Timing of onset of contraceptive effectiveness in Norplant implant users. II. Effect on the ovarian function in the first cycle of use.

The objective of this study was to time the onset of contraceptive effectiveness in Norplant implant users, when the capsules were inserted beyond the first 7 days of the cycle, based on the immediate effect on the ovarian activity. A total of 42 healthy women requesting Norplant implant contraception were enrolled at clinics in Santo Domingo, Dominican Republic, and in Baltimore, Maryland. Implants were inserted on days 8-13 of the menstrual cycle. Blood samples for estradiol (E2), progesterone (P), luteinizing hormone (LH) (in a subset of 12 women), and levonogestrel (LNG) assay, were taken at 0 h and at 6, 12, 24, 72, and 168 h postinsertion. Ovulation, as defined by P > 2.5 ng/mL, occurred in 40% of subjects. A short lasting, frequently blunted, LH peak occurred within 12 h postinsertion, in all these subjects. The remaining subjects had anovulatory cycles with two distinct E2 profiles: continuously increasing E2 levels to a high mean of 414.3 pg/mL (28%), or no sustained increase in E2 (32%). Most cycles (86%) in which Norplant was inserted with high E2 levels (> 175 pg/mL) were ovulatory, whereas none were ovulatory with low E2 (< 100 pg/mL) at insertion. Based on the endocrine effects of Norplant implant insertion in the midadvanced follicular phase, in which ovulation will either occur within 48 h of insertion or will be impaired, additional contraceptive protection is necessary only for 3 days.

Timing of onset of contraceptive effectiveness in Depo-Provera users. II. Effects on ovarian function.

OBJECTIVE: To determine the timing of onset of contraceptive effectiveness after the first injection of 150 mg of depot medroxyprogesterone acetate (DMPA) administered between days 8 and 13 of the menstrual cycle. DESIGN: Descriptive, prospective study. SETTING: A tertiary university referral center. PATIENT(S): Thirty healthy women between 18 and 40 years of age. INTERVENTION: Volunteers were injected with DMPA between days 8 and 13 (5 women on each day) of the menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian function determined by serum levels of E2 and progesterone and follicular development evaluated by vaginal ultrasound. RESULT(S): In nine (30%) of 30 women studied, DMPA did not prevent ovulation. All ovulations occurred in women receiving DMPA between days 10 and 13 of the cycle. No woman who received injections on day 8 or 9 ovulated. Ovulation suppression was more effective in women with low ovarian activity. All ovulation occurred within 3 days after the injection. CONCLUSION: A back-up contraceptive method, used after the 7th day of the menstrual cycle, is recommended for up to 7 days after the first injection of DMPA.

PIP: To ensure ovulation does not occur, it is recommended that Depo-Provera injections be administered within the first 7 days of the menstrual cycle. In some settings, this requirement acts as a barrier to women's free access to injectable contraception. Thus, the present study investigated the timing of onset of contraceptive effectiveness when the first injection of depot medroxyprogesterone acetate is administered between days 8-13 of the menstrual cycle. 30 women 18-40 years of age attending a university referral center in Campinas, Brazil, in 1995-96, were enrolled. Ovulation, detected through serum progesterone and estradiol assays and confirmed by follicle rupture at vaginal ultrasound, occurred in 9 cases (30%). No ovulations occurred when injection was administered on day 8 (n = 5) or day 9 (n = 5) of the menstrual cycle; only 1 of the 5 women treated on day 10 ovulated. On the other hand, 4 of the 10 women treated on days 11 and 12 and 4 of the 5 injected on day 13 showed evidence of ovulation. All ovulation occurred within 3 days after injection. Ovulation occurred only among women who had serum estradiol levels of 100 pg/ml and above and a leading follicle diameter greater than 13 mm at the time of injection. Ovulation suppression was more effective in women with low ovarian activity. A back-up contraceptive method used for 4 days after Depo-Provera injection should provide sufficient protection when the method is administered after day 7 of the menstrual cycle. However, given the uncertainty of the assumption of short viability of the human oocyte, it is safer to recommend 1 week's use of a back-up method or abstinence.

Timing of onset of contraceptive effectiveness in Depo-Provera users: Part I. Changes in cervical mucus.

