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Further study on the effect of norethisterone enanthate, an injectable contraceptive on body functions.

One hundred and fortythree healthy Bengali women have received norethisterone enanthate, as injectable contraceptive in doses of 200 mg. intramuscularly at intervals of 10 to 12 weeks. The drug have been found to be almost 100 percent effective in the control of fertility. Menstrual disturbance, e.g. amenorrhoea, irregular bleeding and spotting, appeared to be the main complaints of the clients during the initial period of the therapy; but these did not persist long. There was no ill effect of the drug on lactation. No significant change in body weight, blood pressure, platelet count, fasting blood sugar, serum cholesterol and total plasma protein level was observed following administration of norethisterone enanthate over one year.

Adolescent↗

Response of unmarried adolescents to contraceptive advice and service in Nigeria.

The responses of a group of all unmarried, sexually active teenagers in a developing country to offers of contraceptive service were assessed in a prospective, 30-month study at a teaching hospital family planning center. Teenagers of this group constituted 7.2% of the clinic population. The default rate was very high (43.0%) and was most noticeable among users of oral contraceptives. The intrauterine device seemed more acceptable, as were injections of norethisterone enanthate. Possible reasons for this pattern of response are given, and the authors suggest giving new consideration to making the intrauterine device more suitable for and acceptable to teenagers of developing countries. The place of norethisterone enanthate in teenage contraception is also discussed.

Adolescent↗

[Ultrastructure of the prolactin cells of the pituitary gland of female rats after stimulation with norethisterone enanthate].

Prolactine cells of rat anterior pituitary gland were studied with the electron microscope in thin sections and freeze-etch replicas after treatment with norethisterone-oenanthate. A pathological secretory process is caused in this cell type in rats, when treated with this compound. Prolactine cells grow in number and volume of single cells. This is especially due to an enormous proliferation of the Golgi apparatus. In the same time, however, exocytosis of hormonal secretory granules is apparently reduced. Therefore, serum hormone level remains nearly normal.

Animals↗

Review of ovulation return upon discontinuation of once-a-month injectable contraceptives.

Once-a-month combined injectable preparations draw their contraceptive efficacy from continuous ovulation suppression. When their use is discontinued, ovulation resumes within a few weeks or a few months, depending on the formulation. After use of the dihydroxyprogesterone acetophenide 150 mg/estradiol enanthate 5 mg combination for one to two years, ovulation returns in most subjects 3-4 months after discontinuation of treatment. Similarly, recent data show that after 2-year use of the depot-medroxyprogesterone acetate 25 mg/estradiol cypionate 5 mg or the norethisterone enanthate 50 mg/estradiol valerate 5 mg combination, approximately 70% women have resumed ovulation by the third month post-treatment. This is shorter than the time for return of ovulation experienced by ex-users of progestogen-only injectable contraceptives.

Contraceptive Agents, Female↗

A study of adrenal corticol function and its reserve activity in long-acting injectable contraceptive users.

Adrenal function and its reserve capacity were studied in eighteen healthy non-lactating women who received depot-medroxyprogesterone acetate (DMPA: 9 subjects) and norethisterone enanthate (NET-EN: 9 subjects) as long-acting injectable contraceptives. Methodological assessments included: (i) morning fasting concentration of serum cortisol; (ii) diurnal variation of adrenal corticol activity as evidenced by cortisol concentration in serum samples taken at 0700 and 1600 hours; (iii) urinary free cortisol excretion; and (iv) cortisol response to insulin-induced hypoglycaemia. None of these assessments was significantly altered by contraceptive administration. This finding indicates that the subject's ability to release cortisol in response to a stressful situation, as well as to normal day-to-day activity, was not impaired by these contraceptive steroids.

Adrenal Cortex↗

Pituitary response to LHRH in long-term users of injectable contraceptives.

