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Termination of second trimester pregnancy with gemeprost and misoprostol: a randomized double-blind placebo-controlled trial.

A prospective randomized double-blind placebo-controlled trial was conducted in 70 subjects to determine whether pre-treatment with misoprostol could facilitate termination of second trimester pregnancy by gemeprost. The women received either 400 micrograms oral misoprostol or placebo tablets 12 hours before the administration of vaginal pessary of gemeprost 1 mg every 3 hours. There were no significant differences in induction-abortion interval and the amount of gemeprost required between the misoprostol and the placebo group. There was no significant difference in the incidence of side effects or analgesic requirement between the two groups. We conclude that oral misoprostol is not useful in facilitating termination of second trimester pregnancy by gemeprost.

Abortion, Induced↗

Ripening procedures.

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Administration, Intravaginal↗

Termination of early pregnancy through a combination of the antiprogestin and prostaglandin analogue.

Termination of early pregnancy (less than 49 days of amenorrhea) was induced in 75 patients with the combination of the antigestagen mifepristone and a prostaglandin analogue, meteneprost. After 48 h a single oral dose of 600 mg of mifepristone was followed by a 10 mg meteneprost vaginal pessary. Pregnancy was confirmed by clinical and ultrasound examinations and plasma HCG assessment. Complete abortion occurred in 72 patients (96%) and the three others required a surgical uterine aspiration. Bleeding continued for 4 to 12 days (mean = 8). Uterine pain and side effects occurred during the 3 h following the use of prostaglandin. Only minor analgesic were required in 30 patients. The combination of mifepristone and meteneprost is a safe and effective method to terminate an early pregnancy.

16,16-Dimethylprostaglandin E2↗

Use of menopausal estrogens and medroxyprogesterone in the United States, 1982-1992.

OBJECTIVE: To describe trends in the prescription of menopausal estrogens and medroxyprogesterone in the United States. METHODS: Annual estimates of the number of prescriptions for menopausal estrogens and medroxyprogesterone and descriptive information on patients and providers were obtained from two pharmaceutical marketing research data bases, the National Prescription Audit and the National Disease and Therapeutic Index of IMS America. RESULTS: An estimated 13.6 million prescriptions were dispensed for oral menopausal estrogens in 1982, and 31.7 million in 1992, a 2.3-fold increase (P = .0001). In 1992, Premarin, the only oral conjugated estrogen currently approved for use, was the most frequently dispensed brand-name pharmaceutical in the United States. Dispensed prescriptions for Estraderm, a transdermal estradiol first marketed in 1986, increased from 1.5 million in 1987 to 4.7 million in 1992. Dispensed prescriptions for oral medroxyprogesterone also increased from 2.3 million prescriptions in 1982 to 11.3 million in 1992, a 4.9-fold increase (P = .0001). An estimated one in six to one in four postmenopausal women were taking menopausal hormones in 1992. These drugs were prescribed mainly by obstetrician-gynecologists. CONCLUSION: The use of menopausal estrogens and medroxyprogesterone has increased substantially over the past decade. These trends indicate that American women are widely exposed to menopausal hormone replacement.

Administration, Cutaneous↗

Effect of 15(s)15-methyl-PGF2alpha-methyl ester vaginal suppositories on circulating hormone levels in early pregnancy.

Intravaginal administration of 15-methyl-PGF2alpha-methyl ester in the form of suppositories terminated pregnancy in 70 percent of the cases whose last menstrual periods ranged from 35 to 56 days. The use of these suppositories in 49 patients, between 57 to 80 days of gestation, dilated the cervix by 10 mm or more, in one hundred percent of the cases. A decrease in circulating levels of estradiol-17beta and progesterone was observed following 15-methyl-PGF2alpha administration. The mean estradiol-17beta levels declined by about 55.9 percent at 9 hours whereas, the corresponding fall in progesterone was 32.7 percent. This was indicative of a direct action of 15-methyl-PGF2alpha on the corpus luteum. The vaginal use of 15-methyl-PGF2-alpha-methyl ester suppositories thus appears to be a promising method for the termination of early pregnancy and for pre-operative cervical dilatation. The termination of early pregnancy appears to be partly due to the luteolytic effect of 15-methyl-PGF2alpha besides stimulating uterine contractions.