OBJECTIVE: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinic. PATIENT(S): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. INTERVENTION(S): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. RESULT(S): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (< 1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of > 1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. CONCLUSION(S): The data presented in this report confirmed that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle.

PIP: More accurate knowledge of the time of onset of cervical mucus changes after Depo-Provera injection would enable family planning providers to counsel new acceptors to use a backup method only for the amount of time it is really needed. To obtain such data, 30 women from a family planning clinic in Campinas, Brazil, who requested Depo-Provera in 1995-96 were recruited. At baseline, 11 women had a poor cervical mucus score (0-4), 12 had a fair score (3-8), and 7 scored in the good range (9-12). Between 6 and 24 hours after injection, a sharp decline occurred in the cervical mucus score in all but 3 patients (each of whom had a "good" score at baseline). On day 3, 29 women had "poor" mucus and the remaining woman had a cervical mucus score in the fair range. By day 7, 29 women had zero mucus scores; the score in the last woman was 1. 24 hours after injection, sperm penetration (measured by vanguard sperm distance) had decreased to under 1 cm in all but 4 women. At day 3, 1 of the 2 women with good penetration at 24 hours maintained a vanguard sperm distance of 2.5 cm and an estimated sperm count of 15,363. By day 7, sperm penetration was zero in all but 1 woman (0.5 cm). These findings confirm that depot medroxyprogesterone acetate causes profound changes in cervical mucus after injection. The lack of a more complete hostility to sperm penetration at day 3 was unexpected, however. Given the nonavailability of a reliable clinical marker to verify a contraceptive effect at 3 days, it seems prudent to advise new Depo-Provera acceptors to use a backup method for the first 7 days.

Timing of onset of contraceptive effectiveness in Norplant implant users. Part I. Changes in cervical mucus.

OBJECTIVE: To provide scientific data regarding the changes in cervical mucus within the first hours to days after Norplant implant insertion and to estimate when the cervical mucus is hostile enough to suggest a contraceptive effect. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinics. PATIENT(S): Forty-two women who were between days 8 and 13 of their menstrual cycle and who had requested Norplant implants were admitted to the study. INTERVENTION(S): Cervical mucus and blood samples were obtained. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, and serum levels of progesterone, estradiol, and levonorgestrel. RESULT(S): The median cervical mucus score observed at baseline was 6 ("fair"), indicating that the mucus was already somewhat hostile before insertion of the Norplant implants. The median scores declined to 5 at 12 and 24 hours and continued to decrease through day 7 to 2 ("poor"), a score that is judged as hostile to sperm penetration. Overall, 73% of all subjects had a poor cervical mucus score by 3 days after insertion; at 7 days after insertion, 90% exhibited poor mucus and none had a good score. There was a substantial drop in the overall median distance traveled by the vanguard sperm after 12 hours for each cervical mucus score grouping. The distance traveled decreased rapidly between 12 and 24 hours to < 0.5 cm in subjects with fair and poor mucus, and by day 3, 91% of the subjects exhibited poor sperm penetration. CONCLUSION(S): On the basis of our findings, deterioration of the quality of the cervical mucus and sperm penetration is evident by 24 hours after insertion, although not to a level that would suggest adequate protection until 72 hours after insertion. Therefore, we are confident in recommending that backup methods of contraception (e.g, condoms) need not be used for more than 3 days after insertion, even when the implants are inserted close to ovulation. These findings provide policy makers, clinic managers, and clinicians with important information about how they can improve client access to Norplant implants.

PIP: To provide clinicians with evidence as to when the cervical mucus is hostile enough in new Norplant implant acceptors to indicate a contraceptive effect, 42 women requesting Norplant from clinical sites in Santo Domingo, Dominican Republic, and Baltimore, Maryland (US), in 1994-95 were enrolled in a clinical descriptive study. At baseline, when all women were between days 8 and 13 of their menstrual cycle, the median cervical mucus score was 6 ("fair") out of a possible maximum of 12. This score declined to 5 at 12 and 24 hours and continued to decrease through day 7, when it reached 2--a level judged hostile to sperm penetration. Overall, 73% of women had a "poor" cervical mucus score by day 3 and 90% were in this category by day 7. There were substantial drops in the overall median distance travelled by the vanguard sperm and in the percentage of subjects demonstrating poor sperm penetration after 12 hours for each cervical mucus score grouping. 91% of women had poor sperm penetration by day 3 and 93% by day 7. These findings suggest that backup contraceptive protection for the entire cycle after Norplant insertion--a standard recommendation--is not necessary given the profound effect of levonorgestrel on cervical mucus shortly after insertion, even in the event of possible ovulation.

