norethindrone-enanthate and Amenorrhea

Norethisterone enanthate (NET-EN) 50 mg combined with estradiol valerate (EV) 5 mg was studied as a once-a-month injectable contraceptive with regard to effectiveness, cycle control, adverse events and acceptability. In eight Family Planning Centres from five Latin American countries, 931 fertile women were followed-up for a period of 36 months, providing a total of 15,787 woman-months of experience. Only one pregnancy occurred: in the first treated month a few days before the second injection (failure rate 0.08 per 100 woman-years). Under treatment, the first cycle was drastically shortened in most cases, but thereafter cycles tended to recover to pre-treatment patterns. There was a significant decrease of hypermenorrhoea and dysmenorrheic cycles. Intracyclic bleeding and spotting appeared in 1.8% and 2.2%, respectively, and amenorrhea in 2.8% of cycles. The incidence of other adverse events was very low with the exception of weight gain of more than 2 kg (36.8%). The continuation rate at 12 months was 64.7%, at 24 months 31.0% and at 36 months 20.4%. The cumulative discontinuation rate due to bleeding problems was 6.1% and 7.2% due to adverse events at 36 months. The treatment was shown to be a highly effective contraceptive method that offers fairly good cycle control, good tolerance and a continuation rate that makes it suitable for use in family planning programmes in the Latin American area.

Topics: Amenorrhea; Body Weight; Contraceptive Agents, Female; Estradiol; Female; Humans; Injections; Latin America; Norethindrone; Pregnancy; Uterine Hemorrhage

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.

Topics: Adult; Amenorrhea; Blood Pressure; Body Weight; Clinical Trials as Topic; Contraceptive Agents, Female; Estradiol; Female; Humans; Injections; Menstruation; Menstruation Disturbances; Norethindrone; Oligomenorrhea; Random Allocation; Time Factors

A field study of the injectable contraceptive, norethisterone enanthate (NET-EN), was conducted in family planning clinics in Sind and Punjab provinces of Pakistan, to determine the acceptability and feasibility of providing NET-EN in government family planning clinics staffed by Family Welfare Visitors (FWVs). A total of 2147 women were recruited to the study, of whom approximately three-fourths had never previously used contraception. The overall discontinuation rate at one year was 78 per 100 women; the most common reason for discontinuation was bleeding disturbances, including amenorrhea, although returning to the clinic too late for an injection also accounted for a substantial proportion of the discontinuations. Given adequate training, FWVs were shown to be capable of providing NET-EN in family planning clinics, including managing the bleeding disturbances common with this method of contraception. No pregnancies were reported, demonstrating that the method is highly effective when used in a usual family planning clinic situation.

Topics: Adolescent; Adult; Amenorrhea; Clinical Trials as Topic; Contraceptive Agents, Female; Female; Humans; Injections; Menstruation Disturbances; Norethindrone; Pakistan; Parity; Time Factors

Final results are presented from a two-year WHO multinational comparative trial of three regimens: depot-medroxyprogesterone acetate (DMPA) given at 90-day intervals, norethisterone enanthate (NET-EN) given at 60-day intervals for the entire study period (NET-EN (60-day)), and NET-EN given at 60-day intervals for six months and thereafter at 84-day intervals (NET-EN (84-day)). 1587 DMPA subjects were observed for 20,550 woman-months, 789 NET-EN (60-day) subjects were observed for 10,361 woman-months, and 796 NET-EN (84-day) subjects were observed for 10,331 woman-months. This clinical trial represents the largest clinical trial undertaken on injectable contraceptives. After two years, the pregnancy rate with NET-EN (84-day) was 1.4 (+/- 0.6 S.E.) per 100 women, as compared with the two-year rates of 0.4 (+/- 0.3 S.E.) per 100 women observed with DMPA and 0.4 (+/- 0.2 S.E.) with NET-EN (60-day). Both discontinuation rates for amenorrhea and the prevalence of amenorrhea lasting more than 90 days were significantly higher with DMPA than with either NET-EN regimen. Terminations for bleeding problems were similar with the three treatments, despite a better cyclic pattern for the first six months with the NET-EN regimens. The three treatments were comparable with respect to discontinuation rates for other medical or personal reasons, and for all reasons combined. For family planning programs, NET-EN (60-day) has the advantage of low pregnancy rates compared to NET-EN (84-day), and a schedule of administration that does not change. Both NET-EN regimens produce less amenorrhea than DMPA. However, the NET-EN (60-day) regimen has the logistic and economic disadvantage of requiring more frequent injections. All three injectable regimens compare favourably with oral contraceptives in terms of pregnancy and total continuation rates observed in clinical trial settings.