Abortion, Induced↗

Misoprostol and illegal abortion in Fortaleza, Brazil.

Misoprostol, a prostaglandin E1 analogue indicated for ulcer treatment, has been widely used as an abortifacient by women in Brazil, where abortion is legal only in cases of rape or incest, or to save the woman's life. Because misoprostol is an inefficient abortifacient, many women who use it have incomplete abortions and need uterine evacuation. We reviewed the records of women admitted to the main obstetric hospital of Fortaleza, capital of Ceará state, Brazil, between January, 1990, and July, 1992, for uterine evacuation after induced abortion. The number of incomplete abortions induced by misoprostol increased substantially during the first half of 1990, and declined thereafter. Of the 593 cases in 1991, 75% were related to misoprostol, 10% to the use of other specified drugs, and 6% to unspecified drugs. For the remaining 9% the procedure used was not recorded; these included 3% in whom abortion had been induced by a clandestine abortionist. The number of uterine evacuations per month fell from 89 in August, 1990, to 62 in July, 1991, when sales of misoprostol in Ceará state were suspended. The fall continued after the sale of misoprostol ceased, to about 20 cases in December, 1991; numbers remained around this level until June, 1992, sustained by clandestine sales. The lack of access to contraception is the main reason for the large numbers of unplanned pregnancies and is a major public health issue for Brazilian women. The prohibition of abortion creates a void in which misuse of medicines is one extra complication, mainly because of the poor control of drug marketing.

Abortifacient Agents↗

Individualizing treatment of vaginal candidiasis.

Clinicians have a vast array of effective antimycotics for the treatment of vaginal candidiasis. Multiple topical formulations are available, yet there is little evidence to suggest that formulation per se influences outcome. A growing number of highly effective oral systemic antimycotic agents provide the practitioner with additional options. Treatment regimens have also changed with the introduction of shorter, often single-day/single-dose courses of therapy. Not all therapeutic agents have the same activity against vaginal fungal pathogens in that topical azoles tend to be more active than nystatin. Differences in patient characteristics, however, are more important than the differences between antimycotic agents and therapeutic regimens in determining selection of the appropriate antimycotic. Patients with vaginal candidiasis vary with regard to duration and severity of symptoms and past frequency of attacks, distribution of inflammation, and pregnancy status. The clinician should consider all these variables both in selecting the appropriate antimycotic agent and the route of administration and in planning the duration of therapy. Individualized therapy offers additional benefits to patients, who may then enjoy the maximum advantages of antimycotics now available.

Administration, Intravaginal↗

Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone.

Doses of 100 mg of micronized progesterone (P) and of 0.5 mg of micronized estradiol (E2) were administered vaginally and orally, respectively, in the early follicular phase of the menstrual cycle in six premenopausal women. In the second cycle, the same doses were administered in the same subjects, orally for P and vaginally for E2. Serial blood samples were collected and the following steroids were assayed by highly reliable techniques: P, E2, estrone (E1), deoxycorticosterone (DOC), 5 alpha- and 5 beta-pregnanolone and the sulfates of E1, E2, and DOC. Circulating P and E2 levels were higher after vaginal than after oral administration, while those of E1 were similar after either route. Metabolites of P (DOC, DOCS and pregnanolone) were higher after oral administration. Concerning estrogen sulfates, E1S concentrations were similar whichever the route, while those of E2S were lower after oral than after vaginal administration. This study has confirmed that metabolism of ingested P and E2 occurs mainly in the intestine. Moreover, P was predominantly metabolized to 5 alpha-reduced derivatives, whatever the route of administration. In view of the metabolic pathways which are operative and of the peripheral plasma levels which were found, the vaginal route appears to be more adequate than the oral one for hormone replacement therapy.

