The hormonal and peripheral effects of -norgestrel in postcoital contraception

Kesseru, E; Garmendia, Fausto; Westphal, Norbert; Parada, J

doi:10.1016/0010-7824(74)90041-9

Cited by 96 publications

(38 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This dose was effective in modifying cervical mucus, intrauterine pH and intrauterine sperm recovery within 4 h of administration; these local effects may contribute to the efficacy of LNG for EC [41]. Therefore, another possible mechanism of action that should be explored with the CARRA/LNG gel is the effect that LNG may have on sperm migration through cervical mucus [41][42][43][44].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception

et al. 2007

View full text Add to dashboard Cite

Objective: The study was conducted to assess levonorgestrel (LNG) serum levels achieved after a single administration of two different doses of Carraguard vaginal gel containing LNG (CARRA/ LNG), designed for use as microbicide and contraceptive for potential dual-protection. Materials and methods:This was a randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled at two centers. Each subject received a single vaginal administration of CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on day 10-12 of the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h after administration and for the following seven days. LH and progesterone (for a preliminary evaluation of effect on the ovarian function) as well as SHBG were measured in the daily samples.Results: Serum LNG maximum concentrations (C max ) were 14.1 ± 5.1 and 11.7 ± 6.5 nmol/L and T max was 12.0 and 6.0 h for the low and high dose, respectively, with large intersubject variability within the first 48 h. Mean levels at 96 h were 10% of C max . Differences in AUC between both doses were not statistically significant. SHBG levels decreased approximately 25% by day 4 after administration. Luteal activity was observed in 3/6 and 5/6 of the subjects in the low and high dose group, respectively. Conclusion:This study demonstrates that the CARRA/LNG gel can sustain elevated serum levels of the contraceptive steroid for up to 96 h after a single application. The serum levels attained with the 0.75 mg formulation are in the range expected to perturb the ovulatory process as observed in some subjects. The lack of correlation between the administered dose and serum concentrations of the steroid may be related to a rate-limiting absorption of LNG from the vaginal mucosa. The results reported here suggest that the CARRA/LNG formulation has good potential to become a dualprotection method, possibly preventing conception and sexually transmitted infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Kesseru et al reported that, following LNG administration, there is a reduction in the number of sperm recovered from the uterine cavity beginning 3 h after treatment, a pronounced alkalization (capable of immobilizing sperm) of the uterine fluid starting at 5 h and an increased viscosity of the cervical mucus beginning at 9 h, blocking further sperm passage [16].…”

Section: Mechanism Of Actionmentioning

confidence: 98%

Emergency contraception: presently available formulations and controversies surrounding their use

Bastianelli

Farris

2011

Expert Review of Obstetrics & Gynecology

View full text Add to dashboard Cite

Emergency contraception, or postcoital contraception, is a modality of preventing pregnancy after unprotected sexual intercourse or to avert potential contraceptive failure. The controversy revolves around the definitions of pregnancy and induced abortion. If one utilizes the medical definition accepted by the WHO, pregnancy only begins with implantation; therefore, there can be no abortion without a pregnancy and emergency contraception can in no way be equated to an abortion. The problem is that -ethically at least -there is a contention that a new human life begins right after the fertilization process is completed through full syngamy. Thus, using these parameters, it becomes vital to ascertain exactly the mechanism of action of postcoital methods. Emergency contraception exists in two different forms: the hormonal and the intrauterine. Hormonal emergency contraception was first proposed by Yuspe in the form of 100 µg ethynyl oestradiol plus 500 µg levonorgestrel taken twice at a 12-h interval. At the end of the 1900s, a second regimen -consisting of 1500 µg of levonorgestrel, within 12 h -was introduced and found in clinical trials to be more effective than the Yuspe regimen, if taken as early as possible after an unprotected intercourse. This method therefore completely replaced the Yuspe regimen in common use. Over the last 20 years, the WHO has developed a third regimen based on the use of the selective progesterone receptor modulator mifepristone; different dosages have been tested: >50, 50-25 and <10 mg, taken as a single dose, and they have been found to be equally effective, although the incidence of a delayed onset of the subsequent cycle increases with higher dosages. Two clinical studies have now compared the levonorgestrel and the mifepristone regimens; the first, conducted by WHO, compared three options: levonorgestrel, given either twice at the dose of 750 µg, or as a single 1.5-mg dose, and mifepristone, at a single dose of 10 mg. The second compared levonorgestrel (750 µg, twice) with mifepristone (10 mg, single dose). Both studies concluded that all regimens possess similar effectiveness. Recently, a new formulation consisting of a new selective progesterone receptor modulator, ulipristal acetate, has been licensed in several European countries and in the USA. At the single dose of 30 mg it shown to be a more potent inhibitor of ovulation than levonogestrel and can be effectively taken until 120 h after unprotected intercourse.

show abstract

“…Several studies have documented that sperm can be retrieved from the fallopian tubes within 5 minutes to 2 hours after insemination of semen in the vagina (Kesseru et al 1974;Kunz et al 1996;Settlage, Motoshima, and Tredway 1973;Ahlgren 1975). Kunz et al note that spermatozoa are directed preferentially into the tube ipsilateral to the dominant follicle, thereby suggesting that there will be a preferential accumulation at the site of fertilization (Kunz et al 1996).…”

Section: Cervical Mucus Effects Sperm Transport and Capacity To Fermentioning

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

View full text Add to dashboard Cite

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.

show abstract

The hormonal and peripheral effects of -norgestrel in postcoital contraception

Cited by 96 publications

References 14 publications

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception

Emergency contraception: presently available formulations and controversies surrounding their use

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

Contact Info

Product

Resources

About