Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users.

The objective of this study was to determine the relevance of serum estradiol, progesterone and levonorgestrel concentrations to endometrial histology and uterine bleeding associated with long-term Norplant implants use. Eighteen five-year users of Norplant implants had endometrial biopsies and determinations of serum estradiol, progesterone and levonorgestrel concentrations. Correlations among these factors and uterine bleeding were calculated. Proliferative endometrium (but not sex steroid levels) was associated with abnormal bleeding. Neither ovarian steroid nor levonorgestrel concentrations was a predictor of abnormal bleeding. Hyperplastic changes were not seen even with high estradiol and low levonorgestrel levels.

PIP: At the gynecologic clinic of San Francisco General Hospital in California, 18 women aged 27-44 who had used Norplant contraceptive implants for the full 5 years of effectiveness and who had at least 1 year of recurrent episodes of vaginal bleeding agreed to have an endometrial biopsy and a venipuncture for determination of serum estradiol, progesterone, and levonorgestrel levels. Investigators wanted to learn whether hormonal factors contributed to abnormal bleeding patterns in women who had used levonorgestrel-releasing contraceptive implants for 5 years. At the time of biopsy and venipuncture, 13 (72%) women had normal bleeding patterns. Two women had no apparent follicular activity. Six other women (44%) had a low estradiol level (i.e., 100 pg/ml). 14 women (77%) had no signs of luteal development (i.e., progesterone level 3 ng/ml). None of the women had hyperplastic endometrium. The endometrial index was used to describe endometrial histology and ranged from secretory to proliferated characteristics of the endometrium. It differed significantly between Norplant users with normal bleeding and those with abnormal bleeding (0.32 [a mixture of secretory and proliferative characteristics, but especially secretory characteristics] vs. 0.9 [close to full proliferation of the endometrium]; p 0.01). Serum estradiol, progesterone, and levonorgestrel levels were not significantly different between the two groups. These findings suggest that a proliferative endometrium, rather than sex steroid levels, was linked to abnormal bleeding. Thus, abnormal bleeding among long-term Norplant users is probably not a risk factor for developing endometrial cancer.

Removal of levonorgestrel capsules from the biceps muscle.

Multiple levonorgestrel implants were identified and removed from below the biceps fascia using radiography to assist in localization, axillary block for anesthesia, careful dissection, and palpation of the implants within the deep muscle belly. This difficult implant removal demonstrates the importance of both a clinician experienced in levonorgestrel implant removal and a general surgeon experienced in arm surgery when performing such procedures.

Evaluation of a 1-year levonorgestrel-releasing contraceptive implant: side effects, release rates, and biodegradability.

OBJECTIVE: To determine the release rates, effects on ovulation, and side effects of two lengths of a biodegradable, subdermal contraceptive implant containing levonorgestrel in a caprolactone capsule. DESIGN: Phase II randomized clinical trial. SETTING: Public family planning clinic at an urban general hospital. PARTICIPANTS: Forty-eight healthy, parous, ovulating volunteers. INTERVENTION: Subjects were randomly assigned either a 2.5- or a 4.0-cm contraceptive capsule that was worn under the skin of the upper arm for 1 year if not removed earlier for other reasons. MAIN OUTCOME MEASURES: Serum concentrations of levonorgestrel, progesterone, estradiol, and lipoproteins were measured as were metabolic parameters. Vaginal bleeding and other side effects were recorded. After implant removal, remaining levonorgestrel, capsule viscosity, and molecular weight were measured. RESULTS: The 4-cm implant provided serum concentrations of levonorgestrel ranging from 0.65 ng/mL shortly after insertion to 0.20 ng/mL at 12 months, but the 2.5-cm implant resulted in levels too low for contraception. The 4-cm implant suppressed ovulation in approximately 80% of cycles over 1 year of use, but the 2.5-cm implant failed to suppress ovulation. The implants were rapidly and easily inserted and removed. They retained structural integrity through 1 year of use. Of 48 subjects, 32 had abnormal bleeding patterns; the mean number of days of bleeding per month was 7 with 23 days between episodes. Women using capronor maintained normal metabolic parameters except that low-density lipoprotein decreased slightly. CONCLUSIONS: The 4.0-cm implant is a promising contraceptive. There were no important metabolic effects, but there were bothersome minor side effects typical of progestin-only contraception.

