1206 O'BRIEN: MANAGEMENT OF VAGINITIS Canad. Med. Ass. J. May23, 1964, vol.90

J. R. O'BRIEN, B.Sc., M.D., C.M., F.R.C.S. [C], Montreal

ABSTRACT SOMMAIRE Results of treatment of 151 cases of L'auteur passe en revue les r6sultats du vaginitis in patients attending a Ieukorrhea traitement de la vaginite chez 151 malades clinic were studied. The incidence of each venues en consultation .i la clinique pour type of vaginitis is recorded. Analysis of leucorrh6e. L'article classe par cat6gories la results of treatment with six compounds fr6quence de chaque forme de vaginite. De currently used in the therapy of vaginitis l'analyse des r6sultats th6rapeutiques, ii indicated that acetarsol or pimaricin com- apparait que, comme traitement d'attaque, pounds, with their broader spectra of avant instauration d'un traitement sp.ci. activity, appeared to be most useful, prior fique bas6 sur un diagnostic pr6cis au to establishment of a definite diagnosis by moyen de cultures, les m6dicaments les plus means of cultures. Chiordantoin is an utiles sont l'ac6tarsol ou la pimaricine, dont effective antifungal agent and is associated ractivit6 est tr.s .tendue. La chiordantoin with a high percentage of "culture cures". est un antifongique efficace auquel on Resistant cases should be investigated for attribue un pourcentage .lev6 de "gu6risons diabetes mellitus, and many are aided by d'apr.s les cultures". On fera bien de a low carbohydrate diet. Metronidazole was rechercher le diabete sucr6 coinme .tiologie used only for resistant cases of tricho- possible des cas r.sistants, dont la plupart moniasis, with a cure rate of over 80% s'am6liorent avec un r6gime faible en glu- when both partners were treated simul- cides. Le m6tronidazole a .t6 r.serv6 aux taneously. Triple-sulfa vaginal cream was cas rebelles d'infections & trichomonas et effective in over 80% of patients with non- a abouti & la gu6rison dana plus de 90% specific vaginitis; no cases of resistant des car, & condition de traiter simultan6- bacterial infections were encountered. ment les deux partenaires. Une cr.me Dienestrol cream was effective in relieving vaginale contenant trois sulfamides s'est the symptoms of atrophic vaginitis. r.v6l6e efficace chez plus de 80% des malades ayant une vaginite asp6cifique. On n'a pas observe de cas d'infections bact6riennes r.sistantes. Quant & Ia vaginite du type atrophique, elle s'est am6lior.e & la cr.me au di.nestrol. Oanad. Med. Ass. J. May 23,1964, vol. 90 OTBrien: Management of Vaginitts 1207

LEUKORRHEA CLINIC New Patient's First Visit Date. Name. O.P.D. Number.. Age. Marital Status. G. P. Menses././. Dysmenorrhea. Spotting. Other Ulnesses. Operations. Chief Complaint (own words). Discharge: colour .white. yellow. brown.pink. green.. odour .foul. moderate. nil.

amount .. no. of pads per day. irritation.pruritus. dyspareunia. time of occurrence re periods.

duration . months Husband's symptoms. Urinary dysuria.symptoms. frequency. stress incontinence.. Previous treatment: drug. duration. results.,. Physical Examination: Vulva:erythema.excoriation. intertrigo.. Vaginal Mucosa: hyperemic. flea-bitten. flakes. Cervix: erosion. laceration. parous. TJterus: .:.

