Two-year performance of a Nestorone-releasing contraceptive implant: a three-center study of 300 women.
ABSTRACT A 2-year trial of a single Nestorone (NES) rod implant was conducted at three Latin American centers, each enrolling 100 women. We studied the safety, effectiveness and acceptability of this progestin-releasing contraceptive implant. Three pregnancies occurred, the last at 18 months of use. Because no pregnancies were expected in the first 18 months, the trial was halted. At that time, 224 women had completed at least 18 months of use, and 99 women had used the implant for more than 24 months. Few participants used adjunctive contraception between the time the study was halted and the time they had their implant removed. No additional pregnancies occurred before the removal of the last implant. The 2-year cumulative pregnancy rate was 1.7 per 100 with a Pearl index of 0.6 per 100 for the 2-year period. The 1-year and 2-year continuation rates were 80.5 and 66.7 per 100, respectively. Menstrual and medical disturbances were the principal reasons for discontinuation, followed by planned pregnancy. Headache and weight gain frequently led to discontinuation. The NES implant had little important effect on most clinical chemistry and lipid parameters. Over the study course, the mean change in hemoglobin was <1%. Slight modification of the design of this single 2-year implant, restoring features previously examined in clinical trials, is likely to improve its effectiveness. A single NES implant appears to provide acceptable contraception for women.
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ABSTRACT: The relationship between ovarian hormones and bleeding patterns during continuous progestin contraception was studied in 29 women who used Nestorone (NES) releasing implants. Oestradiol and progesterone were measured in blood samples taken twice a week for 6 consecutive weeks, during months 6, 12, 18 and 24 of implant use. Retrospectively, the association between hormonal concentrations and bleeding patterns was evaluated. Twenty-four short (</= 24 days), 36 normal (25-35 days), 27 long (36-90 days) and nine episodes of amenorrhoea, as well as 28 periods of prolonged bleeding, were identified. Short cycles, periods of prolonged bleeding and amenorrhoea were characterized by low oestradiol concentrations. Bleeding after a normal or long cycle regularly occurred after a rise and fall of oestradiol or oestradiol and progesterone. The duration of bleeding was directly and significantly associated with the highest concentration of oestradiol in the previous 15 days in anovulatory cycles. Luteal activity was associated with shorter duration of bleeding. Periods of prolonged bleeding were usually initiated with a drop in oestradiol and over half ended with an increase in oestradiol. It was concluded that changes in endogenous hormone have a significant influence over the bleeding pattern during use of NES implants.Human Reproduction 12/1999; 14(12):3013-7. · 4.67 Impact Factor
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ABSTRACT: Development of contraceptive implant methods, when based on established or on new synthetic chemical entities, is a decadal or multi-decadal process. The process often requires the cooperation of numerous investigators for laboratory work, for early Phase II trials, for dose-finding trials, and for Phase III clinical trials. The Phase III work also requires cooperation with a commercial manufacturer and potential distributor of the product. The Population Council has recently completed developmental work on two levonorgestrel-releasing implants, with filings to regulatory agencies that support extended use of Jadelle implants for 5 years and Norplant implants for 7 years. When the developmental process includes establishing the clinical properties of a molecule not yet approved by regulatory agencies, the minimum development time appears to be two decades. The status and rationale of studies of a new Nestorone-releasing, single implant developed by the Population Council for a period of use of 2 years are presented.Contraception 02/2002; 65(1):113-9. · 3.09 Impact Factor
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ABSTRACT: The concept of transdermal delivery (TD) for steroid application has nowadays been largely accepted for hormone replacement therapy in the menopause. It is only recently that the same concept has been envisaged for contraception. The skin can be penetrated by both estrogens and progestins, provided they are delivered in an appropriate solvent. About 10% of the total dose applied topically is actually absorbed. The transdermal delivery systems (TDS) presently available are either of the reservoir type (membrane-moderated system) or of the matrix dispersion type where the drug is dispersed into a polymer matrix. Estradiol (E2) is the most appropriate steroid for TD and can be combined with progestins to ensure a contraceptive effect. Only potent progestins should be used to achieve effective plasma levels with low doses in order to maintain an acceptable small surface of TDS. TDS changed weekly and delivering both E2 and levonorgestrel (L-NG) at daily dosages of 38.4 (+/- 7.5) and 28.8 (+/- 7.2) micrograms/10 cm2 per day respectively, showed ovulation suppression. Another progestin derived from norprogesterone (ST 1435) has been shown to penetrate the skin when suspended in acetylated lanolin or dissolved in a hydroalcoholic gel and to ensure ovulation suppression at a dose of 2 mg per day in a small number of cycles. These preliminary data demonstrate the feasibility of suppressing ovulation in women by transdermal absorption of steroids. Using TDS for contraception implies that such systems should be perfectly adhesive, well tolerated locally and achieve nearly 100% efficacy. These targets are very challenging, however, the potential advantages are so high that the concept deserves further development.The Journal of Steroid Biochemistry and Molecular Biology 07/1995; 53(1-6):247-51. · 3.98 Impact Factor