Treatment of bleeding problems associated with progestin-only contraceptives: survey results.

Simple, well-documented, effective and inexpensive management approaches are needed for the short-term control of bleeding in progestin-only contraceptive (POC) users. Long-term continuation may improve if acceptable approaches are found to ameliorate these short-term bleeding problems. Family planning providers and researchers were surveyed on the treatment regimens they used for POC-associated bleeding disturbances. Results from this limited survey indicate that no clear indication exists regarding the duration and, severity of bleeding and spotting requiring pharmacologic intervention. Counseling was seen as a critical factor when considering treatment for these problems. This report presents the results of this survey on the different treatment regimens being used by providers throughout the world to treat POC-associated bleeding disturbances.

Five-year evaluation of safety, efficacy and acceptability of Norplant implants in Nepal.

This paper presents findings based on a five-year, noncomparative study of Norplant contraceptive subdermal implants in Nepal. The study was designed to evaluate the contraceptive safety, efficacy, and overall acceptability of Norplant. Four hundred and seven women enrolled in the clinical trial, which began in 1985, at two study sites, located in Patan and Kathmandu. Follow-up visits were scheduled at 1, 3 and 6 months after Norplant insertion and every six months thereafter until removal or at the end of five years. Although five pregnancies were reported during the study, only two women (one from each center) were diagnosed as becoming pregnant while using Norplant. The pooled gross cumulative life-table pregnancy rate was 0.6 per 100 women at the end of five years. The pooled cumulative continuation rate was 62 per 100 women at the end of five years. The three most frequently reported reasons for discontinuation were menstrual problems, personal reasons, and medical reasons. Of the 125 women who completed a five-year user satisfaction questionnaire, the majority of the women (86%) planned to continue using contraception after study completion. Of these women, almost one half said they planned to use a second Norplant set. The findings suggest that the Norplant system is a safe, effective, and acceptable method of contraception among Nepalese women.

Risk factors for discontinuation of Norplant implant use due to menstrual problems.

The objective of the analysis reported here was to examine risk factors for early discontinuation of Norplant implant use due to perceived menstrual problems. Cox's proportional hazard regression model was used to calculate adjusted hazard ratios that would reflect the relationship of selected subject characteristics to the risk of early discontinuation due to perceived menstrual problems. Approximately 13% of the study population discontinued for perceived menstrual problems. At the end of year 2, the gross cumulative life table discontinuation rate for perceived menstrual problems was 9.4 per 100 women and it rose to 16.4 per 100 women at the end of year 5. Women in this study were significantly more likely to discontinue Norplant implant use due to perceived menstrual problems if they had a higher education level (> 12 years), had used no contraceptives in the month before Norplant implant insertion, or had a relatively long average duration of menstrual flow at admission. identifying potential risk factors such as these may help providers to counsel and prepare women to use the Norplant implant method.

A comparative study of two techniques used in immediate postplacental insertion (IPPI) of the Copper T-380A IUD in Shanghai, People's Republic of China.

Chinese women in Shanghai who delivered vaginally and who chose to use an IUD for contraception received a Copper T-380A IUD inserted vaginally within 10 minutes after delivery of the placenta (i.e., immediate postplacental insertion, IPPI). Among them, 97.7% were primipara. The women were randomly divided into two groups: IUD inserted by hand and IUD via ring forceps. The follow-up rate of six months was 95.2%. Using Tietze's life table method and log rank test, the expulsion and other discontinuation rates were compared at three and six months postinsertion between these two different insertion techniques. Expulsions were the main reason for discontinuation. The six-month gross cumulative expulsion rates were 13.3 and 12.7 per 100 women in the hand-insertion group and ring forceps-insertion group, respectively. Discontinuation rates for medical removals (bleeding/pain) were 2.1 and 1.0 in these two groups, respectively. Neither of the differences was statistically significant (p > 0.05). No uterine perforation, infection or pregnancy occurred. The results suggest that these two different insertion techniques do not significantly affect discontinuation rates in vaginal IPPI using the TCu 380A, and the TCu 380A appears to be suitable for postpartum insertion in Chinese women. Other relevant issues, such as breastfeeding and IUD placement in uterine cavity, are also analyzed and discussed in this report.