Topics: Adult; Amenorrhea; Clinical Trials as Topic; Contraception; Contraceptive Agents, Female; Delayed-Action Preparations; Drug Administration Schedule; Female; Fertility; Humans; Injections; Medroxyprogesterone; Medroxyprogesterone Acetate; Norethindrone; Pregnancy

A multicentre phase III clinical trial has been undertaken to compare norethisterone enantate (NET-EN) given by two different treatment regimens and depot-medroxyprogesterone acetate (DMPA). After 18 months of observation, preliminary findings are reported for 1,589 women who received DMPA 150mg every 90 days; 790 women who received NET-EN 200mg every 60 days; and 796 women who received NET-EN, 200mg every 60 days for 6 months, then 200mg every 84 days. The overall discontinuation rates per 100 women were similar for all three treatment groups over the 18 months observation (61.8 - 63.5 per 100 women). The discontinuation rates for bleeding problems and for personal reasons were also similar for all three treatment groups. However, terminations due to amenorrhoea were significantly higher among DMPA users (12.1 and 17.4 per 100 women at 12 and 18 months) as compared with both NET-EN groups (6.8 - 8.2 per 100 women at 12 months and 10.4 - 10.9 per 100 women at 18 months). The only significant difference in pregnancy rates observed between the three groups was a higher rate at 18 months among NET-EN (84 days) users (1.6 per 100 women), as compared with DMPA users (0.2 per 100 women). There was no overall significant difference between the two NET-EN groups, although between the 6 and 18 month's follow-up when the two NET-EN regimens diverged, the NET-EN (84 days) users' pregnancy rate rose significantly, whereas in the NET-EN (60 days) group the pregnancy rate did not change. There was a significantly higher weight gain in those subjects using NET-EN at 60-day intervals compared with those using it at 84-day intervals.. A multicenter phase 3 clinical trial compared norethisterone enanthate (NET-EN) given by 2 different treatment regimens and depot-medroxyprogesterone acetate (DMPA). After 18 months of observation, preliminary findings are reported for 790 women who received NET-EN 200 mg every 60 days; for 796 women who recieved NET-EN every 60 days (200 mg) for 6 months, then 200 mg every 84 days, and for 1589 women who received DMPA 150 mg every 90 days. Overall discontinuation rates and discontinuation for bleeding and personal reasons were similar for all 3 groups after 18 months observation (61.8-63.5/100 women). Terminations due to amenorrhea were significantly higher among DMPA users (12.1 and 17.4/100 women at 12 and 18 months) than among both NET-EN groups (6.8-8.2/100 women at 12 months and 10.4-10.9/100 women at 18 months). The only significant difference in pregnancy rates observed among the 3 groups was a higher rate at 18 months among NET-EN (84 days) users (1.6/100 women), than among DMPA users (0.2/100 women). There was no overall significant difference between the 2 NET-EN groups, although between the 6 and 18 month follow-ups when the 2 NET-EN regimens diverged, the NET-EN (84 days) users' pregnancy rates rose significantly, whereas in the NET-EN (60 days) group, the pregnancy rate did not change. Weight gain was significantly higher in those subjects using NET-EN at 60 day intervals than at 84-day intervals.

Topics: Amenorrhea; Body Weight; Clinical Trials as Topic; Contraceptive Agents, Female; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Medroxyprogesterone; Medroxyprogesterone Acetate; Norethindrone; Pregnancy; World Health Organization

A clinical trial was carried out in which Norigest (200 mg norethisterone oenanthate) was administered by intramuscular injection every 56 days into 383 women studied for 5,521 woman-months of use. No pregnancies occurred. Continuation rates at the end of one, two and three years were 76.6%, 63.7% and 33.8%. Only minor side-effects were recorded. After one year of use, 20.1% women had gained more than 2 kg in weight and 14.8% had lost more than 2 kg. There was marked disruption of the menstrual pattern and irregular bleeding was the major cause of discontinuation. In 38% of the injection intervals analysed, women were amenorrhoeic. Norigest proved an effective and acceptable method of fertility control.

