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 (original) (raw)
Related papers
On the mechanisms of action of short-term levonorgestrel administration in emergency contraception
Contraception, 2001
The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E 2 ) and progesterone (P 4 ) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH ϩ 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P 4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P 4 and E 2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P 4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri-and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.
European Journal of Endocrinology, 2006
Objective: The luteal phase after ovarian hyperstimulation for in vitro fertilization (IVF) is insufficient. Therefore, luteal phase supplementation is routinely applied in IVF. It may be postulated that premature luteolysis after ovarian hyperstimulation is due to supraphysiological steroid levels in the early luteal phase. In the present study, high doses of steroids are administered after the LH surge in normo-ovulatory volunteers in order to investigate whether this intervention gives rise to endocrine changes and a shortening of the luteal phase. Design: Randomized controlled trial. Methods: Forty non-smoking, normal weight women, between 18 and 37 years of age, with a regular menstrual cycle (24-35 days), received either high dosages of estradiol (E 2 ), progesterone (P), E 2 CP or no medication. Blood sampling was performed every other day from the day of the LH surge until LHC 14. Duration of the luteal phase and endocrine profiles were the main study outcomes. Results: Early luteal phase steroid concentrations achieved by exogenous administration were comparable with levels observed following ovarian hyperstimulation for IVF. No difference in the luteal phase length was observed comparing all groups. However, a significant decrease in LH levels could be observed 6 days after the mid-cycle LH surge (P!0.001) in women receiving P, resulting in accelerated decrease of inhibin A production by the corpus luteum (PZ0.001). Conclusion: The present intervention of high-dose steroid administration shortly after the LH surge failed to induce a premature luteolysis regularly in cyclic women. It seems that the induced transient suppression in LH allowed for a timely recovery of corpus luteum function. Other additional factors may be held responsible for the distinct reduction in luteal phase length observed after ovarian hyperstimulation for IVF.
Clinical Endocrinology, 1987
Induction of multiple follicular development in women results in supraphysiological serum oestradiol (Ez) levels and marked reduction of the endogenous LH surge. To examine whether high serum Ez levels at midcycle can suppress gonadotrophin secretion during the LH surge, five normally ovulating women were given an intramuscular injection of 10 mg oestradiol benzoate 6 4 2 h before the expected endogenous LH surge. The results were compared with the preceding untreated control cycle. Serum E2 levels at the onset of the LH surge (mean f SEM) were significantly higher in the oestrogen-treated cycles (13 600k 1963pmol/l) thanin thecontrolcycles(l012f 116pmol/l)(P<0~001). The duration of the LH surge (64.8 f 2.2 h) and LH peak levels (1 36 f 9.6 mIU/ ml) in the oestrogen treated cycles were similar to those in the control cycles (61.2 f 3.9 and 119 9.4 mIU/ml respectively) (mean f SEM). The cycle day on which the LH surge started and the size of the dominant follicle, as assessed by ultrasound, did not differ significantly between the two groups of cycles. These results show that in spontaneous cycles the endogenous LH surge is neither reduced nor amplified by the induction of supraphysiological serum EZ levels during the immediate pre-ovulatory stage.
Contraception, 2010
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. Study Design: Thirty healthy sterilized women with normal ovarian function were studied during one control untreated cycle and one LNGtreated 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. Results: 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. Conclusions: 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.
Fertility and Sterility, 2006
To determine if the combination of leuprolide acetate (LA) and human menopausal gonadotropin (hMG) results in luteal phase dysfunction. Design: A prospective, randomized clinical trial. Setting: A tertiary care university fertility center. Patient(s): One hundred thirty-five couples with various etiologies of infertility. Intervention(s): Patients were prospectively randomized to receive either hMG and intrauterine insemination (IUI) or luteal phase down-regulation with LA, hMG, and IUI. Main Outcome Measure(s): Serum luteal phase progesterone (P) and luteal phase estradiol (E 2 ) were obtained 9 days after hCG administration. Twenty-four-hour urinary P and luteinizing hormone (LH) were analyzed 9 days after human chorionic gonadotropin (hCG). Endometrial biopsies were performed 11 days after hCG and evaluated for luteal phase defects (LPD) using Noyes' criteria. Result(s): No significant differences in the incidence of LPD (11.9% vs. 13.9%), cycle fecundity (16.6% vs. 16.3%), or luteal phase hormone profiles were observed between the groups receiving and not receiving LA. A significant difference in E 2 levels (on the day of hCG administration) between cycles with a luteal phase defect (967 pg/mL Ϯ 106) and without a luteal phase defect (1,422 pg/mL Ϯ 83) was observed (PϽ.05).
