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 ��g/day and EE 15 ��g/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.
Method
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 ���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 ���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.
Conclusion
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.
Keywords
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Article info
Publication history
Published online: November 15, 2005
Accepted:
June 17,
2005
Received in revised form:
May 5,
2005
Received:
August 2,
2004
Identification
Copyright
© 2006 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