PIP: During October 1993 to October 1994, in Shanghai, China, 910 women who delivered vaginally at 13 medical centers and requested IUD contraception were randomly allocated to the group in which the TCu 380A was inserted by hand (470) or to the group in which it was inserted by ring forceps (440) within 10 minutes after delivery of the placenta. This was the first birth for 97.7% of the women. The 6-month follow-up rate was 95.2%. 3-month and 6-month expulsion rates as well as rates for medical and non-medical removals between the two insertion techniques were not significantly different (p 0.05). For example, the 6-month gross cumulative expulsion rate was 13.3% for the hand-insertion group and 12.7% for the ring forceps-insertion group. The discontinuation rate for medical removals (e.g., bleeding, pain) was 2.1% for the hand-insertion group and 1% for the ring forceps-insertion group. The IUD expulsion rate was higher in non-breast feeding women than in breast-feeding women (22.4% vs. 11.9%; p 0.05). No woman in either group suffered from uterine perforation or an infection. No woman conceived. In conclusion, the two different IUD insertion techniques do not have a significant influence on discontinuation rates in vaginal immediate postplacental insertion using the TCu 380A.

Norplant implants acceptability and user satisfaction among women in two African countries.

An analysis of 350 users of Norplant contraceptive subdermal implants from six centers in two African countries (Ghana and Nigeria) indicates that method acceptability remained high among the women who used the method for five years. Overall, 90.1% of the 155 five-year users in these countries reported having a very favorable experience and 9.9% a favorable experience with Norplant implants. Ease of use was cited by 56.1% and duration of use by 13.6% of the women as the most liked characteristics of the method at study completion after five years. Menstrual disturbance was the least liked aspect, by 41.9% of the women. On average, women who discontinued early from the study had fewer living children and were more likely to desire additional children at method adoption than those who completed five years of use; the differences were statistically significant. Differences in level of education and previous use of contraception were not found to be statistically significant between completers and non-completers. Differences in age were not significant in Nigeria, but were marginally significant in Ghana, with completers being older than non-completers. Of the clients who completed this study, 79.2% indicated a desire to continue with contraception and 43.9% planned to have a second set of implants inserted. These findings have important implications for counseling, method access and service sustainability in African countries.

Clinical evaluation of Norplant in Kumasi, Ghana.

A non-comparative study of the Norplant contraceptive subdermal implant system was conducted in Kumasi, Ghana. A total of 100 acceptors were enrolled in the clinical trial, which began in 1987. There were no pregnancies during the first two years of use. Only nine post-insertion medical problems were reported during the first two years of use. One woman in this study requested removal for menstrual pattern changes through two years of use. As assessed through user-satisfaction questionnaires administered at approximately six months of use, there has been an overall positive user experience with Norplant in this study. Although the sample size in this study is small, our results seem to be consistent with other studies and it appears that Norplant offers an effective, safe and acceptable method of contraception for Ghanaian women.

PIP: A two-year pre-introductory study of 100 Norplant acceptors from Kumasi, Ghana, indicated that the contraceptive implants are safe, effective, and acceptable to this population. The mean age of study participants was 31.2 years; they had completed an average of 8.3 years of schooling and had a mean of 4.4 live births. Although 35% did not want any more children, 64% had used no contraceptive method in the month prior to study admission. No pregnancies were reported during interviews at 1, 3, 6, 12, 18, and 24 months post-insertion. The continuation rate was 86.6/100 women at two years, for a total of 2119 woman-months of use. 75 women elected to continue Norplant use, while 12 opted for removal and 13 were lost to follow-up. Reasons for discontinuation included desire for pregnancy (3), husband's insistence (5), travel (2), menstrual problems (1), and tuberculosis (1). Only nine acceptors reported any adverse effects; most frequent were itchiness and infection at the implant site. The incidence of amenorrhea decreased from 27% at the end of the first year of use to 2% by the end of the second year. When asked to identify the most attractive feature of the Norplant system, half the respondents cited its five-year duration of action; most disliked was Norplant's effect on the menstrual cycle. 83.7% indicated they would recommend Norplant to a friend, and 55% expressed an interest in having a second set of implants inserted after the full five years.

