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PubMed1994

New knowledge in the physiology of hormonal contraceptives.

The present review addresses some of the new knowledge regarding the physiology and mechanisms of action of hormonal contraceptives. Specific topics that are discussed include oral contraceptives, intravaginal rings, long-term contraception, gonadotropin-releasing hormone agonists and antagonists, and antiprogestins. It has been shown that in combined oral contraceptives, lower doses of the new progestins (desogestrel, norgestimate, and gestodene) can be used to inhibit ovulation compared with norethindrone and levonorgestrel. In addition, lower doses of ethinyl estradiol are now used with progestins. Estrogen has been added to intravaginal rings containing levonorgestrel or norethindrone acetate to reduce frequency of bleeding. A new ring containing 3-keto-desogestrel is under evaluation. The use of subdermal implants containing levonorgestrel is currently a popular and highly effective method of long-term contraception. Studies show that gonadotropin-releasing hormone agonists and antagonists can provide ovarian suppression, and antiprogestins such as RU486 effectively block the midcycle gonadotropin surge. These and other novel methods of hormonal contraception are still years away from general use.

Administration, Intravaginal↗
PubMed2005

An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection.

Herpes simplex virus 2 (HSV-2) infection causes significant morbidity and is an important cofactor for the transmission of HIV infection. A microbicide to prevent sexual transmission of HSV-2 would contribute substantially to controlling the spread of HIV and other infections. Because RNA interference (RNAi) provides effective antiviral defence in plants and other organisms, several studies have focused on harnessing RNAi to inhibit viral infection. Here we show that vaginal instillation of small interfering RNAs (siRNAs) targeting HSV-2 protects mice from lethal infection. siRNAs mixed with lipid are efficiently taken up by epithelial and lamina propria cells and silence gene expression in the mouse vagina and ectocervix for at least nine days. Intravaginal application of siRNAs targeting the HSV-2 UL27 and UL29 genes (which encode an envelope glycoprotein and a DNA binding protein, respectively) was well tolerated, did not induce interferon-responsive genes or cause inflammation, and protected mice when administered before and/or after lethal HSV-2 challenge. These results suggest that siRNAs are attractive candidates for the active component of a microbicide designed to prevent viral infection or transmission.

Administration, Intravaginal↗
PubMed2004

A randomized, double-blind clinical trial of vaginal acidification versus placebo for the treatment of symptomatic bacterial vaginosis.

BACKGROUND AND OBJECTIVES: Vaginal acidification has been suggested as a means of normalizing the vaginal flora. GOAL: The purpose of this study was to determine the effectiveness of an acetic acid-based vaginal gel in the treatment of bacterial vaginosis (BV). STUDY DESIGN: Forty-four patients with BV were enrolled in a randomized, double-blind clinic trial. Of these, 29 were evaluable. Patients were randomized to receive either 5 mL acetic acid gel (n = 14) or placebo gel (n = 15) intravaginally twice daily for 7 days. Clinical criteria and vaginal Gram stain scores were compared between the initial visit and at 2 weeks after initiating therapy. RESULTS: No significant differences were noted when comparing drug and placebo in terms of subjective or clinical improvement or improvement in Gram stain smears for bacterial vaginosis. CONCLUSION: Vaginal acidification with an acetic acid gel formulated to pH 3.9 to 4.1 was ineffective therapy for bacterial vaginosis.

Acetic Acid↗
PubMed1999

Using amino-cerv after cervical LEEP.

OBJECTIVE: To evaluate the ability of Amino-Cerv to promote healing of the cervix following loop electrical excision procedure (LEEP) of the cervix for cervical intraepithelial neoplasia. STUDY DESIGN: A randomized study was conducted on 48 women in a private office setting. Patients were divided into two groups, to use or not use Amino-Cerv intravaginally for two weeks after the procedure. Statistical analysis of the findings were performed using the chi 2 test. RESULTS: Twenty of 24 (83%) of women using Amino-Cerv had completely healed tissue at four weeks, whereas 12 of 24 (50%) in the untreated group had healed tissue at four weeks. Findings were not statistically significant at two weeks but were statistically significant (P < .005, power = .55) at four weeks after the procedure. CONCLUSION: Amino-Cerv after LEEP of the cervix promotes healing.

Administration, Intravaginal↗
PubMed2002

Intravaginal and intranasal immunizations are equally effective in inducing vaginal antibodies and conferring protection against vaginal candidiasis.

Oophorectomized, estrogen-treated rats were immunized by the intravaginal or intranasal route with a mannoprotein extract (MP) or secreted aspartyl proteinases (Sap) of Candida albicans, with or without cholera toxin as a mucosal adjuvant. Both routes of immunization were equally effective in (i) inducing anti-MP and anti-Sap vaginal antibodies and (ii) conferring a high degree of protection against the vaginal infection by the fungus. These data suggest that appropriate fungal antigens and adjuvant can be used to protect against candidal vaginitis, by either route.

