[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill]. / Estrógenos y Desarrollo del Cerebro Femenino en la Adolescencia: Anticoncepción de Emergencia.

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

Postcoital interceptive activity of Wrightia tinctoria in Sprague-Dawley rats: a preliminary study.

BACKGROUND: This study was aimed to investigate the pregnancy-interceptive activity of the stem bark of Wrightia tinctoria R.Br. (Family Apocynaceae) administered during the preimplantation, peri-implantation and early postimplantation periods by oral route in adult female Sprague-Dawley rats. STUDY DESIGN: The ethanolic extract of the stem bark and its serial fractions were administered to female rats on Days 1-7 or 1-5 postcoitum (Day 1: day of sperm-positive vaginal smear) by the oral route. At autopsy on Day 10 postcoitum, the number and status of corpora lutea and implantations were recorded. For estrogen-agonistic activity, immature rats ovariectomized 7 days earlier received the test extract or the vehicle once daily for 3 days and, at autopsy on Day 4, uterine weight, status of vaginal opening and extent of vaginal cornification were recorded. RESULTS: The ethanolic extract of the stem bark of W. tinctoria R.Br. inhibited pregnancy in 100% of rats when administered orally at a 250-mg/kg dose on Days 1-7 or 1-5 postcoitum. On fractionation, the hexane-soluble, chloroform-soluble, water-soluble and water-insoluble fractions showed 100% anti-implantation effect, while n-butanol-soluble fraction intercepted pregnancy in 75% of animals when administered in the Days 1-5 postcoitum schedule. In immature rat bioassay, the active ethanolic extract and its fractions exhibited moderate to potent estrogen-agonistic activity, which might be responsible for their contraceptive action in this species. CONCLUSIONS: Findings demonstrate the antifertility activity of the ethanolic extract of the stem bark of W. tinctoria and its hexane-soluble, chloroform-soluble, water-soluble and water-insoluble fractions. Studies that pursue promising natural products (to identify contraceptive agents from natural sources lacking potent estrogenic activity) towards a fruitful conclusion for development/lead generation should continue.

Reproductive effects of ethnomedicinal formulation of tape-vine leaves in female rats.

Documented ethno-contraceptive use of Tape-vine or Stephania japonica (THUNB.) MIERS., Syn. Stephania hernandifolia (WILLD.) WALP. leaves is evaluated with regards to post-coital pregnancy interceptive activity of its aqueous extract (AE) and an ethnomedicinal formulation (EF) in Wistar rats. EF at 500 and 250 mg/kg doses induced 66.7% and 33.3% post-coital pregnancy interception respectively and the higher dose exhibited significant reduction in number of litters born and also anti-implantation property. In contrast, none of the dose levels of AE interfered in pregnancy but significant anti-implantation property was observed at doses of 2 and 1 g/kg, even as the higher dose produced significant reduction in number of litters born as well. EF at 500 mg/kg also exhibited significant uterotrophic activity and histological changes in uterus. Pair-wise comparison of sex hormone-levels exhibited significant increment in serum estradiol, LH and FSH but decrease in progesterone levels. Assessed blood lipid-carbohydrate profile exhibited substantial decrease in glucose, cholesterol, VLDL and triglyceride contents and significant increase in HDL. It is concluded that EF probably acts as better post-coital pregnancy interceptive agent through restriction of implantation by alteration of gonadal hormone levels and decline in blood-glucose levels that possibly disrupts oxidative energy metabolism in uterus during implantation. High surge in LH and FSH suggests negligible interference in ovulatory mechanism. This preparation also seems to be free of cardiovascular risk factors. HPTLC and HPLC analysis of both EF and AE exhibited marked chemical differences.

Postcoital ingestion of the aqueous extract of Erythrina falcata Benth prevents pregnancy in the mouse.