Adnexa: . Description of discharge: frothy. cheesy. watery.sanguineous. Remainder of physical:. Clinical Impression:. Cttology. cornification. Microscopic Smear: Trichomonas. pus. hyphae.epithelial cells.. Nickerson's medium culture. date read. Treatment today: Drug. Douches.:.:. Topical cream. Return in Two Weeks on a THURSDAY only (if possible). Date:. CONSULT WITH Dr. Fig. 1 peatedly examined for the presence of active tri- one of the drugs under investigation was often chomonads.1'2 The Trichosel culture was not used not the best choice, owing to an error in the if trichomonads were easily seen on the initial clinical impression, arrived at before the cultures microscopic smear of the discharge; thus its main were reported. The patients were instructed to advantage was to determine whether the complete return to the Leukorrhea Clinic four to seven days eradication of parasites followed treatment. This after treatment was completed, and each patient culture medium also supports the growth of Can- was then examined by the author. At that time dida albicans, thus serving to confirm the results of a repeat pelvic examination, microscopic smear and the more convenient cultures on Nickerson's cultures were again carried out for evaluation of medium. the previous treatment. At that time a reliable diag¬ As a rule an accurate diagnosis could not be nosis could usually be made, and treatment was made until all reports of these investigations were changed to a more specific drug or combination available, at the time of the patient's second visit. of drugs if required, or the initial therapy was As a result, the initial course of therapy involving continued for another course when improvement Cana,d. Med. Ass. 3. 1208 O'BmEN: MANAGEMENT OF VAGINITIS May23, 1964, vol.90 had been noted. The cytological report included also includes a few patients who initially showed data concerning (a) the cornification index of the only .trichomonads but after treatment with metro- vaginal epithelium, which is a reflection of the nidazole* (Flagyl) subsequently developed further estrogen level in the tissue, and (b) the presence symptoms and had a positive culture for Candida of trichomonads. These reports were helpful, there- albicans. fore, in further establishing a correct diagnosis. 4. Non-specific vaginitis and cervicitis: diagnosed Provided that no evidence of cancer or atypism was when no specffic organisms were cultured. Many noted in the cervical cytology studies, cervical of these cases were initially misdiagnosed as moni- erosions or cervicitis were cauterized as necessary. liasis and vice versa. Routine bacterial culture and sensitivity tests were 5. Atrophic or senile vaginitis: diagnosis based not performed unless infection by a specific organ- mainly on the absence of specific organisms and ism, such as the gonococcus, was suspected. Hemo- a low estrogen level reported on the cytological philus vagincilis was not considered a cause of smear. The patients had usually shown clinical vaginitis and thus its presence was not further improvement following local estrogen therapy. investigated.3-5 Description of Drugs Tested CLASSifICATION OF RESULTS OF TREATMENT 1. Compound It: Each suppository contained: ace- The results of treatment were grouped in four tarsol 100 mg.; iodocblorohydroxyquinoline 2 mg.; categories: (a) Complete clinical cure in which benzalkonium chloride 10 mg.; lactic acid 500 mg.; all cultures were negative following treatment; this lactose 300 mg. included