Role of the levonorgestrel intrauterine system in effective contraception
Norgestrel, a synthetic progestin chemically derived from 19-nortestosterone, is six times more potent than progesterone, with variable binding affinity to various steroid receptors. The levonorgestrel-releasing intrauterine system (LNG IUS) provides a long-acting, highly effective , and reversible form of contraception, with a pearl index of 0.18 per 100 women-years. The locally released hormone leads to endometrial concentrations that are 200–800 times those found after daily oral use and a plasma level that is lower than that with other forms of levonorgestrel-containing contraception. The contraceptive effect of the LNG IUS is achieved mainly through its local suppressive effect on the endometrium, leading to endometrial thinning, glandular atrophy, and stromal decidualization without affecting ovulation. The LNG IUS is generally well tolerated. The main side effects are related to its androgenic activity, which is usually mild and transient, resolving after the first few months. Menstrual abnormalities are also common but well tolerated, and even become desirable (eg, amenorrhea, hypomenorrhea, and oligomenor-rhea) with proper counseling of the patient during the choice of the method of contraception. The satisfaction rates after 3 years of insertion are high, reaching between 77% and 94%. The local effect of the LNG IUS on the endometrium and low rates of systemic adverse effects have led to its use in other conditions rather than contraception, as for the treatment of endometrial hyperplasia, benign menorrhagia, endometriosis, adenomyosis, and uterine fibroids.
Luteinizing hormone affects uterine receptivity independently of ovarian function
Reproductive Biomedicine Online, 2003
Luteinizing hormone affects uterine receptivity independently of ovarian function Jan Tesarik obtained his MD degree in 1979 and PhD in 1982. He realized the first successful gamete intra-Fallopian transfer (GIFT) and the first childbirths after oocyte fertilization with round spermatids (1995) and with in-vitro cultured spermatids from a man with meiotic maturation arrest (1998). He developed an original technique for nuclear transfer in mature human oocytes (2000).
Inhibition of estrogen synthesis does not inhibit luteinizing hormone-induced ovulation
American journal of obstetrics and gynecology, 1984
In isolated, perfused rat ovaries, the addition of luteinizing hormone (LH) to the perfusion medium consistently induced follicular ruptures. These ruptures were preceded by a marked increase in the levels of estradiol in the perfusion medium. The addition of 4-hydroxyandrostene-3,17-dione (4-OH-A) to the perfusion medium blocked this increase in estradiol, but did not prevent ovulation. Levels of estradiol in follicular fluid were also reduced during perfusion with LH plus 4-OH-A, in comparison to LH alone. The conclusion drawn was that the marked rise in the production of estrogen by preovulatory follicles of the perfused rat ovary, induced by an ovulatory dose of LH, is not required for ovulation to occur.
Direct Involvement of Luteinizing Hormone in Uterine Function
Reproduction in Domestic Animals, 2000
The e}ect of bovine LH on bovine uterine tissue from three phases of the oestrous cycle was studied[ It was found that in the luteal phase the endometrium\ myometrium and cervix contain a LH receptor "LH!R# mRNA transcript and the 82 kDa receptor protein[ Both LH!R protein and its mRNA were also found in the uterine vein but mainly at pre!oes! tus:oestrus[ Incubation of cervical minces from the luteal phase with LH signi_cantly increased "p ³ 9[94# the intracellular cAMP\ inositol phosphate and cyclooxygenase as well as the production of PGE 1 but not PGF 1a [ Induction of endometrial cyclooxygenase by LH is associated with release of PGF 1a in the late luteal phase and 1 to 3 days postovulation[ In contrast\ in the pre!oestrous:oestrous uterine vein\ the signal for the transcript for LH!R and the LH!R protein was signi_cantly higher than at other stages of the cycle[ Incubation of uterine vein minces from pre!oestrus:oestrus with LH signi_cantly increased intracellular concentration of cyclooxygenase as well as production of both PGE 1 and PGF 1a [ The presence of physio! logically active LH!R in the uterine tissue suggests a direct involvement of LH in uterine function\ i[e[ uterine relaxation by cAMP and PGE 1 and regression of the corpus luteum by uterine PGF 1a [
2012
The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections. methods: Pre-and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n ¼ 11) or GnRHa (n ¼ 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor a (ER-a) were analyzed by immunohistochemistry. results: The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P , 0.05). Expression of ERa and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P , 0.05). No difference was detected between groups for any of the markers. conclusions: LNG-IUS reduced both cell proliferation and the expression of PRA and ERa and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.