AIM: We examined whether the aqueous extract of Erythrina falcata, reputed to be a contraceptive in Peruvian folklore, could prevent pregnancy in the mouse. METHODS: Female mice on Day 1 of pregnancy were given aqueous extract of E. falcata or tap water (control) orally for 4 days. On Day 4 of pregnancy, animals were killed and the embryos were flushed from oviducts and uterus to examine their developmental stage, cell number, mitotic index and micronuclei frequency. Other mice were killed on Day 12 of pregnancy to determine the number of implantation sites. RESULTS: Ingestion of E. falcata diminished the percentage of embryos that progressed to blastocyst stage, reduced the cell number and mitotic index, and increased the micronuclei frequency of early embryos. The number of implantation sites was also reduced in females treated with E. falcata. CONCLUSION: The aqueous extract of E. falcata, ingested during early pregnancy, disturbs preimplantation embryo development and implantation in the mouse. These results provide the first experimental evidence of the contraceptive properties of the aqueous extract of E. falcata.

Role of energy metabolism in the pregnancy interceptive action of Ferula assafoetida and Melia azedarach extracts in rat.

Ethanolic extract of Ferula assafoetida and chloroform fraction of Melia azedarach, both devoid of estrogenic activity, were examined for their pregnancy interceptive property. Treatment of rats from days 1 to 7 of pregnancy with either of the plant extracts resulted in pregnancy failure in about 65-85% of the animals. The possible role of energy metabolism in the antifertility action was investigated by measuring changes in activities of the key enzymes of carbohydrate metabolism in uterus on day 7 of pregnancy. It was observed that on the day 7 of pregnancy, one key enzyme of glycolytic pathway (phosphofructokinase) was significantly reduced in the uteri of treated rats as compared to controls. Hexosemonophosphate pathway also appeared to be sensitive to treatment with the plant extracts and showed an inhibitory effect on the enzyme activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Oxidative energy metabolism through tricarboxylic acid cycle, which is considered to be the main source of energy to the uterus at this stage, was maximally affected by the treatment with several enzymes showing significant inhibition. The two plant materials appeared to interrupt the latter metabolic pathway more significantly. It is thus concluded that plants lacking phytoestrogens may intercept pregnancy by their ability to disrupt energy metabolism in rat uterus during implantation, especially the oxidative pathway.

Pregnancy interceptive activity of Melia azedarach Linn. in adult female Sprague-Dawley rats.

Ethanolic extract of the root of Melia azedarach Linn. (family: Meliaceae) collected from the Institute campus intercepted pregnancy in 60% and 75% adult female rats when administered at 250 and 500 mg/kg daily doses, respectively, on Days 1-10 post-coitum by the oral route. On fractionation, the activity was localized in the chloroform fraction of the ethanolic extract, which showed 80-100% activity at 250 mg/kg daily dose in repeat tests. In animals that became pregnant, there was also a significant reduction in mean number of implantations and all the implantations exhibited signs of resorption. Of the four major compounds isolated in sufficient quantity and characterized from the active chloroform fraction, two compounds showed only marginal (50%) contragestational effect. Further exploration of the active chloroform fraction, which is also devoid of estrogen agonistic activity at the contraceptive dose in immature rat bioassay, is being undertaken to identify and characterize the active principle(s).

[Mifepristone (RU-486), from hell to purgatory]. / Mifepristona (RU-486), del infierno al purgatorio.

Mifepristone (RU 486) is a synthetic steroid obtained by Bailieu in the year 1982. Initially it was used as a abortifacient drug and also as "afterday pill". In this sense it was ethically unacceptable. In France and even in the USA it was banned and the FDA had not given its approval. But in the late five years other uses of this substance were discovered, some of the are very valuable. In this sense, now we are using at new, and it is each practitioner who must decide on the reliability of its indication.

Emergency contraception for midwifery practice.

