The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle

Levonorgestrel (LNG) 0.75 mg administered 12 h apart within 72 h of unprotected coitus, is an established method of emergency contraception (EC). The mechanism of action of LNG used in this manner is unknown. We administered LNG 0.75 mg twice immediately before ovulation, to test the hypothesis that LNG acts as an emergency contraceptive by abolishing the pre-ovulatory lutenizing hormone (LH) surge and thereby delaying ovulation. Twelve women took LNG on or before the day of the first significant rise in urinary LH in 12 cycles. In four women, the LH peak and the onset of next menses were significantly delayed (delay of 16.8 days (SD +/- 8.7) from the day of mean LH peak in placebo cycles). One woman did not ovulate at all, despite a normal LH peak and cycle length. In the remaining eight women, LNG did not affect ovulation or the cycle length, but the length of the luteal phase and the total luteal phase LH concentrations were significantly reduced. We suggest that LNG acts as an emergency contraceptive by other mechanisms as well as delaying the LH surge and interfering with ovulation.     

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

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.     

Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens

Background

The days just prior to ovulation are the most crucial for emergency contraception (EC) efficacy. Ulipristal acetate (UPA) and levonorgestrel's (LNG) capacity to inhibit follicular rupture have never been compared directly at this time of the cycle.

Study Design

Raw data from three pharmacodynamics studies with similar methodology were pooled to allow direct comparison of UPA, LNG and LNG+meloxicam's ability to prevent ovulation when administered orally in the advanced follicular phase, with a leading follicle of ≥18 mm.

Results

Forty eight LNG-treated (1.5 mg) cycles, 31 LNG (1.5 mg) + meloxicam (15 mg), 34 UPA (30 mg) cycles and 50 placebo cycles were compared. Follicle rupture was delayed for at least 5 days in 14.6%, 38.7%, 58.8% and 4% of the LNG-, LNG+meloxicam-, UPA- and placebo-treated cycles, respectively. UPA was more effective than LNG and placebo in inhibiting follicular rupture (p=.0001), while LNG, when administered at this time of the cycle, was not different than placebo. The addition of meloxicam improved the efficacy of LNG in preventing follicular rupture (p=.0292 vs. LNG; p=.0001 vs. placebo; non-significant vs. UPA). UPA was effective in preventing rupture in the 5 days following treatment, even when administered at the time of the luteinizing hormone (LH) surge (UPA 79%, LNG 14% and placebo 10%). None of the treatments were effective when administered on the day of the LH peak. The median time from treatment to rupture was 6 days during the ulipristal cycles and 2 days in the placebo and LNG/LNG+meloxicam cycles (p=.0015).

Conclusion

Although no EC treatment is 100% effective in inhibiting follicular rupture when administered in the late follicular phase, UPA is the most effective treatment, delaying ovulation for at least 5 days in 59% of the cycles. LNG is not different from placebo in inhibiting follicular rupture at this advanced phase of the cycle. No treatment was effective in postponing rupture when administered on the day of LH peak.     

Effect of emergency contraception with levonorgestrel or mifepristone on ovarian function

The mechanism of action of levonorgestrel (LNG) and mifepristone (MIF) in emergency contraception (EC), is still not fully known. The purpose of this study was to evaluate the effect of preovulatory treatment with LNG and MIF on luteal function in more detail. Two days prior to ovulation (day -2; assessed by ultrasound), we administered LNG (0.75 mg twice, 12 h apart) or MIF (10 mg, single dose) to seven women in different cycles. Follicle development was followed by ultrasound. Urinary estrone glucuronide (E1), pregnanediol glucuronide (P4) and luteinizing hormone (LH) were analyzed by enzyme immunoassays daily starting with day -2 for the rest of the menstrual cycle, along with urinary creatinine (C). The treatment caused either a delay or an inhibition of the LH peak in all subjects. A significant delay in P4 levels and an initial suppression of E1 levels were also noted. The development of the leading follicle was either arrested or continued without signs of rupture. This study indicates that, when used for EC, LNG or MIF administered prior to ovulation acts through an impaired ovulatory process and luteal function.     

Effectiveness of levonorgestrel emergency contraception given before or after ovulation--a pilot study

BACKGROUND: Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation. METHOD: Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined. RESULTS: Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data. CONCLUSION: These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.     

