were used in an attempt to replenish healthy vaginal flora. Herbal teas were the second tnost common therapywhen their use was indicated, it was usually for either pain relief or as an emmenagogue. Non-bacterial acidfying remedies also were common, as was garlicone of the more frequently discussed home remedies for a yeast infection. Both acidification treatments and garlic are intended to make the vaginal and urinary environments more hostile to non-healthy flora. Although normal vaginal flora thrive at low pH, the bacteria associated with bacterial vaginosis do not, and garlic has established antimicrobial properties. Alternative pain relief tlierapies also were frequently used to relieve menstrual cramping. DISCUSSION The literature on non-antibiotic therapies for bacterial vaginosis is mixed. Whereas sotiie studies show these therapies to be useful, others find no effect, and the overall study quality is poor. Probiotics,''" acidification agents.'- " '^ and antiseptics'"'"-"all show promise for treating bacterial vaginosis through clinical studies and have a firm theoretical basis for why they should be effective. Some studies have found these agents to be ineffective, however, and it is important that highquality, clinical trials be pursued."'' Women are interested in non-antibiotic therapies for vaginal infections. Only 20% of survey respondents preferred antibiotics; most would be happy using any therapy that was effective; and more than one-third indicated a preference for a probiotic. natural, ornon-aiitibiotic therapy. Almost half of the population had, in fact, used home or natural remedies to treat vaginal or menstrual problems in the past^more women than had purchased over-the-counter treatments with or without physician approval. Even many of the women who did not indicate a preference for a non-antibiotic therapy would be willing

to use oneequivalent numbers of women were willitig to use antibiotics, probiotics. home remedies, and over-the-counter, non-antihiotif therapies. Current use of alternative therapies for general health in this population was similar to (hat seen in a national survey in 1997.' Approximately 42% of the study population used at least one such therapy, with tnore than a third of the population using dietary supplements that ha\'e previously been reported to be frequently used by women." Interestingly, these women used a wide range of home remedies for their reproductive health problems. Although this is partially explained by the source of the population being a woman's health community where several of these treatments are discussed, the frequency of use is surprising. The most common therapies used, yogurt or acidophilus. garlic, and cranberry, are easily prepared or purchased, and do have some scientific basis for effect.'"'^^' The biggest limitation to this study is the non-representative source of the survey population and the relatively lowresponse rate. However, the survey does show a strong interest in natural and alternative therapies by women in this sample and will hopefully help to provide an impetus to future research in this area. High-quality clinical trials of non-antibiotic tberapies for vaginal infections need to be conducted. There is a market for these treatmentsthey just need to be tested and developed.

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AIJFRNATIVE THERAPIES, SErT/OCT 2005, VOI, 11, NO, 5