Complications and risk factors associated with the removal of Norplant implants.

OBJECTIVE: To describe the complications reported at the removal of Norplant implants, and to suggest potential risk factors for these complications. METHODS: Complications at the removal of Norplant implants from 3416 users from 11 countries who participated in preintroductory clinical trials of the method were tabulated. A logistic regression model was used to identify the significant risk factors associated with removal complications. RESULTS: Complications were reported in 4.5% of removals; most often, they were related to broken or deeply placed implants. The most important risk factors were complications at insertion and having an infection at the implant site (at or before removal). CONCLUSION: Proper insertion technique under aseptic conditions is very important in predicting whether Norplant implant removal will be difficult. Although relatively infrequent even now, more vigilant training and the evaluation of some of the newer removal techniques could further reduce the incidence of difficult removals.

Norplant contraceptive acceptability among women in five Asian countries.

An analysis of 1,882 Asian acceptors of Norplant implants indicates that method acceptability remained high among the 882 women who used the method for five years. Women who discontinued early from the study were, on average, younger than those who completed five years of use. Also, they had fewer live births and were more likely to desire additional children. Overall, about 70% of the women in these countries found the Norplant implant method to be very favorable. The majority (> 40%) of the women found the ease and duration of use of the method to be most attractive, while menstrual disturbances were the least-liked aspect of the method. Although it was apparent that there are still some potential obstacles to Norplant implant acceptance, most noticeably concerns about menstrual irregularities, interest in continuing the method after five years of use is high. Further research of issues related to Norplant implant acceptability may improve continuation rates and overall client satisfaction.

PIP: Norplant method acceptability was assessed in women who completed 5 years of use, and their sociodemographic profile was compared with that of those who discontinued early. The population consisted of 1882 women, 882 of whom completed the study. The subjects were from 3 sites in Bangladesh, 2 each in the Philippines, Nepal and Sri Lanka, and 1 in Singapore. Women in the group who discontinued early (noncompleters) were significantly younger (p 0.05) than women who completed 5 years of use (completers): the mean difference in age ranged from 1.4 years in the Philippines to 4.5 years in Singapore. For all subjects the mean educational level varied from 2.1 years in Nepal to 10.0 years in the Philippines. The mean number of live births varied significantly, ranging from 2.1 in Singapore and Sri Lanka to 3.4 in Bangladesh. In all countries, noncompleters had a significantly lower mean number of live births and were more likely to desire additional children. A user satisfaction questionnaire was administered at 5 years postinsertion to completers. In Sri Lanka, almost 90% of the completers indicated very favorable experience, as did more than 70% of the completers in Bangladesh and Singapore. The most liked feature of the implants for completers in Bangladesh, Nepal, and Sri Lanka was its duration for 5 years. Low risk of pregnancy was the most liked feature of the implants in fewer than 25% of the subjects in each country, and as few as 1.6% in Nepal. The least liked feature of the implants for both completers and noncompleters at 6 months was menstrual disturbance. Most completers in all 5 countries (ranging from 87.4% in Sri Lanka to 99.4% in the Philippines) would recommend Norplant implants to a friend. 73.9% of women in Sri Lanka and 91.4% in Singapore planned to continue using contraception after Norplant removal; and Norplant was the most popular choice in Sri Lanka (41.5%), Nepal (49.1%), and Singapore (69.8%).

A comparative study of two low-dose combined oral contraceptives: results from a multicenter trial.

A comparative multicenter clinical trial of two low-dose combined oral contraceptives (OCs) was conducted in Malaysia, Egypt, Thailand, and Mexico. Efficacy, safety and acceptability were investigated in women taking either a norgestrel-based (NG) OC or a norethindrone acetate-based (NA) OC. This paper includes analysis of 892 women, all of whom were at least 42 days but within 26 weeks postpartum and randomly allocated to one of the above OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Baseline sociodemographic characteristics were similar for both groups, as well as compliance. There were nine unintended pregnancies reported; eight of these occurring in the NA group. Adverse experiences were minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. The group taking the NG-based OC had significantly (p < .05) fewer menstrual-related complaints. Discontinuations due to menstrual problems were significantly more common among NA users (primarily amenorrhea). Discontinuations in the NG group were primarily for other personal reasons, e.g. unable to return to the clinic. There was also a significant difference between the two groups for the 11-month gross cumulative life table discontinuation rates due to menstrual problems (p < .01); the NA group had the higher rate.