Every year in the United States, there are an estimated 3.5 million unplanned pregnancies with nearly one third of these attributed to contraceptive failures. Despite the availability of effective contraceptive methods, far too many women still experience unwanted pregnancies. It has been estimated that emergency contraception, also referred to as postcoital contraception or "the morning after pill," can reduce the risk of pregnancy after unprotected intercourse by as much as 75%. When administered within 72 hours of unprotected intercourse, emergency contraception, inhibits implantation of a fertilized ovum. The most common method of emergency contraception, the administration of ethinyl estradiol and dL-norgestrel, was initially described by Yuzpe in 1977. In the past 20 years, multiple studies have demonstrated the effectiveness of commonly prescribed combination oral contraceptives containing ethinyl estradiol and levonorgestrel. For those women in whom estrogen is contraindicated, progestin-only pills or the synthetic androgen Danazol have been used with comparable effectiveness rates. For appropriately selected women, an intrauterine device such as the Paraguard T380A (Ortho Pharmaceuticals, Raritan, NJ) also may be inserted within 5-7 days after unprotected intercourse to reduce the risk of unintended pregnancy. Despite its success and safety, emergency contraception is underused by women and their health care providers. As providers of comprehensive health care, midwives should provide patients with accurate information concerning pregnancy prevention. For many women, obtaining emergency contraception is an entry into the health care system and provides them an opportunity to be educated about safer sex practices, contraception, and the importance of regular health screening. Regularly discussing emergency contraception with patients at routine health visits will enable them to participate fully in their health care decisions and diminish the physical, psychological, and societal stressors associated with unplanned pregnancy.

PIP: Midwives have substantial contact with women who are at risk of unintended pregnancy and are thus ideally placed to promote use of emergency contraception. Emergency contraception has the potential to reduce the risk of pregnancy after unprotected intercourse by as much as 75%. Potential candidates for this method are women who have missed multiple contraceptive pills, incorrectly used barrier methods, unsuccessfully relied on withdrawal, were exposed to a possible teratogen, or were sexually assaulted. Multiple studies have confirmed the effectiveness of postcoital regimens such as oral contraceptives containing ethinyl estradiol and levonorgestrel, progestin-only pills, the synthetic androgen Danazol, or IUD insertion. Nonetheless, emergency contraception remains underutilized in the US and other countries. There is a need for health care providers to begin to integrate this method into the routine education offered to women during comprehensive health care visits. Women who use barrier methods or spermicide alone as their primary birth control method may benefit from having emergency contraception readily available. Printed materials about emergency contraception should be placed in waiting rooms, and office staff should be prompted to schedule patients requesting the method immediately. Visits for emergency contraception offer a valuable opportunity to provide education about sexually transmitted diseases, safer sex practices, and the importance of consistent use of reliable contraception.

Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats.

Hexane extract of the seeds of Nigella sativa L. prevented pregnancy in Sprague-Dawley rats treated orally at 2 g/kg daily dose on days 1-10 post-coitum. Significant antifertility activity was also observed in its column fractions and subfractions. At contraceptive dose, the active hexane extract exhibited only mild uterotrophic activity comparable almost to 0.002 mg/kg dose of 17 varies; is directly proportional to-Ethinylestradiol, but was devoid of any estrogenicity in the immature rat bioassay.

[Documented effect of the morning-after pill. New elements in contraception counseling]. / Dokumenterad effekt av dagen efter-metod. Nya inslag i råd om antikonception.