Topics: Amenorrhea; Blood Pressure; Body Weight; Clinical Trials as Topic; Contraceptive Agents, Female; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Menstruation; Norethindrone

A randomized, single blind comparative trial of norethindrone enanthate (NET-ENT) and depo-medroxyprogesterone acetate (DMPA) was conducted in the Model Clinic, Decca, Bangladesh, to determine if there were differences in reported side effects, reasons for discontinuation and discontinuation rates of these two injectables. On all follow-up visits the proportion of women reporting no bleeding (amenorrhea) was higher for the DMPA clients compared to the NET-ENT clients. Concurrent with these findings, the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients. Concurrent with these findings, the proportion of women reporting irregular bleeding was consistently higher for the NET-ENT clients compared to those receiving DMPA. By the fourth injection, less than 15% of the clients in both drug groups still reported having regular cyclic bleeding (4 of the 26 DMPA clients and 4 of the 28 NET-ENT clients). Five of the 133 women on DMPA and 6 of the 106 women on NET-ENT became pregnant while using the injectables. At the end of one year of follow-up, 14 of the 133 DMPA and 14 of the 106 NET-ENT clients were still continuing (came back for a fifth injection).. This comparative trial of norethindrone enanthate (NET-ENT) and depo-medroxyprogesterone acetate (DMPA) was conducted in a randomized, single blind manner in a clinic in Bangladesh to assess discontinuation rates, reasons for discontinuation, and variablility of side effects between these 2 injectable contraceptives. Of a total of 239 women, 106 received NET-ENT (200 mg) and 133 received DMPA (150 mg). DMPA was given every 12 weeks after the first injection and NET-ENT was given every 10 weeks after initial injection. Oral estrogen therapy was made available to women in this study based on the following criterion: 1) spotting/bleeding lasting more than 7 days; 2) heavy bleeding; or 3) 3 or more months of amenorrhea if this disturbed the subject. For menstrual pattern variability, a larger proportion of women reported irregular bleeding when given NET-ENT than did those with DMPA. On the other hand, on all follow-up visits the proportion of women reporting amenorrhea was higher for DMPA compared with NET-ENT users. However, by the 4th injection, fewer than 15% of clients in both experimental groups still reported regular cyclic bleeding (4 of 26 in DMPA group and 4 of 28 in NET-ENT). 11 pregnancies occurred during treatment, 5 in the DMPA group and 6 in the NET-ENT group. Continuation after 1 year totaled 28 clients, 14 from each group. The primary reasons for discontinuation were pregnancy; medical reasons, including symptoms and fear of symptoms; nonmedical reasons such as desire for more children, or death of husband; or loss to follow-up: the number of clients in the DMPA group discontinuing for these reasons were 5, 48, 17, and 49, respectively, and the respective numbers among NET-ENT users were 6, 34, 24, and 28.

Topics: Adult; Amenorrhea; Bangladesh; Clinical Trials as Topic; Female; Humans; Injections, Intramuscular; Medroxyprogesterone; Medroxyprogesterone Acetate; Menstruation Disturbances; Norethindrone; Pregnancy; Random Allocation

This paper reports on the common experience of vaginal wetness amongst South African users of progestogen-only injectable contraceptives. The observations emerged in the course of a community-based cross-sectional household survey undertaken in a rural district of KwaZulu-Natal in South Africa. The purpose of the survey was to elicit self-reporting on side effects of injectable contraceptive methods. Eight hundred and forty-eight women aged 15-49 were interviewed and 22.1% reported current use of an injectable contraceptive method, either depot medroxyprogesterone acetate (Depo-Provera) or norethisterone oenanthate (Nur-Isterate). Other modern methods used were oral hormonal contraceptives (4.5%), male condoms (1.3%), the intrauterine device (0.1%), and tubal ligation (0.1%). Vaginal wetness was reported by 18.4% of users and was one of the most common side effects, second only to amenorrhoea (62.5%). It was also what 17.5% of the women liked least about using this method. According to almost half the respondents, men regard women who use the injectable contraceptive as "wet", "cold" and/or "tasteless". These survey findings were supported by participants of 14 focus group interviews held in the sub-district. Since some South African men may prefer dry sex the perception that the injectable contraceptive increases vaginal wetness may be problematic for women who use it. Whilst vaginal wetness can only be classified as a subjective side effect at this stage, further investigations are needed as many South African women opt to use this method.