Administration, Intravaginal↗

Influence of route of administration on progesterone metabolism.

While inducing similar progesterone levels, the ratio of 5 alpha- and 5 beta-pregnanolone/progesterone plasma concentrations has been dramatically increased after oral as opposed to vaginal administration, in a cross-over study. The known psychotropic effects of 5 alpha- and 5 beta-pregnanolone lead to different indications and precautions for oral and vaginal administration of progesterone.

20-alpha-Dihydroprogesterone↗

Insulin-like growth factor-binding protein-1: a biochemical marker of endometrial response to progestin during hormone replacement therapy.

OBJECTIVES: To compare immunohistochemical localization of insulin-like growth factor binding protein-1 (IGFBP-1) in endometrial stromal cells with endometrial morphology during three regimens of continuous combined hormone replacement therapy. METHODS: Endometrial samples for morphological examination and immunohistochemical staining with monoclonal antibody against IGFBP-1 were obtained from 30 menopausal women before treatment and after 12 and 24 months of continuous combined hormone replacement therapy. All women received percutaneous estradiolgel releasing 1.5 mg estradiol daily. Regarding progestins, patients were divided into three groups: one group (n = 15) had a 20 micrograms/24 h levonorgestrel-releasing intrauterine device (LNG-IUD); the women in the other two groups received micronised natural progesterone either 100 mg orally (n = 7) or 100-200 mg vaginally (n = 8) daily, 25 days per calendar month. RESULTS: Before treatment the endometrium of all women was atrophic or subatrophic and no IGFBP-1 could be detected in any of the samples which contained enough stromal cells for evaluation. After 12 and 24 months of treatment, epithelial atrophy with decidual transformation in stroma was detected in all specimens in the LNG-IUD group, and IGFBP-1 was localized in decidualized stromal cells in all samples. In the other two groups, no signs of progestin effect were detected by microscopic examination in any of the endometrial samples and IGFBP-1 staining was completely negative in all of them. CONCLUSION: A striking difference occurred in both morphological and biochemical response in the endometrium of women treated with LNG-IUD compared with those receiving oral or vaginal micronised progesterone during continuous combined HRT. Micronised progesterone at doses used in this study turned out to be ineffective to prevent the proliferative effect of estrogen. Immunohistochemical localization of IGFBP-1 in endometrial stromal cells strongly correlated with decidual reaction in all endometrial specimens exposed to LNG-IUD, suggesting that the immunostaining of IGFBP-1 can be used as a means of assessing the strength of progestin effect in the endometrium during HRT.

Administration, Cutaneous↗

Prostaglandin E2 in induction of labour: a pharmacokinetic study of dose and treatment protocols.

The absorption of administered prostaglandin E2 (PGE2) into the term uterus was analysed, by measurement of intrauterine PGE2 and PGF 2 alpha, in 137 women. Amniotic fluid was sampled after elective Caesarean section, or at rupture of the membranes, and fetal membranes were collected after delivery of the placenta. Within 2 h of administration of a PGE2 pessary (500 micrograms), a significant elevation in amniotic fluid PGE2 was detected. Exogenous PGE2 stimulated the production of intrauterine PGE2 and PGF2 alpha, causing an elevated PGE2 concentration in amniotic fluid, and increased PGF2 alpha in fetal membranes. These studies indicate that the administration of as little as 500 micrograms of PGE2 pessary, resulted in elevated intrauterine PGE2. Exogenous PGE2 (2.5 mg) administration resulted in increased concentrations of PGF2 alpha in the fetal membranes. Considerable local release of PGs was observed at the site of membrane rupture, and this influenced the method of amniotic fluid sampling used in this study.

Administration, Intravaginal↗

A randomized controlled comparison of sublingual and vaginal administration of misoprostol for cervical priming before first-trimester surgical abortion.