A multicenter comparative trial of triphasic and monophasic, low-dose combined oral contraceptives.

A comparative multicenter clinical trial of two combined oral contraceptives (OCs) was conducted at clinics located in the Sudan, Sri Lanka, Chile, the Dominican Republic and Ecuador. The trial was designed to determine if there were differences in efficacy, safety and acceptability between a triphasic and a low-dose monophasic OC. This report includes analysis of 1088 women. At each center, subjects were randomly allocated to one of the two OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. There were two accidental pregnancies attributed to user failure reported during the study period; one in the triphasic group and one in the monophasic group. Adverse experiences were mainly minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding. Both OCs were safe and effective.

PIP: Researchers compared the efficacy, safety, and acceptability of a triphasic oral contraceptive (OC), Triquilar, with those of a monophasic OC, Lo-Femenal, among 1088 women attending clinics in Chile, the Dominican Republic, Ecuador, Sri Lanka, and the Sudan. Both OCs contained levonorgestrel and ethinyl estradiol. 90% of women in each group exhibited good user compliance. Only 1 unplanned pregnancy occurred in each group, and both pregnancies were attributed to user failure. The gross cumulative efficacy rates at 11 months were 0.3/100 woman-years for the triphasic OC and 0.2/100 woman-years for the monophasic OC. The continuation rate at 11 months was lower for Lo-Femenal than it was for Triquilar (80.8% vs. 84.6%), but the difference was not significant. The leading side-effect-related reason for discontinuation in both groups was headache. Another key reason for OC discontinuation in both groups was personal reasons, such as planning a pregnancy. Most women in both groups did not have menstrual complaints (78.8% for the Triquilar group and 77.1% for the Lo-Femenal group). Intermenstrual bleeding rates were low (7.6% for the Triquilar group and 9% for the Lo-Femenal group). Significant intercenter differences for women reporting intermenstrual bleeding and side effects (e.g., headaches) existed (p .05). Women from both groups at the clinic in the Sudan always had lower reports of intermenstrual bleeding than those at the other clinics. In fact, no woman discontinued OC use because of intermenstrual bleeding in the Sudan. Women in Sri Lanka reported fewer side effects than those in other countries, suggesting they could better tolerate OCs than the other women. This multicenter study's findings indicates that both Triquilar and Lo-Femenal are effective and safe. In addition, they exhibit good cycle control.

A five-year clinical evaluation of Norplant contraceptive subdermal implants in Bangladeshi acceptors.

A non-comparative study of the Norplant contraceptive subdermal implant system was conducted in Dhaka, Bangladesh. The study was designed to evaluate the contraceptive efficacy, safety and overall acceptability of Norplant implants. Six hundred women were enrolled in the clinical trial, which began in 1985 at three study sites. Follow-up visits were scheduled at 1, 3, and 6 months after Norplant implant insertion, and every six months thereafter until removal or at the end of five years. There were no post-insertion pregnancies during Norplant implant use in this study. After five years of Norplant implant use, there was no clinically significant change in body weight, systolic or diastolic blood pressure. Less than 3% of the women ever reported having any significant medical problems such as migraine, respiratory or cardiac problems during the study. The gross cumulative continuation rate was 41.2 per 100 women at the end of five years. The two most frequently reported reasons for discontinuation during the study were menstrual problems and desired pregnancy. Of the women who completed the five-year user satisfaction questionnaire, the majority of the women (86.3%) planned to continue using contraception after study completion. Of these women, approximately one-third said they planned to use another Norplant set. The findings presented suggest that the Norplant system is a highly effective, safe and acceptable method among Bangladeshi women.