Administration, Intranasal↗
PubMed2005

Comparison of changes in pre-induction cervical factors' scores following ripening with transcervical foley catheter and intravaginal misoprostol.

The study compares the changes in the cervical factors in pre-induction cervical ripening with both transcervical Foley catheter and Intravaginal Misoprostol. This was a randomised prospective study of pregnant women, with singleton gestations who presented for antenatal care and delivery at a tertiary health institution in the South-western Nigeria between 1st March 2003 and 31st March 2004. One hundred and two (102) patients received 50microg intravaginal Misoprostol and Ninety-six (96) received size 16F Transcervical Foley catheters. Both groups were similar at the baseline. Misoprostol group showed greater improvement in the final cervical length score, with 38.4% and 58.6% scoring 2 and 3 respectively, in contrast with the Foley catheter group where 77.7% had final score of 1, with only 16% scoring 2 and none scored 3 (P = 0.00). Ninety-one percent of the patients in the misoprostol group achieved the maximum cervical consistency score of 2, contrasting with the 31.9% in the Foley Catheter group (P = 0.00). 64.9% of the patients in the Foley catheter group did not achieve appreciable change in cervical consistency. Our findings indicate that intravaginal misoprostol was more effective in improving the scores of cervical length and consistency, while transcervical Foley catheter was better at improving the cervical os dilatation score at pre-induction cervical ripening. The clinical implication is that, patients for pre-induction cervical ripening can be selected for either of these ripening agents based on which cervical factors require improvement in scores

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score < or = 6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E2 gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring. RESULTS: The median interval from randomization to delivery was 4 days in the prostaglandin E2 group (range 0 to 28 days) versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 +/- 1.0 weeks vs 40.5 +/- 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E2-treated patient, but no intervention was required. CONCLUSIONS: Outpatient low-dose prostaglandin E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.

Administration, Intravaginal↗
PubMed1999

Vaginally applied diquat intoxication.

CASE REPORT: We report the case of a woman who introduced 20 mL of diquat concentrate intravaginally. Abdominal pain, vomiting, diarrhea, burning chest pains, and somnolence appeared within the first 24 hours. The vulva and vagina were corrosively inflamed. Acute renal failure appeared on the third day and was treated by 6 hemodialyses over 6 days. The patient was dysarthric with spastic tetraparesis for 3 months. The electroencephalogram, diffusely slow on day 3, was normal on day 28. The electromyoneurogram was normal at all times. Biopsy of a peripheral nerve performed on day 57 following intoxication showed no myelin or axonal alterations.

Administration, Intravaginal↗
PubMed1986

Progesterone therapy in mares with abnormal oestrous cycles.

In two studies in Holland and France a total of 41 mares found either to be in anoestrus or showing continuous oestrous behaviour during the early part of the covering season were treated with a progesterone releasing intravaginal device. Of the 32 mares in the first study, 24 ovulated after treatment and 11 became pregnant to a covering at the induced oestrus. In the second study all but one of the nine mares showed oestrus, seven ovulated and six became pregnant at the post treatment oestrus. By the end of the covering season 15 of the 21 mares treated for anoestrus and seven of the 11 mares treated for persistent oestrus were found to be in foal.

Administration, Intravaginal↗
PubMed1999

[Therapeutic and prophylactic effect of LH-release in cattle].

In this study, LH release in response to the GnRH agonist buserelin and during treatment with a progesterone-releasing intravaginal device (PRID) was studied. A dose of 20 micrograms buserelin induced a more pronounced LH release than 4, 8, 40 and 80 micrograms. After injection of buserelin, pituitary response to a second buserelin injection was markedly reduced for at least 24 hours. Repeated buserelin injections at an interval of several hours therefore cannot be recommended. LH release was markedly suppressed by treatment with PRID. Two PRID tended to be more effective than one. After PRID removal, LH release increased significantly.

Administration, Intravaginal↗
PubMed2004

Oxytocin decreases corticosterone and nociception and increases motor activity in OVX rats.

OBJECTIVES: In the present study the effects of oxytocin administered subcutaneously (s.c.) or intravaginally (i.vag.) on spontaneous motor activity, nociceptive thresholds and plasma corticosterone levels were examined in female ovariectomized (OVX) rats. METHODS: Oxytocin (1 mg/kg s.c. or 100 microg i.vag.) was administered once a day for 10 days to OVX rats. Controls received saline s.c. or cellulose gel i.vag. Spontaneous motor activity was observed in an open-field arena, nociceptive thresholds were investigated by the tail-flick test, and corticosterone and oxytocin plasma levels were measured by radioimmunassay, 3, 4 and 5 days respectively, after the end of the treatment period. RESULTS: Both oxytocin administered s.c. and i.vag. increased forward locomotion (p<0.05) and nociceptive thresholds (p<0.05) significantly. In addition, oxytocin s.c. increased the amount of locomotor activity (p<0.05). Plasma corticosterone levels were decreased (p<0.05) and oxytocin levels were unchanged when measured 5 days after the last administration of oxytocin s.c. or i.vag. CONCLUSION: The present data indicate that oxytocin induces a spectrum of long-lasting effects in OVX rats, including an increase in spontaneous motor activity, elevation of nociceptive thresholds and decrease of corticosterone levels. Similar effects may be induced by estrogens. In addition, these data indicate that i.vag. administration of oxytocin may be used to induce oxytocin-mediated effects.

Administration, Intravaginal↗
PubMed2006

Reproductive performance of lactating dairy cows and heifers resynchronized for a second insemination with an intravaginal progesterone-releasing device for 7 or 8d with estradiol benzoate injected at the time of device insertion and 24h after removal.

One aim of this study was to compare the reproductive performance of cows and heifers when resynchronizing returns to estrus for a second insemination by treating with an intravaginal progesterone-releasing device (IVD) for 7 or 8d when estradiol benzoate (EB) was administered at the start of treatment and again 24h after device removal. An additional aim was to document the pattern of onset and characteristics of estrus with each resynchrony treatment. Lactating cows in three herds were synchronized for a first estrus and AI by treatment with an IVD for 8d, starting on Day 0, cloprostenol (0.5 mg im) at device removal and EB at device insertion (2.0 mg im) and 24h after removal (1.0 mg im). Cows were resynchronized for a second estrus starting on Day 23 by reinsertion of IVDs for 7 (IVD-7-EB; n=449) or 8d (IVD-8-EB; n=445) with EB (1.0 mg im) administered at device insertion and 24h after removal. Cows were resynchronized for a third estrus by administration of EB (1.0 mg im) on Day 46, but subsequent treatments (no further treatment, reinsertion of CIDR or administration of EB on Day 55) varied among herds as part of separate studies. Maiden heifers (7-Day, n=68; 8-Day, n=69) were similarly treated as cows in a separate herd, but doses of EB were always 1.0 mg im at device insertion and 0.75 mg im 24h after removal. Heifers were not resynchronized for a third estrus. Cattle were inseminated on detection of estrus at each synchronized estrus. Cumulative pregnancy rates 4 week (66.0%, 276/418 versus 59.1%, 247/418) and 7 week (72.7%, 304/418 versus 67.7%, 283/418) after the start of AI were greater (P<0.05) in the IVD-7-EB cows compared to the IVD-8-EB cows, respectively; this was associated with a 9% increase in conception rates at the second estrus (P=0.051) in the IVD-7-EB cows. Treatment did not significantly affect reproductive performance in heifers. Characteristics of estrus measured with radiotelemetry did not differ significantly between the two treatment groups, but more cows were detected in estrus 36 h after removal of IVDs in the IVD-8-EB cows compared to the IVD-7-EB cows (P<0.05). We concluded that reproductive performance in resynchronized dairy cows but not heifers was greater following resynchronization of estrous cycles after AI with an IVD for 7 compared to 8d when EB was injected at the start of treatment and 24h after device removal.

Administration, Intravaginal↗
PubMed1991

Comparison of intravenous oxytocin with and without vaginal prostaglandin E2 gel in term pregnancy with premature rupture of membranes and unfavorable cervix.

Forty-seven nulliparous term pregnant women with PROM and unfavorable cervix, were randomly divided into 23 patients who were observed for four hours then followed by intravenous oxytocin, and 24 patients who were given 3 mg PGE2 gel intravaginally then followed by intravenous oxytocin four hours later. No statistically significant difference was observed between the two treatment groups with regard to Bishop score four hours after observation, intravenous oxytocin to delivery time, Apgar score at 1 and 5 minutes and maternal puerperal complications in both groups. It can be concluded that PGE2 did not significantly improve Bishop score or shorten the induction to delivery time in cases of PROM with unfavorable cervix. Intravenous oxytocin is still preferable both in terms of cost and effectiveness.

Administration, Intravaginal↗
PubMed1994

Intravaginal misoprostol versus dinoprostone as cervical ripening and labor-inducing agents.

OBJECTIVE: To compare dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for ripening the cervix and inducing labor at term. METHODS: Sixty-three women were randomized to receive 100 micrograms misoprostol or 3 mg dinoprostone, both as intravaginal tablets. RESULTS: There was no statistical difference between the groups for pre-induction status. The mean Bishop scores before drug insertion were almost identical. Twelve hours after insertion, the mean change in the Bishop score was significantly higher in those receiving misoprostol (5.0 versus 3.3) (P = .008). However, there were no significant differences in induction-to-delivery interval, spontaneous labor rates, type of delivery, fetal outcome, or maternal complications. CONCLUSION: Misoprostol is as effective as dinoprostone for inducing labor at term.

