Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study).

Abnormal vaginal discharge syndrome (AVDS) is a commonly observed gynaecological complaint for which women seek medical attention. The present study was conducted in six Indian Council of Medical Research centres with Praneem polyherbal tablets (PPT), to determine their efficacy in the treatment of symptomatic women with AVDS. Data are given on 141 subjects investigated. In total, 137 women (97%) reported complete (n=62, 44%) and partial (n=75, 53%) relief from symptoms after use of PPT for seven consecutive days. On speculum examination, 71 (74%) women were confirmed to be cured of AVDS. Microbiological tests could only be conducted microscopically for Trichomonas vaginalis, Candida albicans and bacterial vaginosis. It was observed that all women with T. vaginalis had this infection cured by PPT, and the cure rate was 77% for C. albicans and 68% for bacterial vaginosis. Seventy-eight women (55%) reported a transient burning sensation, mostly on the first 2 d of intake of PPT; however, they continued to use the tablets for the prescribed 7 d. This study lays the basis for an extended Phase II/III clinical trial, preferably randomized and comparing a larger number of women to confirm the safety and efficacy of PPT.

Comparison of four nonculture diagnostic tests for Chlamydia trachomatis infection.

OBJECTIVE: Chlamydia trachomatis (CT) is one of the commonest sexually transmitted diseases leading to urethritis, epididymitis, prostatitis in men and urethritis, cervicitis, endometritis and pelvic inflammatory disease, sometimes complicated by infertility and ectopic gestation in women. Since culture of fastidious bacteria in a monocellular medium is not available in most laboratories we compared direct immunofluorescence antigen detecting test (DFA) with three other nonculture tests-antigen detecting enzyme immunoassay (EIA), Papanicolaou staining (Pap) and Geimsa stain for endocervical swabs from women in reproductive age group. METHODS: Three hundred and fifty seven women between 16 and 41 years of age and attending family welfare clinics of IRR were evaluated for the presence pap smears. In 100 cases DFA staining was compared with Geimsa staining. RESULTS: DFA test was positive in 60/357 (16.8%), EIA in 29 (8.1%) of cases and Pap smear in 37 (10%) cases. In the second group DFA was positive in 17 (17%) and Geimsa in 10 (10%) cases. CONCLUSION: Amongst the four tests DFA showed maximum sensitivity. ELISA is less expensive but has lower sensitivity. Pap stain also has less sensitivity and good specificity, the quality of smear is likely to affect the diagnosis. Though Geimsa stain is cheapest, for chlamydial cervicitis in our experience it was not as sensitive as DFA. Thus each laboratory must decide the method depending on its resources.

Contraceptive knowledge, attitude and practices of men in rural Maharashtra.

Since men are the dominant decision makers in India, it is prudent to discover the knowledge, perception, attitudes and contraceptive practices of men to improve their involvement in the reproductive health needs of families. Three thousand and seventy-two married men from a tribal Primary Health Centre (PHC) area in Thane district of Maharashtra State, India were surveyed with special emphasis on investigating the reasons for not accepting male methods. The majority of them not only had no concept of family spacing, but had not even taken any initiative to improve their knowledge or acceptance of condom/ vasectomy. Men who were aware of contraceptive methods had little knowledge of their correct use. Of the men, 53.7% had positive views about their role in family planning while 66.2% of men stressed the need to improve the acceptance of male methods by providing knowledge and information through sources such as radio, television, door-to-door campaigning and interpersonal communications. Thirty per cent emphasized the need to improve the availability and quality of services. This study indicates a pressing need for effective intervention strategies, both at the community and the clinic level, backed with efficient counselling, motivation and provision of services in rural and remote areas.

Chlamydia trachomatis detected in cervical smears from Copper-T users by DFA test.

OBJECTIVE: This study was carried out to determine the prevalence of Chlamydia trachomatis (CT) antigen in endocervical smears from women using the Copper-T200 (Cu-T) intrauterine device and comparing them with nonusers. METHODS: The direct fluorescent antibody (DFA) test was used to detect the CT antigen (CT Ag). RESULTS: A total of 422 women between 17 and 42 years of age was evaluated. Out of these 71 (16.8%) were positive for CT Ag. Among Cu-T users (n = 222), 14.0% were positive. The duration of Cu-T use varied from 6 to 80 months. Among nonusers (n = 200), the DFA test was positive in 20.0% (p = 0.11, NS). However, as a whole, symptoms related to genital tract infection were significantly more common in Copper-T users than in nonusers (p < 0.02) and signs were relatively more common in Cu-T users but not significantly so (p = 0.16). Similarly, as a group, symptoms as well as signs were significantly more common in all DFA-positive cases than in all negative cases (p < 0.02). Among Cu-T users, symptoms were relatively more common, and signs were significantly more common, in women positive for CT Ag than in the negative cases (p < 0.04). There were two cases of mild pelvic inflammatory disease (PID) diagnosed clinically, one in a Copper-T user, and the other a nonuser, both being positive by the DFA test. CONCLUSION: There was no correlation between the duration of Copper-T use and percent positivity for CT Ag. Although milder genital tract symptoms and signs were more common in women with chlamydial cervicitis, clinically PID appears to be uncommon (0.5%). PID in this study was not related to Copper-T use but related to chlamydial cervicitis in this group of women with low risk sexual behavior.

