Comparative acceptability of combined and progestin-only injectable contraceptives in Kenya. Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive. A multicentre phase III comparative study of two hormonal contraceptive preparations NET-OEN (50 mg) + E2 valerate (5 mg) given every month and NET-OEN (200 mg) given every 2 months as intramuscular injection--a report of 12-month study. Indian Council of Medical Research Task Force on Hormonal Contraception. Comparative study of the effects of two once-a-month injectable steroidal contraceptives (Mesigyna and Cyclofem) on lipid and lipoprotein metabolism. United Nations Development Programme/United Nations Population Fund/World Health Organization/World Bank, Special Programme of Research, Development and Research Training in Human Reproduction. Comparative phase III clinical trial of two injectable contraceptive preparations, depot-medroxyprogesterone acetate and Cyclofem, in Vietnamese women. A multicentred phase III comparative clinical trial of Mesigyna, Cyclofem and Injectable No. 1 given by intramuscular injection to Chinese women. II. The comparison of bleeding patterns. Effectiveness of Cyclofem in the treatment of depot medroxyprogesterone acetate induced amenorrhea. Once-a-month injectable contraceptives, Cyclofem and Mesigyna, in Egypt. Efficacy, causes of discontinuation, and side effects. Premenopause contraception with monthly injectable Mesigyna with special emphasis on serum lipid and bone density patterns. A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature.
We compared 12-month continuation rates, menstrual bleeding patterns and other aspects of acceptability between users of Cyclofem and users of Depo-Provera.
                The life-table method was used to calculate quarterly continuation rates. In all, 360 Kenyan women were randomly assigned to one of the two contraceptives. User-satisfaction questionnaires were administered at 6 and 12 months or at discontinuation, whichever occurred first.
                The 1-year continuation rate was 75.4% for Depo-Provera users versus 56.5% for Cyclofem users (p<.001). Main reasons for discontinuation included difficulty making clinic visits (45.1% for Cyclofem vs. 40% for Depo-Provera), menstrual changes (14.1% vs. 12.5%) and nonmenstrual problems (15.5% vs. 12.5%). None of the Depo-Provera users and 8.5% of the Cyclofem users claimed frequency of visits as the main reason for discontinuation. In all, 70.6% of the Depo-Provera users were amenorrheic after 12 months, as were 20.8% of the Cyclofem users.
                The 1-year continuation rate was higher for Depo-Provera than for Cyclofem. There was no important difference in discontinuation rates because of menstrual problems; the difference mainly reflected the frequency of visits required. The pharmacodynamics of the combination of dihydroxyprogesterone acetophenide (DHPA) and estradiol enanthate (E2-EN) following its intramuscular administration at two doses were studied in 16 healthy women of reproductive age. Subjects were randomly allocated in two groups: group I (n = 9) received the combination DHPA 150 mg + E2-EN 10 mg on three consecutive monthly injections, while group II (n = 7) received half-dose of the same formulation. Ovarian function and endometrial bleeding patterns were investigated in all participants for one pre-treatment cycle, three treatment intervals and two post-treatment cycles. The results disclosed that ovulation was inhibited for at least 30 days following DHPA/E2-EN administration in all participants from both groups. The circulating estradiol levels 30 days after last injection were slightly elevated as compared with those observed in normal early follicular phase. Return to ovulatory cycles was documented within 90 days after treatment. The length of the bleeding-free intervals during treatment was shortened in both groups, particularly in group II. No significant changes in HDL-cholesterol levels were observed throughout the study. It is envisaged however, that large modification of the formulation and additional long-term safety studies will be required prior to its recommendation. A phase III randomized clinical trial was undertaken to compare the efficacy, side effects and acceptability of a combined monthly injectable preparation containing NET-oenanthate (NET-OEN) (50 mg) plus oestradiol valerate (E2 Val.) (5 mg) with NET-OEN only (200 mg) given every two months. A total of 849 subjects were observed for 7817 woman-months of contraceptive use. Net discontinuation rates due to involuntary pregnancy at 12 months