Innovations in contraception: the Norplant system.

The Norplant (Huhtamaki Oy/Leiras Pharmaceuticals, Turku, Finland) contraceptive system is a safe, highly effective, reversible method of hormonal contraception. The system consists of six flexible match-size implants that are implanted in the inner aspect of the upper arm. This sustained-release system delivers the progestin levonorgestrel at levels sufficient to prevent pregnancy for as long as 5 years. Norplant is a convenient, easy-to-use method. Adequate counseling of potential users and appropriate selection of patient users are important determinants of patient satisfaction with Norplant.

PIP: The Norplant implant is described: the release rates and serum levels of levonorgestrel, the mode of action, the indications and contraindications, the effectiveness, incidence of ectopic pregnancy related to Norplant use, metabolic effects, advantages and disadvantages, insertion, the role of counseling, and management of side effects (menstrual bleeding changes, headache, weight changes, mastalgia, and acne), continuation rates and reasons for termination, and removal. Norplant is currently the most effective method of contraception. Counseling is important in order to provide women with as much information for informed consent and to increase awareness and interest in Norplant. In a clinical trial in California, 95% expressed a high level of satisfaction upon implant removal and 71% desired Norplant again; 91% recommended Norplant to friends. 82% reported the side effect of menstrual change; 66% reported 2 or more side effects. Clinical development is ongoing for other sustained release contraceptives. Norplant was developed by the International Committee for Contraceptive Research of the Population Council, and manufactured by Huhtamaki Oy/Leiras Pharmaceuticals in Turku, Finland. Clinical trials have been conducted since 1975. 20 nations have approved its use, and more than 1.5 million women use it. Silastic rubber tubing encapsulates 6 capsules of 36 mg/capsule crystalline levonorgestrel, a strong progestin. Implantation is done just under the skin in a fan shape; levonorgestrel is released at 80 mcg/day for 6 months, and 30-35 mcg/day for the remainder of use. The mode of action is not completely understood, but the assumption is that it is similar to the progestin-only pills. The mechanisms that alter fertility are 1) the change in hypothalamic-pituitary level to inhibit midcycle luteinizing hormone surge, while follicle stimulating hormone and estradiol levels remain within the normal range, 2) the thickening of the cervical mucus which prevents the entry of sperm into the upper genital tract, and 3) the suppression of the estrogen-induced cyclical maturation of the endometrium. It is not an abortifacient. Contraindications are few, but include active thrombophlebitis, undiagnosed abnormal genital bleeding, known or suspected pregnancy, benign or malignant liver tumors, and known or suspected breast cancer of progestin-dependent neoplasms.

Prophylaxis in caesarean section with cefmetazole and cefoxitin.

A prospective, randomized, open comparison of three 1 g doses of cefmetazole with three 2 g doses of cefoxitin for non-elective Caesarean section was performed. Sixty-nine patients were evaluated. The two groups were comparable with respect to labour characteristics that might influence risk of postoperative infectious morbidity. Similarly, the nature of the bacterial contamination/infection of the amniotic fluid at the time of Caesarean section was comparable in the two groups. The only infectious morbidity noted was endomyometritis. The incidence was the same in both groups, 5/50 (10%) in the cefmetazole group and 2/19 (10.5%) in the cefoxitin group. Febrile morbidity, as reflected in the fever index, was not significantly different between the groups, 10.2 +/- 18.5 degree hours in the cefmetazole group and 7.5 +/- 11.7 degree hours in the cefoxitin group. Cefmetazole appeared to be equivalent to cefoxitin in reducing post-Caesarean section endomyometritis.