Postcoital treatment with levonorgestrel does not disrupt postfertilization events in the rat

Levonorgestrel (LNG), a progestin widely used for regular hormonal contraception, is also used for emergency contraception (EC) to prevent pregnancy after unprotected intercourse. However, its mode of action in EC is only partially understood. One unresolved question is whether or not EC prevents pregnancy by interfering with postfertilization events. Here, we report the effects of acute treatment with LNG upon ovulation, fertilization and implantation in the rat. LNG inhibited ovulation totally or partially, depending on the timing of treatment and/or total dose administered, whereas it had no effect on fertilization or implantation when it was administered shortly before or after mating, or before implantation. It is concluded that acute postcoital administration of LNG at doses several-fold higher than those used for EC in women, which are able to inhibit ovulation, had no postfertilization effect that impairs fertility in the rat.     

On the mechanisms of action of short-term levonorgestrel administration in emergency contraception.

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 (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 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 P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 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.     

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

BackgroundThe 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 DesignThirty 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.ResultsLNG 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.ConclusionsLNG 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.     

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

Background

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 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.

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.     

使用母体乐375 SL IUD与左炔诺孕酮紧急避孕的临床研究

目的:评价母体乐375 SL IUD用于紧急避孕的安全性、有效性和可接受性。方法:以100例无保护性生活后120小时内放置MLCu375 SLIUD者为IUD组,术前行尿妊娠试验检查,排除已有妊娠;另110例无保护性生活后72小时内口服LNG 0.75mg,12小时后再服0.75mg者为LNG组,服药前行尿妊娠试验排除已有妊娠。结果:IUD组经产妇高于LNG组(P<0.05),紧急避孕距性生活的时间及其它一般情况两组无差别;IUD组避孕有效率为100％,LNG组为91.40％,两组的实际妊娠数均明显低于预期妊娠数(P<0.05);IUD组在排卵日及其后置器者19.14有点滴出血,但无盆腔炎及大出血的发生。LNG组18％有恶心等副作用但不需处理,其中有36.36％妇女有月经延迟现象,无需特殊处理。讨论:本文提示含铜IUD用于紧急避孕安全有效,最好在性生活5日内放置,且可以长期避孕。对于未产妇和有生殖器炎症放置IUD禁忌者可建议口服LNG等紧急避孕药物。     

Mechanism of emergency contraception with gestrinone: a preliminary investigation

BACKGROUND: A previous investigation showed that among 120 healthy women treated with a single oral dose of gestrinone for emergency contraception (EC), there was only one pregnancy. The effect of a single oral dose of gestrinone given for EC on ovarian function and endometrial development was studied. STUDY DESIGN: Healthy fertile women were randomly assigned to Group A (n=8) or Group B (n=7). Gestrinone 5 mg was orally administered to each woman before (Group A) or after (Group B) ovulation. The day of ovulation was determined by transvaginal ultrasound and by urinary luteinizing hormone (LH) measured by enzyme immunoassay (One Step LH Ovulation Test). An endometrial biopsy was performed during implantation. Endometrial maturation and expression of markers of endometrial receptivity were analyzed. The tested markers were integrins alpha(1)beta(1), alpha(4)beta(1) and beta(3). Serum estradiol (E(2)) and progesterone (P) levels in serum were determined by radioimmunoassay, and estradiol receptors and progesterone receptors (PRs) in the endometrium were assessed by immunohistochemistry. RESULTS: Gestrinone administered during the periovulatory period did not affect follicular development, ovulation, menstrual cycle length and E(2) and P levels but decreased the expression of PR in the endometrium. Integrin alpha(4)beta(1) tended to increase after treatment with gestrinone without reaching statistical significance. CONCLUSION: The mode of action of gestrinone used for EC is probably inhibition of implantation by acting on the endometrium rather than inhibition of ovulation.     