later follow-up at thee- and six-month Supplied as vaginal suppositories to be inserted intervals. (b) Some clinical improvement noted, every morning and evening. Usual course was 10 days. but one or other cultures remaining positive follow- 2. Compound 114:: Each tablet contained: pimaricin ing treatment (includes early recurrences). (c) No 50 mg.; amylocaine HCl 15 mg.; benzalkonium clinical improvement noted, cultures remaining chloride 1 mg. Supplied as vaginal tablets, one tablet to be inserted positive. (d) Symptoms aggravated or definite al- every evening for 10-20 days. lergic or toxic manifestations noted. 3. Compound III§: A triple sulfa vaginal cream The types of vaginitis and their incidence are containing: sulfathiazole 3.42%; sulfacetamide 2.86%; shown in Table I. n'benzoylsulfanilamide 3.70%; urea 0.64%; cream base -q.s.-100%. TABLE I. Supplied in a tube with disposable applicators, the contents of one applicator to be inserted twice daily No.of for 10-20 days. Type of discharge patients Incidence Another preparation of these agents was supplied Trichornoniasis alone.55 36 Moniiasis alone.31 20 as vaginal tablets, each tablet containing: sulfathiazole Combined trichomoniasis and 172 mg.; sulfacetamide 143 mg.; n'benzoylsulfanilamide moniiasis.25 16 184 mg.; urea 13 mg. Non-specific vaginitis or cervicitis 33 22 One tablet to be inserted twice daily for 10-20 days. Atrophic or senile vaginitis 5 3 Specific bacterial vaginitis 4. Compound IVII: An antifungal cream containing: (gonococcus).2 1 chlordantoin (active ingredient) 1%; benzalkonium Total patients available for chloride 0.05%. follow-up.151 Supplied with disposable applicators. Recommended Patients referred to the Vaginitis Clinic 341 dose: the contents of one applicator twice daily for Annual Attendance, Gynaecology Outpatient Clinic two weeks. 1331 new patients 2992 revisits 5. Compound V.: A specific trichomonicidal agent containing metronidazole. Active ingredient: 1-2'hy- droxyethyl-2-methyl-5-nitroimidazole. TYPES OF VAGINITIS TREATED Supplied as oral tablets, 250 mg. twice daily for Five types of vaginitis are reported for each drug 10 days for both husband and wife, and as vaginal under trial; the diagnostic criteria for each are as suppositories-500 mg., to be inserted every evening follows: for 20 days. 6. Compound VP0: An estrogenic vaginal cream con- 1. Trichomoniasis alone: absence of other specffic taining as its active ingredient the synthetic estrogen organisms and presence of active trichomonads on dienestrol, 0.1 mg./g. of cream, and benzoic acid wet smear or growth in the Trichosel broth after preservative 0.2%. as long aslO days of incubation. Supplied as a vaginal cream with applicator. The 2. Moniliasis alone: Methods of diagnosis have contents of one applicator to be used daily for 7 to previously been reported.6 Presence of Candida 14 days, then reduced to one every 48 hours. albicans on Nickerson's medium after as long as *Poulenc Ltd. five days of aerobic culture at room temperature. tMetrogyne-Metro Drug Ltd.. Montreal, Que. $Pimafucln-Canada Duphar Ltd.. London. Ont. 3. Combined trichomoniasis and moniliasis: both §Sultrln-Ortho Pharmaceutical canada Ltd. ISporostacin-Ortho Pharmaceutical canada Ltd. organisms present at the initial examination and ¶1Flagyl-Poulenc Ltd., Montreal. diagnosed by the above-listed criteria. This group *.Dienestrol-Ortho Pharmaceutical (canada) Ltd.. Toronto. Canad. Med. Ass. J. May23, 1964, vol.90 O'B1UEN: MANAGEMENT OF VAGINITIS 1209

