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PubMed2002

Scanning electron microscopic (SEM) changes of the endometrium in women taking high doses of levonorgestrel as emergency postcoital contraception.

Endometrial surface changes by scanning electron microscope were studied in three women who intentionally took high doses of levonorgestrel as an emergency postcoital contraceptive. Based upon findings of a close link between endometrial receptivity and surface integrity, significant alterations of the uterine lining structure may represent a drug effect accomplishing endometrial contraception. High doses of levonorgestrel (4-6 times more than recommended) caused detectable changes on the surface regardless of the menstrual cycle phase when the medication was taken. Cycle classification was based on estradiol and progesterone hormone levels, which corresponded to the menstrual diary. Comparison to control specimens displayed marked restructuralization of the endometrium. As a main feature, the number of ciliated cells were reduced, and cilia disappeared in the proliferative and periovulatory phase. In the secretory phase, pinopodia disappeared and the endometrial integrity broke down. The contraceptive effect of levonorgestrel seems to be accomplished by alteration of the endometrial surface and, therefore, receptivity.

Adolescent↗
PubMed1977

Ethinylestradiol and dl-norgestrel as a postcoital contraceptive.

Six hundred and eight women were treated with 200 microgram of ethinylestradiol and 2 mg of dl-norgestrel, administered in two divided doses, as a postcoital contraceptive. Criteria for entry into the study included definite unprotected coital exposure within the previous 72 hours and the absence of any contraindications to the use of estrogen/progestin-containing compounds. Women with coital exposures outside of the 72-hours-to-treatment time frame were excluded. Four hundred and sixty-four of the patients were cycling regularly and, of these, 152 were exposed at midcycle. Only one patient became pregnant as a result of probable method failure as compared with the minimal estimated number of 12 to 30 pregnancies.

Adolescent↗
PubMed1977

Postcoital contraceptive effects of agonist analogs of luteinizing hormone-releasing hormone.

Various analogs of synthetic hypothalamic luteinizing hormone-releasing hormone (LH-RH) were evaluated for agonistic (ovulation-inducing), postcoital contraceptive, and direct uterotrophic activities. All analogs showing agonistic activity also possessed the ability to terminate pregnancy, as did LH-RH; there appeared to be a direct relationship between agonistic and postcoital potency and activity. The highly potent and active LH-RH agonist, D-[Ala]6-des-[Gly]10-pro9-ethylamide-LH-RH, proved to be the most potent and active postcoital preimplantational and postimplantational antifertility agent. In contrast to LH-RH, none of the analogs tested in the hypophysectomized animal produced a uterotrophic effect, revealing a selective extrapituitary effect of the parent hormone. The collective data demonstrate that peptides derived from LH-RH and bearing agonistic properties can terminate pregnancy postcoitally, via disruption of the pituitary-ovarian reproductive complex. Possible mechanisms are discussed, and the use of members of this neurohormonal class as potential profertility agents should be weighed with caution.

Animals↗
PubMed1998

Postcoital contraceptive activity of some indigenous plants in rats.

Crude ethanolic extract of seeds of Cichorium intybus and aerial parts of Guetterda andamanica, Memcylon lushingtonii, and Solanum crassypetalum and their fractions were evaluated for postcoital contraceptive efficacy in adult female Sprague-Dawley rats. The extracts were administered orally in days 1-10 postcoitum, and significant contraceptive activity was observed. On fractionation, the activity was localized primarily in the chloroform- or butanol-insoluble fractions. The activity in these fractions was invariably associated with a significantly reduced number of implantations.

Animals↗
PubMed1981

Evaluation of STS-557 as a postcoital contraceptive in the baboon.

