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[Deficiencies of the müllerian ducts induced by norethindrone in the female chick embryo].

Norethindrone produces two effects on müllerian ducts (MD) of female chick embryos. It induces the loss of the lower end of both ducts, as a result of a stop in their development, before 8 days. After 12 days NET causes regressions of the upper part of the MD particularly of the oviduct. NET like estrogens are the only known substances which present these both properties.

Abnormalities, Drug-Induced↗

Phase II clinical study of implanted norethindrone pellets for longterm contraception in women. Program for Applied Research on Fertility Regulation.

The use of subcutaneously implanted fused pellets made of norethindrone (NET) and pure cholesterol was evaluated as a means of longterm contraception (6 months) in 81 women at three clinics. Fifty-one women used pellets containing 103 mg NET (3 pellets) and 30 women used pellets containing 138 mg NET (4 pellets). There were no serious local reactions to the pellets. There was no apparent initial NET burst effect and serum NET levels remained constant over the follow-up period. Median NET serum levels were similar (p greater than 0.10) for women who used 3 or 4 pellets. Most menstrual cycles showed no evidence of ovulation (i.e., serum progesterone levels did not exceed 5 ng ml-1: the proportion of women with serum progesterone levels greater than 5 ng ml-1 was lower with the 4 pellet dose. For women who used either 3 or 4 pellets there was an increase (p less than 0.05) in the number of days of bleeding or spotting. There was a decrease in the incidence of dysmenorrhea (p less than 0.05) for both groups of women. There was a low incidence of side effects and complications. There were two pregnancies; both occurred in women using 3 pellets.

Adult↗

[Column switching HPLC method for determination of in vivo release of norethindrone-alpha, beta-poly (3-hydroxypropyl)-DL-asparamide conjugate].

An HPLC method for the determination of in vivo release of norethindrone-alpha, beta-poly (3-hydroxypropyl)-DL-asparamide (NET-PHPA) conjugate was established using column switching technique. The sample prepurification could be omitted. It was extracted by a precolumn (ODS, 9-11 microns) and the analytical column was packed with ODS (15 cm x 4 mm ID. Shimpac CLC). The mobile phases were water and methanol--water (7:3) respectively. The experiment showed that the recovery from serum was 82.6%, the RSD within day was 1.3-1.8% and that in day-to-day was 0.7-5.6% (n = 4).

Animals↗

Long-term contraception with norethindrone subcutaneous capsules.

Norethindrone (NET) contained in silicone rubber, for slow release, was implanted subcutaneously. The rate of release of NET was 10-12 mug/day/10 mm length of the silicone rubber. The total length of the implants used varied from 100 mm to 200 mm. During the whole observation time 562 women months, 14 a-cidental pregnancies occurred. The pregnancy rate decreased with increasing length of implants. The implants produced a transient ovulation suppression, which subsided in four to five cycles. The plasma levels of NET stabilized at a level which was less than that reached by daily oral administration of 350 mug of NET. The high pregnancy rate and the great number of implants required render the method impractical for contraception. However, the active life-span of implants is three years and because there were few minor side-effects, the method was well accepted.

Contraception↗

Effect of norethindrone acetate in the treatment of symptomatic endometriosis.

OBJECTIVE: The purpose of the study was to evaluate the efficacy of norethindrone acetate (NA) treatment in 52 women with dysmenorrhea, dyspareunia, noncyclic pelvic pain who had a diagnosis of endometriosis by laparoscopy. RESULTS: Dysmenorrhea and noncyclic pelvic pain were relieved in 48/52 (92.3%) and 25/28 (89.2%) of patients, respectively. Overall pain relief was obtained in 49/52 (94.2%) of patients. Breakthrough bleeding, of variable severity, was the most common side effect experienced by 30 patients (57.6%); however, only 4 patients (7.7%) dropped out for this side effect. One other patient dropped out for severe breast tenderness, and three for noncyclic pelvic pain. In general, treatment was successful in 44/52 (84.5%) of patients with the above symptoms. CONCLUSION: NA seems to be a cost-effective alternative with relatively mild side effects in the treatment of symptomatic endometriosis.

Adult↗

A simple high-throughput enzymeimmunoassay for norethisterone (norethindrone).

A direct enzymeimmunoassay having the sensitivity required for determining norethisterone concentrations in small aliquots of plasma (10 microliter) has been developed. This assay featured a solid phase antiserum raised against a norethisterone-11 alpha-hemisuccinyl/bovine serum albumin conjugate. The antiserum was coupled to cyanogen bromide-activated magnetisable cellulose, and antibody-bound and free fractions were separated by a simple magnetic device. A norethisterone/horseradish peroxidase conjugate was used as the label; o-phenylenediamine/hydrogen peroxide being the substrate for colour development. The results obtained by this direct EIA, which allowed processing of at least 100 samples per day, were compared with those of a well-validated enzymeimmunoassay featuring solvent extraction and centrifugal separation of antibody-bound and free steroid; the results were in excellent agreement (n = 30; r greater than 0.99) suggesting the usefulness of the simple high-throughput procedure for processing the large sample numbers generated by field investigations and pharmacokinetic studies.

Centrifugation↗