Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial.

In a multicenter 1-year trial of contraceptive vaginal rings (rings) involving 150 women, three dose combinations of the progestin Nestorone (NES) and ethinylestradiol (EE) were compared with respect to effectiveness, safety and acceptability. Mean in vitro drug release rates for the three doses were 150 and 15, 150 and 20 and 200 and 15 microg/day of NES and EE, respectively. Each ring remained in situ for 21 days, removed for 7 days and then reinserted for a total of 13 cycles of use.

Nestorone: clinical applications for contraception and HRT.

The 19-nor derivatives of progesterone are referred to as "pure" progestational molecules as they bind almost exclusively to the progesterone receptor (PR) without interfering with receptors of other steroids. In this category is Nestorone, which has strong progestational activity and antiovulatory potency with no androgenic or estrogenic activity in vivo. These properties make it highly suitable for use in contraception and hormonal therapy (HT).

Estradiol-progesterone interaction during the preparation of vaginal rings.

An unexpected enhanced release, in vitro, of estradiol (E2) was observed on the preparation of vaginal rings containing E2 and progesterone (P) in a silicone elastomer. The present work deals with exploring the reason(s) behind this enhanced E2 release. The effect of the ring design (i.

Ovarian function during use of vaginal rings delivering three different doses of Nestorone.

Contraceptive vaginal rings delivering various progestins alone or in combination with estrogen have been previously studied, showing adequate steroid vaginal absorption and acceptability by the users. Nestorone progestin (NES) is a potent 19-nor-progesterone derivative, inactive by the oral route, but an excellent option for vaginal delivery. The purpose of this study was to evaluate ovarian function during 6 months of continuous use of progestin-only vaginal rings delivering 3 different doses of NES: 50, 75, and 100 microg per day.

Vaginal rings for contraception in lactating women.

Contraceptive methods for breastfeeding women should be safe for the mother and infant and should not interfere with lactation. Progestin-only methods meet these conditions and can be used from the sixth week postpartum. Because all progestins are excreted in milk, those that are insufficiently active by the oral route are preferable to avoid any possible effect on the baby.

Progestin-only contraceptive rings.

Several progestin-only long acting contraceptives are currently available in the form of implants or injectables. Vaginal rings are another contraceptive option in the final stages of development. These steroid-containing polymer rings are placed in the vagina, providing relatively constant drug release, thus allowing for lower effective doses.

A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol.

Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San Francisco, and Sydney. A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles. Serum estradiol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels were assayed twice weekly in all four treatment cycles.

Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring.

The study population included 159 women aged 18 to 37 years requiring contraception (60 in Sydney, 99 in Los Angeles). The design consisted of a 6 month study of a contraceptive vaginal ring (CVR) releasing 20 micrograms ethinyl estradiol and 1 mg of norethindrone acetate daily over two successive cycles with a new ring on each of three different insertion regimens. A total of 831 woman-months of exposure were recorded, and 129 women completed the study.

Contraceptives for lactating women: a comparative trial of a progesterone-releasing vaginal ring and the copper T 380A IUD.

From approximately one week before normal ovulation resumes, lactating women require protection against pregnancy by a contraceptive that is safe for both infant and mother in a multicenter one-year study, the natural hormone, progesterone, delivered vaginally by a sequence of four contraceptive rings designed for continuous use, was evaluated as a contraceptive for nursing mothers in comparison with the Copper T 380A IUD. Individual rings release in effective average dose of 10 mg day for a 3 month period. Evaluation included measures of lactational performance as well as of contraceptive efficacy and safety to mother and child.

Estradiol delivery by vaginal rings: potential for hormone replacement therapy.

Objectives: To determine if delivery of estradiol from elastomeric vaginal rings gives estradiol blood levels in the range associated with effective estrogen replacement therapy and to determine the relation between in vitro estradiol release from the rings and blood levels in vivo. Secondary objectives related to changes in lipoprotein cholesterol, changes in climacteric symptoms, and evaluation of acceptability to users.

Methods: Three ring variants releasing approximately 100, 150 and 200 micrograms/day of estradiol in vitro were used through 22 days in 21 postmenopausal women, 7 on each dose levels.

Dose-finding study of a contraceptive ring releasing norethindrone acetate/ethinyl estradiol.

A core design contraceptive vaginal ring (CVR) with average daily release of 650 mcg of norethindrone acetate (NA) and 30 mcg of ethinyl estradiol (EE) inhibited ovulation and controlled vaginal bleeding well, but caused some nausea. This study was designed to minimally alter the dose of steroid to see if nausea could be reduced without loss of contraceptive efficacy. This 30/650 CVR was compared to a CVR releasing 20 mcg of EE and 1000 mcg of NA (20/1000) and another releasing 25 mcg of EE and 650 mcg of NA (25/650) in 69 subjects.