Administration, Intravaginal↗
PubMed1993

Dry and tight: sexual practices and potential AIDS risk in Zaire.

Both men and women in central Zaire like a 'dry, tight' vagina because it increases pleasure during sexual intercourse. In focus group interviews, they described wiping and washing procedures, as well as 30 different substances, mostly leaves and powders, that women can insert into the vagina to produce the desired effects. Women who use leaves said they crush them, insert them for several hours, then remove them before intercourse. Women who insert powders leave them in place during intercourse. Individual interviews with 99 women (half of them unmarried prostitutes and half married women) showed that over one-third of each group had used intravaginal drying or tightening substances at some time. Vaginal examinations by a physician revealed that several of the substances cause inflammatory lesions of the vagina and cervix. Furthermore, some products cause extreme dryness that could foster epithelial trauma during coitus, both for the woman and for her partner. Breaks in the epithelium may promote the passage of organisms that cause AIDS and other sexually-transmitted diseases. Thus the sexual practices of drying and tightening the vagina may be increasing the risk of infection.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Routes of inoculation and the immune response to a resolving genital flavivirus infection in a novel murine model.

The prolonged, abnormal immune response patterns produced by many sexually transmitted viruses have been intensively studied. Because normal antiviral immune responses in the vagina are less well-defined, we developed a resolving murine model using vaginal inoculation with the flavivirus, West Nile virus. Infection resulted in 12% mortality, with sterile protective immunity to vaginal or systemic re-challenge. B-cell numbers increased in the vaginal mucosa from day 1-7 after primary infection, while similar increases in B220(+), CD4(+) and CD8(+) lymphocytes in the draining lymph node were delayed by 48 h. By day 4 postinfection, a MHC-II(+) dendritic cell population became depleted from the stroma and formed aggregates below the basement membrane at points of demonstrable epithelial infection. In contrast, primary systemic or intradermal inoculation resulted in 80-90% mortality, but also conferred protective sterile immunity to vaginal West Nile virus re-challenge. Intravaginal and intradermal immunization elicited comparable, accelerated accumulation of larger B-cell numbers in the mucosa and draining lymph node upon intravaginal re-challenge than systemic immunization. However, accumulation of CD4(+) T cells in both sites in the intradermally immunized group was significantly greater than in intravaginally or systemically immunized mice. Accelerated accumulation of dendritic cells occurred at periodic sub-basement membrane sites in the absence of detectable virus 1 day after vaginal re-challenge, irrespective of the route of immunization. These data illustrate the diversity of possible effective immune responses to West Nile virus in the vaginal mucosa. They show primary vaginal inoculation produces effective immunity to flavivirus infection with lower mortality than other routes and suggest a local role for vaginal mucosal dendritic cells in both primary and secondary responses.

Administration, Intravaginal↗
PubMed1987

[Comparison between prostaglandin E2 gel and oxytocin in medically indicated labor induction].

The use of prostaglandins (PG) increasingly replaces the "classical" method of induction of labour by means of oxytocin and amniotomy, the last-named method being associated, especially in women with an unripe cervix, with side effects like prolonged labour and a higher rate of obstetric surgery. In this study the point of interest was whether prostaglandins offer any advantages over the classical method in respect of efficacy and maternal and foetal tolerance. 99 patients subdivided into primiparae and multiparae were randomly assigned to group A or B. In group A labour was induced with 1 mg resp. 2 mg PGE2 intravaginally at an interval of 6 hours. In group B the method of induction consisted of intravenous oxytocin and amniotomy. The success rate of induction was almost equal in both groups. However, in those patients where PGE2 induction did not succeed and who could not be delivered within 12 hours the cervical score was significantly improved in comparison to the oxytocin group. Based on the experience reported in the literature, one might speculate that an increased dosage could still improve the results of vaginally administered PGE2 gel.

Administration, Intravaginal↗
PubMed1995

[Comparison of vaginal devices CIDR and PRID in ovariectomized cows using hormone analysis].

Plasma concentrations of progesterone and estradiol were compared in 7 ovariectomised cows after application of 2 different intravaginal releasing devices. Peak concentrations of 4-6 ng/ml progesterone were found within 2 hours after application of the devices. From day 2 to day 6 concentrations sank continuously to 2 ng/ml. Progesterone levels of 1-2 ng/ml prevailed from day 6 to the day of removal of the pessaries (day 12 for PRID, day 15 for CIDR). No differences between the two devices were detected. Increased concentrations of estradiol were found for PRID only, reaching maximum levels of 6-7 pg/ml plasma 150 minutes after application.

Administration, Intravaginal↗