A postcoital interceptive action of STS-557, a synthetic progestin, has been reported in the mouse, rat, and baboon. In the present study we reinvestigated the effects in the baboon with a modification of the original protocol: prolongation of the mating period from 6 to 48 hours. The time of mating was determined by observation of the perineal sex skin and the pattern of plasma estradiol in the periovulatory period. STS-557 (0.4 mg) was administered 6 hours after the initiation of mating, which was continued for an additional 42 hours. Controls received an empty gelatin capsule in the same mating protocol. Conception rate in the control baboons (n = 20) was 25%; in the STS-557-treated baboons (n = 18) it was 22%. There was also no difference in the pattern of plasma estradiol and progesterone in control versus treated baboons, either in pregnant or in nonpregnant animals. All pregnancies were normal. In light of the earlier report of effective postcoital action in the baboon from a single administration of STS-557 after a breeding period limited to 6 hours, our results indicate that the effect of a single dose is brief, and may not be clinically useful.

Animals↗
PubMed1987

Postcoital contraception with levonorgestrel during the peri-ovulatory phase of the menstrual cycle. Task Force on Post-ovulatory Methods for Fertility Regulation.

The contraceptive efficacy and side effects of postcoital levonorgestrel used repeatedly during the peri-ovulatory period of one cycle was examined in 259 women. All subjects were of proven fertility in their present union and had ovulatory cycles as assessed from pre-treatment BBT charts. The mean number of coital acts during the treatment cycle was 7.5 (SD:2.6) and the mean number of 0.75 mg levonorgestrel tablets taken during the peri-ovulatory period was 4.0 (SD:1.2). Two pregnancies, both considered to be method failures, occurred, giving a failure rate of 0.8% per treated cycle. Although the overall effect of levonorgestrel on menstrual cycle length was small and insignificant, menstrual cycle disturbances were not uncommon. Intermenstrual bleeding or spotting occurred in 8.5% of the treated cycles and 12.5% of the cycles were less than 20 or more than 35 days. Other side effects, mainly nausea, headache and dizziness, were reported by about 20% of the subjects but the apparent incidence of these complaints varied markedly between the nine participating centres from 0% to just over 50%. The data suggest that repeated postcoital use of levonorgestrel is probably not a viable approach to fertility regulation for the majority of women who have regular intercourse and wish to limit the number of their pregnancies.

Adult↗
PubMed1986

Effect of diazepam and phenobarbital sodium on postcoital contraceptive efficacy of ethinyl estradiol in rats.

Diazepam, a well known tranquilizer, and ethinyl estradiol have frequently been prescribed together in rape cases. These two drugs were reported to possess an opposite action on uterine motility. Phenobarbital, a typical enzyme inducer, has been prescribed together with ethinyl estradiol in some cases as a sedative-hypnotic. The present study was, therefore, designed to investigate the possible interferences of diazepam or phenobarbital sodium on postcoital contraceptive efficacy of ethinyl estradiol (4 micrograms/kg/day) in rats. All tested doses of diazepam (1, 2 and 4 mg/kg/day) or phenobarbital sodium (30 and 60 mg/kg/day) appear to have no effect on the efficacy of ethinyl estradiol when either of them was administered from D3 to D5 or from D1 to D5 of pregnancy. In addition, neither diazepam nor phenobarbital sodium at the highest doses used showed an effect on pregnancy.

Animals↗
PubMed1989

Postcoital contraception: a family planning study.

The New Zealand Family Planning Association undertook a prospective study of Yuzpe's postcoital method of contraception (0.1 mg ethinyloestradiol and 1 mg d1-norgestrel taken within 72 hours of unprotected intercourse and repeated 12 hours later). The study also used pills containing levonorgestrel. Both pill formulations were equally effective. All participants were drawn from six family planning branches throughout the country. The study covered a period of one year. There were 909 participants with 8% lost to follow up. Strict criteria excluded women on medication or hormone therapy. The ages ranged from 11 to 43 years with 92% aged 19 years and under. Results revealed an overall failure rate of 2.3% and a significantly higher failure rate (4.49%) if the method was taken after 48 hours of unprotected intercourse and a significantly lower failure rate (1.22%) if taken before 12 hours of unprotected intercourse. Vomiting occurred in 17% but it did not affect the failure rate.

Adolescent↗
PubMed1976

Luteinizing hormone and progesterone in women under postcoital contraception with D-norgestrel.