A contraceptive vaginal ring releasing norethindrone acetate and ethinyl estradiol.

A core design contraceptive vaginal ring (CVR) releasing 650 mcg of norethindrone acetate (NA) and 10, 20, 30 or 65 mcg of ethinyl estradiol (EE) daily was developed and tested in 99 women. The CVR inhibited ovulation well with 30 or 65 mcg EE. Vaginal bleeding was better controlled than in 23 control women using NA/EE oral contraceptives.

Evaluation of four different contraceptive vaginal rings: steroid serum levels, luteal activity, bleeding control and lipid profiles.

Four different models of contraceptive vaginal rings were tested during three cycles for luteal activity, bleeding control, plasma lipoproteins and serum levels of the contraceptive steroids. Two progestins, levonorgestrel acetate (LNGA) and ST 1435, alone or in combination with ethynyl-estradiol (EE) were tested. The rings released 100 ug/day of the progestins and 30 ug/day of EE.

Contraception in hypertensive women using a vaginal ring delivering estradiol and levonorgestrel.

Contraception with a vaginal ring (CVR) that delivers estradiol and levonorgestrel was used during a mean of 15.6 menstrual cycles in 12 hypertensive women. Blood pressure (BP) was measured 5 times on each visit during 2 pretreatment control cycles; during the 1st, 2nd, 4th, 6th, and from the 9th to 12th cycles of CVR use; and again after a 1-month recovery period.

Measurement of ethynylestradiol and levonorgestrel incorporated into sustained release contraceptive formulations.

High performance liquid chromatography was used to measure the concentrations of ethynylestradiol (EE) and levonorgestrel (LNG) released from contraceptive devices into aqueous medium containing the cationic detergent, benzalkonium chloride. Most of the detergent was removed after solvent extraction of the steroid, although small amounts of it remained in the steroid phase. Over the course of many injections into octasilyl (C8) or octadecylsilyl (C18) reversed-phase columns, the chromatographic profile of EE was gradually altered with multiple peaks emerging.

Fertility regulation in nursing women: VIII. Progesterone plasma levels and contraceptive efficacy of a progesterone-releasing vaginal ring.

The objectives of this trial were to test the contraceptive efficacy and measure progesterone plasma levels of women using progesterone-releasing rings during lactation. Two types of rings delivering an average of about 5 mg or 10 mg of progesterone per day were tested in 128 healthy nursing women. A control group was formed by 127 Copper T users.

Ovarian function, bleeding control and serum lipoproteins in women using contraceptive vaginal rings releasing five different progestins.

Ovarian function, bleeding patterns and serum lipoproteins were studied in women using contraceptive vaginal rings (CVRs) of dimethyl-polysiloxane impregnated with steroids. The different CVRs were used for about 10 cycles each. The following groups were studied, with the daily steroid dosage given in parentheses.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. III-Menstrual patterns. An international comparative trial.

Menstrual events among users of contraceptive vaginal rings (CVRs), releasing levonorgestrel and estradiol, were studied in comparison with a combined oral contraceptive, Nordette, in multicentered trials. CVRs were made with outside diameters of 50 and 58 mm and released about 250 micrograms and 290 microgram of levonorgestrel and 150 microgram and 180 microgram of estradiol per day, respectively. The CVRs were used continuously for 3 weeks and then removed for 1 week.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II-Subjective and objective measures of effects. An international comparative trial.

Comparative clinical trials of 2 sizes of contraceptive vaginal rings and of an oral contraceptive were undertaken at 8 investigational sites (9 clinics). More than 500 women enrolled on each of the 3 study regimens. Side effects of the rings and of Nordette, the oral contraceptive, were evaluated by noting spontaneous complaints, by recording medications taken and by physical examination.

Vaginal progesterone for contraception.

Silastic vaginal rings impregnated with progesterone (P) or progesterone and estradiol (E) were used in nine women for thirty 21-day cycles to study the effect on ovarian function. The average daily rates of release of P and E from the rings were 2.2 mg/day and 220 microgram/day, respectively.

Release of contraceptive steroids from sustained release dosage forms and resulting plasma levels.

The correlations of plasma levels of levonorgestrel, megestrol acetate and norgestrienone with the doses delivered from subdermal implants and contraceptive rings have been examined. Differences in plasma levels as large as three-fold between different subjects receiving nearly identical doses were observed with all three steroids. The relative plasma levels seen from one subject to another showed high consistency over time.