PIP: In 1987 the Swedish social and health service issued advice about contraception with factual recommendations about the available contraceptive methods. Since 1987 a new copper IUD and a hormonal IUD have been introduced, and a number of reports have been published about the short- and long-term effects of combined oral contraceptives (OCs). Therefore, the pharmaceutical bureau issued new recommendations. For postcoital contraception, the effectiveness of 4 high-dose OCs has been convincingly proven when given in 2 doses within 72 hours after intercourse; also the insertion of an IUD postcoitally has been mentioned. Another method is the hormonal IUD, Levonova, which has been recommended for women who need long-term and safe contraception. The new copper IUD with a large copper surface (Gyne-T- Slimline) can even be recommended to women who face an increased risk of ectopic pregnancy on the basis of documented high contraceptive effectiveness. A new recommendation concerning the use of the IUD is that women who had a copper or hormonal IUD inserted at around age 40 do not have to exchange the well-functioning IUD after the prescribed duration of use of 5-8 years. The use of combined OCs had also been contraindicated in women aged 35-40 because of the risk of cardiovascular complications with earlier high-dose preparations. However, new studies have not been able to confirm that women of this age group who do not smoke and have no cardiovascular risk factors run any kind of increased risk of cardiovascular complications. Thus, even after 40 women could use OCs. The net effect of comparing the advantages and disadvantages of OCs is positive. This overwhelming positive effect has even led to suggestions about the sale of OCs without a prescription.^ieng

Antigestagenic activity of Ixora finlaysoniana in rat.

Oral administration of crude ethanolic extract of the serial parts of Ixora finlaysoniana Wall. ex G. Don to adult female rats at 250 mg/kg dose on days 1-5 or 1-7 post-coitum prevented pregnancy in 100% rats. The extract was also effective when administered on days 1 or 1-3 post-coitum, but the minimum effective dose increased with decreased duration of administration and was 1000 mg/kg and 500 mg/kg, respectively, in the two schedules. At lower doses, a significant reduction in implantation number and increased post-implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed after administration of 1000 mg/kg dose of the extract during the peri-implantation period. A slight acceleration in tubal transport rate of embryos and delay in blastocyst formation were observed in rats treated postcoitally with the single anti-implantation dose of the extract. Significantly fewer embryos were recovered after their entry into the uterus. Except in one rat receiving 250 mg/kg dose of the extract on days 1-5, in which one apparently normal zona-free blastocyst was recovered from the uterus, uterine flushings of none of the nonpregnant animals contained any unimplanted embryos by day 10 post-coitum. In immature rat bioassay, the extract was found to possess estrogenic activity as evidenced by dose-dependent increase in uterine weight and cornification of the vaginal epithelium at doses ranging from 50-1000 mg/kg. At the 500 and 1000 mg/kg doses, it also induced premature opening of the vagina. Taking 100% increase in uterine weight as the parameter, the extract was found to be about 1.6X10(5) times less estrogenic than ethinylestradiol. The extent and duration of estrogenic responses exerted by single contraceptive dose of the extract were also markedly lower than that induced by ethinylestradiol. The extract was devoid of any estrogen antagonistic or synergistic activity and did not affect ovarian prenidatory estrogen or progesterone synthesis. The findings indicate that the extract at its contraceptive dose a) exerts a differential estrogenic response at the fallopian tube and the uterine levels, b) does not appear embryocidal, but causes slight asynchrony in development and tubal transport rate of pre-implantation embryos, which together with their loss through vagina after entry into the uterus, due to estrogenic action of the extract, might contribute to its anti-implantation action, and c) its anti-implantation and post-implantation resorptive actions are not mediated via altered ovarian function.