Ultrasonographic monitoring of ovarian follicles in women using norethisterone for contraception.

OBJECTIVE: The purpose of this study was to examine the effect of intranasal and oral norethisterone (NET) on ovarian folliculogenesis. METHODS: Sixteen healthy, sterilized women with regular menstrual cycles were recruited to the study. NET 300 micrograms per day was administered orally (n = 8) or intranasally (n = 8) for two consecutive menstrual cycles. Serial pelvic ultrasonography was performed to monitor ovarian follicular growth. RESULTS: Ultrasonographic evidence of normal follicular growth and ovulation was observed in 10 cycles whilst 22 cycles were anovulatory. Formation of follicular cysts was seen in 14 cycles, 13 of which were anovulatory and in one ovulation was observed in the opposite ovary. The size of the cysts varied between 27 and 44 mm. The cysts disappeared when NET treatment was discontinued. A positive correlation between cyst size and estradiol levels was observed with intranasal NET in 50% of cyst cycles. In three cycles, although normal follicular growth and endocrine profile were observed, the follicles failed to rupture. These were classified as luteinized unruptured follicles. Immature follicles < 10 mm were seen in six cycles. CONCLUSION: The study showed that NET administered either orally or intranasally evidently disturbs normal follicular growth and rupture.

The prevalence of Chlamydia trachomatis in young women.

BACKGROUND: Chlamydia trachomatis infection is common in women with pelvic inflammatory disease, infertility and ectopic gestation. In this study we examined the prevalence of this infection in young women undergoing routine gynaecological checks. METHODS: Three hundred and five women aged between 19 and 41 were included in our study. Endocervical smears were collected by speculum examination, air-dried, acetone-fixed and stained for chlamydial antigen using fluorescein-labelled monoclonal antibody. RESULTS: Ninety-five per cent of the women were asymptomatic. Only 5% had mild symptoms such as white discharge, abdominal pain or profuse periods; 34% gave a history of white discharge only. Chlamydial antigen was detected in cervical smears from 47 (15%) women. Of these, 9 (19%) had symptoms at examination and 20 (43%) had symptoms within 2 months. On gynaecological examination 25 women (53%) had minor signs such as erosion or cervicitis and only 1 (2%) had uterine tenderness suggestive of mild pelvic inflammatory disease. CONCLUSIONS: It is important to diagnose chlamydial infection early because in its later stages it is associated with an ascending infection and serious complications. Young, relatively asymptomatic women should be screened for the presence of this organism.

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women.

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.

Ultrasonographically observed preterm grade III placenta and perinatal outcome.

Ultrasound studies of placenta were conducted in 270 singleton normal pregnancies. Women were enrolled between 31 and 34 weeks of gestation and were followed up for the outcome of pregnancy. Women with grade III placental maturity comprised the study group (n = 64) and those with grade I placenta were enrolled as control group (n = 206). Another 100 normal women were enrolled to note the prevalence of grade III placenta at term. There was an increased incidence of intrauterine growth retardation (6.20%) and fetal distress (7.8%) in the study group compared with the control group (nil), which was statistically significant. The incidence of low birth weight was also higher (34.37%) in the study group compared with the control group (22.33%). Three women in the study group developed preeclampsia at subsequent follow up visit but none in control group (P less than 0.01). Prevalence rate of grade III placenta at term was 28%. In view of these findings preterm grade III placenta is found to be a sensitive predictor of poor perinatal outcome.

Serum progesterone and norethisterone levels following injection of norethisterone enanthate in different sites and doses.

Serum progesterone (P) and norethisterone (NET) levels following injection of norethisterone enanthate (NETEN) were studied in 11 regularly menstruating women. In 6 subjects 200 mg NETEN was administered to the gluteal (IG) or deltoid (ID) region sequentially. The serum P levels remained anovulatory (less than 4 ng/mL) up to 12 weeks. Serum NET levels were similar whether injection was given IG or ID (paired t - test, NS). In 5 subjects given a 150-mg dose, serum P levels remained anovulatory up to 11 weeks. Serum NET levels declined faster than with the 200-mg dose, but the difference was not significant (Student's t - test, NS). Wide inter-subject variations were seen in both groups. NETEN therefore can effectively be administered in gluteal or deltoid regions. A lower dose of 150 mg may have contraceptive potential on an 8-week schedule.