The site of gonadotrophin inhibition in long-term users of injectable contraceptives is still debatable. The pituitary response to LHRH (50 micrograms, I.V.) was assessed in 32 women. Sixteen cases were using either medroxyprogesterone acetate (DMPA; n = 8 150 mg I.M. every three months) or norethisterone enanthate (NET-EN; n = 8, 200 mg every 2 months) for at least 18 months. The remaining cases (n = 16) were normal fertile females not using any hormonal contraceptive (control group). The pituitary response to LHRH injection in both injectable subgroups was nearly identical to that in the control group. Neither the basal levels nor the net increase in gonadotrophins following LHRH injection were significantly different in the study groups from those of the control group. Long-term use of DMPA or NET-EN does not affect the pituitary responsiveness to LHRH injection and the pituitary is not a primary site for ovulation inhibition in these cases.

Adult↗

Effects of synthetic steroid contraceptives on biliary lipid composition of normal Mexican women.

The effects of two hormonal contraceptives upon the biliary lipid composition of Mexican women were evaluated in a prospective study. Twenty-one healthy volunteers of reproductive age were allocated into three groups (7 subjects each). Group I served as the experimental control (all subjects were bearing a non-medicated IUD), group II received i.m. norethisterone enanthate (NET-e) 200 mg every two months, and group III received an oral combination of 1-norgestrel 150 micrograms and ethinyl estradiol 30 micrograms. The bile lithogenic index as assessed by the relative proportion of cholesterol to bile acids and lecithin was determined in duodenal bile samples obtained before (baseline), during (4 months), and after (12 months) contraceptive administration. The results indicated that NET-e administration resulted in a slight although significant increase of the lithogenic index while the oral formulation did not. The overall data were interpreted as demonstrating that administration of these steroid contraceptives does not constitute a risk factor in terms of gallstone formation in the population studied. The estrogen-like behavior exhibited by NET-e is discussed.

Adult↗

A clinical study on injectable contraceptive Noristerat.

Results of a clinical study involving 382 subjects using the injectable contraceptive Noristerat (norethisterone enanthate) is presented. The maximum number of acceptors were between 21-25 years of age and had been married for 6-10 years. 50% began their 1st injection within 1 year of the last childbirth. Continuation rates were very high and about 75% returned for their 2nd injection. Among the users, weight gain was seen more commonly than weight loss. There was no significant change in blood pressure. 52.2% reported a menstrual pattern which was within the acceptable range of normal, while only 12.7% had amenorrhea. 15% showed other types of menstrual disturbance. Only 1 woman in the series became pregnant. Menstrual abnormality was the most common cause for discontinuation among the 71 subjects available for interview.

Age Distribution↗

Low dose injectable contraceptive norethisterone enanthate 20mg monthly - II. Metabolic side effects.

Metabolic effects of a long-acting low dose injectable contraceptive, norethisterone enanthate 20-mg, monthly injections (Neten-20), was tested in 13 women belonging to the low income groups over a period of 1 year. No change was observed in hemoglobin, hematocrit, glucose tolerance, plasma lipids, iron, calcium, or serum glutamate-oxaloacetate transaminase after treatment. Marginal rise in albumin and fall in some globulin fractions was observed. The slight fall seen in serum alkaline phosphatase could be attributed to a change in lactation status. Vitamin A, pyridoxine and riboflavin status were not altered. A peculiar aberration in the tryptophan-niacin pathway as indicated by rise in kynurenic acid excretion after tryptophan load was observed. This could be corrected by multivitamin therapy. These data suggest that the use of Neten-20 for one year does not lead to adverse metabolic effects analogous to those seen with combination type oral contraceptives.

Alkaline Phosphatase↗

Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters.