Feasibility study of Nestorone-ethinylestradiol vaginal contraceptive ring for emergency contraception

OBJECTIVE: The Nestorone/ethinylestradiol (NES/EE) vaginal ring is being developed as a regular contraceptive method by the Population Council. This ring is designed to release NES 150 microg/day and EE 15 microg/day during 1 year. Here, we report a Phase I clinical trial to determine the usefulness of this ring for emergency contraception. To that end, we tested the ability of this ring to interfere with ovulation when it is inserted during the follicular phase. METHOD: Forty-eight women protected from the risk of pregnancy by nonhormonal methods were divided into three groups, which differed by the size of the dominant follicle at the time of ring insertion: 12-14 mm (n = 16), 15-17 mm (n = 18) and >or=18 mm (n = 14) diameter. The NES/EE ring was left in the vagina for 7 consecutive days, after which it was removed. The growth of the leading follicle and plasma levels of estradiol, progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the ensuing 5 days after ring insertion were determined. Afterwards, steroid hormones were measured twice a week, until menses took place. All women had a control cycle before the ring cycle, and the range of maximum follicular diameter assigned to each volunteer was the same for the control and the ring cycle at the time when placebo was ingested or the ring inserted. RESULTS: During the 5-day period after ring insertion with follicles 12-17 mm, ovulation was absent in 25 of 34 cycles (p < .01 vs. control), and ovulatory dysfunction (absent, blunted or mistimed LH peak) occurred in 8 of the 9 remaining cycles (33/34 ovulatory processes altered; p < .005 vs. control). After ring insertion with follicles >or=18 mm in diameter, ovulation did not occur in 2 of 14 cycles or was dysfunctional in 7 of the 12 remaining cycles (9/14 ovulatory processes altered; p<.025 vs. control). Altogether, 87.5% of ring cycles (42/48) had either no ovulation or ovulatory dysfunction in the 5-day study period, in contrast to 39.6% (19/48 cycles) in control cycles (p < .001). Among follicles that failed to rupture within the 5-day study period, none ruptured later on in the ring-treated cycles, while 9 of 16 did so in control cycles. Sixty-two percent of ring-treated cycles were shorter than 24 days. Nausea, vaginal discharge and abdominal pain were the most frequently reported adverse events during ring use. CONCLUSION: Interference with 87.5% of ovulatory processes, without ovulation occurring later in the cycle and shortening of cycle length, suggests the NES/EE ring may be used as an emergency contraceptive method, with the potential advantage of providing continuing contraception after it has performed its emergency function.     

Effect of a single vaginal administration of levonorgestrel in Carraguard gel on the ovulatory process: a potential candidate for "dual protection" emergency contraception

OBJECTIVE: The study was conducted to evaluate the effect of Carraguard vaginal gel containing 0.75 mg of levonorgestrel (CARRA/LNG gel) administered in a single dose at different stages of follicle development over subsequent follicle rupture and hormonal levels. METHOD: Randomized, blinded, cross-over study comparing the effects of a single administration of CARRA/LNG gel or Carraguard (CARRA) gel. Twenty-four healthy women were enrolled in two centers. The gels were administered when the follicle had reached diameters of 12-14, 15-17 and > or =18 mm in eight women each. Volunteers were followed for one treatment, one washout cycle and a second treatment cycle. Follicle rupture or nonrupture was assessed by transvaginal ultrasound. Luteinizing hormone, estradiol and progesterone levels were measured daily for 5 days following treatment, and three times per week until menses. RESULTS: No follicular rupture within the 5-day period following administration was observed in 74% and 30% of the CARRA/LNG and CARRA gel treatment cycles, respectively, while ovulation was documented in 4% and 61%, respectively. The overall proportion of cycles with lack of follicular rupture or ovulatory dysfunction (follicle rupture preceded by an inadequate LH surge) was 96% for CARRA/LNG and 39% in the CARRA gel cycles. CONCLUSION: Single vaginal administration of 0.75 mg LNG in CARRA gel in the late follicular phase is effective for interfering with the ovulatory process.     

Ulipristal acetate: a new emergency contraceptive that is safe and more effective than levonorgestrel

Ulipristal acetate (UPA), a selective progesterone receptor modulator, when taken as a single 30-mg dose, is safe and effective for emergency contraception up to 5 days (120 h) following unprotected intercourse. This indication has been approved in Europe since May 2009 and was approved by the US FDA in August 2010. The older progesterone-only emergency contraceptive, levonorgestrel (LNG), is approved only up to 72 h after unprotected intercourse. UPA is effective in delaying or inhibiting ovulation, even if taken 24 to 48 h prior to expected ovulation, a time when LNG is no longer effective. A recent meta-analysis of two randomized clinical trials showed UPA to have a pregnancy risk 42% lower than LNG up to 72 h, and 65% lower in the first 24 h following unprotected intercourse. In a randomized trial enrolling women up to 5 days after unprotected intercourse, significantly more pregnancies were prevented with UPA than with LNG when taken beyond 72 h.     