Luteinizing hormone (LH) and progesterone (Pg) levels in blood were measured simultaneously by radioimmunoassay during 53 menstrual cycles in order to investigate the effect of 400 mug of D-norgestrel, administered postcoitally, on pituitary and ovarian function. Of 31 control cycles, 2 appeared to be anovulatory, since the LH peak and subsequent Pg elevation were absent. Twenty-nine cycles showed typical LH surges in the middle of the cycle, followed by a manifold Pg increase. Twelve women received 5 to 13 tables of D-norgestrel. A total absence or at least marked suppression of LH and Pg elevations was observed. In a third group, D-norgestrel was administered on scheduled days. Each woman ingested one to four tablets between the 6th and 18th days of the cycle. Two or more tablets disturbed LH and Pg ovulatory patterns. Of four women who received a tablet on day 10, one failed to show characteristic ovulatory patterns and three exhibited a delay in the time of the LH and Pg increase. These results demonstrate that D-norgestrel in a postcoital regimen alters pituitary and ovarian function, strongly suggesting an antiovulatory effect.

Contraceptives, Postcoital↗
PubMed1978

[Postcoital contraception in primates. I. Action mechanism of a potential postovulatory fertility-inhibiting substance STS 456 in the baboon (Papio hamadryas)].

With the substance STS 456, an estrogenic active steroid, a high fertility inhibition could be obtained in the pavian, when administered p. o. over a 5 day period postcoital. The effectiveness and also the side effects were dose dependent. The antifertility mechanism is based on an luteolytic effect, demonstrated by analytical hormonal investigations. The inhibition of the synthesis of steroids in the ovary affected not only progesterone but also the estrogens.

Animals↗
PubMed1978

[Postcoital contraception in primates. II. Examination of STS 153 and STS 287 as interceptives in the baboon (Papio hamadryas)].

The interceptive activity of 2 new synthesized steroid compounds: STS 153 (17 beta-Phenylaminocarbonyloxy-estra-1,3,5(10)-triene-3-methyl ether and STS 287 (16 alpha-Bromo-17 beta-[N',N'-dimethylhydrazino]-carbonyloxy-estra-1,3,5(10)-triene-3-methyl ether) and of 17 alpha-Ethynylestradiol was investigated in baboons.--Postcoital oral administration of 1--3 mg/kg b. w. STS 153 for 5--7 days and of 1 mg/kg b. w. STS 287 for 5 days resulted in a fertility inhibition of about 90% and 95% respectively. A dose of 2 mg/kg b. w. of ethynylestradiol was necessary to attain complete fertility inhibition. Following administration of STS 153 and STS 287, side effects were not observed. Pharmacokinetic aspects are discussed.

Animals↗
PubMed1991

A multicenter clinical study on two types of levonorgestrel tablets administered for postcoital contraception.

Contraceptive efficacy, cycle control and side effects of two types of 0.75 mg levonorgestrel tablets taken postcoitally during the periovulatory period of one cycle were studied in a multicenter trial involving 361 women. No significant differences were found between the two types of levonorgestrel pills in terms of contraceptive efficacy, cycle control and side effects. The failure rate observed (1.4% per treated cycle) was similar to that reported for other hormonal approaches to emergency postcoital contraception. Intermenstrual bleeding or spotting occurred in 11.5% of the cycles and anovulation as assessed from BBT charts in 14.4% of cycles. One or more side effects were reported by 22.2% of subjects. The relatively frequent occurrence of cycle disturbances and subjective side effects make it unlikely that the repeated postcoital use of levonorgestrel would be an acceptable routine method of contraception for most women.

Adult↗
PubMed1986

The biochemistry of human endometrium after two regimens of postcoital contraception: a dl-norgestrel/ethinylestradiol combination or danazol.

