Hormonal evaluation and midcycle detection of intrauterine glycodelin in women treated with levonorgestrel as in emergency contraception

Durand, Marjorie; Koistinen, Riitta; Chirinos, Mayel; Rodrı́guez, José Luis; Zambrano, Elena; Seppälä, Markku; Larrea, Fernando

doi:10.1016/j.contraception.2010.05.015

Cited by 18 publications

(23 citation statements)

References 21 publications

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“…The direct action of progesterone brings this protein to its highest expression during the human endometrial receptivity period (Taylor et al 2000). In women who took LNG as an emergency contraceptive 2 days before the LH surge, the concentration of PAEP in uterine flushes measured at LHC1 was significantly elevated when compared with control cycles (Durand et al 2010). This provides a possible new explanation of the contraceptive effect of LNG around the fertilization window, as it has also been reported that LNG can inhibit sperm-oocyte interaction.…”

Section: Discussionmentioning

confidence: 70%

Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium

Vargas¹,

Tapia-Pizarro²,

Henríquez³

et al. 2011

Journal of Molecular Endocrinology

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The hypothesis that levonorgestrel (LNG) used as an emergency contraceptive interferes with endometrial receptivity remains unproven. We compared the endometrial gene expression profile during the receptive period after administering a single dose of LNG 1 . 5 mg or placebo on day 1 of the luteal phase. An endometrial biopsy was done on day LHC7 or LHC8 and samples were taken from seven volunteers, each one contributing with one cycle treated with placebo and another with LNG. The expression of 20 383 genes was determined using cDNA microarrays. Real-time RT-PCR was used 1) to confirm the differences found in DNA microarray analysis and 2) to determine the effect of LNG on transcript levels of C3, C4BPa, COX2, MAOA, S100A4, and SERPINB9, known to be upregulated during receptivity, and on cPLA2a, JAK1, JNK1, CTSL1, and GSTP1, known to respond to mifepristone. Additional endometrial biopsies were done during the pre-receptive (LHC3) and receptive (LHC7) period and samples were taken from eight untreated volunteers in order to determine the changes associated with acquisition of receptivity of 14 genes. Mean levels of PAEP, TGM2, CLU, IGF2, and IL6ST mRNAs increased after administering LNG while those of HGD, SAT1, EVA1, LOC90133, ANXA1, SLC25A29, CYB5A, CRIP1, and SLC39A14 decreased. Except for the level of ANXA1 transcript, all changes remained within the range observed in untreated controls, and none of the transcripts responding to mifepristone changed in response to LNG. Post-ovulatory administration of LNG caused minimal changes in gene expression profiling during the receptive period. Neither the magnitude nor the nature or direction of the changes endorses the hypothesis that LNG interferes with endometrial receptivity.

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Section: Discussionmentioning

confidence: 70%

Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium

Vargas¹,

Tapia-Pizarro²,

Henríquez³

et al. 2011

Journal of Molecular Endocrinology

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“…Vegetables (leafy green vegetables and beetroot, in particular) 57, 61–64 are the main source of inorganic nitrate in the diet (>80%). Nitrate is also directly absorbed in the gastrointestinal tract (without requiring conversion to nitrite), with high bioavailability (>90%) 65 and circulates in plasma with a half-life of ~6–8 hours, in contrast to nitrite, which has a short half-life (~30–40 minutes).…”

Section: The Nitrate–nitrite–no Activation Pathwaymentioning

confidence: 99%

“…69, 70 Oral cavity commensal bacteria reduce nitrate to nitrite, which has a high oral bioavailability (>90%). 61, 63, 64 Nitrite present in the blood stream is reduced directly to NO, a reaction catalyzed by several molecules, particularly deoxygenated myoglobin, 36, 71–73 and deoxygenated hemoglobin, 74 but also xanthine oxidoreductase, 75 mitochondrial respiratory chain enzymes 76 , aldehyde oxidase 77 , carbonic anhydrase, 78 vitamin C 79 , polyphenols 80, 81 and even endothelial NO synthase. 82, 83 Importantly, the conversion of nitrite to NO occurs much more rapidly in the context of hypoxia 84 and acidosis.…”

Section: The Nitrate–nitrite–no Activation Pathwaymentioning

confidence: 99%

The Nitrate-Nitrite-NO Pathway and Its Implications for Heart Failure and Preserved Ejection Fraction

Chirinos

Zamani

2016

Curr Heart Fail Rep

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The pathogenesis of exercise intolerance in patients with heart failure and preserved ejection fraction (HFpEF) is likely multifactorial. In addition to cardiac abnormalities (diastolic dysfunction, abnormal contractile reserve, chronotropic incompetence), several peripheral abnormalities are likely to be involved. These include abnormal pulsatile hemodynamics, abnormal arterial vasodilatory responses to exercise, and abnormal peripheral O2 delivery, extraction and utilization. The nitrate-nitrite-NO pathway is emerging as a potential target to modify key physiologic abnormalities, including late systolic LV load from arterial wave reflections (which has deleterious short- and long-term consequences for the LV), arterial vasodilatory reserve, muscle O2 delivery, and skeletal muscle mitochondrial function. In a recently completed randomized trial, the administration of a single dose of exogenous inorganic nitrate has been shown exert various salutary arterial hemodynamic effects, ultimately leading to enhanced aerobic capacity in patients with HFpEF. These effects have the potential for both immediate improvements in exercise tolerance and for long-term “disease-modifying” effects. In this review, we provide an overview of key mechanistic contributors to exercise intolerance in HFpEF, and of the potential therapeutic role of drugs that target the nitrate-nitrite-NO pathway.

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“…Consistent with their 2001 paper, Durand et al found that LNG delivered before the LH surge had significant effects on key luteal function parameters needed for implantation of embryos. Reduced progesterone levels, shortened luteal phases, blunted LH levels, and impaired luteal phase endometrial expression of progesteronedependent glycodelin-A, were prominent findings of this serial research (Durand et al 2005(Durand et al , 2010. Three final studies suggest that LNG-EC alters luteal function with respect to shortened luteal phase and increased vaginal bleeding (Cheng et al 2008;Raymond et al 2006;Gainer et al 2006).…”

Section: Corpus Luteum Dysfunctionmentioning

confidence: 96%

“…The present review synthesizes the available recent literature with particular reference to the large phase III clinical study (Noéet al 2011). This study, together with the previous ones (Palomino, Kohen, and Devoto 2010;Durand et al 2010;Croxatto et al 2004;Durand et al 2001;Marions et al 2002;Marions et al 2004;Okewole et al 2007;Hapangama, Glasier, and Baird 2001;Massai et al 2007), enables for a direct modeling of the relationship between follicular size, the time to ovulation, and the effects of LNG-EC, as proposed by Mikolajczyk and Stanford (2007).…”

Section: Prevention Of Ovulationmentioning

confidence: 99%

Does Levonorgestrel Emergency Contraceptive have a Post-Fertilization Effect? A Review of its Mechanism of Action

Peck

Rella²,

Tudela

et al. 2016

Linacre Q

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Background: 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. Objective: 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. Conclusion: 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. Lay Summary: 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 preovulation, it may have a post-fertilization MOA.

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Hormonal evaluation and midcycle detection of intrauterine glycodelin in women treated with levonorgestrel as in emergency contraception

Cited by 18 publications

References 21 publications

Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium

Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium

The Nitrate-Nitrite-NO Pathway and Its Implications for Heart Failure and Preserved Ejection Fraction

Does Levonorgestrel Emergency Contraceptive have a Post-Fertilization Effect? A Review of its Mechanism of Action

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