were 0.2 and 1.1 per 100 users for one monthly and two monthly injectable preparations, respectively. Although the monthly preparation was found to be efficacious and the subjects using the monthly preparation had a better bleeding pattern, the net discontinuation rate at 12 months due to menstrual disturbances did not show any significant difference between the two preparations. With proper counselling and motivational strategies, it is likely that acceptability of monthly injectables can be further enhanced. A 1-year longitudinal multicenter study was undertaken to monitor the effects on lipid metabolism of two once-a-month injectable contraceptive preparations, Mesigyna (50 mg norethisterone enanthate and 5 mg estradiol valerate and Cyclofem (25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate). A total of 357 volunteers from four centers (Hangzhou, Havana, Jakarta, and Shanghai) were monitored during one pretreatment cycle, the third and ninth injection intervals, and during one post-treatment cycle, approximately 3 months after the 9-month period of treatment was completed. With both preparations, changes were observed at 3 months of use, remained essentially unchanged during treatment, and returned to pretreatment levels after discontinuation of use. With Mesigyna, changes consisted mostly of decreases in high density lipoprotein cholesterol (HDL-C, -10%), apolipoprotein AI (-9%), and triglycerides (-15%). With Cyclofem, changes were even smaller. With both, variations in lipid levels mirrored closely the pharmacokinetics of each preparation and the biphasic nature of the injection intervals. A multicenter clinical trial was conducted in Viet Nam, comparing two injectable contraceptive preparations: the three-monthly injectable depot-medroxyprogesterone acetate (DMPA) and the once-a-month injectable Cyclofem. A total of 600 volunteers were randomized to the two treatment groups and followed for one year. No pregnancy occurred during the trial. Approximately one quarter of the women in each group discontinued early from the trial. In the DMPA group, this was mostly because of amenorrhea and vaginal bleeding irregularities. In the Cyclofem group, an equal number discontinued because of menstrual problems and personal reasons. These personal reasons are probably related to the inconvenience of having to return to the clinic for injection on a monthly basis. Thus, Vietnamese women experience less side effects with Cyclofem than with DMPA, and once Cyclofem is made more widely available and is more accessible, it may better meet their needs than does DMPA. Between 1988 and 1992, a randomized phase III clinical trial was conducted in China to compare three monthly injectable contraceptives: Mesigyna, Cyclofem and Injectable No. 1. This paper presents a detailed analysis of the menstrual diaries provided by 5098 (89%) of the subjects. In total, 902, 903 and 913 diaries were analyzed to compare bleeding patterns induced by Mesigyna, Cyclofem and Injectable No. 1. The first withdrawal bleeding usually occurs 14-20 days after the first injection for all three of these preparations. Thereafter, 50% of Mesigyna users had precisely 3 bleeding/spotting episodes every 90 days, 50% of Cyclofem users had 2-3 and 50% of Injectable No. 1 users had 3-4 episodes every 90 days. Relative to users of Mesigyna or Cyclofem, Injectable No. 1 users had 2-3 more bleeding/spotting days, and a shorter length of bleeding/spotting-free intervals in each period. 63.7%, 41.4% and 60.6% of subjects using Mesigyna, Cyclofem and Injectable No. 1, respectively, had bleeding patterns similar to their untreated patterns in the first 90-day period. The percentages increased to 82.2% 67.8% and 75.0% in the fourth 90-day period. A total of 1815 diaries for Mesigyna and 1802 for Cyclofem were analyzed for more in depth comparison of these two methods. The number of bleeding/spotting days over four periods showed little difference between the two group, but there were more spotting days and there was greater individual variability among Cyclofem users.