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Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

Adult

The effects of long-acting injectable contraceptives on carbohydrate metabolism.

Carbohydrate metabolism, as assessed by the intravenous glucose tolerance test (i.v.-GTT), was studied in 19 healthy, non-lactating women who received injectable contraceptives containing either medroxyprogesterone acetate (DMPA) (10 subjects) or norethisterone enanthate (Net-En) (9 subjects). Tests were made prior to treatment and at intervals over a period of 15 months thereafter. Results obtained indicate that carbohydrate metabolism is not impaired by either of the two progestogens, and neither pyruvate nor cortisol concentrations changed significantly over the period of observation. However, the insulin release in response to glucose loading underwent interesting alterations during treatment. These abnormalities returned promptly to normal after withdrawal of treatment.

Adult

A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives.

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.

Amenorrhea

Effect of norethisterone enanthate on the blood count and endometrial histology of Indian women.

Endometrial histology and the haematological indices were studied in women receiving 200 mg of norethisterone enanthate (NET-EN) at 60-day intervals for 24 months as a method of contraception. Significant elevations occurred in the haemoglobin concentration and red blood cell counts during one year of therapy, while eosinophil counts showed a transient increase at 4 months of trial. The changes in the haematological indices seem to be due to stimulation of the erythropoietic system by NET-EN and may also be attributable to diminished blood loss due to amenorrhoea during the course of therapy. The endometrial histology revealed proliferative glands at 2 months which turned quiescent at 6-12 months of NET-EN therapy. Long-term use of 18 months showed atrophic changes with few glands, narrow lumina and stromal oedema.

Blood Cells

Phase IV study of the injection Norigest in Pakistan.

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.

Adolescent

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

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

A clinical trial of norethisterone oenanthate (Norigest) injected every two months.

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.

Amenorrhea

Effect of injectable norethisterone oenanthate (Norigest) on blood lipid levels.

Lipid concentrations were measured in 74 blood samples from 61 women who had been using the injectable contraceptive Norigest (norethisterone oenanthate) for between 2 to 4-1/2 years. There were no significant changes in the concentrations of total cholesterol, total triglycerides and low density and very low density lipoprotein cholesterol but high density lipoprotein cholesterol was significantly reduced. The reduction in serum HDL-C levels was not correlated with either the serum norethisterone concentrations or the length of use of Norigest nor was it affected by obesity or smoking.

Adult

Contraception with progestagens in systemic lupus erythematosus.

To test the efficacy and tolerance of progestagens as contraceptives in systemic lupus erythematosus (SLE), 200 mg IM norethisterone enanthate was administered to 10 patients, 0.03 mg/day oral levonorgestrel to 15 patients and they were compared with 18 control patients. There were 4 episodes of active SLE in 48 patient-months on norethisterone enantate and 6 episodes in 122 patient-months on levonorgestrel as compared with 9 episodes of active disease in 298 control patient-months (p = ns). There were no pregnancies and intermenstrual bleeding led to discontinuation of medication in 30% of patients. Progestagens may be an alternative contraceptive method in SLE.

Adult

Effect of norethisterone enanthate on endometrial bleeding and changes in coagulation function, ovarian hormones and endometrial histology in Thai women.

Endometrial bleeding and alteration in blood coagulation, fibrinolysis, ovarian function and endometrial morphology were studied in twelve normally menstruating women who received the injectable contraceptive norethisterone enanthate (NET-EN) 200mg at 60-day intervals. Levels of clotting factor VII declined significantly during episodes of irregular bleeding compared to those during both normal pretreatment menstruation and the bleeding-free period during treatment. Antithrombin III and fibrinolytic activity, expressed by euglobulin lysis time, showed no marked change. The average level of progesterone during the bleeding-free period was slightly but significantly lower than that during the bleeding period. There were no significant alterations in the mean levels of estradiol and the ratio of estradiol to progesterone. The endometrial biopsies showed considerable individual variation and seem to be independent of the effects of NET-EN on ovarian function.

Adult