PIP: Colony-bred immature (25-35 gm) and adult (180-220 gm) Sprague-Dawley rats were administered orally an 85% ethanolic extract of powdered aerial parts of Ixora finlaysoniana suspended in distilled water. The extract prevented pregnancy in 100% of rats at a dose of 250 mg/kg on days 1-5 or 1-7 post coitus. However, 1000 mg/kg and 500 mg/kg doses were required to achieve complete contraception increasing with decreased duration of administration of the extract. At sub contraceptive doses, a significant reduction in implantation and a marked increase in post implantation resorption rate were observed in all the schedules. Almost complete resorption of all implantations was observed at 1000 mg/kg dose of the extract administered on days 5-7 post coitus. Single oral anti implantation dose (1000 mg/kg) of the extract administered within 24 hours of coitus induced slight acceleration of tubal transport of embryos. Fewer extract-treated rat embryos were recovered from the Fallopian tubes compared with controls on days 4 and 5 to (p 0.01). 1 normal zona free blastocyst was also recovered from the uterine flushings of a rat treated with a 250 mg/kg dose on days 1-5 post coitus, but uterine flushings of none of the 43 remaining nonpregnant rats treated with the various doses on days 1, 1-3, 1-5, or 1-7 yielded any unimplanted embryos by day 10 post coitus. Doses ranging from 50 to 1000 mg/kg once daily for 3 consecutive days induced a dose-independent increase in uterine weight (p 0.001) vs. controls and cornification of the vaginal epithelium in bilaterally ovariectomized rats. Premature opening of the vagina was observed only at 500 and 1000 mg/kg doses. A single oral contraceptive dose of 1000 mg/kg induced a significant increase (p 0.05) vs. the control group in uterine weight and premature opening of the vagina and 40-60% vaginal cornification in all treated rats. In comparison, a single oral contraceptive dose (1.5 mg/kg) of ethinyl estradiol induced stronger and longer estrogenic responses; uterine weight gain at all time intervals was significantly more than with the extract.

Post-coital antifertility activity of the marine plant, Achrostichum aureum L. in rat.

The ethanolic extract of A. aureum and its fractions were evaluated for postovulatory antifertility activity in female rats. The water soluble fraction of ethanolic (95%) extract prevented (100%) pregnancy when administered to female rats on days 1-7 postcoitum. This fraction was found devoid of both estrogenic and antiestrogenic activities.

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.

Post-ovulatory contraception.

It is possible to prevent pregnancy after unprotected intercourse by suppressing ovulation, inhibiting fertilization or interfering with tubal transport and/or implantation of the early embryo. IUCDs probably prevent implantation by stimulating the release of prostaglandins from the endometrium but are not acceptable to many women. Post-coital contraceptive steroids, e.g. high-dose oestrogens, are associated with a relatively high incidence of side-effects and must be taken within 72 hours of coitus. As these agents are effective by creating a uterine environment unfavourable for implantation, it may be possible to use antigestagens or antioestrogens in this way. It is already known that an antigestagen in combination with a prostaglandin is a highly effective method of inducing abortion in very early pregnancy. The corpus luteum is essential for the maintenance of pregnancy and its destruction by a luteolytic agent should dislodge the implanting embryo. If an effective method of preventing implantation could be developed which was relatively free from side-effects, it should be possible to use it as a regular form of contraception to be taken only when the risk of pregnancy had occurred.

PIP: The methods known to be practical for post-ovulatory contraception, defined as any substance or device used after coitus to prevent establishment of pregnancy up to 14 days after ovulation are reviewed. Most are used only in emergency for a single episode of unprotected intercourse or failed contraception, exceptions being the "visiting pill" of norethindrone used for migrant workers in China, and the IUD when inserted for this purpose as well as ongoing contraception. The physiology of ovulation, fertilization, transport of the ovum, and implantation of the blastocyst are reviewed. Estimates of the odds of becoming pregnant after an isolated unprotected intercourse range from 10-25%. High-dose estrogens, either stilbestrol (no longer used in the U.S.), ethinyl estradiol 5 mg, or conjugated estrogens 30 mg, have been used since early trials in the 1960s. Estrogen must be given for 5 days, started within 72 hours of coitus, and cause several unpleasant side effects, notably nausea, vomiting, mastalgia, and menstrual irregularity. Although no incidents have been reported, they are contraindicated for those at risk of thromboembolism. The failure rate is about 0.7%. Combined estrogen and progestagen, known as the Yuzpe method, consists of 2 dose of 100 mcg ethinyl estradiol and 1 mg norgestrel, repeated in 12 hours. The reported failure rates range from 0.2%-7.4%. Insertion of a copper IUD is effective post-coitally within 66 days, with failure rate less than 0.1%. The antiestrogen Danazol, which actually acts as an antigonadotrophin, can be used as a postcoital agent, in divided doses of 800 or 1200 mg 12 hours apart within 72 hours of exposure. Published failure rates are 2.5 and 0.9% with these doses. Progestagens alone have been studied by WHO, but failure rates were as high as 10.1% in women with frequent intercourse. Regular use was not recommended since cycles became unpredictable. Studies are being conducted on RU-486 and prostaglandins for postcoital use, in comparison with the Yuzpe regimen. A true luteolytic agent for women would seem to be the perfect postcoital agent, yet none exist.

Biochemical and histological studies of reproductive organs in cyclic and ovariectomized rats supporting a non-hormonal action for neem oil.

Subcutaneous administration of neem oil to cyclic rats caused significant damage to the luminal epithelium of the uterus and to the uterine glands. It also decreased glycogen and total protein contents in the ovary and uterus, while the activity of acid phosphatase in these organs was increased significantly. Studies in ovariectomized rats revealed that the administration of neem oil decreased protein and glycogen content and increased acid phosphatase activity in the uterus whereas its conjoint administration with estradiol dipropionate or progesterone did not cause significant changes relative to those seen with the steroids per se. Histological studies in ovariectomized rats also supported the relatively inert action of neem oil when given with hormones. It was concluded that the histological and biochemical alterations observed were due to the toxicological potential of the neem oil rather than to hormonal properties.

Postcoital contraception.

Changes in sexual mores have led to the need for an effective emergency postcoital contraceptive agent. To meet this need various individual steroids, either alone or in combination, have been evaluated and shown to be effective in preventing pregnancy as a result of a single, unprotected coital act. No drug has received specific marketing approval in North America for this purpose. However, in western Europe, the combination of ethinyloestradiol and levonorgestrel is marketed specifically for use as a postcoital contraceptive agent. Intrauterine copper contraceptive devices have also been shown to be effective postcoital contraceptive agents, but their applicability is confined to a specific segment of the population. Other agents are also being investigated for their postcoital contraceptive effectiveness, including prostaglandins, anti-progestins, GnRH agonists, super agonists and antagonists, and HCG antagonists. Sufficient interest exists in postcoital contraception that the World Health Organization has undertaken, through their task force dealing with postcoital, once-a-month and menses-inducing agents, to develop other postcoital drugs.

PIP: Changing sexual mores have led to the need for an effective postcoital contraceptive agent. Postcoital contraception is, in theory, an emergency form of contraception designed to prevent pregnancy after a single unprotected coital exposure, not an ongoing method of fertility control. However, in South America, both levonorgestrel and quingestanol acetate have been used as continuous postcoital contraceptive agents. In terms of emergency methods, high dose estrogens alone or low dose estrogen in combination with a progestin have been used effectively. Postcoital agents are belived to exert their contraceptive effect on the implantation process either by alteration in endometrial enzymatic or metabolic activity or by some other means. Copper intrauterine devices are also under investigation as postcoital agents, but their use is not considered appropriate in young, nulliparous women with multiple sexual partners. Other methods being researched for this purpose include prostaglandins; antiprogestins; gonadotropin releasing hormone agonists, super agonists, and antagonists; and human chorionic gonadotropin antagonists.

Postcoital contraceptive efficacy and hormonal profile of Lepidium capitatum.