Anovulatory luteal cycles in primates

The short-term therapy with gonadotropins and inhibitors of prostaglandin synthesis was administered to 12 adult cycling cynomolgus monkeys to study morphology and functions of anovulatory luteinized follicles. In Group 1, five monkeys (6 cycles) received human menopausal gonadotropin (hMG 10 I.U. FSH/10 I.U. LH per 1 kg) on cycle day (c.d.) 5 and 6. Human chorionic gonadotropin (hCG 50 I.U. per 1 kg) and hMG (5 I.U. LH and 5 I.U. FSH per 1 kg) were given at 12:00 on c.d. 7. Indomethacin (15 mg/kg) was injected at 16:30 on c.d. 7 and 08:30 on c.d. 8. Ovarian biopsy was obtained in 2 cycles. In Group 2, 7 monkeys (33 cycles) received single injection of hCG (50 I.U./kg) and hMG (5 I.U. FSH/5 I.U. LH/kg) four to one days before the expected ovulation. Two doses of Naproxen-sodium were given orally 4 and 20 hours later. After treatment, females were kept with males for 5 to 7 days. Laparotomy was performed one week after treatment. Ovarian biopsy was obtained in 5 cycles. Treatment in the midfollicular phase caused premature luteinization of the follicles and suppression of ovulation in all cycles. Histological studies revealed presence of luteinized follicles. Serum progesterone was elevated. Luteal phase averaged 13.6 days (vs. 15.8 days in ovulatory cycles). Treatment in the late follicular phase resulted in luteinization of the dominant follicle and inhibition of ovulation in 20 (61%) cycles. Luteal phase lasted 17.1 days. Serum progesterone was elevated to low or midluteal values. Gross evidence of ovulation was present in 13 (39%) cycles. One pregnancy occurred. All monkeys returned to regular, ovulatory cycles after the experiments were terminated.     

Preference for and efficacy of oral levonorgestrel for emergency contraception with concomitant placement of a levonorgestrel IUD: a prospective cohort study

ObjectivesWe assessed intrauterine device (IUD) preference among women presenting for emergency contraception (EC) and the probability of pregnancy among concurrent oral levonorgestrel (LNG) plus LNG 52 mg IUD EC users.MethodsWe offered women presenting for EC at a single family planning clinic the CuT380A IUD (copper IUD) or oral LNG 1.5 mg plus the LNG 52 mg IUD. Two weeks after IUD insertion, participants reported the results of a self-administered home urine pregnancy test. The primary outcome, EC failure, was defined as pregnancies resulting from intercourse occurring within five days prior to IUD insertion.ResultsOne hundred eighty-eight women enrolled and provided information regarding their current menstrual cycle and recent unprotected intercourse. Sixty-seven (36%) chose the copper IUD and 121 (64%) chose oral LNG plus the LNG IUD. The probability of pregnancy two weeks after oral LNG plus LNG IUD EC use was 0.9% (95% CI 0.0–5.1%). The only positive pregnancy test after treatment occurred in a woman who received oral LNG plus the LNG IUD and who had reported multiple episodes of unprotected intercourse including an episode more than 5 days prior to treatment.ConclusionsStudy participants seeking EC who desired an IUD preferentially chose oral LNG 1.5 mg with the LNG 52 mg IUD over the copper IUD. Neither group had EC treatment failures. Including the option of oral LNG 1.5 mg with concomitant insertion of the LNG 52 mg IUD in EC counseling may increase the number of EC users who opt to initiate highly effective reversible contraception.ImplicationsConsideration should be given to LNG IUD insertion with concomitant use of oral LNG 1.5 mg for EC. Use of this combination may increase the number of women initiating highly effective contraception at the time of their EC visit.     