Actinomyces in cervical smears of women using intrauterine contraceptive devices.

Cervical smears from 1,784 women who attended the family planning clinics of the Institute for Research in Reproduction were examined for the presence of Actinomyces-like organisms. Among 815 intrauterine contraceptive device (IUD) users, the repeat smears from 57 women were positive for Actinomyces-like organisms, giving a prevalence rate of 6.99%. Immunofluorescent staining using specific antisera confirmed the presence of A. israelii in all 57 women. Forty IUD users whose smears were positive for Actinomyces-like organisms underwent bacteriologic culture studies; A. israelii was isolated in 23 of these cases. The clinical findings at the time of smear collection in the 57 IUD users were within normal limits. The initial cervical smears of all IUD users and both the initial and repeat smears of all nonusers were negative for Actinomyces-like organisms. The data indicate that prolonged use (greater than 2 years) of an inert or copper intrauterine device promotes the overgrowth of Actinomyces in the vagina and that this can be detected by routine cervical cytology.

PIP: Cervical smears from 1784 women who attended a family planning clinic in India were examined for the presence of Actinomyces-like organisms. There were 57 (7%) positive smears among the 815 IUD users in this group. Bacteriologic culture studies were carried out in 40 of these women and Actinomyces israelii was isolated in 23 cases. The initial cervical smears of all IUD users and both the initial and repeat smears of all nonusers were negative for Actinomyces. None of the positive smears involved women with less than 1 year of IUD use and only 4 cases were positive with 1-2 years of IUD use. There was no association between the presence of Actinomyces-like organisms and type of IUD, however. The cervical and pelvic examination findings in the 57 women with positive Actinomyces smears were within normal limits at the time of smear collection. These findings suggest that longterm IUD use promotes the outgrowth of Actinomyces in the vagina. Routine cervical cytology and clinical observation are recommended for the early detection of possible pelvic inflammatory disease in these women.

Salivary antipyrine half-life during injectable progestagen contraception.

Antipyrine pharmacokinetics were studied in 6 healthy women before and 2, 8 and 12 weeks after administering the injectable progestagen (progestin), norethisterone (norethindrone) enanthate 200mg intramuscularly. Additionally, antipyrine kinetics in 5 women who had previously used the injectable contraceptive for 8 to 14 months were compared with values obtained in 14 non-users. Antipyrine was measured in saliva using a spectrophotometric method, following an oral dose of 18 mg/kg bodyweight. In the 6 women studied prospectively the mean salivary antipyrine half-life was 14.91 +/- 1.5 hours (SEM) before administering the injection, and 13.56 +/- 0.73 at 2 weeks, 15.13 +/- 1.86 at 8 weeks and 15.21 +/- 2.46 hours at 12 weeks after the injection. The mean antipyrine half-life in the 5 long term users of injectable progestagen was 14.21 +/- 2.53 hours compared with 13.66 +/- 0.98 hours in non-users. The results of this study suggest that - in contrast to published data on combined oral contraceptives - neither short nor long term use of parenteral norethisterone enanthate in Indian women is associated with significant alterations in antipyrine clearance.

Effect of low estrogen combination oral contraceptive on metabolism of aspirin and phenylbutazone.

Plasma levels of aspirin and phenylbutazone were estimated before and during administration of low estrogen combination type oral contraceptive for two menstrual cycles in ten and seven female volunteers, respectively. Aspirin was administered at doses of 300 and 600 mg, while phenylbutazone was administered at a dose of 400 mg. Blood samples were collected at intervals of 1, 2, 4, 6, and 8 h for aspirin and 2, 4, 6, 8, 24, 48, 72, and 80 h for phenylbutazone. Plasma levels, plasma half-life (t1/2), as well as area under curve (AUC) for aspirin after use of oral contraceptive revealed lower values. Phenylbutazone levels were not affected. Repeat studies of plasma t1/2 and AUC for aspirin after discontinuation of oral contraceptive showed values similar to basal levels.

