EVALUATION OF 4 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. Luteal activity was detected among users of the progestin-only rings: 4 of 8 cycles with ST 1435 and 2 of 10 with LNGA. Only one of the 18 cycles studied with the two combined rings showed luteal activity, but the measurement of contraceptive steroid in plasma suggested that this subject delayed reinsertion of the ring for about one week in that particular cycle. Breakthough bleeding was observed in 12 of 30 cycles of use of the progestin-only rings, and in only 2 of 27 cycles with the combined models. No significant changes in total cholesterol or its HDL-fraction were observed. However, the only reduction observed in HDL-cholesterol was among users of the LNGA-only ring. It is concluded that the two combined CVR models offer good possibilities of high effectiveness and bleeding control and merit further development.46438739

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. Luteal activity was detected among users of the progestin-only rings: 4 of 8 cycles with ST 1435 and 2 of 10 with LNGA. Only one of the 18 cycles studied with the two combined rings showed luteal activity, but the measurement of contraceptive steroid in plasma suggested that this subject delayed reinsertion of the ring for about one week in that particular cycle. Breakthough bleeding was observed in 12 of 30 cycles of use of the progestin-only rings, and in only 2 of 27 cycles with the combined models. No significant changes in total cholesterol or its HDL-fraction were observed. However, the only reduction observed in HDL-cholesterol was among users of the LNGA-only ring. It is concluded that the two combined CVR models offer good possibilities of high effectiveness and bleeding control and merit further development. © 1992.464387398Mishell, Talas, Parlow, Moyer, Contraception by means of a Silastic vaginal ring impregnated with medroxyprogesterone acetate (1970) Am J Obstet Gynecol, 107, pp. 100-107World Health Organization's Special Programme Of Research, Development, Research Training in Human Reproduction, Task Force on Long-Acting Systemic Agents for Fertility Regulation, Microdose intravaginal levonorgestrel contraception: a multicentred clinical trial. I. Efficacy and side effects (1990) Contraception, 41, pp. 105-124Mishell, Jr., Moore, Roy, Brenner, Page, Clinical performance and endocrine profiles with contraceptive vaginal rings containing a combination of estradiol and d-norgestrel (1978) Am J Obstet Gynecol, 130, pp. 55-62Sivin, Mishell, Jr., Victor, Diaz, A multi-center study of levonorgestrel-estradiol contraceptive vaginal rings. I — Use effectiveness. An International comparative trial (1981) Contraception, 24, pp. 341-358Faundes, Hardy, Reyes, Pastene, Portes-Carrasco, Acceptability of the contraceptive vaginal ring by rural and urban populations in two Latin American countries (1981) Contraception, 24, pp. 394-414Roy, Krauss, Mishell, Casagrande, Pike, The effect on lipids and lipoproteins of a contraceptive vaginal ring containing levonorgestrel and estradiol (1981) Contraception, 24, pp. 429-449Ahren, Lithell, Victor, Vessby, Johansson, Comparison of the metabolic effects of two hormonal contraceptive methods: an oral formulation and a vaginal ring. II. Serum lipoproteins and apolipoproteins (1981) Contraception, 24, pp. 451-468Roumen, Dieben, Assendorp, Bouckaert, The clinical acceptability of a non-medicated vaginal ring (1990) Contraception, 42, pp. 201-207Lahteenmaki, Hammond, Luukkainen, Serum non-protein bound percentage and distribution of the progestin ST 1435: No effect of ST 1435 on plasma SHBG and CBG binding capacities (1983) Acta Endocrinol, 102, pp. 307-313Lahteenmaki, Weiner, Lahteenmaki, Johansson, Luukkainen, Contraception with subcutaneous capsules containing ST 1435, pituitary and ovarian function and plasma levels of ST 1435 (1981) Contraception, 23, pp. 63-75Weiner, Johansson, Plasma levels of d-norgestrel, estradiol and progesterone during treatment with silastic implants containing d-norgestrel (1978) Contraception, 18, pp. 335-353Nilsson, Nygren, Ethynil estradiol in peripheral plasma after oral administration of 30 ug and 50 ug to women (1978) Contraception, 18, pp. 469-475Rosner, A simplified method for the quantitative determination of testosterone-estradiol binding globulin activity in human plasma (1972) J Clin Endocrinol Metab, 34, pp. 983-988Odlind, Elamsson, Englund, Victor, Johansson, Effects of estradiol on sex hormone binding globulin (1982) Acta Endocrinol, 101, pp. 248-253Edqvist, Johansson, Radioimmunoassay of oestrone and oestradiol in human and bovine peripheral plasma (1972) Acta Endocrinol (Copenh), 71, pp. 716-730Thorneycroft, Stone, Radioimmunoassay of serum progesterone in women receiving oral contraceptive steroids (1972) Contraception, 5, pp. 129-146Coutinho, Da Silva, Carreira, Sivin, Long-term contraception with a single implant of the progestin ST 1435 (1981) Fertil Steril, 36, pp. 737-740Laurikka-Routti, Haukkamaa, Heikinheimo, A contraceptive vaginal ring releasing ethynil estradiol and the progestin ST 1435: bleeding control, serum steroid concentrations, serum lipids and serum chemistry (1990) Contraception, 42, pp. 111-11

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). Due to its high potency, very low doses of Nestorone may be delivered via long-term sustained-release delivery systems. Nestorone, 75 or 100μg per day, released by vaginal ring has suppressed ovulation in women, with inhibition of follicular maturation. A vaginal ring releasing both 150μg of Nestorone and 15μg of ethinyl estradiol per day has effectively suppressed ovulation for 13 consecutive cycles. Nestorone has also been used effectively in a single implant for contraception in breastfeeding women and shows promise for use in transdermal systems as a contraceptive or for HT when combined with estrogen

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.e., putting P and E2 in the same compartment or in adjacent or separate compartments) was studied. The effects of the curing temperature as well as the curing time were also investigated. The possible interaction(s) between P and E2 on simple heating of their mixtures was investigated using infrared (IR), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) techniques. Also, the dissolution behavior of P, E2, and their mixture before and after heating was studied. The ring design, with respect to the position of the steroid layer(s), affected the release of P and E2 from the vaginal rings. Curing the rings at higher temperatures (≥140°C) for ≥30 min resulted in an enhanced release of the steroids, especially E2. The IR, DSC, phase diagram, and NMR results indicate that an interaction between P and E2, leading to the formation of a molecular complex, took place. It was concluded that putting P and E2 in the same compartment and curing by heating at a high temperature and for an extended time promoted this kind of interaction. The greater hydrophobicity of the interaction product, relative to that of E2, was considered the main reason behind the enhanced in vitro release of E2 from the vaginal rings