Topics: Adolescent; Adult; Amenorrhea; Contraceptive Agents, Female; Cross-Sectional Studies; Family Characteristics; Female; Focus Groups; Health Knowledge, Attitudes, Practice; Humans; Injections, Intramuscular; Interviews as Topic; Medroxyprogesterone Acetate; Middle Aged; Norethindrone; Qualitative Research; Rural Population; Sexual Partners; South Africa; Vaginal Discharge

Fifty-six women using depot-norethisterone enanthate injections for contraception for 2 years or more were compared with a control group of 48 women not using hormonal contraception. No significant difference was found between the study group and controls for Factors VIIc and Antithrombin III. Factor Xc was reduced in women who had used the injections for over two but less than five years [controls: mean 90.3% SD31.2 vs users for 2-5 yr: 78.7% SD17.1, 95%CI difference in means -0.3, -22.9]. In the group using Net-En for five years or more, Factor Xc was significantly higher than in the control group, but only by 14% of the mean control value [users for over 5 yr: 103.2% SD15.2, 95%CI difference in means 3.1, 22.7]. Haemoglobin levels, red cell count and packed cell volume were higher in those using the injections than in the control group. Changes in the platelet count were not statistically significant. Twenty-three women using the injection agreed to keep menstrual diaries. Of these, 20 experienced amenorrhoea for more than two consecutive injection intervals (112 days). It is concluded that long-term use of norethisterone enanthate is not associated with any markedly deleterious effects on Factor VIIc, Xc, or antithrombin III or haemoglobin levels. Amenorrhoea of 4 months or more can be expected after two years of continuous use.

Topics: Adult; Amenorrhea; Antigens; Antithrombin III; Blood Coagulation Factors; Contraceptives, Oral, Synthetic; Delayed-Action Preparations; Erythrocyte Count; Erythrocyte Volume; Factor VII; Factor X; Female; Hemoglobins; Humans; Injections; Menstruation; Middle Aged; Norethindrone; Time Factors

Unpredictable disturbance of the menstrual cycle is the major problem associated with use of all progestogen-only methods of contraception. This even occurs with those methods which do not usually suppress ovulation, but the disturbance is generally less severe with lower dosage systems. The commonest changes include amenorrhoea and irregular, scanty and infrequent bleeding, but may sometimes involve episodes of prolonged or frequent spotting or light bleeding. Heavy bleeding is rare. Although some abnormalities of endometrial vascular morphology and function have been identified, the mechanisms of abnormal bleeding are poorly understood. Management centres around effective pretreatment counselling and continued support at follow-up. Sometimes a single course of oestrogen therapy may be helpful. This is safe and effective at stopping a particular episode of bleeding provided that an adequate duration of oestrogen effect is given (eg. an oral 2 to 3 week course or a single intramuscular injection). However, experienced investigators rarely use oestrogens and repeated courses are not recommended. There is clearly a major need for basic research in this area, and for the development of improved systems to minimise the problem.

Topics: Administration, Oral; Amenorrhea; Contraceptive Agents, Female; Counseling; Estrogens; Female; Humans; Levonorgestrel; Medroxyprogesterone; Medroxyprogesterone Acetate; Menstruation Disturbances; Norethindrone; Norgestrel; Time Factors

This report summarises a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA, and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience of these contraceptives. A wide range of approaches are described. The most frequently emphasised aspect of management is thorough pre-treatment counselling with further support and counselling at follow-up visits. Oestrogens in various forms are widely used for the treatment of prolonged, frequent or heavy episodes of bleeding, but nowadays are not usually used for the induction of withdrawal bleeding in women with amenorrhoea. Heavy or "severe" bleeding appears to be very uncommon and figures of 1-2% were frequently mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral oestrogen, including the combined pill, are more likely to successfully stop an episode of bleeding than short courses. However, there are no hard data to show that a course of oestrogen treatment has any beneficial effect on long-term bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be very little risk associated with the short-term oestrogen regimens currently used. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. It is clear that the bleeding disturbances associated with DMPA and NET-EN use are poorly understood and that urgent research is necessary to clarify pathophysiological mechanisms and improve management.. This report summarizes a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience with these contraceptives. A wide range of approaches are described. The most frequently emphasized aspect of management is thorough pretreatment counseling with further support and counseling at follow-up visits. Estrogens in various forms are widely used for the treatment of prolonged, frequent, or heavy bleeding episodes, but now are not usually used for induction of withdrawal bleeding episodes in women with amenorrhea. Heavy or severe bleeding appears very uncommon and figures of 1-2% are mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral estrogen, including the combined pill, are more likely to successfully stop an episode of heavy bleeding than short courses. However, there are no hard data to show that a course of estrogen treatment has any beneficial effect on longterm bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be little risk associated with short-term estrogen regimens currently in use. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. Clearly, bleeding connected with DMPA and NET--EN use are poorly understood and research is necessary to clarify pathophysiological mechanisms and improve management.

Topics: Amenorrhea; Contraceptive Agents, Female; Curettage; Estrogens; Female; Humans; Medroxyprogesterone; Medroxyprogesterone Acetate; Menorrhagia; Menstruation Disturbances; Norethindrone; Oligomenorrhea