OBJECTIVE: The purpose of this study was to compare the effectiveness of the sublingual and vaginal administration of misoprostol for cervical priming before surgical termination of pregnancy. STUDY DESIGN: In a randomized controlled trial, 74 primigravid women who were undergoing surgical abortion were assigned randomly to receive misoprostol (400 microg) sublingually or vaginally. RESULTS: There was no statistically significant difference in the cumulative force that was required to dilate the cervix to 9 mm, for baseline cervical dilatation, for priming to abortion interval, for operating time, or for intraoperative blood loss between the two groups. Women in the sublingual group had more nausea (P=.008), vomiting (P=.01), diarrhea (P=.01), and unpleasant mouth taste (P=.0001) compared with the women in the vaginal group. In the sublingual group, 65% of women were satisfied with the route of misoprostol administration compared with 78% in the vaginal group (P=.11). Most of the staff members (84%) said that they would recommend the sublingual administration of misoprostol (P=.0001). CONCLUSION: The sublingual administration of misoprostol is an effective alternative to vaginal administration for cervical priming before surgical abortion; despite a higher incidence of side effects, there was high patient and staff acceptability.

Abortifacient Agents, Nonsteroidal↗

Randomized controlled trial of misoprostol for second-trimester pregnancy termination associated with fetal malformation.

OBJECTIVE: Our purpose was to compare the effectiveness, women's views of the termination procedure, and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostaglandin PGF(2alpha) for second-trimester pregnancy termination (STPT). STUDY DESIGN: We randomized 217 women, 15 to 24 weeks' gestation, into 3 groups. Oral (OM) and vaginal (VM) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours. The intra-amniotic PGF(2alpha) (IAPG) group received 40 mg of PGF(2alpha) followed by oxytocin infusion. Women completed self-administered questionnaires 3 weeks after the termination procedure. Umbilical cord samples were collected at delivery for karyotype analysis. The primary outcome was the time from start of the procedure to placental delivery. Secondary outcomes were maternal complications, women's acceptance of the termination procedure, and success rates of umbilical cord culture. RESULTS: The time was longer for the OM group (30.5+/-14.4 hours) compared with the VM group (18.3+/-8.2 hours) and the IAPG group (21.1+/-10.2 hours), P<.001 for both comparisons. Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups, P<.001. Failure rates for umbilical cord cultures were 9.6%, 17.0%, and 45.6% for the VM, OM, and IAPG groups, respectively. CONCLUSION: Oral misoprostol is less effective than intra-amniotic PGF(2alpha) or vaginal misoprostol for STPT. Women report vaginal misoprostol more acceptable than other methods. Umbilical cord culture failure rate is highest in the IAPG group.

Abortifacient Agents, Nonsteroidal↗

Prospective randomized clinical trial of inpatient cervical ripening with stepwise oral misoprostol vs vaginal misoprostol.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of stepwise oral misoprostol vs vaginal misoprostol for cervical ripening before induction of labor. STUDY DESIGN: Two hundred and four women between 32 to 42 weeks of gestation with an unfavorable cervix (Bishop score < or = 6) and an indication for labor induction were randomized to receive oral or vaginal misoprostol every 4 hours up to 4 doses. The oral misoprostol group received 50 microg initially followed by 100 microg in each subsequent dose. The vaginal group received 25 microg in each dose. The primary outcome was the interval from first misoprostol dose to delivery. Patient satisfaction and side effects were assessed by surveys completed after delivery. RESULTS: Ninety-three (45.6%) women received oral misoprostol; 111 (54.4%) received vaginal misoprostol. There was no difference in the average interval from the first dose of misoprostol to delivery in the oral (21.1 + 7.9 hrs) and vaginal (21.5 + 11.0 hrs, P = NS) misoprostol groups. The incidence of hyperstimulation in the oral group was 2.2% vs 5.4% in the vaginal group, P = NS. Eighteen patients in the oral group (19.4%) and 36 (32.4%) in the vaginal group underwent cesarean section (P < .05). This difference was attributed to better tolerance of more doses of misoprostol by the women in the oral group. There was no difference in side effects (nausea, vomiting, diarrhea, shivering) between groups. Fourteen percent of women in the vaginal group versus 7.5% in the oral group were dissatisfied with the use of misoprostol (P = NS). CONCLUSION: Stepwise oral misoprostol (50 microg followed by 100 microg) appears to be as effective as vaginal misoprostol (25 microg) for cervical ripening with a low incidence of hyperstimulation, no increase in side effects, a high rate of patient satisfaction, and is associated with a lower cesarean section rate.

