Schneider, A. P., Kubat, C., & Zainer, C. M. (2016). Appreciation for analysis of how levonorgestrel works and reservations with the use of meloxicam as emergency contraception. The Linacre Quarterly, 83(1), 52-68. https://doi.org/10.1080/00243639.2016.1145894
Schneider AP, Kubat C, Zainer CM. Appreciation for analysis of how levonorgestrel works and reservations with the use of meloxicam as emergency contraception. Linacre Q. 2016;83(1):52-68. doi:10.1080/00243639.2016.1145894
Schneider, Andrew Patrick, et al. "Appreciation for analysis of how levonorgestrel works and reservations with the use of meloxicam as emergency contraception." The Linacre Quarterly, vol. 83, no. 1, 2016, pp. 52-68.
Authors object to meloxicam as emergency contraception after assault
The authors argue that meloxicam as emergency contraception puts the embryo at risk, replying to a 2014 review. In one study of 87 women, about 7 out of 10 ovulated after taking levonorgestrel in the five days before ovulation. No pregnancy occurred among 13 expected. The paper is a commentary with no new data.
Key Findings
In the Durand study of 45 sterilized women, 12 of 15 (80%) given levonorgestrel early in the cycle did not ovulate. All 30 women dosed later ovulated.
In the Noé study, 62 of 87 women who took levonorgestrel on days -5 to -1 ovulated (71%). Thirteen pregnancies were expected among the 87 women, and none occurred.
From the Novikova report of 99 women, the authors calculate that at most 3.7 percent of prevented pregnancies could come from blocked ovulation. The same calculation puts other mechanisms at 96.3 percent.
In macaques, 6.5 percent of meloxicam-treated females became pregnant against 33.3 percent of controls, an 80 percent calculated efficacy. The macaque authors conclude ovulation typically still occurs.
Interpretation
The paper is a reply commentary. The authors recalculate from other groups' published tables and reason from animal and pharmacology literature. The authors run no trial and pool no data. Several figures are their own derivations, such as the 3.7 and 96.3 percent shares. The meloxicam findings come from macaques, cattle and mice. The authors also argue from Catholic teaching on embryo protection, a moral premise the data cannot test.
RRM Context
The authors stress ovulation timing throughout their analysis. They cite a study in which only 23 percent of women in the peri-ovulatory phase named their cycle stage correctly. Fertility awareness-based methods record fertile-window signs day by day. The authors also separate levonorgestrel, a progestin, from progesterone, the body's own hormone.
Our editorial summary of this paper, not the article's abstract.
Abstract
This paper is a response to Dr. Kathleen Raviele's recent article on her critical analysis of the use of levonorgestrel given to women postsexual assault and her suggestion that the use of Meloxicam may be an ethical alternative.
To assess the possibility of a postfertilization effect in regard to the most common types of hormonal emergency contraception (EC) used in the US and to explore the ethical impact of this possibility. DATA A MEDLINE search (1966-November 2001) was done to identify all pertinent English-language journal articles. A review of reference sections of the major review articles was performed to identify additional articles. Search terms included emergency contraception, postcoital contraception, postfertilization effect, Yuzpe regimen, levonorgestrel, mechanism of action, Plan B. The 2 most common types of hormonal EC used in the US are the Yuzpe regimen (high-dose ethinyl estradiol with high-dose levonorgestrel) and Plan B (high-dose levonorgestrel alone). Although both methods sometimes stop ovulation, they may also act by reducing the probability of implantation, due to their adverse effect on the endometrium (a postfertilization effect). The available evidence for a postfertilization effect is moderately strong, whether hormonal EC is used in the preovulatory, ovulatory, or postovulatory phase of the menstrual cycle. Based on the present theoretical and empirical evidence, both the Yuzpe regimen and Plan B likely act at times by causing a postfertilization effect, regardless of when in the menstrual cycle they are used. These findings have potential implications in such areas as informed consent, emergency department protocols, and conscience clauses.
To model the effectiveness that can be obtained if levonorgestrel-only emergency contraception (EC) acts only through disrupting ovulation, in relation to other effects that may occur before or after fertilization and accounting for delays in administration. We modeled follicular growth as a function of follicular size, using known day-specific probabilities of conception and known disruption of ovulation by levonorgestrel-only EC, to estimate the expected effectiveness of EC. Combined data from multiple clinical studies. PATIENT(S): Simulation models. INTERVENTION(S): Disruption of ovulation. MAIN OUTCOME MEASURE(S): Effectiveness in the form of proportion of pregnancies prevented. RESULT(S): With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay). CONCLUSION(S): The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects. Additional data with follicular ultrasound and precise measures of delay between intercourse and EC administration would yield greater insight into effectiveness and mechanisms of action.
Peck R et al., 2016·Linacre Q·Free full text on PubMed Central
Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function. The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects. The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect. Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug's mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA.
Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation. Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined. Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data. These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.
Reproductive Endocrinology › Ovarian Hormones › Progesterone · Ethics and Policy › Reproductive Ethics › Embryo Status · Therapeutics › Hormonal Agents › Progesterone and Progestins
Christine M Zainer
Chris Zainer, C Zainer
PMID 27833182 27833182 DOI 10.1080/00243639.2016.1145894 10.1080/00243639.2016.1145894 Schneider 2nd et al. 2016, Schneider 2nd 2016
Cite this article
Schneider, A. P., Kubat, C., & Zainer, C. M. (2016). Appreciation for analysis of how levonorgestrel works and reservations with the use of meloxicam as emergency contraception. The Linacre Quarterly, 83(1), 52-68. https://doi.org/10.1080/00243639.2016.1145894
Schneider AP, Kubat C, Zainer CM. Appreciation for analysis of how levonorgestrel works and reservations with the use of meloxicam as emergency contraception. Linacre Q. 2016;83(1):52-68. doi:10.1080/00243639.2016.1145894
Schneider, Andrew Patrick, et al. "Appreciation for analysis of how levonorgestrel works and reservations with the use of meloxicam as emergency contraception." The Linacre Quarterly, vol. 83, no. 1, 2016, pp. 52-68.
Keywords
Abortifacient, Breakthrough Ovulation, Medically Induced Abortions, Mobic for Women, NSAID, Progesterone, Prostaglandins, The Use of Meloxicam Post Sexual Assault, The Use of Levonorgestrel Post Sexual Assault
