Delgado, G., & Davenport, M. L. (2012). Progesterone use to reverse the effects of mifepristone. The Annals of pharmacotherapy, 46(12), e36. https://doi.org/10.1345/aph.1R252
Delgado G, Davenport ML. Progesterone use to reverse the effects of mifepristone. Ann Pharmacother. 2012;46(12):e36. doi:10.1345/aph.1R252
Delgado, George, and Mary L. Davenport. "Progesterone use to reverse the effects of mifepristone." The Annals of pharmacotherapy, vol. 46, no. 12, 2012, pp. e36.
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Progesterone after mifepristone preceded 4 term births in 6 women
Four of 6 women who took mifepristone and then received progesterone delivered healthy term newborns. All six had asked for reversal. Physicians trained in NaProTECHNOLOGY gave the progesterone. None had taken misoprostol when progesterone began. This case series has no comparison group.
Key Findings
Six women who took mifepristone and then sought reversal received progesterone. A seventh patient was lost to follow-up.
Four of the 6 women delivered healthy term newborns. In those four, the authors noted no untoward effects of progesterone and no birth defects.
Two abortions occurred: one soon after the first progesterone dose, with incomplete data, and one in a woman whose live embryo was not documented.
No woman had taken misoprostol when progesterone began. In the four who delivered, the first progesterone dose came 30 to 72 hours after mifepristone, at 7 to 11 weeks of gestation.
A PubMed search from 1996 to May 2012 found no trials or case studies on progesterone to reverse mifepristone.
Interpretation
A case series reports what happened to a small group of women, here six who asked for reversal. With no comparison group, it cannot show that progesterone caused any pregnancy to continue. The authors name two possible confounders: mifepristone loses effect as gestational age rises, and some women had no documented viable pregnancy before taking it. The women chose reversal themselves. The authors call for clinical trials to find the best protocol.
RRM Context
The treating physicians trained in NaProTECHNOLOGY at the Pope Paul VI Institute. Their rationale is receptor biology: progesterone competes with mifepristone at the progesterone receptor. The paper cites FDA trials in which an ongoing living embryo after mifepristone ranged from less than 1% before 49 days to 9% at 57-63 days. Any reversal report sits against that background rate.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To present a series of cases demonstrating successful reversal of mifepristone effects in women who chose to reverse the medical abortion process.
Case Report
Four of 6 women who took mifepristone were able to carry their pregnancies to term after receiving intramuscular progesterone 200 mg.
Discussion
Mifepristone has been available in the US since 2000. By 2008, approximately 25% of abortions prior to 9 weeks were accomplished with mifepristone. Some women who take mifepristone wish to reverse the medical abortion process. Progesterone competes with mifepristone for the progesterone receptor and may reverse the effects of mifepristone. A PubMed literature search from 1996 to May 2012 did not reveal any trials or case studies evaluating the efficacy of progesterone use to reverse the effects of mifepristone.
Conclusions
Health care professionals should be aware of the possible use of progesterone to reverse mifepristone in women who have begun the medical abortion process by taking mifepristone and then change their minds.
Some women who take mifepristone, a progesterone receptor antagonist, in order to terminate their pregnancies, change their minds and desire to stop the medical abortion process. There are only two articles in the medical literature documenting the reversal of the effects of mifepristone.
We present and analyze a series of women who attempted to reverse the effects of mifepristone by taking supplemental progesterone to determine if the reversal of the effects mifepristone with progesterone is possible and safe. Additionally, we compare different progesterone regimens to determine relative efficacies.
This is an observational case series of 754 patients who decided to attempt to reverse the medical abortion process after taking mifepristone but before taking the second drug in the protocol, misoprostol. We followed the patients, who were given progesterone in an effort to reverse the effects of mifepristone, and conducted statistical analyses to determine the efficacies of different protocols compared to a control mifepristone embryo survival rate, derived from the literature.
Intramuscular progesterone and high dose oral progesterone were the most effective with reversal rates of 64% (P < 0.001) and 68% (P < 0.001), respectively. There was no apparent increased risk of birth defects. The reversal of the effects of mifepristone using progesterone is safe and effective.