Abortifacient Agents, Nonsteroidal↗

Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: an alternate tocolytic approach.

OBJECTIVE: We examined the hypotheses that vaginal indomethacin is more effective for prolonging gestation, and mediates its tocolytic actions via changes in cervical matrix metalloproteinase (MMP) activity, compared to oral. STUDY DESIGN: Pregnant rabbits induced with mifepristone received oral or vaginal indomethacin; or oral or vaginal vehicle once daily for 2 days. Premature delivery, fetal ductus arteriosus, and cervical MMP activity were assessed. RESULTS: Vaginal indomethacin delayed delivery >72 hours in 100% of the rabbits, extending gestation to 28.2 +/- 0.5 (P < .01) versus 26.4 +/- 0.3, 25.8 +/- 0.5, and 26.5 +/- 0.3 days, for vaginal placebo, oral indomethacin, and oral vehicle, respectively. Fetal ductus arteriosus was patent in all groups. Vaginal indomethacin decreased MMP-1, -8, and -9 activities and increased TIMP-1 levels in the cervix. CONCLUSION: Vaginal indomethacin is more effective than oral for prolonging gestation in the rabbit. Its tocolytic effects may be mediated, in part, by alterations in cervical MMP activity.

Administration, Intravaginal↗

A pilot study of mifepristone in combination with sublingual or vaginal misoprostol for medical termination of pregnancy up to 63 days gestation.

Of the total women included in the study, 96 women chose to receive misoprostol 600 microg sublingually while 53 women received misoprostol 800 microg vaginally 36-48 h after receiving mifepristone 200 mg. Complete abortion occurred in 93 women (98.9%) in the sublingual and 51 women (96.2%) in the vaginal group (p = 0.27). The mean induction-to-abortion interval was 3.2 h (SD = 1.4) in the sublingual and 4.1 h (SD = 1.5) in the vaginal group (p = 0.02). The mean gestation at abortion in weeks was 7.1 (SD = 1.0) in the sublingual and 7.7 (SD = 1.3) in the vaginal group (p = 0.003). Women in the sublingual group experienced more vomiting (p = 0.03), diarrhea (p = 0.02) and unpleasant taste in their mouth (p = 0.0001) while those in the vaginal group experienced more headache (p = 0.002). Of women in the sublingual group, 77% were satisfied with the route of misoprostol administration compared to 68% in the vaginal group (p = 0.25). These findings now need to be assessed in the context of a randomized controlled trial.

Abortifacient Agents, Nonsteroidal↗

The combined contraceptive vaginal ring, NuvaRing, and tampon co-usage.

We investigated the effect of tampon co-usage on systemic exposure to etonogestrel (ENG) and ethinylestradiol (EE) from the combined contraceptive vaginal ring, NuvaRing. One cycle of ring use consists of 3 weeks of ring use followed by a 1-week ring-free period. Fourteen healthy women were randomized to use both NuvaRing and tampons (Kotex( regular) or NuvaRing alone for one cycle; participants then switched to the alternate treatment regimen for a second cycle of ring use. The first tampon was self-administered on day 8 of the interaction cycle; 4 tampons a day were used for 3 consecutive days. Tampon co-usage did not result in any changes in serum ENG or EE concentrations and is thus not expected to compromise the ring's contraceptive efficacy.

Administration, Intravaginal↗