TABLE II. Drug: Compound I (vaginal suppositories) Dose: One suppository twice daily for 10 days Complete cure, clinical improve- Clinical ment, negative improvement Symptoms culture after culture remains No clinical worse, Type of discharge No. of paticnts treatment positive improvement toxic Trichomoniasis alone.21 8 7 5 Moniliasis alone.9 5 3 1 Combined trichomoniasis and moniiasis.7 1 3 3 Non-specific vaginitis.7 6 1 Atrophic vagim.1 1 Total patients treated.45 21 14 9 cure rate: trichomoniasis alone.. 8/21 38% 7/21 33% 5/21 28% cure rate: moniliasis alone. 5/9 59% 3/9 33% 1/9 11% % cure rate: non-specific vaginitis.. §/7 86%

No speeffic douche was recommended during applied to routine office use, except perhaps the treatment, and with certain drugs, douching was Trichosel broth culture. However, in this study the contraindicated. latter only served as a control procedure for The results of treatment with these agents are evaluating the effectiveness of each drug. The value of Trichosel broth cultures as a diagnostic presented in Tables II to VII. aid is actually not much greater than that of an DIscussIoN experienced examiner using the wet-smear tech- nique. It also seems obvious that one cannot The incidence of the various types of vaginitis treat all types of vaginitis with a single drug, or encountered in this study appears to agree with with a mixture of three of four agents in combina- that reported by other investigators.7'8 Most of the tion, each designed to control a specffic organism. compounds under investigation had already had Cost should be considered and medical common adequate clinical trials to test their effectiveness sense used in planning the management of cases in the treatment of the various speeffic types of of vaginitis. Such a plan should incorporate an vaginitis.3' 8-18 inexpensive and convenient method of ensuring It is apparent that the examiners' initial diag- accurate diagnosis and appropriate therapy. nostic impression in patients with vaginitis is not Once a clinical impression was gained at the always correct, nor does it agree with subsequent initial examination, the policy in this study was to culture reports. Thus many instances of complete prescribe an inexpensive broad-spectrum prepara- mistreatment are recorded here, and up to 60% tion aimed at relieving symptoms until a positive of moniliasis cases were wrongly diagnosed diagnosis could be made by the time of the pa- initially.6 It is therefore obvious that adequate tient's next visit. Thus either Compound I or Com- diagnostic procedures within a general plan of pound II was routinely prescribed in the first investigation and treatment are essential for the instance. Subsequently the more specific and usu- good management of these patients. All of the ally more costly drugs were used if the clinical methods described in this study could be readily results indicated that such a change was warranted.

TABLE III. Drug: Compound II (vaginal tablets) Dose: Initial treatment: one tablet daily for 10 days. Some recurrent cases were given one tablet twice daily for 10 days. Complete cure, clinical improve- Clinical ment, negative improvement Symptoms culture after culture remains No clinical worse, Type of discharge No. of patients treatment positive improvement toxic TrichomoniasiR alone 29 5 11 13 Moniliasis alone.11 5 4 1 1 Combined trichomoniasis and moniiasis.6 3 2 1 Non-specific vaginitis.7 4 3 Atrophic vagim.2 2 Total patients treated.55 19 20 15 1 5/29 17% 11/29 38% 13/29 45% 5/11 45% 4/11 36% 1/11 10% 4/7 57% 3/7 43% TABLE IV. Drug: Compound III (vaginal tablets or cream) Dose: One tablet or applicator twice daily for two to three weeks Cwnplete cure, clinical improve- Clinical ment, negative improvement, Symptoms culture after culture remains No clinical worse, Type of discharge No. of patients treatment positive improvement toxic Trichomoniasis alone.5 1 4 Moniiasis alone.14 9 5 Combined trichonomiasis and muniliasis.1 1 Non-specific vaginitis.23 20 3 Atrophic vaginitis.2 2 Total patients treated.45 22 14 9

Drug: Compound IV (vaginal cream) Dose: One applicator twice daily for two to three weeks Complete cure, clinical improve- Clinical ment, negative improvement, Symptoms culture after culture remaine No clinical worse, Type of discharge No. of patients treatment positive improvement toxic Trichomoniasis alone.4 4 Moniiasis alone.38 32 5 1 Combined trichomoniasis and moniliasis.11 11 Non-specific vaginitis.2 1 1 Atrophic vaginitis.1 1 Total patients treated.56 33 16 5 % cure rate: moniiasis alone.. 32/38 84% 5/38 13% 1/38 3% symptoms in over 80% of cases. It is of little fections. As expected, poor results were obtained value in the treatment of trichomoniasis or monili- when specific organisms other than Candida were asis, although some cases of atrophic vaginitis present. No side effects were noted in any patients. appeared to improve with this treatment alone. Several patients, who initially failed to respond, No side effects were noted in any patient. The eventually showed complete disappearance of organism H. vaginalis, if present, appeared to be symptoms and negative cultures after a prolonged well controlled by this drug. There were no cases course of this agent together with a diabetic dietary of bacterial vaginitis which did not respond to this regimen with or without oral hypoglycemic drugs. agent or which required further cultures and sensi- 5. Compound V: This potent trichomonicidal tivity determinations. Two cases of gonococcal in- agent was used in this study mainly in the treat¬ fection responded to parenteral penicillin therapy ment of persistent, severe or recurring cases of

TABLE VII. Drug: Compound VI (vaginal cream) Dose: One applicator twice daily for two to three weeks Complete cure, clinical improve- Clinical ment, negative improvemerU, Symptoms cuUure after cuUure remains No clinical worse or Type of discharge No. of patients treatment positive improvement toxicity Trichomoniasis alone. Combined trichomoniasis and moniliasis. Non-specific vaginitis. Atrophic vaginitis. Total patients treated.