左旋18-甲基炔诺酮用于紧急避孕的效果与不良反应评价

目的和方法:对100例月经规律,未避孕或避孕措施失败性交后72小时内的妇女,口服左旋18-甲基炔诺酮(LNG),观察避孕效果与不良反应,并以50例妇女应用紧急避孕的经典方法Yuzpe法作对照。结果:LNG组2例妊娠,Yuzpe组1例妊娠,按Wilcox方法推算,避孕有效率分别为83％和82％,但LNG组的不良反应明显降低,P<0.001,优于经典的Yuzpe法。结论:推广使用LNG法将有利于减少非意愿妊娠,保障妇女身心健康。     

Effect on pregnancy rates of the delay in the administration of levonorgestrel for emergency contraception: a combined analysis of four WHO trials

Background

Levonorgestrel is an effective method for emergency contraception (EC) and is used worldwide. Consistent with its mechanism of action in delaying ovulation, the earlier it is administered within 72 h of an unprotected act of intercourse, the more effective it is. There is uncertainty, however, about its effectiveness after 72 h. This analysis explores the effect of 24-h intervals of delay in levonorgestrel administration on pregnancy rates when used until 120 h of an unprotected act of intercourse.

Study Design

Data were analyzed from 6794 women participating in four World Health Organization randomized trials and receiving 1.5 mg of levonorgestrel for EC in a single dose or split into two doses 12 h apart, within 48, 72 or 120 h of an act of unprotected intercourse. The pregnancy rates among women in successive days after an unprotected act of intercourse and odds ratios of pregnancy were calculated using logistic regression with the first day as the reference.

Results

For the four trials combined, odds ratios for pregnancy in the second, third and fourth day with respect to the first day were not significantly different from 1 at the 5% level of significance. On the fifth day, the odds ratio of pregnancy compared to the first day was almost 6.

Conclusions

Levonorgestrel for EC should be administered as soon as possible after unprotected intercourse. Delaying levonorgestrel administration until the fifth day after unprotected intercourse increases the risk of pregnancy over five times compared with administration within 24 h. It is uncertain whether levonorgestrel administration on the fifth day still offers some protection against unwanted pregnancy.     

左炔诺孕酮(LNG)配伍十一酸睾酮(TU)对精子生成抑制差异的研究

目的:探讨左炔诺孕酮(LNG)埋植剂和十一酸睾酮(TU)针剂配伍应用对男性精子生成抑制作用所产生明显个体差异的原因。方法:征集自愿对象16名,前臂埋植两根型皮下埋植剂,每根含LNG 75mg,并于3周后每月肌注针剂TU 250mg,共3次。根据精子密度不同将完成研究的16位男性志愿者分为两组,反应组(简称R组)7人,无反应组(简称N组)9人。比较两组间的血清FSH、LH、T和LNG水平的变化趋势及差异。结果:皮埋后,R组的FSH水平显著低于N组,但其LH水平高于N组(P<0.05);两组间血清T水平无显著性差异(P>0.05);R组的血清LNG水平高于N组(P<0.05);R组的血清T/LH比值显著低于N组(P<0.05)。结论:在应用LNG埋植剂配伍TU过程中,体内血药浓度(LNG和T)的高低,促性激素FSH的抑制程度,精子生成的潜在能力以及Leydig细胞的功能状态是抑制精子生成差异的重要原因,也可能是影响男性激素避孕方法有效性的一个重要因素。     

Levonorgestrel administration in emergency contraception: bleeding pattern and pituitary-ovarian function

BACKGROUND: This study was conducted to evaluate the effects of levonorgestrel administration for emergency contraception (EC) on bleeding pattern and pituitary-ovarian function. STUDY DESIGN: In 69 women with a reported stable menstrual cycle length of 24-34 days, we investigated bleeding patterns following EC administration in the follicular (n=26), periovulatory (n=14) and luteal (n=29) phase. In a subgroup of 8 women, hormonal evaluation and ultrasonography were performed. RESULTS: EC taken in the follicular, but not in the periovulatory or luteal phase, significantly shortened cycle length by 10.9+/-1 days. The subsequent cycle was not affected. EC taken in the late preovulatory phase, prior to the gonadotrophin surge, suppressed ovulation (n=7), while ovulation was not blocked when EC was given during an ongoing luteinizing hormone (LH) pulse (n=1). CONCLUSIONS: Our data indicate that EC given before the onset of the luteinizing hormone (LH) surge inhibits ovulation and hastens the end of the current menstrual cycle. Subsequently, the length of the following menstrual cycle returned as prior to treatment. By contrast, levonorgestrel administered after the expected ovulation has no effect on menstrual cycle length.