PIP: From February 1985 to February 1986, researchers enrolled 600 18-40 year old women at the Dhaka Medical College and Hospital, the Institute of Postgraduate Medicine and Research, and the Mohammadpur Fertility Services and Training Centre in a 5-year clinical trial to evaluate the contraceptive efficacy, safety, and acceptability of Norplant subdermal implants in Bangladesh. They scheduled the women to return for follow-up visits 1, 3, and 6 months after insertion and every 6 months thereafter until removal or at the end of 5 years. No pregnancies after insertion occurred during the study. The gross cumulative continuation rate was 93.9% at 1 year and 72.3% at 2 years. The 5-year cumulative continuation rate was 41.2% which was much lower than that in other Asian countries (e.g., 52.3% in Sri Lanka and 78.2% in Indonesia). The 5-year cumulative discontinuation rate for menstrual problems was 30.7% which was higher than that of other studies. It may have been higher because Bangladeshi women do not tolerate well and accept changes in bleeding patterns, especially since menstrual bleeding prevents them from prayer and taking part in sexual activity. 45.3% of all women requesting early Norplant removal complained of menstrual problems, especially prolonged heavy bleeding (75% of women requesting removal for menstrual problems). Most menstrual problem removals took place during the 2nd year and fell thereafter. Desired pregnancy was the second most common reason for removal (18.6%). The gross discontinuation rate for nonmenstrual side effects was just 2.2%, the main side effect being headaches. 97.5% of women who completed the 5-year study considered their experience with Norplant favorable. The leading reason for a favorable rating for Norplant was its duration of use (64.5%). Menstrual changes comprised the least favorable component of Norplant among women who completed the study (63.3%). 33% of women still wanting to use contraception after 5 years of Norplant use said they would use Norplant again.

A multicenter clinical trial of a progestin-only oral contraceptive in lactating women.

A non-comparative study of a progestin-only oral contraceptive (POC) containing 75 micrograms norgestrel was conducted at 22 sites in 14 countries. This study was designed to evaluate safety, contraceptive efficacy, and the overall acceptability of a POC in breastfeeding women. A total of 4,088 women entered the study over a three-year period and 29,399 woman-months of experience was gathered. Women had follow-up visits at 2, 6, and 11 months after admission. Headaches and vaginal discharge were the medical complaints most commonly reported by women, both prior to and after admission. Menstrual problems were reported by 59% of the women after admission. Of the 3,714 women who returned for at least one follow-up visit, 1,101 (29.6%) discontinued through month 11. The 11-month total discontinuation percentage, including those lost to follow-up (25.3%) was 51.6%. The most common reason given for discontinuation was a woman's desire for a change in contraceptive method. Only 4.9% discontinued pill use for menstrual problems, a percentage far below those generally reported for POCs. Twenty-nine unintended pregnancies occurred through 11 months giving a gross cumulative life table rate of 1.2 per 100 women (Pearl Index = 1.4). The POC appears to be a safe, effective and acceptable contraceptive option for postpartum breastfeeding women.

A comparative study of 35 mcg and 50 mcg combined oral contraceptives: results from a multicenter clinical trial.

A comparative multicenter clinical trial of two combined oral contraceptives (OCs) differing only in the estrogen content (35 mcg ethinyl estradiol versus 50 mcg mestranol) was conducted at five clinics located in Yugoslavia, Egypt, Sri Lanka, Costa Rica and Mexico. The trial was designed to determine the differences between Norinyl 1+35 (Syntex) and Norinyl 1+50 (Syntex) in rates and reasons of discontinuation, and frequency of selected side effects which might contribute to method discontinuation. This report includes analysis of 1698 women, all of whom were interval patients (at least 42 days but within 26 weeks postpartum), randomly allocated to one of the above OCs between October 1982 and January 1984. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Significantly more women in the Norinyl 1+35 group (p less than .001) reported intermenstrual bleeding (primarily staining and spotting), as well as an increase in the occurrence of intermenstrual bleeding compared to women in the Norinyl 1+50 group. There were no significant differences between the groups for side effects with the exception of more women in the Norinyl 1+50 group (p less than .05) reporting breast discomfort. The lost to follow-up rate at 12 months was 19.3% for both the Norinyl 1+35 and the Norinyl 1+50 groups. The total discontinuation rate (including women lost to follow-up) at 12 months was 43.5% for the Norinyl 1+35 group and 41.0% for the Norinyl 1+50 group. There were no significant differences between the two groups for gross cumulative life table discontinuation rates (p greater than .05). There were six accidental pregnancies attributed to user failure reported during the study period; four in the Norinyl 1+35 group and two in the Norinyl 1+50 group.