% cure rate: atrophic vaginitis . 3/3 100% with three negative chocolate-agar cultures follow- trichomoniasis, especially after failure of other ing treatment. There was no significant difference therapy. The results here showed an 83% cure rate in clinical results using the tablets or the cream. with negative cultures after one course of treat¬ However, some patients preferred one form and ment. This compares favourably with the results some the other. of other investigators.1115 In most instances, com¬ 4. Compound IV: This is an antifungal cream bined oral and vaginal treatment was prescribed, designed specifically for treatment of vaginal as was simultaneous oral treatment of the male moniliasis. The active ingredient, chlordantoin, partner. No serious toxic reactions were noted, appears to act by penetrating the fungus cell mem- although several patients complained of mild brane. In this study, 84% of patients had negative nausea and a bad taste in the mouth. Only one cultures for Candida albicans following treatment patient diseontinued treatment because of the side with this agent. It is well tolerated when used in effects. Most women reported that their husbands conjunction with metronidazole for concurrent in- never felt better while on treatment, but others 1212 O'B1UEN: MANAGEMENT OF VAGINITIS Canad. Med. Ass. 3.90

apparently refused to take the pills on the grounds diabetes mellitus, psychoneuroses, systemic diseases that there was nothing wrong with them. Twenty or other associated conditions. per cent of the patients with trichomoniasis alone, All of the drugs studied in this trial appear to treated with metronidazole, subsequently de- have a place in the current management of vagin- veloped symptoms of moniliasis with positive itis. Compound I (Metrogyne-Metro) and Com- cultures. However, in all of these the monilial infec- pound II (Pimafucin-Canada Duphar), with their tion was mild; in some it cleared spontaneously broader spectrum of activity, appear to be most while others required a single course of chlordan- useful prior to establishment of a definite diagnosis. tom therapy for the relief of symptoms. Compound III (Sultrmn-Ortho) is effective in cases 6. Compound VI: This is a vaginal cream con- of non-specffic bacterial vaginitis. With the excep- taining a synthetic estrogen. It was used frequently, tion of the two patients with gonorrhea, no patient but only six patients so treated were available for in this series required further antibiotic therapy. adequate follow-up. In only three cases was posi- Compound IV (Sporostacin-Ortho) is an extremely tive evidence of teleatrophy obtained on the cyto- effective antifungal agent and its administration is logical smear. Valid conclusions cannot be drawn followed by a high percentage of "culture cures". from such a small series. All patients treated re- Patients with persistent infestation should be in- sponded well, however, and there were no side vestigated for diabetes mellitus, and many patients effects. with vaginal moniliasis are aided by a low carbo- hydrate diabetic diet. Compound V (Flagyl- In this series there were 17 patients with re- Poulenc) is a potent and effective anti-trichomonal current moniliasis who were investigated for agent with few serious side effects. However, it diabetes mellitus. Thirteen had positive family must be used in adequate dosage, and both male histories of diabetes and two were diabetics under and female partners should be treated if best re- poor control. Three showed an impaired glucose sults are to be obtained. Compound VI (Dienestrol tolerance curve, and in them symptoms of vaginitis -Ortho) is effective in