PIP: Plasma levels of aspirin and phenylbutazone were estimated before and during the administration of low estrogen combination type oral contraceptive (OC) for 2 menstrual cycles in 10 and 7 female volunteers, respectively. Aspirin was administered at doses of 300 and 600 mg.; phenylbutazone was administered at a dose of 400 mg. Blood samples were collected at intervals of 1, 2, 4, 6, and 8 hours for aspirin and 2, 4, 6, 8, 24, 48, 72, and 80 hours for phenylbutazone. Plasma levels, area under curve (AUC), and plasma half life (t1/2) of aspirin were significantly lower during OC use as compared with predrug data. This was applicable to both doses of aspirin. Plasma levels of phenylbutazone did not show significant differences. Since there were significant alterations in plasma levels of aspirin during OC use, the study was repeated after a drug free interval of 3-5 months. A rise in plasma levels and t1/2 was observed after discontinuation of OC. Tmax for aspirin was not consistently altered during OC use, but the Pmax was reduced in all cases during OC use and was found to recover in all the 7 subjects studied after discontinuation of OC. Salicylate levels in 5 women using OC for more than 2 years were similar to the levels before administration of OC.

A study of interaction of low-dose combination oral contraceptive with Ampicillin and Metronidazole.

Plasma levels of norethisterone (NET), ethinyl estradiol (EE), Ampicillin or Metronidazole were estimated in 16 women, who were taking low-dose oral combination contraceptive pills (containing norethisterone acetate 1 mg and ethinyl estradiol 30 microgram) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither Ampicillin nor Metronidazole therapy altered the 'peak' or 24-hour plasma levels and area under the curve, for NET and EE. Furthermore, oral contraceptive treatment did not alter the 'peak' levels of Ampicillin or Metronidazole. Progesterone (P) levels were in the anovulatory range in all Ampicillin treated cycles. However, in Metronidazole treated group, two out of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole, where only one women showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by P rise of more than 4 ng/ml in three out of 25 Metronidazole treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that one out of three women showing a P rise (greater than 4 ng/ml( during concurrent Metronidazole therapy, also showed ovulatory P values in oral contraceptive-only treated cycles. Furthermore, in the control group also, one out of 10 women had ovulatory P levels (greater than 4 ng/ml) in oral contraceptive-only treated cycles.

PIP: Plasma levels of (NET) norethisterone, (EE) ethinyl estradiol, Ampicillin, or Metronidazole were estimated in 16 women who were taking low-dose (OC) oral contraceptives (containing norethisterone acetate, 1 mg, and ethinyl estradiol, 30 mcg) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither drug altered the peak or 24-hour plasma levels and area under the curve for NET and EE. Furthermore, OC treatment did not alter the peak levels of either Ampicillin or Metronidazole. (P) Progresterone levels were in the anovulatory range in all Ampicillin-treated cycles. However, in Metronidazole-treated group, 2 of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole and only 1 woman showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by a P rise of more than 4 ng/ml in 3 of 25 Metronidazole-treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that 1 out of 3 women showing a P rise ( 4 ng/ml) during concurrent Metronidazole therapy also showed ovulatory P values in OC-only treated cycles. Furthermore, in the control group, 1 out of 10 women had ovulatory P levels ( 4 ng/ml) in OC-only treated cycles.

Serum progesterone in women with lactational amenorrhoea.

PIP: A cross-sectional study was conducted to detect the return of ovulation in 56 women with (LA) lactational amenorrhea ranging from 2-12 months. As serum progesterone of 5 ng/ml provides an indirect evidence of ovulation. It was estimated by radioimmunoassay in 4 blood samples collected weekly over a period of 1 month in all the women. 37 women showed persistently low values of progesterone ( 5 mg/ml) throughout the study period. The other 19 women had serum progesterone of 5 ng/ml in 1 or several samples. 13 of these women, however, continued to have LA beyond 1 month in spite of the detection of high circulating progesterone. The possibility of pregnancy was excluded in all of them. The endometrial refractoriness to the circulating steriods is proposed as a mechanism of persistent LA.^ieng

A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs.

Low-dose combination contraceptive (containing norethisterone acetate 1 mg and ethinyl estradiol 30 micrograms) was administered to women receiving concurrent therapy with either Rifampicin or "triple" antitubercular treatment consisting of paraaminosalicylic acid (PAS), isonicotinic acid hydrazide (INH) and streptomycin. Plasma levels of norethisterone (NET) and ethinyl estradiol (EE), PAS and INH were measured and the area under curve (AUC) was calculated for NET and EE. Rifampicin treatment (9 women) caused a statistically significant reduction of the plasma NET levels as well as the AUC of NET. In this group of women, though a trend for reduction in EE levels was observed in individual subjects, it was not statistically significant. Out of 7 regularly menstruating women on Rifampicin therapy, 2 showed a premenstrual rise of plasma progesterone (P) levels (> 4 ng/ml) suggesting an ovulatory cycle and 3 experienced menstrual irregularities. In contrast, plasma levels of NET and EE as well as their AUCs were not altered in 8 women receiving "triple" antitubercular therapy. Only one woman out of 8, had menstrual irregularity and all women had P levels in the anovulatory range. Furthermore, oral contraceptive treatment did not alter the plasma levels of PAS and INH.