title: Feasibility study of Nestorone-ethinylestradiol vaginal contraceptive ring for emergency contraception.
abstract: OBJECTIVE
  The Nestorone/ethinylestradiol (NES/EE) vaginal ring is being developed as a regular contraceptive method by the Population Council. This ring is designed to release NES 150 microg/day and EE 15 microg/day during 1 year. Here, we report a Phase I clinical trial to determine the usefulness of this ring for emergency contraception. To that end, we tested the ability of this ring to interfere with ovulation when it is inserted during the follicular phase.
  
  
  METHODS
  Forty-eight women protected from the risk of pregnancy by nonhormonal methods were divided into three groups, which differed by the size of the dominant follicle at the time of ring insertion: 12-14 mm (n = 16), 15-17 mm (n = 18) and >or=18 mm (n = 14) diameter. The NES/EE ring was left in the vagina for 7 consecutive days, after which it was removed. The growth of the leading follicle and plasma levels of estradiol, progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the ensuing 5 days after ring insertion were determined. Afterwards, steroid hormones were measured twice a week, until menses took place. All women had a control cycle before the ring cycle, and the range of maximum follicular diameter assigned to each volunteer was the same for the control and the ring cycle at the time when placebo was ingested or the ring inserted.
  
  
  RESULTS
  During the 5-day period after ring insertion with follicles 12-17 mm, ovulation was absent in 25 of 34 cycles (p < .01 vs. control), and ovulatory dysfunction (absent, blunted or mistimed LH peak) occurred in 8 of the 9 remaining cycles (33/34 ovulatory processes altered; p < .005 vs. control). After ring insertion with follicles >or=18 mm in diameter, ovulation did not occur in 2 of 14 cycles or was dysfunctional in 7 of the 12 remaining cycles (9/14 ovulatory processes altered; p<.025 vs. control). Altogether, 87.5% of ring cycles (42/48) had either no ovulation or ovulatory dysfunction in the 5-day study period, in contrast to 39.6% (19/48 cycles) in control cycles (p < .001). Among follicles that failed to rupture within the 5-day study period, none ruptured later on in the ring-treated cycles, while 9 of 16 did so in control cycles. Sixty-two percent of ring-treated cycles were shorter than 24 days. Nausea, vaginal discharge and abdominal pain were the most frequently reported adverse events during ring use.
  
  
  CONCLUSIONS
  Interference with 87.5% of ovulatory processes, without ovulation occurring later in the cycle and shortening of cycle length, suggests the NES/EE ring may be used as an emergency contraceptive method, with the potential advantage of providing continuing contraception after it has performed its emergency function.
authors.affiliation: Instituto Chileno de Medicina Reproductiva, Jose Ramon Gutierrez 295, Apt 3, Santiago, Chile. hcroxatto@icmer.org
authors.forename: Horatio B
authors.initials: HB
authors.lastname: Croxatto
authors.forename: Vivian
authors.initials: V
authors.lastname: Brache
authors.forename: Rebecca
authors.initials: R
authors.lastname: Massai
authors.forename: Francisco
authors.initials: F
authors.lastname: Alvarez
authors.forename: M L
authors.initials: ML
authors.lastname: Forcelledo
authors.forename: Margarita
authors.initials: M
authors.lastname: Pavez
authors.forename: Leila
authors.initials: L
authors.lastname: Cochon
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Salvatierra
authors.forename: Aníbal
authors.initials: A
authors.lastname: Faundes
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D044363:Contraception, Postcoital / Q000379:methods*; D004958:Estradiol / Q000097:blood; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle; D009653:Norprogesterones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006080:Ovarian Follicle / Q000000981:diagnostic imaging; D010060:Ovulation; D011374:Progesterone / Q000097:blood; D014463:Ultrasonography; D014592:Uterine Hemorrhage / Q000453:epidemiology
chemical_list: D009653:Norprogesterones; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; C029167:ST 1435; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone