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.

Oral misoprostol for prevention of postpartum hemorrhage by paramedical workers in India.

OBJECTIVE: To study whether paramedical workers from rural primary health centers in India are able to administer oral misoprostol and actively manage the third stage of labor to prevent postpartum hemorrhage (PPH). METHOD: Cluster randomization was used to enroll 1200 women at 30 peripheral health centers from 5 states in India, 600 forming the study's intervention group (active management of the third stage of labor with 600 mug of oral misoprostol) and 600 forming the comparison group (in which the current government guidelines for the prevention of PPH were followed). The primary outcome was blood loss after delivery, which was measured using a calibrated blood collection drape. RESULTS: Age, literacy level, occupation, and gravidity were similar in the 2 groups. More than 70% of women in both groups had moderate anemia (hemoglobin level <10 g/dL). Paramedical workers followed instructions in almost all deliveries in the intervention group (99%). There was a significant reduction in duration of the third stage of labor (7.9 +/- 4.2 min vs. 10.9 +/- 4.3 min; p < .001) and median blood loss after delivery (100 mL vs. 200 mL; p < .001) in the intervention group. Overall, a low incidence of PPH was observed (<1%) in both groups. A greater number of women had moderate to severe shivering (12.7% vs. 0.5%) and a temperature higher than 38 degrees C (9.7% vs. 4.3%) in the intervention group, which was statistically significant. CONCLUSION: Simple interventions can be easily implemented in rural health care settings to reduce the blood loss during labor. This finding has significant implications for developing countries, in which the prevalence of anemia is high.

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Vaginal bleeding patterns of women using different contraceptive methods (implants, injectables, IUDs, oral pills)--an Indian experience. An ICMR Task Force Study. Indian Council of Medical Research.

Irregularity in vaginal bleeding patterns is the most common clinical side effect causing discontinuation of the method reported by the-users of the newer contraceptive methods, especially hormonal ones. An objective assessment of vaginal bleeding pattern is, therefore, critical in evaluation of a new contraceptive method for its acceptance and continued use. The menstrual diary records of women participating in clinical trials of several contraceptive methods undertaken by the Indian Council of Medical Research were analysed. It was observed that the long-acting progestogen-only hormonal contraceptives like levonorgestrel (LNG)-releasing subdermal implants Norplant or intrauterine devices (LNG-IUD) as well as injectable contraceptive NET-EN 200mg given 2 or 3 monthly produced disturbances in bleeding pattern in the majority of their users. Very heavy or prolonged bleeding, a potential health hazard was uncommon and a shift more towards infrequent bleeding was observed. In Norplant-II implants users, 75 to 80% of women had irregularities in bleeding pattern during the first year of use which improved with prolonged use. However, even at 4 years of use, about half of the users of Norplant-II implants continued to have irregular bleeding patterns. The bleeding disturbances occurred in 80% users of 200mg NET-EN injectable contraceptives also during first year of use, however unlike Norplant-II implants users, there was no improvement with prolonged use. Combined monthly injectable contraceptives containing 50mg NET-EN and 5mg estradiol valerate caused less bleeding problems with half of the users experiencing normal pattern during one year of its use. Combined low-dose oral pills, both triphasic and monophasic, produced much better cycle control as compared to any of the other hormonal contraceptive-treated groups; about 90% of combined oral pill users had normal bleeding patterns during one year of method use. The use of copper IUDs was associated with increased bleeding in 18 to 20% of women during the initial period of three months which improved with prolonged use. It was observed that the women having frequent or prolonged bleeding had discontinued the contraceptive method more often as compared to those having delayed bleeding episodes or oligomenorrhoea. However, discontinuation rates due to bleeding irregularities at one year were lower in Norplant-II implants users as compared to other long acting hormonal contraceptive methods such as injectables or IUDs in spite of similar or better bleeding patterns in women using these methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacodynamic effects of levonorgestrel (LNG) administered either orally or subdermally to early postpartum lactating mothers on the urinary levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in their breast-fed male infants.

Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infant's circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 micrograms daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences (P greater than 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group (n=10) when compared with oral minipill or Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children.

Phase II randomized comparative clinical trial of Norplant (six capsules) with Norplant-2 (two covered rods) subdermal implants for long-term contraception: report of a 24-month study. National Programme of Research in Human Reproduction.

In a randomized clinical study, contraceptive efficacy and bleeding patterns were studied in a group of healthy, regularly menstruating, non-lactating women (n = 84) using two 4.4 cm covered silastic rods containing levonorgestrel, Norplant(R)-2, and compared with another group of women (n = 88) using six 3.4 cm capsules also containing levonorgestrel, Norplant(R). The silastic rods or capsules were placed subdermally in the medial aspect of the upper arm. No method failure was reported up to 24 months of use in this study with either of the device. The bleeding pattern was also similar for both devices as indicated by average episode length, number of bleeding runs and number of spotting days. The continuation rates with both devices were over 80 per 100 users at the end of 12 months and over 65 per 100 users at the end of 24 months. Discontinuations due to expulsion of the device, bleeding problems or personal reasons were few and similar for both devices. The results suggest that silastic-covered rods, Norplant(R)-2, which are comparatively easier to insert and remove and have similar clinical effect, could replace capsules, Norplant(R), as a long-term reversible subdermal contraceptive.

Indian Council of Medical Research. Task Force on Hormonal Contraception: Phase II randomized clinical trial with norethisterone oenanthate 50 mg alone and in combination with 5 mg or 2.5 mg of either estradiol valerate or cypionate as a monthly injectable contraceptive.

A Phase II multicentric study was carried out to compare the different contraceptive treatment schedules of the monthly injectable consisting of norethisterone oenanthate (NET OEN) 50 mg either given alone or in combination with estrogen esters, 2.5 or 5 mg of estradiol valerate (E2 Val.) or estradiol cypionate (E2 Cyp.). A total of 364 women were observed for 1686 months of use. Analysis of the bleeding pattern data indicated that NET OEN 50 mg when given alone gave rise to delayed cycles and/or amenorrhoea. However, the addition of estrogen esters in a dose of either 2.5 or 5 mg provided significantly better bleeding patterns. Of the different treatment schedules investigated, the combination of NET OEN 50 mg with E2 Val. 5 mg provided more consistent and better cycle control. These findings however need further validation on a larger study sample.