PIP: Hexane soluble fraction of the Lepidium captiatum plant collected in Himachal Pradesh, India, was administered orally to colony bred albino mice, rats, and golden hamsters to test the plant's postcoital antifertility efficacy and estrogenic and antiestrogenic activities. 2.5 kg of the whole air-dried and powdered plant was extracted 4 times with 90% ethanol, which was evaporated under reduced pressure. The resultant aqueous suspension was partitioned 3 times with hexane and concentrated under vacuum to achieve the hexane soluble and hexane insoluble fractions. Oral administration of 250 mg/kg of crude ethanolic extract of the whole plant on postcoital days 1-5 prevented pregnancy in about 77% of mated female rats. The hexane soluble fraction inhibited pregnancy in 100% of the rats at a dose of 250 mg/kg and in 50% at 125 mg/kg. In comparison to controls, there was a significant reduction in implantation number at both 125 mg/kg and 625 mg/kg doses. The extract failed to prevent pregnancy in hamsters even at a daily dose of 500 mg/kg on postcoital days 1-5. No contraceptive efficacy of the hexane insoluble extract was observed in rats or hamsters. The extract exhibited potent estrogenic activity at the contraceptive dose, without antiestrogenic activity. A significant uterotrophic effect was seen even at 1/40 of the contraceptive dose. When administered orally for 3 consecutive days, the hexane soluble fraction induced normal implantations at 250 mg/kg and lower doses in adult female mice undergoing experimentally induced delayed implantation. The maximum response in terms of the percentage of pregnant animals and the average number of implantations was observed at 125 mg/kg dose. The experimental results confirm the frank estrogenicity of the extract.^ieng

Flowers of Hibiscus rosa-sinensis, a potential source of contragestative agent: I. effect of benzene extract on implantation of mouse.

In mouse, the benzene extract of Hibiscus rosa-senensis flowers was administered at four different dose levels (250-1000 mg/kg body weight/day) from day 1-4 postcoitus. Anti-implantation response and associated changes in the uterine chemical composition were studied. With an increase in the dosage of the extract, the percentage of implantation failure increased. At the dose level of 1 gm/kg body weight, the extract led to failure of implantation in 93% of the mice. The effect was accompanied by adversely altered uterine weight, its protein content and alkaline and acid phosphatase activity. In another experiment, influence of the extract on uterine uptake of progesterone was studied in bilaterally ovariectomized mice treated with or without estrogen. It exerted neither inhibitory nor stimulatory influence on uterine progesterone uptake in untreated castrated mice but the estrogen-induced increase in the uptake level was significantly inhibited by the extract. Failure of uterine bed preparation due to antiestrogenic potentiality of the extract has been discussed as the plausible cause of implantation failure.

[Current status of the development of interceptive agents]. / Zum Stand der Entwicklung von Interzeptiva.

An account is given of present applications of interceptively acting substances. Pharmaceuticals used so far for postcoital conception (oestrogens, gestagens, and combinations of these) are suitable for single application, but their regular use is limited by side-effects. Various approaches are being taken to the development of effective interceptives for high-continuity application but with low side-effects. Antigestagens, LHRH-analogues, and immunological contraceptives seem to be among the most promising classes of substances for the above purpose. Yet, none of these substances has been developed as yet to the level of clinical applicability.

PIP: An account is presented of the current uses of interceptively acting substances. Pharmaceuticals used thus far for postcoital contraception (estrogens, gestagens, and combinations of these) are suitable for a single application, but their regular use is limited by side effects. Various approaches are now being taken to develop effective contraceptives for continuous application which have few side effects. Antigestagens, LHRH-analogues, and immunological contraceptives are among the most promising classes of substances for the above purpose, yet none of these has yet achieved a level of clinical applicability. (author's modified)

[Steroid and nonsteroid postcoital contraceptives]. / Steroidnye i nesteroidnye kontratseptivy postkoital'nogo deistviia.

It has been shown experimentally that a combined use of estrogen-norsteroids prostaglandins and neurotropic substances during preimplantation period produces the most potent contraceptive effect. Analysis of the action mode of combined small doses of steroids, prostaglandins and neurotropic drugs suggests that the contraceptive action is underlain by the inhibitory effect on incretion produced by the luteinizing hormone, this effect being in its turn a reason for variation in the amount and condition of the developing fetuses.