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Norethisterone enanthate as an injectable contraceptive in puerperal and non-puerperal women.

Norethisterone enanthate (NET-EN) was intramuscularly administered to 5 puerperal women and 20 non-puerperal women for a total of 366 months. Contraceptive effectiveness and side effects of the drug were evaluated. Basal levels of LH, FSH, prolactin (PRL), estradiol 17 beta (E2) and progesterone (P) were measured in blood samples collected from 5 non-puerperal women, while LH, FSH, PRL and norethisterone (NET) plasma levels were evaluated in puerperal women. NET was also assayed in plasma from breast-fed newborns. No woman became pregnant. Side effects consisted of only menstrual abnormalities. Ovulation (P plasma levels higher than 2000 pg/ml) was achieved in 3 patients during the first month of NET-EN treatment but luteal function appeared to be insufficient. In puerperal women, NET plasma levels showed a course similar to the one observed outside puerperium. Lactation was not inhibited, and NET transfer to newborn through milk was negligible, since NET was undetectable in newborn plasma when maximal levels were measured in the mother. It was concluded that NET-EN is an effective contraceptive drug, deprived of major side effects, and particularly useful in women affected by metabolic diseases or during puerperium.

Chorionic Gonadotropin↗

Serum phospholipid fractionation after the use of long-acting progestational contraceptives.

The effect of the two long-acting progestational contraceptive injection, depot-medroxyprogesterone acetate (DMPA) and norethisterone onenathate (NET-OEN), on blood phospholipid fractions were studied in eighteen women. The post-injection results showed a significant increase in total serum phospholipids, serum lecithin and serum cephalins. Serum lysolecithin was significantly decreased while serum sphingomyelin showed no significant change. The mechanisms responsible for these phospholipid changes remain somewhat unclear. However deranged liver function may share in its explanation.

Adult↗

Hemostatic changes in women using a monthly injectable contraceptive for one year.

The effect of consecutively injecting a one-a-month contraceptive (norethisterone enantate 50 mg with estradiol valerate 5 mg) for one year on haematological parameters was evaluated in 42 Chinese women. The healthy volunteers were randomly allocated to either the treatment group (22) or a control group (20). Blood samples were collected in the follicular and luteal phases of a pretreatment cycle, on days 28 +/- 3 after the 1st, 3rd, 6th, 12th injections and in the luteal phase of the post-treatment cycle. The results showed that in both groups, prothrombin time and fibrinogen fluctuated significantly, and leucocyte count was not significantly changed during the whole course. Factor VIII-related antigen and antithrombin III (AT-III) antigen showed minor changes, although in the 3rd treatment cycle, the differences between the two groups in both parameters reached statistical significance. A progressive and significant decrease in Factor X and AT-III functional activity occurred with the monthly injectable treatment, decreasing by about 14% and 20%, respectively, after 12 months of treatment. Haemoglobin levels were increased in the treatment group after the 3rd injection and remained at the higher level during the study period. It is doubtful whether these changes are likely to be of clinical relevance.

Adult↗

Management of amenorrhea due to contraceptive injectables by temporary IUD insertion.

Amenorrhea is a common side effect of injectable contraceptive. Lippes loops were inserted in 22 amenorrheic women who continued injectable contraception, and in 6 cases with prolonged postinjectable amenorrhea. The occurrence and rhythm of subsequent bleeding was recorded. IUD insertion induced bleeding in most cases of continued injectable users but it was usually irregular and unpredictable. It was regular in 6 subjects only while the IUD was in situ. After the removal of the IUD, the majority regained the state of amenorrhea within 3 months. Temporary IUD insertion had a positive impact on continuation (a mean additional rate of 18 months of use) among subjects who had wished to terminate the method because of amenorrhea. This procedure of temporary IUD insertion may serve to provide these women with an alternative contractive approach. In the postinjectable amenorrhea group, temporary IUD insertion induced bleeding during IUD application as well as after its removal, which was more predictable than that in the continued users. IUD insertion may facilitate return of regular menses and resumption of fertility in amenorrheic women who stop injectable contraception.

Age Factors↗

Norethisterone levels in maternal serum and milk after intramuscular injection of norethisterone oenanthate as a contraceptive.

There is concern that the breast-fed infant whose mother is receiving intra-muscular progestogens for contraception will be exposed to significant quantities of the steroid. Norethisterone levels in maternal serum and milk were studied throughout an injection interval after intramuscular administration of 200mg norethisterone oenanthate. Milk samples were taken at the beginning and at the end of the feed. Norethisterone concentrations in milk were very much lower, but declined more slowly, than serum concentrations. Post-suckling concentrations were higher than pre-suckling concentrations. Experiments in adults receiving an oral dose of norethisterone in cow's milk comparable to that ingested by an infant in a day resulted in low serum levels. It is concluded that only very low concentrations of norethisterone would be present in the infant's circulation.

Breast Feeding↗

Blood hormone levels in egyptian women on norethisterone oenanthate.

Ten Egyptian women who were using the injectable contraceptive norethisterone oenanthate (NET-OEN) for at least 6 months were monitored weekly for a period of 12 weeks by measuring 3 pituitary hormones (FSH, LH and prolactin) and 2 ovarian hormones (oestradiol 17-B and progesterone). It was concluded that NET-OEN is a strong ovulation inhibitor, at least after its use for 6 months. Prolactin levels were depressed and this is in contradiction with the findings in rats.

Adult↗

WHO special programme of research, development and research training in human reproduction. Task force on long-acting agents for the regulation of fertility.

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.

Amenorrhea↗