Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle

Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14000, Mexico.
Contraception (Impact Factor: 2.34). 07/2005; 71(6):451-7. DOI: 10.1016/j.contraception.2005.01.003
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This study examined serum glycodelin concentrations and endometrial expression during the luteal phase following oral administration of levonorgestrel (LNG) at different stages of the ovarian cycle. Thirty women were recruited and allocated into three groups. All groups were studied during two consecutive cycles, a control cycle and the treatment cycle. In the treatment cycle, each woman received two doses of 0.75 mg LNG taken 12 h apart on days 3-4 before the luteinizing hormone (LH) surge (Group 1), at the time of LH rise (Group 2) and 48 h after the rise in LH was detected (Group 3). Serum progesterone (P) and glycodelin were measured daily during the luteal phase, and an endometrial biopsy was taken at day LH +9 for immunohistochemical glycodelin-A staining. In Group 1, serum P levels were significantly lower, serum glycodelin levels rose earlier and endometrial glycodelin-A expression was weaker than in Groups 2 and 3, in which no differences were found between control and treatment cycles. Levonorgestrel taken for emergency contraception (EC) prior to the LH surge alters the luteal phase secretory pattern of glycodelin in serum and endometrium. Based on the potent gamete adhesion inhibitory activity of glycodelin-A, the results may account for the action of LNG in EC in those women who take LNG before the LH surge.

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Available from: María Del Carmen Cravioto, Sep 28, 2014
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    • "Durand M et al. [34] analyzed endometrial expression and serum glycodelin concentrations during the luteal phase following oral levonorgestrel at various stages of the ovarian cycle. All the participants were studied during two consecutive cycles, namely a control cycle and the treatment cycle. "
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    ABSTRACT: Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be.
    BMC Women's Health 04/2014; 14(1):54. DOI:10.1186/1472-6874-14-54 · 1.50 Impact Factor
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    • "In addition, Durand et al. [7] demonstrated that when LNG is taken within this window, a premature appearance of glycodelin in serum is observed at the time of ovulation. Although this observation is important, because of the well-known inhibitory effects of intrauterine glycodelin-A on sperm binding to the zona pellucida [8], the glycodelin concentration in serum was far below [7] that required for sperm-egg binding inhibition [8]. In this context, the purpose of the present study was to assess the presence of glycodelin-A in uterine flushing at the midcycle of ovulatory women treated with LNG during the preovulatory phase of their menstrual cycles. "
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    ABSTRACT: The study was conducted to assess the effects of levonorgestrel (LNG) on hormonal behavior and on the secretory pattern of intrauterine glycodelin at the midcycle of ovulatory women. Thirty healthy sterilized women with normal ovarian function were studied during one control untreated cycle and one LNG-treated cycle. In the treated cycle, each woman received two doses of 0.75 mg of LNG 12 h apart during the preovulatory phase approximately 2 days before the LH surge. Daily follicle development recordings were performed until follicle rupture was observed, and serum glycodelin, LH, estradiol, estrone and progesterone were measured as well. In addition, glycodelin concentrations were assayed in uterine flushing obtained on Days LH+1 and LH+12. LNG did not modify follicle rupture in 20 of 30 women. In spite of ovulatory progesterone and the occurrence of follicle rupture in these women, luteal phase length was significantly decreased, as well as the serum concentrations of LH, estradiol and estrone in the periovulatory phase. Glycodelin in serum and uterine flushings was significantly elevated in the periovulatory phase when compared to control cycles. LNG taken at the dose used in emergency contraception before the LH surge increased prematurely serum and intrauterine concentrations of glycodelin at the time of ovulation. Since there are well established glycodelin inhibitory effects upon fertilization, these results may represent an additional action of LNG in situations where the intervention did not interfere with ovulation.
    Contraception 12/2010; 82(6):526-33. DOI:10.1016/j.contraception.2010.05.015 · 2.34 Impact Factor
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    • "Inappropriate expression of glycodelin-A by sustained delivery of LNG has been observed in women using LNG-releasing intrauterine system (LNG-IUS) and subdermal contraceptive implants (Mandelin et al., 1997, 2001). Additionally, the administration of LNG for EC prior to the LH surge alters the luteal phase expression pattern of glycodelin-A in serum and endometrium (Durand et al., 2005). Because it has been reported that the local application of LNG into the tail of the epididymis of rats impairs the in vivo fertilizing potential, suggesting that the drug has a direct effect on spermatozoa (Nikkanen et al., 2000), our group has "
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    ABSTRACT: The objectives were firstly to assess acrosome reaction (AR) status of spermatozoa following uterine flushing, secondly to measure levonorgestrel (LNG) levels in serum and in uterine flushing fluid and finally to measure endometrial glycodelin-A expression after administration of LNG as a form of emergency contraception (EC). Forty-eight experiments were conducted on 15 regularly menstruating women. Four groups were formed based on different intercourse to treatment interval and treatment to recovery of spermatozoa and the biopsies. Twenty-four and forty-eight hours after treatment, there were 14.5 +/- 3.9 x 10(6) and 17.3 +/- 6.8 x 10(6) sperm recovered from the uterus, respectively. There were no differences between the AR rate and the endometrial glycodelin-A staining intensity in an LNG or placebo treated cycles. The LNG in uterine flushing medium represented 1.38% of the values observed in serum 24 h after the LNG intake. Twenty-four and forty-eight hours after administration of EC, neither the proportion of AR sperm, nor the glycodelin-A level was influenced by 1.5 mg of LNG. LNG did not impair the cervical mucus either because viable spermatozoa were found in the genital tract 36-60 h after coitus and 24-48 h after LNG intake. The mechanism of action of LNG as EC remains unknown.
    Human Reproduction 09/2007; 22(8):2190-5. DOI:10.1093/humrep/dem119 · 4.57 Impact Factor
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