relieving the symptoms of cleared dramatically on treatment with oral hypo- atrophic vaginitis. glycemic agents and chlordantoin. The remaining patients, after several weeks of combined diet and SUMMARY chlordantoin therapy, were well controlled by One hundred and fifty-one of 341 patients attend- diabetic diet alone. ing the Leukorrhea Clinic of the Royal Victoria Montreal Maternity Hospital were available for ade- CoNcLusIoNs quate follow-up studies after treatment with six The management of vaginitis may be divided different compounds currently available for the treat- ment of vaginitis. The incidence of each type of into three phases: vaginitis is described and results of treatment with 1. At the first consultation, which should include each individual compound are analyzed. The effective- along with the .history a pelvic examination, ness of each of these compounds was checked by thorough inspection of the involved parts, and a culture, as well as by clinical results. An outline for the wet vaginal smear, a tentative diagnosis can be management of the average case of vaginitis seen in made on clinical grounds. Because of the proba- office practice is suggested. The most appropriate use bility of diagnostic error prior to receiving results of each of the compounds investigated is considered. of cultures, initial therapy should be simple and Appreciation is extended to Dr. Win. Cornett and Ortho inexpensive, with a, broad-spectrum preparation Pharmaceutical (Canada) Ltd., for their grant-in-aid and such as Compound I (Metrogyne-Metro) or Com- their generous supply of Nickerson's medium, Sultrin, Sporostacin and Dienestrol Cream. pound II (Pimafucin-Canada Duphar). Routine Appreciation is also extended to Canada Duphar Ltd. Nickerson's culture is strongly advised; the more for the supply of Pimafucin and their grant-in-aid, and to elaborate Trichosel broth culture is not recom- Metro Drug Ltd. for their supply of Metrogyne. mended for office use. A cytological smear is essential, as it should be used in the investigation RSFERENCES 1. KUPFERBERG A mt. Rec. Med., 168: 709, 1955. of any new gynecological patient. 2. TRUSSELL, it E.: Trichomonas vaginalis and tricho- moniasis, charles c Thomas, Springfield, ill., 1947. 2. A second examination one or two weeks later 3. HELTA!, A. AND TALEGHANY, P.: Amer. J. Obstet. Gijnec., 77: 144, 1959. is necessary, not only to establish an accurate diag- 4. LAPAGE, S. P.: Acta Path. Microbiol. Scand., 52: 34, 1961. 5. EDMUNDS, P. N.: J. Ob8tet. Gijnaec. Br&t. Emp., 68: 917, nosis, but to evaluate the response to the initial 1959. 6. O'BRIEN, J. R.: Canad. Med. A88. ,f., 90: 1073, 1964. therapy. If this has been good a similar course of 7. DIEHL, W. K., FRIEMAN, S. AND LINSAo, G. S.: Obetet. Oynec., 17: 593, 1961. treatment should probably be repeated before the 8. LANG, W. R.: J. A. M. A., 174: 1814, 1960. 9. MENDEL E B AND BoNE, F. W.: Amer. J. Ob8tet. (lynec., patient is discharged; if not, more specffic treat- 82: .40, 1961. ment should be directed against the known patho- 10. CAZEMIER, C. et aL: Antibiot. Med., 6: 601, 1959. 11. KEIGHLEY, E. B.: Brit. Med. ,T., 2: 93, 1962. gen. 12. ROBINSON, S. C.: (Janad. Med. Ass ,t 84: 948, 1961. 13. ROBINsON, S. C. AND JOHNSTON, D. *.: Ibid., 85: 1094, 3. Subsequent follow-up visits at monthly inter- 1961. 14. FORTIER, L.: Gynaecologia (Basel), 149 (SuppL): 158, vals may be necessary to ensure complete and 1960. 15. LUTHRA, R. AND BOYD, J. R.: Amer. ,T. Obstet. (jtijnec., permanent cures. Stubborn cases may require 83: 1288, 1962. 16. MTYRDOOTI, R. AND BLOCH, W. P.: Brit. Med. J., 2: 678, further investigation-for example, to rule out 1959.