Van der Meer YG et al., 1983·Journal of Psychosomatic Obstetrics & Gynecology
A double-blind cross-over placebo controlled trial was carried out to compare progesterone 200 mg with a placebo, both given in rectal suppositories, in 20 patients with the pre-menstrual syndrome (PMS). Each kind of suppository was used twice daily from mid-cycle to the onset of menstruation during two successive cycles. Six patients did not complete the trial. Daily scores for a number of psychological and somatic symptoms were recorded by the participants. Mean symptom scores in the last seven days of the pre-menstruum did not differ significantly between the two treatment periods. The participants did not express a significant preference for the progesterone therapy. Mean blood levels of FSH, oestradiol, prolactin and LH, determined on the first day of menstruation did not differ between the two periods of treatment. Side effects, in the form of electrolyte abnormalities or hepatic or renal function disturbances, were not seen. In this trial, progesterone 200 mg twice daily by the rectal route was not more effective than the placebo.
Progesterone supplementation reverses 83% of transcript changes in the secretory endometrium induced by postovulatory mifepristone, potentially mitigating its antiprogestogenic effects. Mifepristone (RU486) antagonizes progesterone signaling in human endometrium interfering in the secretory phenotype after estradiol priming. The objective of the present study was to determine effect in the endometrial transcript profile of progesterone supplementation after the administration of 200 mg of the antiprogestin mifepristone 48 h after the LH peak (LH+2, LH+0 = LH peak). Endometrial samples were obtained on LH+7 after vaginal administration of micronized progesterone 200 mg/day for 3 days in nine women of proven fertility, each one contributing with one cycle treated with progesterone and another with a placebo. In addition, endometrial samples were obtained in LH+7 from a subgroup of four women with no administration of mifepristone, with each one contributing with one cycle treated with vaginal progesterone supplementation or placebo as a reference. RNA-seq was used to identify transcripts significantly regulated under the administration of progesterone vs placebo with or without postovulatory mifepristone. We observed that 713 transcripts changed significantly in the endometrium under mifepristone after progesterone supplementation in group A. Of these, progesterone reversed approximately 83% of the transcripts affected by mifepristone in the secretory endometrium. Bioinformatic analyses revealed that these transcripts were enriched in genes associated with mitochondrial function, particularly oxidative phosphorylation. In addition, NR2C2 and DLX1 were identified as potential transcription factors that may mediate the effects of progesterone in the endometrium. We conclude that progesterone supplementation after postovulatory mifepristone administration can reverse the antiprogestogenic effects for most of the affected endometrial transcripts.
A study was designed to see if the use of prophylactic progesterone vaginal suppositories (PVS) reduced the risk of spontaneous abortions in women with a history of at least one spontaneous abortion. PVS was employed during the luteal phase to the end of the first trimester. The dosage was initially 50 mg/day, but was increased according to the endometrial biopsy and doubled as soon as pregnancy was established. Only 10 women (10%) aborted, and 8 of these 10 were successful in their next PVS-treated pregnancies. Overall there were 12 losses in 132 pregnancies (9%) in these PVS-treated patients. Forty-two percent of untreated controls aborted (10/24). The results suggest that PVS is effective in reducing the risk of spontaneous abortions in high-risk patients.
Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).
Therapeutics › Hormonal Agents › Progesterone and Progestins · Pregnancy › Early Pregnancy › Progesterone Support · Reproductive Endocrinology › Ovarian Hormones › Progesterone
Mary L Davenport, George Delgado
M Davenport, G Delgado
PMID 23191936 23191936 DOI 10.1345/aph.1R252 10.1345/aph.1R252 Delgado et al. 2012, Delgado 2012
Cite this article
Delgado, G., & Davenport, M. L. (2012). Progesterone use to reverse the effects of mifepristone. The Annals of pharmacotherapy, 46(12), e36. https://doi.org/10.1345/aph.1R252
Delgado G, Davenport ML. Progesterone use to reverse the effects of mifepristone. Ann Pharmacother. 2012;46(12):e36. doi:10.1345/aph.1R252
Delgado, George, and Mary L. Davenport. "Progesterone use to reverse the effects of mifepristone." The Annals of pharmacotherapy, vol. 46, no. 12, 2012, pp. e36.
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