Alternative Therapies for Bacterial Vaginosis

Refrrentes
1. Boris S, Bardes C. Role played hy Uuiohuiiih i:i lonrrolliiig the popiiialion of vaginal jialhogeiLs. ,UJIrnfti'i liitnt. 20(XI; 2:543-54fi. 2, l-isenberg D.M. Davis RB, Ediier SL. et al. Trends in alternative mediiine u\e in ihe United Stales. 1090-1997: results ofa tiilliiw-up naiional survey. JAMA. 1998; Reid tl. Brute AV\', leaser N, et al. Oral probiotics ran resolve urogenital int'ectiotis. FEMS Imtnmu'l Mfil Miirolml 20(11: 30:49-52. Reid c;, Beiieniiaii I). Huini-ciianii C. Bruce AW. Probiotic iMctohacillus dose required ti> restore and maiiUaiii a mimial \aijinal flora.ffiM.S'/mmuMiVjUft/.W/froi/iV.2001; 32(1);37-4I. Chimura T. [Fxobgical ireaimejii ut'bacterial vaginosis and vaginitis with Bii>-Lhrft|. I/Ill JAiiiibn-t. 1998; 51:759-7i.;3-Japanese. Parent D. Bossens M. Bayol D et al. Therapy ol'battcrial vaginosis using exogenouslyapplied Lactobacilli acidiiphili and a low dose of estriol: a placebo-controlled multicentric clinical trial. Arznamitteljor.'iihung. 1996; 4t):68-73. Shaiev E. Ballinii S, Weiner E, Colodner R. Keness V. Ingestinn of yogurt containing l.aiiiibacillus acidopliilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis. Arik Fam Med. 199B; 5:593-596. Chimura T. Kunayama T. Murayama K. Numazaki M. lEcoUigical treatment of bacterial vagmosis].JptiJ Aritibiiil. 1995; 48:4 32-43 6. Japanese. Pattman RS, Sankar KN, Watson PC, VVardropper AC. .An audit ol Gynatren (a Lutohiuillu\ iiailophilus lynphilisate) vaccination in women with rectirrent bacterial vaginosis-/H//5m4/aS. 1994:5:299. Neri A. Sabah C, Samra Z. Bacterial vagiiwsis iti pregnancy treated with yoghurt. Ada Ohstcl CrneolSiiiml. 199:i; 72:17-19Fredrics.son B. Englund K, Weintraub L, Olund A. Nord (.'?., Fcologica! trealnient ut bacterial vaginosis. t(iwirtl987; 1:271), van df VVijgert J. Fullern A. Kelly C. et al. Phase 1 Trial o( the Topical Microbicide Biitter<lel: Safety Kcsults Irom Riur International Sites. / Acijuir immune Defir Syndr. 2(H}1; 26:21-27. ' Boeke AJ, DekketJI!, vanEijkJT, Kostense PJ, Beiemer PI). Effect otlat Lie aiid suppositories compared witb iiral metronidazolc and placebo in baiterial vaginosis: a randomised clinical trial. Ctiitourm Med. 1993:69:388-392.

14. 15.

Ifi, 17.

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Hoist Ii, Brandberg A. Treatment ot baclerial vaginosis in pregnancy with a lactate gel. SamdJhitei! Dis 1990; 22:625-626. Andersch B, Torssman L, Lincoln K, Torstensson P. Treatment of Bacterial Vaginosis with an Acid Cream: A Comparison between the Effect of Lactate-tiel and Mftronidazole.Gi'wm'/OfeM/niW, 1986:21:19-25. Blaikwell Al.. Tea ireeoil and anaerobic (bacterial) vaginosis- Lattirl. 1991; 337:300. Richardson BA. l.avreys L. Martin HLJr, et al. Evaluation ofa low-dose ni)noxynol-9 gel for the prevention of sexually transmitted diseases: a randomized clinical trial- Sex Transm D;s. 2(N11; 2H::4-400. WewalkaC"j,StaryA. BosseB. Duerr HE, Reimer K-Efficacy of povidone-iodine vaginal suppositories in the treatment of bacterial vaginosis. Derinatnlogy, 2002; 204 SuppI 1:79-8.5. Petersen EE, Weissenbacher ER, Hengst P, et a l Local treatment of vaginal infections of varying etiology with dequalinium chloride or povidone iodine. A randomised, doubleblind, active-controlled, multicentric clinical study. Arzneimilteijoruhung. 2002; 52:706-715. Ison CA. Taylor RF. Link C, et al. Local treatment (or bacterial vagino.sis. Br Med} iClirt te(//1987; 295:886. Raiten DJ, Picciano MK Coates PM. Dietary supplement use in women: current status and future directions-introduction and rimferem-e summary. / Nutr. 2003: 133:1957S-i960SKiel RJ. Nashelsky J, Robbins B. Does cranberry juice prevent nr treat urinary tract infection?/ft(m frail. 2003; 52:154-155. Tesch BJ. Herbs commonly used by women: an evidence-based review. Am j Obstet Cwnvl 2003; I8K:S44-S5r..

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20. 21-

22, 23.

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