A comparative study of a progestin-only oral contraceptive versus non-hormonal methods in lactating women in Buenos Aires, Argentina.

A non-randomized comparative clinical trial of the progestin-only oral contraceptive (POC), Ovrette (75 mcg norgestrel) (Wyeth), versus non-hormonal methods was conducted at two clinics in Buenos Aires, Argentina. The trial was designed to assess the breast-feeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Five-hundred women were allocated to either the progestin-only pill group (n = 250) or to the non-hormonal group (n = 250) and were followed up monthly for six months after admission. Measurements in mean infant weight, mean infant length, and mean head circumference were similar throughout the follow-up period. Non-hormonal users reported significantly more self-perceived decreases in milk production at the 5th and 6th month follow-up intervals. Acceptance and continued use of the pill were excellent, with only one woman discontinuing because of a pregnancy which was attributed to user failure. The principal side effect reported by women in both groups was intermenstrual bleeding.

PIP: A nonrandomized, comparative, clinical trial of the progestin only oral contraceptive (OC) Ovrette (75 mcg norgestrel) vs. nonhormonal methods was conducted at 2 clinics in Buenos Aires, Argentina. The trial was designed to assess breast-feeding patterns of women choosing progestin- only OCs and nonhormonal methods of contraception and to study the relationship between lactation and the clinical performance of the OC. 500 women were allocated to either the progestin-only pill group (n=250) or t o the nonhormonal group (n=250) and were followed monthly for 6 months after admission. Measurements in mean infant weight, mean infant length, and mean head circumference were similar throughout the follow- up period. Nonhormonal users reported significantly more self-perceived decreases in milk production at the 5th an 6th month follow-up intervals. Acceptance and continued use of the pill were excellent, with only 1 women discontinuing because of a pregnancy which was the result of user failure. The principal side effect reported by women in both groups was intermenstrual bleeding.

A comparative clinical trial of Norinyl 1 + 35 versus Norinyl 1 + 50 in Merida, Yucatan, Mexico.

A comparative clinical trial of two combined oral contraceptives differing only in estrogen type and dosage was conducted at the Centro de Investigaciones Hideyo Noguchi in Merida, Yucatan, Mexico. The trial was designed to determine the differences between Norinyl 1 + 50 (Syntex) and Norinyl 1 + 35 (Syntex) in rates of discontinuation and frequency of selected side-effects which might contribute to method discontinuation. Three hundred women were randomly assigned to either the Norinyl 1 + 35 group or to the Norinyl 1 + 50 group and follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. In the Norinyl 1 + 35 group, more women experienced an increase in intermenstrual bleeding (primarily staining and spotting) (p less than 0.05), breast discomfort (p less than 0.05) and nausea than in the Norinyl 1 + 50 group. There was a significantly higher discontinuation rate for personal reasons, such as desired change of method and method not needed, among the women taking Norinyl 1 + 35 (p less than 0.05). The largest number of discontinuations comprised women discontinuing for menstrual problems in both groups. The life-table total discontinuation rate at 12 months was 52.0 for the Norinyl 1 + 35 group and 50.7 for the Norinyl 1 + 50 group. The lost-to-follow-up rates at 12 months were 17.8 for the Norinyl 1 + 35 group and 22.8 for the Norinyl 1 + 50 group.

The influence of cyclic nucleotides on macromolecular synthesis in cultured neural retina cells.

1. The effect of cyclic nucleotides on aggregates of dispersed embryonic neural retina cells was examined in order to study their influence upon macromolecular synthesis, i.e. protein and DNA. 2. Cyclic AMP, dibutyryl cAMP, cyclic GMP and dibutyryl cGMP were used at various concentrations (5 x 10(-4) -5 mM). 3. The incorporation of labeled precursors into DNA and protein were used to monitor the effect of cyclic nucleotides on cultured aggregates. 4. All nucleotides exhibited a stimulatory effect at 5 x 10(-4) and 5 x 10(-3) mM on macromolecular synthesis, with resulting growth and proliferation of chick neural retina cells. 5. High concentrations (5 x 10(-1) and 5 mM) of cyclic nucleotides exhibited an inhibitory effect upon macromolecular synthesis and a marked cytotoxic effect.