A combination of 0.5 mg levonorgestrel (in 1 mg dl-norgestrel) and 0.1 mg ethinylestradiol was administered to eight volunteers 48 hours after the start of the luteinizing hormone surge. A second dose was given 12 hours later. Endometrial samples were obtained 24 hours after the first dose was given. The steroid receptor concentration was compared with ovulatory spontaneous cycles. The dl-norgestrel/ethinylestradiol combination caused a significant reduction in receptor concentration. Isocitrate dehydrogenase (a progestin-sensitive enzyme) was also altered, suggesting an effect on endometrial metabolism. Danazol was used in a similar fashion, with two doses each of 400 mg. Nine volunteers were studied. A similar pattern of alteration of endometrial biochemistry was demonstrated but did not reach statistical significance. The relevance to the postcoital use of hormones is discussed.

Adult↗
PubMed1991

Postcoital contraceptive action in rats of a hexane extract of the aerial parts of Ferula jaeschkeana.

The hexane extract of Ferula jaeschkeana aerial parts was studied at an oral dose of 25 mg/kg per day for its postcoital effects in pregnant rats. Ovaries of treated rats remained in a cyclic state rather than undergoing pregnancy as demonstrated by constant ovulation accompanied by newly formed corpora lutea. Follicles were present in different stages of development. Uterine histoarchitecture of treated rats appeared non-receptive for implantation. No decidcoma were observed on day 5 of pregnancy and the luminal epithelium remained unresponsive. Uterus was non-oedematous and lumen was considerably wider. Administration of the extract caused increases in the protein and glycogen content of ovary and uterus, while the activity of acid phosphatase remained essentially unchanged and the activity of alkaline phosphatase was increased. The volume of uterine fluid in the treated rats was increased considerably on day 5 post coitum. It appears that the histological and biochemical modifications in the ovary and uterus of treated pregnant rats do not support the preparation of uterus for implantation.

Alkaline Phosphatase↗
PubMed1995

Levonorgestrel as a postcoital contraceptive.

Time-release pellets of levonorgestrel (LNG), the progestogenic hormone contained in the contraceptive system Norplant, were implanted subdermally in mice, after the animals had mated and ovulated but before uterine implantation of embryos would have occurred, to examine whether the hormone could reduce the number of embryos that subsequently implanted and, if so, when it had to be administered in the postcoital period to achieve that effect. Hybrid female mice (C57BL x CBA) were paired with breeder males (CD-1) and LNG pellets were implanted on day 0, the day on which copulation plugs were found, or on day 2 or day 3 in the postcoital period. Mice in some groups were sacrificed on day 14 of the gestation period, and numbers of fetuses and/or resorption sites were counted, while mice in other groups were allowed to go to term. When LNG pellets were implanted subdermally on day 0 of the postcoital period, pellets designed to release 1.5 mg of hormone in 21 days failed to exhibit a contraceptive effect, but pellets designed to release 5 mg of hormone in 90 days were totally effective in preventing uterine implantation of embryos. Although the 5 mg pellets did not prevent embryos from implanting in all cases when administered on day 2, they prevented pregnancies from going to term by causing resorption of those embryos that did implant. When the pellets were implanted as late as day 3 in the postcoital period, uterine implantation of embryos occurred and fetuses were carried to term. Results of the study indicate that subdermal implants of LNG inserted postcoitally can prevent uterine implantation of embryos in mice, and thereby prevent pregnancy, despite fertilization of oocytes having occurred, if the hormone implants are inserted before day 3 of the postcoital period.

Animals↗
PubMed1993

Endometrial suction in luteal phase as a method of late postcoital contraception.

In a pilot study group of 25 women presenting in our clinic after exposure at ovulation to undesired pregnancy, endometrial suction by means of a Pipelle catheter was performed. Sixteen of the 25 women had proven fertility and 9 had never tried to conceive. The women were aged 18 to 38 years. Pathological dating of endometrial sampling verified that the patients were actually post-ovulation in all cases studied. hCG tests were performed 10 to 14 days after endometrial suction and all were negative. We conclude that endometrial suction in the luteal phase is a possible means of postcoital non-hormonal contraception, and we are currently expanding our study.

Adolescent↗