One-hundred-and-thirty normally menstruating females were subgrouped equally and enrolled from the family planning clinic to study the clinical performance of the monthly injectable contraceptives medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg (Cycloprovera) and norethisterone enanthate 50 mg + estradiol valerate 5 mg (HRP-102) and their effects on some metabolic parameters. The contraceptive efficacy after 6 months of use for both drugs was 100%. No change in menstrual pattern occurred in 74% of Cycloprovera users and 67.3% of HRP-102 users. A statistically significant decrease (P less than 0.01) occurred in HDL-cholesterol and total serum protein values and a statistically significant increase (P less than 0.01) was observed in hematocrit value of Cycloprovera users only. Body weight and blood pressure values after 6 months of drug use showed no statistically significant changes in both groups. Also, no statistically significant changes were noticed in both groups for hemoglobin, post-prandial blood glucose, cholesterol, A/G ratio, SGPT and SGPT values following 6 months of injectable contraceptive use. None of the injectable users developed cervical dysplastic changes cytologically.

Alanine Transaminase↗

Long-term use of depot-norethisterone enanthate: effect on blood lipid fractions.

This is the third report of a metabolic study on 56 long-term users (24 for 2-5 yr; 32 for over 5 yr) of the injectable contraceptive norethisterone enanthate (Net-En) and deals with the effects on the blood levels of lipoprotein fractions. There was no significant difference between this group and a group of 30 non-users in serum concentrations of triglycerides, total cholesterol, low density and very low density lipoproteins. There was a significant reduction in mean high density lipoprotein levels between the controls and the user groups (16% for the intermediate duration and 12% for the longer duration). Age, ethnic group, body-mass index and a close family history of cardiovascular disease were taken into account, as were various lifestyle factors: diet, exercise, alcohol consumption and smoking. In a smaller group, levels of apoproteins A and B were also assayed. There was a significant reduction in apoprotein A between controls and all users, but the significance was lost on adjusting for confounding variables. Consideration was given to the ratio of total cholesterol to high density lipoprotein cholesterol as an index of coronary risk. There were no significant differences in the total cholesterol:HDL-C ratio between controls and user groups. There was a significant interaction with ethnic group (Caucasian or Afro-Caribbean) in the response to duration of use.

Adult↗

Mesigyna once-a-month combined injectable contraceptive: experience in Latin America.

A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.

Adolescent↗

Fertility control.

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Chemical Phenomena↗

[Depot gestagens].

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Clinical Trials as Topic↗

Fertility following discontinuation of different methods of fertility control.

The possibility of permanent sterility following use of modern contraceptive agents is a concept which causes great concern amongst members of the lay public. However, a thorough review of the literature gives a great deal of reassurance on this topic. The combined oral contraceptive pill causes slight delay, and the injectable contraceptives a moderate delay in the return of fertility following discontinuation, but there is no evidence of a greater likelihood of permanent infertility than in the normal population. The progestogen-only minipill should be risk-free, but final data are lacking. Epidemiological studies do not indicate an increased risk of infertility following IUD use, but it seems likely that there must be a very small number of IUD users who develop permanent infective damage to the Fallopian tubes. Barrier methods and periodic abstinence probably do not have any significant effect on subsequent fertility. Barrier methods could be protective. Therapeutic abortion may have a small deleterious effect on long-term reproductive success, but the data are inconclusive. Detailed information on fertility following use of other methods is not available.

Abortion, Induced↗

Return of ovulation and fertility in women using norethisterone oenanthate.

The return of ovarian activity was studied in 20 women who had discontinued norethisterone oenanthate after using the injectable contraceptive for 6 months to 5 years. Follicular activity returned within 70 days of discontinuing in four women and within 90 days in a further seven. In only 4 women was the return of follicular activity associated with a rise in the serum progesterone level. The serum norethisterone concentration was usually less than 1 ng/ml at the time of return of ovarian activity and was lower in women in whom ovarian activity returned before day 90 than in those in whom it returned after day 90. Of 40 women who discontinued norethisterone oenanthate, pregnancy occurred in 14 women within 12 weeks of discontinuing and in 21 (52.5%) within 6 months. The findings suggest that there is no impairment of fertility in women using norethisterone oenanthate.

Adult↗