(ABSTRACT TRUNCATED AT 250 WORDS) A total of 100 women who were using depot medroxyprogesterone acetate (DMPA) for contraception and who had experienced at least 6 months of drug induced amenorrhea, were randomized to either switching their method of contraception to Cyclofem, or continuing with DMPA. At the end of 6 months, 82% of the Cyclofem users had experienced some vaginal bleeding, compared with 10% of DMPA users. Time to resumption of vaginal bleeding was related to the duration of DMPA use to the duration of DMPA induced amenorrhea, and to the body mass index of the user. Over the 6 months of follow-up, 94% of Cyclofem users complained of some side effects, compared with 22% of DMPA users. The most frequently cited problems among Cyclofem users included breast tenderness, abdominal pain, and dysmenorrhea; yet a third of these women opted to stay on Cyclofem at the end of the study. It is concluded that switching to Cyclofem is a new option for DMPA users who are concerned about amenorrhea. Although using Cyclofem in this setting will not meet the needs of all such women, its effectiveness in inducing vaginal bleeding justifies a trial in those who have no contraindication to estrogen treatment. A clinical trial of the two once-a-month injectable contraceptives, Cyclofem and Mesigyna, used for 1 year was carried out in Egypt involving a total of 2252 women living in different Egyptian localities, representing urban/rural and Upper/Lower Egyptian populations. Women were randomly assigned to either one of the two study preparations and followed a standard protocol for a comparative assessment of the efficacy, side effects, and acceptability of the two preparations. Both contraceptives proved to be highly acceptable, with continuation rates of 63.2 per 100 women-years for Cyclofem and 61.6 for Mesigyna at the end of 12 months of use. The cumulative discontinuation rates per 100 women-years for method failure were 0.19 for Cyclofem users and 0.41 for Mesigyna users. Menstrual problems were the most frequently reported side effects in both groups. Discontinuation rates because of amenorrhea were 2.74 in the Cyclofem group compared to 1.38 in the Mesigyna group, whereas the rates of discontinuation because bleeding problems were significantly higher among Mesigyna users (11.54) compared to the Cyclofem group (7.39). There was no significant difference between the two groups regarding the discontinuation rates from other medical and personal causes. There were insignificant changes in the systolic and diastolic blood pressure values recorded at follow-up; only one Cyclofem user developed systemic hypertension (160/100 mm Hg) after 6 months of use and was discontinued for that reason. On the other hand, a constant weight gain averaging 0.33 kg/month was observed in both groups; however, weight gain was not considered a major cause of method discontinuation. This 2-year study compared Mesigyna(R) administered to 49 pre-menopausal women between 38 and 50 years, to 99 women fitted with an IUD (Nova-T). A complete lipoprotein assessment was carried out before treatment and at 6, 12, and 24 months of treatment. A bone densitometry was performed on half of the women, and an endometrial biopsy was taken from half of the Meisgyna group before and at the end of the first and second year. No pregnancy occurred with Mesigyna use while three pregnancies were observed with the IUD. The incidence of bleeding anomalies was higher in the Mesigyna group, with a discontinuation rate for these reasons of 20% versus 4% for IUD (p <0.05). The duration of bleeding days as well as dysmenorrhea were less with Mesigyna. No differences were seen in the pattern of intermenstrual bleeding and spinal bone density between both groups. No patient developed endometrial hyperplasia after treatment, thus endometrial risk seemed not to be increased. Total and LDL cholesterol, and apolipoproteins did not show modifications. A slight decrease in total triglycerides, HDL and HDL(2) cholesterol, and IDL lipoproteins was observed with Mesigyna. The present study appears to be the first using a monthly injectable hormonal contraceptive and monitoring its influence on lipid patterns in premenopausal women. Mesigyna proved to be a highly effective and low risk agent for premenopausal users. The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding.
                Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques.
                Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p <0.05). However, there was no significant difference between endometrial vascular density during treatment with Cyclofem or DMPA. Total bleeding days in the first and second 3-month time intervals were 28 +/- 23 and 18 +/- 12 days in DMPA users and 22 +/- 14 and 16 +/- 9 days in Cyclofem users, respectively, Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups.
                This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.
While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward improving the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.